Acute Radiation Syndrome (A Spectrum of Disease) Doran Christensen, DO Associate Director, REAC/TS

Acute Radiation Syndrome Systemic Effects from Acute Radiation Exposure Systemic Effects from Acute Radiation Exposure Multi-Faceted Spectrum of Disease Multi-Faceted Spectrum of Disease Involvement of One or more Organ Systems Involvement of One or more Organ Systems Systemic Effects from Acute Radiation Exposure Systemic Effects from Acute Radiation Exposure Multi-Faceted Spectrum of Disease Multi-Faceted Spectrum of Disease Involvement of One or more Organ Systems Involvement of One or more Organ Systems

Ionization Process Density of Ionization Trail Density of Ionization Trail Chemical Bonds Chemical Bonds DNA Damage DNA Damage Subcellular components Subcellular components Mitotic Delay Mitotic Delay Repair Repair Complete Complete Incomplete Incomplete Residual Damage? Measureable? Residual Damage? Measureable? Density of Ionization Trail Density of Ionization Trail Chemical Bonds Chemical Bonds DNA Damage DNA Damage Subcellular components Subcellular components Mitotic Delay Mitotic Delay Repair Repair Complete Complete Incomplete Incomplete Residual Damage? Measureable? Residual Damage? Measureable?

Exposure Principles Total vs. Partial Body Irradiation Total vs. Partial Body Irradiation Threshold Effect of Dose Threshold Effect of Dose Threshold Threshold D 50 Dose D 50 Dose Dose Rate Dose Rate Dose Protraction or Fractionation Dose Protraction or Fractionation Total vs. Partial Body Irradiation Total vs. Partial Body Irradiation Threshold Effect of Dose Threshold Effect of Dose Threshold Threshold D 50 Dose D 50 Dose Dose Rate Dose Rate Dose Protraction or Fractionation Dose Protraction or Fractionation

Radiation Effects Stochastic - All-or-Nothing Effect Occurrence Probability is Function of Dose Stochastic - All-or-Nothing Effect Occurrence Probability is Function of Dose Increased Risk of Developing Cancer Increased Risk of Developing Cancer Inheritable Mutations Inheritable Mutations Deterministic - Effect Severity is a Function of Dose (Commonly Associated with Threshold) Deterministic - Effect Severity is a Function of Dose (Commonly Associated with Threshold) Inflammatory Response Inflammatory Response Organ Failure Organ Failure Fibrosis Fibrosis Stochastic - All-or-Nothing Effect Occurrence Probability is Function of Dose Stochastic - All-or-Nothing Effect Occurrence Probability is Function of Dose Increased Risk of Developing Cancer Increased Risk of Developing Cancer Inheritable Mutations Inheritable Mutations Deterministic - Effect Severity is a Function of Dose (Commonly Associated with Threshold) Deterministic - Effect Severity is a Function of Dose (Commonly Associated with Threshold) Inflammatory Response Inflammatory Response Organ Failure Organ Failure Fibrosis Fibrosis

Radiation Effects E f f e c t Dose Deterministic E f f e c t Dose Stochastic

Law of Bergonié and Tribondeau (1906) More Differentiated Cells are Less Sensitive More Differentiated Cells are Less Sensitive Actively Proliferating Cells are More Sensitive Actively Proliferating Cells are More Sensitive Radiosensitivity is Proportional to Mitotic and Developmental Activity Duration Radiosensitivity is Proportional to Mitotic and Developmental Activity Duration More Differentiated Cells are Less Sensitive More Differentiated Cells are Less Sensitive Actively Proliferating Cells are More Sensitive Actively Proliferating Cells are More Sensitive Radiosensitivity is Proportional to Mitotic and Developmental Activity Duration Radiosensitivity is Proportional to Mitotic and Developmental Activity Duration Rapidly Dividing Cells that Are Poorly Differentiated and Have a Long Mitotic Period Are Very Radiosensitive

Exceptions:Exceptions: Lymphocyte - Most Radiosensitive Cell Lymphocyte - Most Radiosensitive Cell Oocyte - Non Mitotic Cell Oocyte - Non Mitotic Cell Lymphocyte - Most Radiosensitive Cell Lymphocyte - Most Radiosensitive Cell Oocyte - Non Mitotic Cell Oocyte - Non Mitotic Cell

