CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0416/04165.txt

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$Unique_ID{BRK04165}
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$Title{Radiation Syndromes}
$Subject{Radiation Syndromes Radiation disease Radiation reaction Radiation
sickness Radiation effects Radiation illness Radiation injuries}
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Copyright (C) 1986, 1987, 1988, 1989 National Organization for Rare
Disorders, Inc.

264:
Radiation Syndromes

** IMPORTANT **
It is possible the main title of the article (Radiation Syndromes) is not
the name you expected.  Please check the SYNONYMS listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Radiation disease
     Radiation reaction
     Radiation sickness
     Radiation effects
     Radiation illness
     Radiation injuries

General Discussion

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Radiation syndromes describe the harmful effects - acute, delayed, or
chronic - produced by exposure to ionizing radiations.  Tissues vary in
response to immediate radiation injury according to the following descending
order of sensitivity:

     (1) lymph cells
     (2) reproductive organs
     (3) proliferating cells of the bone marrow
     (4) epithelial cells of the bowel
     (5) top layer (epidermis) of the skin
     (6) liver cells
     (7) epithelium of the little lung sacs (alveoli) and bile passages
     (8) kidney epithelial cells
     (9) endothelial cells of the membranes around the lungs, lining the chest
cavity (pleura) and the abdominal cavity (peritoneum)
     (10) nerve cells
     (11) bone cells
     (12) muscle and connective tissue.

Generally, the more rapid the turnover of the cell, the greater the
radiation sensitivity.

Symptoms

The following information describes radiation syndromes which can develop as
a result of high doses (e.g., an atomic explosion) to small doses (e.g.,
repeated x-rays over a period of days or weeks).

The disruption of cell renewal systems and direct injury of other tissues
produce clearly defined clinical syndromes:

1. ACUTE RADIATION SYNDROMES
The syndromes depend on dose, dose rate, affected area of the body, and
the period of time elapsing after exposure.  They are:

A.  CEREBRAL SYNDROME
Cerebral syndrome is produced by extremely high total body doses of
radiation (greater than 3000 rads).  This syndrome is always fatal, and
consists of three phases:  a prodromal period of nausea and vomiting; then
listlessness and drowsiness; and, finally, a more generalized component
characterized by tremors, convulsions, impaired muscular coordination
(ataxia) and death within a few hours.

B.  GASTRO-INTESTINAL SYNDROME
This syndrome can occur when the total dose of radiation is smaller but
still high (400 or more rads).  It is characterized by intractable nausea,
vomiting and diarrhea that lead to severe dehydration, diminished plasma
volume, vascular collapse and death.

C.  HEMATOPOIETIC SYNDROME
This syndrome occurs at exposure of between 200 to 1000 rads.  Initially
it is characterized by lack of appetite (anorexia), apathy, nausea and
vomiting (Gastrointestinal syndrome) which may be maximal within 6 to 12
hours after exposure.  Symptoms then subside so that within 24 to 36 hours
after exposure the patient appears to have no symptoms.  During this period
of relative well-being, the lymph nodes, spleen and bone marrow begin to
atrophy, leading to underproduction of all types of blood cells
(pancytopenia).  In the peripheral blood, lack of lymph cells (lymphopenia)
commences immediately, reaching a peak within 24 to 36 hours.  Lack of
neutrophils, a type of white blood cell, develops more slowly.  Lack of blood
platelets (thrombocytopenia) may become prominent within 3 or 4 weeks.
Increased susceptibility to infection develops due to a decrease in
granulocytes and lymphocytes, impairment of antibody production and
granulocyte migration, decreased ability to attack and kill bacteria,
diminished resistance to diffusion in subcutaneous tissues, and bleeding
(hemorrhagic) areas of the skin and bowel that encourage entrance and growth
of bacteria.  Hemorrhage occurs mainly due to the lack of blood platelets.

With acute total body radiation greater than 600 rads, hematopoietic or
gastrointestinal malfunction generally will be fatal.  With doses of less
than 600 rads, the probability of survival is inversely related to the total
dose.

2. ACUTE RADIATION SICKNESS
Acute "radiation sickness" following radiation therapy (particularly of
the abdomen), is characterized by nausea, vomiting, diarrhea, anorexia,
headache, malaise and rapid heartbeat (tachycardia) of varying severity.  The
discomfort subsides within a few hours or days.

