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Free radicals and environmental toxins
UAEM/IRIEM ABSTRACTS
(central venous %02 saturation greater than 70% and approaching the arterial value). Bedside tests, such as the Lee-Jones reaction on gastric contents, may give diagnostic clues, but there are many interferences from commonly ingested agents. The prognosis in cyanide poisoning is generally good if the patient reaches medical care before sustaining a cardiac arrest. Patients usually either succumb or fully recover. Isolated patients have had persistent encephalopathic sequelae. Unique North American clinical experiences with cyanide poisoning have included the 1982 Chicago cyanide tampering incident, recent autopsy data from the Cook County (Illinois) Institute of Forensic Medicine, and cyanide poisoning from the use of laetrile as an antineoplastic agent. The Chicago tampering incident involved replacement of acetaminophen with cyanide in Extra Strength Tylenol ® capsules. Seven persons died in this bizarre incident, Post-mortem cyanide levels were obtained from five of the victims. Multiple blood and urine cyanide and thiocyanate levels were obtained from one victim who survived for nearly 40 hours. Tainted capsules remaining in bottles used by the victims were analyzed and found to contain between 117 and 858 mg/capsule of potassium cyanide. Autopsy data from the Cook County Institute of Forensic Medicine for the period March 1984 to January 1985 revealed eight fatalities (0.2% of all reported deaths) due to cyanide poisoning. Various blood, urine, and tissue cyanide levels were obtained. Between 1977 and 1983, nine cases of cyanide poisoning from laetrile were reported in the North American literature. Two of these victims died. The only antidotes currently available for cyanide poisoning in the United States are amyl nitrite, sodium nitrite, and sodium thiosulfate in the Lilly Cyanide Antidote Kit ®. Other antidotes available in Europe are dicobalt EDTA (Kelocyanor ®) and the combination hydroxycobalamin/ sodium thiosulfate. The hydroxycobalamin/sodium thiosulfate combination recently has been designated an orphan drug by the Food and Drug Administration. Hyperbaric oxygen has been proposed as a treatment for cyanide poisoning. While animal research has shown equivocal efficacy, anecdotal clinical experience indicates that hyperbaric oxygen should be used in those patients not having a satisfactory clinical response to other supportive measures and antidote.
3
Organophosphate Insecticides
Lester M Haddad, MD, Director, Emergency Department, Washington County Hospital (MIEMSS Trauma/Regional Center), Hagerstown, Maryland; Clinical ASsistant Professor, Department of Emergency Medicine, Georgetown University Hospital, Washington, DC The organophosphate insecticides have replaced DDT and the organochlorine insecticides as the agricultural agent of choice. Because of their unstable chemical structure, they disintegrate into harmless radicals within days after application, and do not persist in body tissue or the environment [as does DDT). The concept that a chemical can penetrate the intact skin without producing sensation, or that such a small quantity of chemical can be fatal, is simply not grasped by the general public, and herein lies the danger of the highly toxic organophosphate insecticides. The basic science of the human autonomic nervous system comes into focus with organophosphate poisoning, as acetylcholinesterase is inhibited. The clinical presentation of organophosphate poisoning, clinical guidelines to therapy with the physiologic antidote atropine and the specific biochemical antidote pralidoxime; unusual clinical presentations; and complications will be reviewed.
14 152/94
Free Radicals and Environmental Toxins
Steven D Aust, PhD, Professor, Department of Biochemistry, Center for the Study of Active Oxygen in Biology and Medicine, Michigan State University, East Lansing, Michigan Some chemicals that contaminate our environment exert their toxic effects by virtue of their ability to form free radicals. In the absence of sufficient quenching reactions, these reactive radicals can attack biomolecules, resulting in their oxidative degradation. Biological membranes which contain polyunsaturated fatty acids are most susceptible to oxidative degradation (lipid peroxidation), although oxidation of DNA may have more severe biological consequences. Free radical species can be generated by at least two mechanisms in vivo. The first, of which carbon tetrachloride is the classic example, is the biotransformation of the chemical to a free radical species. Metabolism of CC14 to the trichloromethyl radical by the hepatic mixed-function oxidase system results in the initiation of lipid peroxidation, protein-lipid cross linkages and trichloromethyl adducts with DNA, protein, and lipid. The second mechanism for forming free radicals involves their reduction to less stable free radical intermediates which are oxidized by molecular oxygen to give superoxide (O2-~. In the presence of transition metals such as iron, O2 ~ can be converted to other oxygen radical species such as the hydroxyl radical (.OH), an extremely powerful oxidant capable of cleaving DNA, oxidizing protein, and initiating lipid peroxidation. Under many conditions, lipid peroxidation appears not to be initiated by .OH, but rather by an iron-oxygen complex. Regardless of the identity of the initiating species, transition metals are required for most of the deleterious reactions of oxygen. Superoxide and certain organic radicals have been found to release iron from ferritin.