Radiosensitive Cells Red Marrow Red Marrow Epithelial Cells of GI System, Lung Epithelial Cells of GI System, Lung Epithelium of Lens Epithelium of Lens Germinative Cells of Testis and Ovary Germinative Cells of Testis and Ovary Endothelial Cells of Blood Vessels Endothelial Cells of Blood Vessels Red Marrow Red Marrow Epithelial Cells of GI System, Lung Epithelial Cells of GI System, Lung Epithelium of Lens Epithelium of Lens Germinative Cells of Testis and Ovary Germinative Cells of Testis and Ovary Endothelial Cells of Blood Vessels Endothelial Cells of Blood Vessels

Radiosensitive Cells (contd) Pluripotential Stem Cells Pluripotential Stem Cells Rapid Mitotic Rate Rapid Mitotic Rate Form Intermdiate Precursors and then Mature Elements. Form Intermdiate Precursors and then Mature Elements. Cells with Large Nuclei Cells with Large Nuclei Interphase Death Interphase Death Lymphocyte, Oocyte and Salivary Gland Lymphocyte, Oocyte and Salivary Gland Pluripotential Stem Cells Pluripotential Stem Cells Rapid Mitotic Rate Rapid Mitotic Rate Form Intermdiate Precursors and then Mature Elements. Form Intermdiate Precursors and then Mature Elements. Cells with Large Nuclei Cells with Large Nuclei Interphase Death Interphase Death Lymphocyte, Oocyte and Salivary Gland Lymphocyte, Oocyte and Salivary Gland

Effects of Radiation Protraction Prodromal Component (Gy) Vomiting Diarrhea Vomiting Diarrhea BriefProtractedBriefProtracted ExposureExposureExposureExposure ExposureExposureExposureExposure D D Threshold Threshold NUREG / CR 4214, Part II, p. 21

GI Cellular Hierarchy IAEA – UNSCEAR 1988

Skin Cellular Hierarchy IAEA – UNSCEAR 1988

Phases of Acute Radiation Syndrome Prodromal Stage Prodromal Stage Latent Stage Latent Stage Manifest Illness Manifest Illness Recovery Time (60 days) ExposureExposure

Acute Radiation Syndrome Components of Radiation Effects: Components of Radiation Effects: Prodromal ( Gy) Prodromal ( Gy) Hematological ( Gy) Hematological ( Gy) Respiratory ( Gy) Respiratory ( Gy) Cutaneous( Gy) Cutaneous( Gy) Gastrointestinal ( Gy) Gastrointestinal ( Gy) Neurovascular ( Gy) Neurovascular ( Gy) Combined Injury Combined Injury Components of Radiation Effects: Components of Radiation Effects: Prodromal ( Gy) Prodromal ( Gy) Hematological ( Gy) Hematological ( Gy) Respiratory ( Gy) Respiratory ( Gy) Cutaneous( Gy) Cutaneous( Gy) Gastrointestinal ( Gy) Gastrointestinal ( Gy) Neurovascular ( Gy) Neurovascular ( Gy) Combined Injury Combined Injury

Prodromal Component ( Gy and higher) Immediate Effect of Cell Membrane Damage Immediate Effect of Cell Membrane Damage Mediated by Inflammatory Elements of Cell Destruction Mediated by Inflammatory Elements of Cell Destruction Mediated Neurologically by Parasympathetic System Mediated Neurologically by Parasympathetic System Immediate Effect of Cell Membrane Damage Immediate Effect of Cell Membrane Damage Mediated by Inflammatory Elements of Cell Destruction Mediated by Inflammatory Elements of Cell Destruction Mediated Neurologically by Parasympathetic System Mediated Neurologically by Parasympathetic System

Prodromal Component (Gy) Vomiting Diarrhea Vomiting Diarrhea BriefProtractedBriefProtracted ExposureExposureExposureExposure ExposureExposureExposureExposure D D Threshold Threshold NUREG / CR 4214, Part II, p. 21 TBI Dose Estimates for Prodromal Symptoms