3. DELAYED EFFECTS OF RADIATION

A.  INTERMEDIATE EFFECTS
Prolonged or repeated exposure to low radiation doses from a variety of
sources may produce absence of menstruation (amenorrhea), decreased fertility
in both sexes, decreased libido in the female, anemia, decreased white blood
cells (leukopenia), decreased blood platelets (thrombocytopenia), and
cataracts.  More severe or highly localized exposure causes loss of hair,
skin atrophy and ulceration, thickening of the skin (keratosis), and vascular
changes in the skin (telangiectasia).  Ultimately it may cause a type of skin
cancer called squamous cell carcinoma.  Another type of cancer, osteosarcoma,
may appear years after swallowing radioactive bone-seeking nuclides such as
radium salts.  Injury to exposed organs may occur occasionally after
extensive radiation therapy for treatment of cancer.

Kidney function changes include a decrease in renal plasma flow,
glomerular filtration rate (GFR), and tubular function.  Following a latent
period of six months to one year after extremely high does of radiation,
protein in the urine, kidney insufficiency, anemia and high blood pressure
may develop.  When cumulative kidney exposure is greater than 2000 rads in
less than 5 weeks, kidney failure with diminished urine output may occur in
about 37% of cases.

Large accumulated doses of radiation to muscles may result in painful
myopathy with atrophy and calcification.  Very rarely, these changes may be
followed by cancer, usually a sarcoma.

Radiation pneumonitis and subsequent pulmonary fibrosis may occur when
cancer metastases to the lung are irradiated.

Radiation inflammation of the sac around the heart (pericarditis) and of
the heart muscle (myocarditis) have been produced by extensive radiotherapy
of the middle region between the lungs (the mediastinum).

Myelopathy may develop after a segment of the spinal cord has received
cumulative doses of greater than 4000 rads.  Following vigorous therapy of
abdominal lymph nodes for seminoma, lymphoma, ovarian carcinoma, or chronic
ulceration, fibrosis and perforation of the bowel may develop.

Skin redness (erythema) and skin ulceration were observed fairly often
during the era of high voltage x-ray therapy, but the high-energy photons
produced by modern cobalt units or accelerators penetrate deeply into tissues
and have virtually eliminated those complications.

B.  LATE SOMATIC AND GENETIC EFFECTS
Radiation alters the "information system" of proliferating cells of the
body and germ cells.  With body cells this may be manifested ultimately as
somatic disease such as cancer (leukemia, thyroid, skin, bone), or cataracts.
Studies of animals exposed to radiation indicate that such exposure shortens
life.  It is asserted, but not proven, that there is a "threshold" dose for
leukemia, and that the incidence increases with dose.  Thyroid cancer has
been observed 20 to 30 years after x-ray treatment for adenoid and tonsillar
hypertrophy.  Thus x-ray treatment for nonmalignant conditions is now rarely
used except in highly unusual situations.

When cells are exposed to radiation, the number of mutations is
increased.  If mutations are perpetuated by procreation, this will cause
genetic defects.  The possibility of mutations presents a serious medical,
ethical and philosophic problem with respect to unborn generations.  It
imposes a moral obligation to limit radiation exposure to an absolute minimum
for valid diagnostic or therapeutic purposes, and to strictly control
occupational and environmental exposure.  The potential harm, however, should
be kept in perspective.  Some investigators suggest that no measurable
effects will occur below a certain threshold while others insist that any
radiation is potentially harmful.

Causes

In the past, harmful sources of ionizing radiation were limited primarily to
high-energy x-rays used for diagnosis and therapy, and to radium and related
radioactive materials.  Present sources of potential radiation include
nuclear reactors, cyclotrons, linear accelerators, alternating gradient
synchrotons, and sealed cobalt and cesium sources for cancer therapy.
Numerous artificial radioactive materials have been produced for use in
medicine and industry by neutron activation in reactors.

The accidental escape of moderate to large amounts of radiation from
reactors has occurred several times.  Radiation exposure from reactor
accidents (like Chernobyl) during the first 30 years (up to 1975) resulted in
more than 30 serious exposures with 7 deaths.  Nuclear power generators in
the United States must meet stringent federal standards that limit effluent
radioactivity to extremely low levels.  Although background radioactivity in
the earth and the atmosphere increased during the years of atmospheric
nuclear weapons testing, it appears to have generally stabilized at present
levels.  Ionizing radiation, whether in the form of x-rays, neutrons,
protons, alpha or beta particles, or gamma-rays, produces ionization in
tissues.  In addition to the early somatic effects of large doses of
radiation (clinically observable within days), changes in the DNA of rapidly
proliferating cells may become manifest as a disease or as a genetic defect
in offspring many years later.

