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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, and impaired muscular coordination (ataxia). Life-threatening complications may occur 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 life-threatening complications.

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.

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.

Radiation Syndromes can affect males and females in equal numbers.

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.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

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

REVIEW ARTICLES
Feldmeier JJ, Hampson NB. A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach. Undersea Hyperb Med. 2002;29:4-30.

Lehmann AR. Replication of damaged DNA in mammalian cells: new solutions to an old problem. Mutat Res. 202;509:23-34.

Mendelsohn FA, Divino CM, Reis ED, et al. Wound care of radiation therapy. Adv Skin Wound Care. 2002;15:216-24.

Bismar MM, Sinicrope FA. Radiation enteritis. Curr Gastroenterol Rep. 2002;4:361-65.

Gandhi OP. Electromagnetic fields: human safety issues. Annu Rev Biomed Eng. 2002;4:211-34.

Moysich KB, Menezes RJ, Michalek AM. Chernobyl-related ionizing radiation exposure and cancer risk: an epidemiological review. Lancet Oncol. 2002;3:269-79.

Dainiak N. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 2002;30:513-28.

Kilpatrick JJ. Nuclear attacks. RN. 2002;65:46-51.

Winkelmann RA, Tretyakov FD, Startsev NV, et al. Cause-of-death registers in radiation contaminated areas of the Russian Federation and Kazakhstan. Radiat Environ Biophys. 2002;41:5-11.

Gilbert ES, Land CE, Simon SL. Health effects from fallout. Health Phys. 2002;82:726-35.

Murphy GM. Photoprotection: public campaigns in Ireland and the UK. Br J Drmatol. 2002;146 Suppl 61:31-33.

Brooks AL. Biomarkers of exposure and dose: state of the art. Radiat Prot Dosimetry. 2001;97:39-46.

Rydberg B. Radiation-induced DNA damage and chromatin structure. Acta Oncol. 2001;40:682-85.

FROM THE INTERNET
RADIATION HEALTH EFFECTS RESEARCH RESOURCE. Ionizing Radiation Health Effects Forum. nd. 4pp.
www.radefx.bcm.tmc.edu/ionizing/ionizing.htm

McCarthy PL. Personal Communication to Radefx. Disaster Preparedness for radiation Accidents: Patient treatment and management for acute radiation syndromes… Treatment Modalities for acute radiation Exposure. nd. 3pp.
www.radefx.bcm.tmc.edu/ionizing/subject/risk/patient.htm

Virtual Naval Hospital. USDoD. Radiation Syndromes. Last modified: 1/10/2003: 3pp.
www.vnh.org/EWSurg/ch07/07RadiationSyndromes.html