Hematopoietic Component ( Gy and higher) Lymphocytes Lymphocytes Neutrophils Neutrophils Thrombocytes Thrombocytes Erythrocytes Erythrocytes Lymphocytes Lymphocytes Neutrophils Neutrophils Thrombocytes Thrombocytes Erythrocytes Erythrocytes

Hemogram 3 Gy (300 Rad) TBI Exposure Source – REAC / TS Diagram – Human Irradiation 3 Gy (300 Rads)

Gastrointestinal Component ( Gy and higher) Symptoms Symptoms Mechanisms Mechanisms GI Epithelial Sterilization - 15 Gy GI Epithelial Sterilization - 15 Gy Veno-Occlusive Disease of Liver Veno-Occlusive Disease of Liver Symptoms Symptoms Mechanisms Mechanisms GI Epithelial Sterilization - 15 Gy GI Epithelial Sterilization - 15 Gy Veno-Occlusive Disease of Liver Veno-Occlusive Disease of Liver

Respiratory Component ( Gy and higher) Sensitive from Highly Vascular Tissue Sensitive from Highly Vascular Tissue Endothelial Cells Endothelial Cells Type II Alveolar Cell Type II Alveolar Cell Effect is Dose-Rate Related Effect is Dose-Rate Related Pneumonitis Pneumonitis Fibrosis Fibrosis Sensitive from Highly Vascular Tissue Sensitive from Highly Vascular Tissue Endothelial Cells Endothelial Cells Type II Alveolar Cell Type II Alveolar Cell Effect is Dose-Rate Related Effect is Dose-Rate Related Pneumonitis Pneumonitis Fibrosis Fibrosis

Pulmonary Lethality Syndrome Dose Rate (Gy/hr)Threshold (Gy) NUREG / CR-4214, Part II, p. 55

Neurovascular Component ( Gy and higher) Brain Cells are Fixed, Post-Mitotic Cells Brain Cells are Fixed, Post-Mitotic Cells Weak Link -- Stromal Cells Weak Link -- Stromal Cells Endothelial Cells Turnover Endothelial Cells Turnover 2 Months to 3 Years (3 Days) 2 Months to 3 Years (3 Days) EEG Changes Doses as Low as 1 Gy EEG Changes Doses as Low as 1 Gy Brain Cells are Fixed, Post-Mitotic Cells Brain Cells are Fixed, Post-Mitotic Cells Weak Link -- Stromal Cells Weak Link -- Stromal Cells Endothelial Cells Turnover Endothelial Cells Turnover 2 Months to 3 Years (3 Days) 2 Months to 3 Years (3 Days) EEG Changes Doses as Low as 1 Gy EEG Changes Doses as Low as 1 Gy

Neurovascular Component (continued) Gy - Glial Cell Damage Gy - Glial Cell Damage 10 Gy - Morphologic Changes 10 Gy - Morphologic Changes Gy- Vascular Lesions Gy- Vascular Lesions 40 Gy - White Matter Necrosis 40 Gy - White Matter Necrosis 60 Gy - Demyelinization 60 Gy - Demyelinization Gy - Glial Cell Damage Gy - Glial Cell Damage 10 Gy - Morphologic Changes 10 Gy - Morphologic Changes Gy- Vascular Lesions Gy- Vascular Lesions 40 Gy - White Matter Necrosis 40 Gy - White Matter Necrosis 60 Gy - Demyelinization 60 Gy - Demyelinization

Ovarian Function Ovarian Dose (Gy)Results 0.6-No Deleterious Effect Some Risk for Ovulatory Suppression in Women over % Women Aged Have Permanent Suppression Remainder have Temporary Amennorrhea 100% Women Over 40 have Permanent Suppression % Women Aged Have Permanent Suppression Remainder have Temporary Amennorrhea > % Permanent Ovulatory Suppression Ovarian Dose (Gy)Results 0.6-No Deleterious Effect Some Risk for Ovulatory Suppression in Women over % Women Aged Have Permanent Suppression Remainder have Temporary Amennorrhea 100% Women Over 40 have Permanent Suppression % Women Aged Have Permanent Suppression Remainder have Temporary Amennorrhea > % Permanent Ovulatory Suppression NUREG / CR-4214, p II-70