Total dose, and dose rate, determine somatic or genetic effects of
radiation.  The units of measurement commonly used in determining radiation
exposure or dose are the roentgen, the rad and the rem.  The roentgen (R) is
a measure of quantity of x or gamma ionizing radiation in air.  The radiation
absorbed dose (rad) is the amount of energy absorbed in any substance from
exposure, and applies to all types of radiation.  The R and the rad are
nearly equivalent in energy for practical purposes.  The rem is used to
correct for the observation that some types of radiation, such as neutrons,
may produce more biological effect for an equivalent amount of absorbed
energy; thus the rem is equal to the rad multiplied by a constant called the
"quality factor".  For x and gamma radiation the rem is equal to the rad.
The rad and the rem are currently being replaced in the scientific
nomenclature by two units that are compatible with the International System
of Units, namely the gray (Gy), equal to 100 rads and the Sievert (Sv), equal
to 100 rem.

DOSE RATES
The dose rate is the radiation dose/unit of time.  From the very low dose
rates of unavoidable background radiation (about 0.1 rad/yr), where no effect
can be detected, the probability of measurable effects increases as the dose
rate and/or total dose increases.  An observable effect becomes quite certain
after a single dose of several hundred rads.  As a rule, large doses of
radiation are of concern because of their immediate somatic effects, while
low doses are of concern because of the potential for possible late somatic
and long-term genetic effects.  The effects of radiation exposure on an
individual are cumulative.

The area of the body exposed to radiation is also an important factor.
The entire human body can probably absorb up to 200 rads acutely without
fatality.  However, as the whole-body dose approaches 450 rads the death rate
will approximate 50%, and a total whole-body dose of greater than 600 rads
received in a very short time will almost certainly be fatal.  By contrast,
many thousands of rads delivered over a long period of time (e.g. for cancer
treatment), can be tolerated by the body when small volumes of tissue are
irradiated.  Distribution of the dose within the body is also important.  For
example, protection of bowel or bone marrow by appropriate shielding will
permit survival of the exposed individual from what would be an otherwise
fatal whole-body dose.

Therapies:  Standard

PREVENTION
To avoid fatal or serious overexposure to radiation it is necessary to
rigorously enforce protective and preventative measures and adherence to the
maximum permissible dose (MPD) levels.  These values are listed in "Basic
Radiation Criteria", NCRP Report No. 39, published by the National Council on
Radiation Protection and Measurements (P.O. Box 30175, Washington, D.C.
20014).

TREATMENT
Contamination of the skin by radioactive materials, should be immediately
removed by copious rinsing with water and special solutions containing an
agent such as EDTA (ethylenediamine tetraacetic acid), a chelating agent
which binds many radioactive isotopes.  Small puncture wounds must be cleaned
vigorously to remove contamination.  Rinsing and removal of contaminated
tissue are necessary until the wound is free of radioactivity.  Ingested
material should be removed promptly by induced vomiting or by washing out the
stomach if exposure is recent.  If radioiodine is inhaled or ingested in
large quantities, the patient should be given Lugol's solution or saturated
solution of potassium iodide to block thyroid uptake for days to weeks, and
diuresis should be promoted.  Monitoring of exposed patients is mandatory,
using Geiger counters or sophisticated whole-body counters.  Urine should be
analyzed for non-gamma-emitting radionuclides if exposure to these agents is
suspected.  Radon breath analysis can be done in cases of suspected radium
ingestion.

For the acute cerebral syndrome, treatment is symptomatic and supportive.
It is aimed at combating shock and lack of oxygen, relieving pain and anxiety
and sedation for control of convulsions.

If the gastro-intestinal syndrome develops after external whole-body
irradiation, the type and degree of therapy will be dictated by the severity
of the symptoms.  After modest exposure, antiemetics and sedation may
suffice.  If oral feeding can be started, a bland diet is tolerated best.
Fluid, electrolytes, and plasma may be required in huge volumes.  The amount
and type will be dictated by blood chemical studies (especially electrolytes
and proteins), blood pressure, pulse, urine output, and skin turgor.