5
Emergency Department Response to Radiation Accidents
Robert C Ricks, PhD, Director, Radiation Emergency Assistance Center/Training Site (REAC/TS), Oak Ridge Associated Universities, Oak Ridge, Tennessee Perceptions regarding medical management of the radiation accident victim often are obscured by misunderstanding, fear, or uncertainty. Emergency physicians and nurses may feel that ultraspecial facilities, equipment, and resources are needed to assess and care for the radiation accident victim while providing minimal risk to responders. This presentation will describe a proper response protocol, with emphasis on adaptation of everyday procedures to meet the patient's needs as well as the structure of a radioiogical emergency response team. Aspects of facility preparation, patient reception/triage, contamination control, radiological monitoring, decontamination, and post-emergency patient transfer will be covered. Decontamination procedures covered will include those for intact skin, hair, eyes, wounds, and internally deposited radionuclides. The difference between handling the patient exposed to radiation and the patient contaminated with radioactive material will be demonstrated. Physical and biological samples needed to assess status of both exposed and contaminated patients will be presented. Appropriate case histories drawn from the REAC/TS Registry files documenting worldwide radiation accident history will be reviewed. Finally, questions most frequently asked by emergency medical responders regarding their involvement in radiation accidents will be reviewed, with emphasis on whether there is a medical emergency following a radiation accident. [This abstract is based on work performed under Contract No. DE-ACOS-760R00033 between the Department of Energy, Office of Health and Environmental Research, and Oak Ridge Associated Universities.]
6
New Concepts of Radiation Accidents m Biology
Eugene L Saenger, MD, EL Saenger Radioisotope Laboratory, Annals of Emergency Medicine
15:1 January 1986
(central venous %02 saturation greater than 70% and approaching the arterial value). Bedside tests, such as the Lee-Jones reaction on gastric contents, may give diagnostic clues, but there are many interferences from commonly ingested agents. The prognosis in cyanide poisoning is generally good if the patient reaches medical care before sustaining a cardiac arrest. Patients usually either succumb or fully recover. Isolated patients have had persistent encephalopathic sequelae. Unique North American clinical experiences with cyanide poisoning have included the 1982 Chicago cyanide tampering incident, recent autopsy data from the Cook County (Illinois) Institute of Forensic Medicine, and cyanide poisoning from the use of laetrile as an antineoplastic agent. The Chicago tampering incident involved replacement of acetaminophen with cyanide in Extra Strength Tylenol ® capsules. Seven persons died in this bizarre incident, Post-mortem cyanide levels were obtained from five of the victims. Multiple blood and urine cyanide and thiocyanate levels were obtained from one victim who survived for nearly 40 hours. Tainted capsules remaining in bottles used by the victims were analyzed and found to contain between 117 and 858 mg/capsule of potassium cyanide. Autopsy data from the Cook County Institute of Forensic Medicine for the period March 1984 to January 1985 revealed eight fatalities (0.2% of all reported deaths) due to cyanide poisoning. Various blood, urine, and tissue cyanide levels were obtained. Between 1977 and 1983, nine cases of cyanide poisoning from laetrile were reported in the North American literature. Two of these victims died. The only antidotes currently available for cyanide poisoning in the United States are amyl nitrite, sodium nitrite, and sodium thiosulfate in the Lilly Cyanide Antidote Kit ®. Other antidotes available in Europe are dicobalt EDTA (Kelocyanor ®) and the combination hydroxycobalamin/ sodium thiosulfate. The hydroxycobalamin/sodium thiosulfate combination recently has been designated an orphan drug by the Food and Drug Administration. Hyperbaric oxygen has been proposed as a treatment for cyanide poisoning. While animal research has shown equivocal efficacy, anecdotal clinical experience indicates that hyperbaric oxygen should be used in those patients not having a satisfactory clinical response to other supportive measures and antidote.