Sperm Production Testicular Dose (Gy)Results Temporary Oligospermia % Temporary Aspermia from mo Post-Irradiation Full Recovery by 48 mo % Temporary Aspermia from mo Full Recovery Beginning at mo % Temporary Aspermia from mo Recovery Beginning at mo % Aspermia Beginning at mo No Recovery Observed after 40 mo Testicular Dose (Gy)Results Temporary Oligospermia % Temporary Aspermia from mo Post-Irradiation Full Recovery by 48 mo % Temporary Aspermia from mo Full Recovery Beginning at mo % Temporary Aspermia from mo Recovery Beginning at mo % Aspermia Beginning at mo No Recovery Observed after 40 mo NUREG / CR-4214, p II-73

Radiation Skin Injury Effects Effects Time Frame Time Frame Injury Course Injury Course Effects Effects Time Frame Time Frame Injury Course Injury Course

Radiation Skin Injury.75 Gy- Hair Follicles Change.75 Gy- Hair Follicles Change 3 Gy - Epilation 3 Gy - Epilation 6 Gy - Erythema 6 Gy - Erythema 10 Gy - Dry Desquamation 10 Gy - Dry Desquamation 20 Gy - Wet Desquamation (Transepithelial Injury) 20 Gy - Wet Desquamation (Transepithelial Injury).75 Gy- Hair Follicles Change.75 Gy- Hair Follicles Change 3 Gy - Epilation 3 Gy - Epilation 6 Gy - Erythema 6 Gy - Erythema 10 Gy - Dry Desquamation 10 Gy - Dry Desquamation 20 Gy - Wet Desquamation (Transepithelial Injury) 20 Gy - Wet Desquamation (Transepithelial Injury)

Skin Effects EffectParameter Brief Protracted Exposure Exposure Exposure Exposure ErythemaThreshold36 D TransepithelialThreshold1040 InjuryD EffectParameter Brief Protracted Exposure Exposure Exposure Exposure ErythemaThreshold36 D TransepithelialThreshold1040 InjuryD NUREG / CR-4214, p II-68

Skin Effects Effect Single Onset Dose (Gy) Time Dose (Gy) Time Epilation3 - 7~18 days Erythema days Erythema days Pigmentation Pigmentation Dry Desquamation days Dry Desquamation days Moist Desquamation days Moist Desquamation days That Heals That Heals Telangiectasia mo - years Telangiectasia mo - years Nonhealing Necrosis > 60months, years Nonhealing Necrosis > 60months, years Effect Single Onset Dose (Gy) Time Dose (Gy) Time Epilation3 - 7~18 days Erythema days Erythema days Pigmentation Pigmentation Dry Desquamation days Dry Desquamation days Moist Desquamation days Moist Desquamation days That Heals That Heals Telangiectasia mo - years Telangiectasia mo - years Nonhealing Necrosis > 60months, years Nonhealing Necrosis > 60months, years NUREG / CR-4214, p II-68

El Salvador Patient + 32 Days Hyperpigmentation ( Bronzing )

El Salvador Patient + 32 Days Dry Desquamation

El Salvador Patient + 32 Days Transition to Wet Desquamation

El Salvador Patient + 32 Days Wet Desquamation

TriageTriage By Conventional Injuries By Conventional Injuries Trauma Trauma Burns Burns By Radiation Injury By Radiation Injury Prodromal Symptoms Prodromal Symptoms Hematologic Picture Hematologic Picture By Conventional Injuries By Conventional Injuries Trauma Trauma Burns Burns By Radiation Injury By Radiation Injury Prodromal Symptoms Prodromal Symptoms Hematologic Picture Hematologic Picture