Management of the hematopoietic syndrome, with its obvious potentially
lethal factors of infection, hemorrhage and anemia, is similar to treatment
of marrow hypoplasia and pancytopenia from any cause.  Antibiotics, fresh
blood, and platelet transfusions are the main therapeutic aids.  However, a
side effect of platelet transfusions may be development of an immune response
to future platelet transfusions.  Rigid germ-free conditions (asepsis) during
all skin-puncturing procedures is mandatory as is strict isolation to prevent
exposure to disease-causing germs.

Concurrent anticancer chemotherapy or use of other marrow-suppressing
drugs, should be avoided.

Bone marrow transplants have proven helpful in some cases.  If a whole
body radiation dose greater than 200 rads is suspected, and if granulocytes
and platelets continue to decrease and fall to less than 500 and 20,000/cu
mm, respectively, compatible bone marrow transplantation should be made.  With
use of cyclosporin to prevent rejection of the graft, a marrow transplant will
most likely increase the probability of survival.  Thirteen people at
Chernobyl who received estimated total body doses of radiation between 5.6 to
13.4, underwent bone marrow transplants after the Chernobyl accident.  Two
transplant recipients survived.  Others died of various causes including
burns, graft-vs-host disease, kidney failure, etc.  Therefore, the success
of bone marrow transplantation for radiation sickness was inconclusive.

In dealing with late somatic effects due to serious chronic exposure,
removal of the patient from the radiation source is the first step.  With
radium, thorium, or radiostrontium deposition in the body, prompt
administration, orally and by injection, of chelating agents such as EDTA
will increase the excretion rate.  However, in the late stages these agents
appear to be useless.  Radiation ulcers and cancers require surgical removal
and plastic repair.  Radiation-induced leukemia is treated like any similar
spontaneously occuring leukemia.  Anemia is corrected by blood transfusion.
Bleeding due to lack of platelets (thrombocytopenia) may be reduced by
platelet transfusions.

No effective treatment for sterility, or for ovarian and testicular
dysfunction (except for hormone supplementation in some cases), is available.

Therapies:  Investigational

Transplantation of liver tissue cells from fetuses into the bone marrow is
being investigated as a substitute for bone marrow transplants, especially in
young children whose immune systems have totally failed.  Once the liver
cells are transplanted in the bone marrow, the fetal liver cells begin to
function like bone marrow cells and start producing blood cells.  There is
less likelihood of this procedure causing graft-versus-host disease than in
bone marrow transplantation.  However, this experimental procedure has not
yet been proven effective in humans, so more research is needed before it can
be considered as a safe and effective treatment.

Eight Brazilian patients with radiation sickness were treated with
granulocyte-macrophage colony stimulating factor (GM-CSF) during 1987.  This
is a genetically-engineered version of a natural human protein.  GM-CSF may
boost the immune system, which is destroyed by excessive radiation, by
stimulating production of certain white blood cells (granulocytes in the bone
marrow.)  Four of the eight Brazilian radiation victims showed a significant
recovery of their immune systems, but four others died.  More research is
needed to determine the safety and effectiveness of this treatment.

This disease entry is based upon medical information available through
August 1989.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Radiation Syndromes, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     National Association of Radiation Survivors (NARS)
     78 El Camino Real
     Berkeley, CA  94705

     American Cancer Society
     1599 Clifton Rd., NE
     Atlanta, GA  30329
     [phone]

     Leukemia Society of America
     733 Third Avenue
     New York, NY 10017
     [phone]

     National Council on Radiation Protection and Measurements
     7910 Woodmont Avenue
     Bethesda, MD 20814

     NIH/National Cancer Institute
     9000 Rockville Pike, Bldg. 31, Rm. 1A2A
     Bethesda, MD 20892
     1-800-4-CANCER

The National Cancer Institute has developed PDQ (Physician Data Query), a
computerized database designed to give doctors quick and easy access to many
types of information vital to treating patients with this and many other
types of cancer.  To gain access to this service, a doctor can contact the
Cancer Information Service offices at 1-800-4-CANCER.  Information
specialists at this toll-free number can answer questions about cancer
prevention, diagnosis, and treatment.

     International Tremor Foundation
     360 W. Superior St.
     Chicago, IL  60610
     [phone]

References

Basic Radiation Protection Criteria; recommendations of the National Council
on Radiation Protection and Measurements, National Council on Radiation
Protection and Measurements (1984).

BONE MARROW TRANSPLANTATION AFTER THE CHERNOBYL ACCIDENT, Alexandr Baranov,
et al.; N Eng J of Med.  (July 27, 1989, issue 321, (4)).  Pp. 205-212.