3
Organophosphate Insecticides
Lester M Haddad, MD, Director, Emergency Department, Washington County Hospital (MIEMSS Trauma/Regional Center), Hagerstown, Maryland; Clinical ASsistant Professor, Department of Emergency Medicine, Georgetown University Hospital, Washington, DC The organophosphate insecticides have replaced DDT and the organochlorine insecticides as the agricultural agent of choice. Because of their unstable chemical structure, they disintegrate into harmless radicals within days after application, and do not persist in body tissue or the environment [as does DDT). The concept that a chemical can penetrate the intact skin without producing sensation, or that such a small quantity of chemical can be fatal, is simply not grasped by the general public, and herein lies the danger of the highly toxic organophosphate insecticides. The basic science of the human autonomic nervous system comes into focus with organophosphate poisoning, as acetylcholinesterase is inhibited. The clinical presentation of organophosphate poisoning, clinical guidelines to therapy with the physiologic antidote atropine and the specific biochemical antidote pralidoxime; unusual clinical presentations; and complications will be reviewed.
14 152/94
Free Radicals and Environmental Toxins
Steven D Aust, PhD, Professor, Department of Biochemistry, Center for the Study of Active Oxygen in Biology and Medicine, Michigan State University, East Lansing, Michigan Some chemicals that contaminate our environment exert their toxic effects by virtue of their ability to form free radicals. In the absence of sufficient quenching reactions, these reactive radicals can attack biomolecules, resulting in their oxidative degradation. Biological membranes which contain polyunsaturated fatty acids are most susceptible to oxidative degradation (lipid peroxidation), although oxidation of DNA may have more severe biological consequences. Free radical species can be generated by at least two mechanisms in vivo. The first, of which carbon tetrachloride is the classic example, is the biotransformation of the chemical to a free radical species. Metabolism of CC14 to the trichloromethyl radical by the hepatic mixed-function oxidase system results in the initiation of lipid peroxidation, protein-lipid cross linkages and trichloromethyl adducts with DNA, protein, and lipid. The second mechanism for forming free radicals involves their reduction to less stable free radical intermediates which are oxidized by molecular oxygen to give superoxide (O2-~. In the presence of transition metals such as iron, O2 ~ can be converted to other oxygen radical species such as the hydroxyl radical (.OH), an extremely powerful oxidant capable of cleaving DNA, oxidizing protein, and initiating lipid peroxidation. Under many conditions, lipid peroxidation appears not to be initiated by .OH, but rather by an iron-oxygen complex. Regardless of the identity of the initiating species, transition metals are required for most of the deleterious reactions of oxygen. Superoxide and certain organic radicals have been found to release iron from ferritin.
5
Emergency Department Response to Radiation Accidents
Robert C Ricks, PhD, Director, Radiation Emergency Assistance Center/Training Site (REAC/TS), Oak Ridge Associated Universities, Oak Ridge, Tennessee Perceptions regarding medical management of the radiation accident victim often are obscured by misunderstanding, fear, or uncertainty. Emergency physicians and nurses may feel that ultraspecial facilities, equipment, and resources are needed to assess and care for the radiation accident victim while providing minimal risk to responders. This presentation will describe a proper response protocol, with emphasis on adaptation of everyday procedures to meet the patient's needs as well as the structure of a radioiogical emergency response team. Aspects of facility preparation, patient reception/triage, contamination control, radiological monitoring, decontamination, and post-emergency patient transfer will be covered. Decontamination procedures covered will include those for intact skin, hair, eyes, wounds, and internally deposited radionuclides. The difference between handling the patient exposed to radiation and the patient contaminated with radioactive material will be demonstrated. Physical and biological samples needed to assess status of both exposed and contaminated patients will be presented. Appropriate case histories drawn from the REAC/TS Registry files documenting worldwide radiation accident history will be reviewed. Finally, questions most frequently asked by emergency medical responders regarding their involvement in radiation accidents will be reviewed, with emphasis on whether there is a medical emergency following a radiation accident. [This abstract is based on work performed under Contract No. DE-ACOS-760R00033 between the Department of Energy, Office of Health and Environmental Research, and Oak Ridge Associated Universities.]
6
New Concepts of Radiation Accidents m Biology
Eugene L Saenger, MD, EL Saenger Radioisotope Laboratory, Annals of Emergency Medicine
15:1 January 1986