Modified USSR Classification (1986) Class 1 Class 2 Class 1 Class 2 Prodrome >3 hrs*1 - 3 hrs* Lymphs (3-6 days) TBI Dose Gy Gy Survival Estimate Probable w / o tx Possible w / o tx Class 3 Class 4 Class 3 Class 4 Prodrome hr <.5 hr Lymphs (3-6 days) <100 TBI Dose Gy , 16 Gy Survival Estimate Probable w / txNot Likely Class 1 Class 2 Class 1 Class 2 Prodrome >3 hrs*1 - 3 hrs* Lymphs (3-6 days) TBI Dose Gy Gy Survival Estimate Probable w / o tx Possible w / o tx Class 3 Class 4 Class 3 Class 4 Prodrome hr <.5 hr Lymphs (3-6 days) <100 TBI Dose Gy , 16 Gy Survival Estimate Probable w / txNot Likely Mettler FA, Kelsey CA, Ricks RC Eds. Medical Management of Radiation Accidents. Boca Raton: CRC Press, 1990, p. 72. *Barabanova A. REAC/TS Newsletter. Winter 1992, Oak Ridge, TN, p 1-2. Mettler FA, Kelsey CA, Ricks RC Eds. Medical Management of Radiation Accidents. Boca Raton: CRC Press, 1990, p. 72. *Barabanova A. REAC/TS Newsletter. Winter 1992, Oak Ridge, TN, p 1-2.

Andrews Lymphocyte Nomogram From Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels of Radiation. In Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Agency, 1965, pp Vienna, International Atomic Energy Agency, 1965, pp From Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels of Radiation. In Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Agency, 1965, pp Vienna, International Atomic Energy Agency, 1965, pp n Confirms suspected radiation exposure n Determines significant hematological involvement n Serial CBCs every 6 h n Confirms suspected radiation exposure n Determines significant hematological involvement n Serial CBCs every 6 h

Goans Nomogram – The Next Advance Goans, RE, Clinical Care of the Radiation-Accident Patient: Patient Presentation, Assessment, and Initial Diagnosis in Ricks RC, Berger ME, OHara FM, The Medical Basis for Radiation Accident Preparedness – The Clinical Care of Victims, p18.

Combined-Injury Triage when Radiation Doses are Known* Conventional TriageChanges in Expected Triage Category Categories if Injuries are following Only Trauma Whole-Body Radiation Dose (Gy) No Radiation Exists 4.5 (450 rad) Prodrome Onset< 3 h1 – 3 h< 1 h ImmediateImmediate Immediate Expectant DelayedDelayed Expectant Expectant MinimalMinimal Expectant Expectant ExpectantExpectant Expectant Expectant *Decision based on whole-body radiation dose, assuming all casualties are wearing personal dosimeters Source: Medical Consequences of Nuclear Warfare, 1989, p. 39

Combined Injury

Combined Injury - Total Body Irradiation + Burns Rat Model AFRRI Medical Effects of Nuclear Weapons Course Triage and Treatnent of Radiation Casualties Lecture, slide 35

Treatment Overview Supportive Care Supportive Care Surgical Recommendations Surgical Recommendations Selective Gut Decontamination Selective Gut Decontamination Bone Marrow Transplants (not as successful) Bone Marrow Transplants (not as successful) Biological Response Modifiers Biological Response Modifiers Cytokines (more successful) Cytokines (more successful) Complications of Acute Radiation Syndrome Complications of Acute Radiation Syndrome Supportive Care Supportive Care Surgical Recommendations Surgical Recommendations Selective Gut Decontamination Selective Gut Decontamination Bone Marrow Transplants (not as successful) Bone Marrow Transplants (not as successful) Biological Response Modifiers Biological Response Modifiers Cytokines (more successful) Cytokines (more successful) Complications of Acute Radiation Syndrome Complications of Acute Radiation Syndrome

Supportive Care Fluid and Electrolyte Replacement Fluid and Electrolyte Replacement Reverse Isolation Reverse Isolation Total Parenteral Nutrition Total Parenteral Nutrition Empiric Antibiotics for Documented Infection Empiric Antibiotics for Documented Infection Fluid and Electrolyte Replacement Fluid and Electrolyte Replacement Reverse Isolation Reverse Isolation Total Parenteral Nutrition Total Parenteral Nutrition Empiric Antibiotics for Documented Infection Empiric Antibiotics for Documented Infection

Supportive Care (contd) Irradiated Blood Products Irradiated Blood Products Enteral Feedings Enteral Feedings Intravenous Glutamine Intravenous Glutamine Sucralfate Sucralfate Irradiated Blood Products Irradiated Blood Products Enteral Feedings Enteral Feedings Intravenous Glutamine Intravenous Glutamine Sucralfate Sucralfate

Surgical Recommendations Based on Immunocompetence Status (neutropenia immunocompetence) Based on Immunocompetence Status (neutropenia immunocompetence) Life-Saving / Major Surgery within h Life-Saving / Major Surgery within h Elective Procedures until days Following Hematopoietic Recovery Elective Procedures until days Following Hematopoietic Recovery Based on Immunocompetence Status (neutropenia immunocompetence) Based on Immunocompetence Status (neutropenia immunocompetence) Life-Saving / Major Surgery within h Life-Saving / Major Surgery within h Elective Procedures until days Following Hematopoietic Recovery Elective Procedures until days Following Hematopoietic Recovery Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds) Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229

Selective Gut Decontamination Historical Background Historical Background Non-Systemic Abx vs. Systemic Abx Non-Systemic Abx vs. Systemic Abx Fluoroquinolones Fluoroquinolones Ciprofloxacin, Ofloxacin Ciprofloxacin, Ofloxacin Norfloxacin Norfloxacin Historical Background Historical Background Non-Systemic Abx vs. Systemic Abx Non-Systemic Abx vs. Systemic Abx Fluoroquinolones Fluoroquinolones Ciprofloxacin, Ofloxacin Ciprofloxacin, Ofloxacin Norfloxacin Norfloxacin

Cytokine Combinations IL-3/G-CSF IL-3/G-CSF IL-3/GM-CSF IL-3/GM-CSF IL-3/G-CSF IL-3/G-CSF IL-3/GM-CSF IL-3/GM-CSF

Acute Radiation Syndrome Complications Hematologic/Gastrointestinal Hematologic/Gastrointestinal Interstitial Pulmonary Fibrosis Interstitial Pulmonary Fibrosis Veno-occlusive Disease of the Liver Veno-occlusive Disease of the Liver Herpes Simplex (HSV) Reactivation Herpes Simplex (HSV) Reactivation Cytomegalovirus (CMV) Reactivation Cytomegalovirus (CMV) Reactivation Combined Injuries Combined Injuries Hematologic/Gastrointestinal Hematologic/Gastrointestinal Interstitial Pulmonary Fibrosis Interstitial Pulmonary Fibrosis Veno-occlusive Disease of the Liver Veno-occlusive Disease of the Liver Herpes Simplex (HSV) Reactivation Herpes Simplex (HSV) Reactivation Cytomegalovirus (CMV) Reactivation Cytomegalovirus (CMV) Reactivation Combined Injuries Combined Injuries

Any Questions?

ReferencesReferences NUREG / CR-4214, Health Effects Models for Nuclear Power Plant Accident Consequence Analysis: Low LET Radiation, Part II: Scientific Bases for Health Effects Models, US Nuclear Regulatory Commission, Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds)Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229 AFRRI Medical Effects of Nuclear Weapons Course Triage and Treatnent of Radiation Casualties Lecture, slide 35 IAEA, The Radiological Accident in San Salvador, 1989 Ricks RC, Berger ME, OHara FM, The Medical Basis for Radiation-Accident Preparedness – The Clinical Care of Victims, Parthenon Publishing Group, Inc: New York:2002. Saenger EL, Andrews GA, Linnemann RE, Wald N: Radiation Accident Preparedness -Medical and Managerial Aspects. Science-Thru-Media: New York 1981, p 15. NUREG / CR-4214, Health Effects Models for Nuclear Power Plant Accident Consequence Analysis: Low LET Radiation, Part II: Scientific Bases for Health Effects Models, US Nuclear Regulatory Commission, Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds)Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229 AFRRI Medical Effects of Nuclear Weapons Course Triage and Treatnent of Radiation Casualties Lecture, slide 35 IAEA, The Radiological Accident in San Salvador, 1989 Ricks RC, Berger ME, OHara FM, The Medical Basis for Radiation-Accident Preparedness – The Clinical Care of Victims, Parthenon Publishing Group, Inc: New York:2002. Saenger EL, Andrews GA, Linnemann RE, Wald N: Radiation Accident Preparedness -Medical and Managerial Aspects. Science-Thru-Media: New York 1981, p 15. Revision 6.1 – 17 Apr 2004