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Radiation critical care report to u.s. dept. of defense

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  • 1. The Untold Travesty of Nuclear Non-DefenseI created the following slide show in 2005 at the request of Prof. NormanEnde, M.D., who for the past ten years has tried in vain to encourage stateand federal authorities to adopt his medical blueprint for treating masscasualties due to high dose radiation exposure.Dr. Ende then reviewed and forwarded this slide show to Lt. Gen. P.K.Carlton, M.D., former Air Force Surgeon General, for his presentation to theDOD and NORAD. General Carlton called Ende’s strategy for using cordblood as a first line of medical defense against a catastrophic nuclearnightmare, “The only hope for those who might be saved.”Ende’s plan reveals medical potentials that threaten a vastly lucrativemedical paradigm re the treatment of any condition requiring bone marrowreconstitution. Hence Americans remain without a shred of medical hopeshould the unthinkable occur.J. Perry Kelly, author of “The Sibyl Reborn”
  • 2. Radiation Injury: Critical Care Acute radiation syndrome (ARS) is an acuteillness caused by irradiation of the whole body (or a significant portion of it).In general, the higher the dose the greater the severity of early effects and the greater the possibility of late effects.Depending on dose, the following syndromes can manifest:
  • 3. • Skin syndrome, characterized by loss of epidermis and possibly dermis, called “radiation burns;” can occur with other syndromes.• Hematopoietic syndrome, characterized by deficiencies of white blood count, lymphocytes and platelets, immunodeficiency, increased infectious complications, bleeding, anemia, and impaired wound healing; total body exposure > 2 Gy (200 rads).• Gastrointestinal syndrome - characterized by loss of cells lining intestinal crypts and loss of mucosal barrier, with alterations in intestinal motility, fluid and electrolyte loss with vomiting and diarrhea, loss of normal intestinal bacteria, sepsis, and damage to the intestinal microcirculation; >10 Gy• Cerebrovascular/CNS syndrome - primarily associated with effects on the vasculature and resultant fluid shifts. Signs include vomiting and diarrhea within minutes of exposure, confusion, disorientation, cerebral edema, hypotension, and hyperpyrexia. Fatal in short time; >30 Gy 3
  • 4. Acute Radiation Syndrome: Exposure Less Than 2 Gy (200 rad)Nausea and vomiting due to radiation are seldomexperienced unless exposure is at least 0.75 Gy.Patients without symptoms in 24 hours will mostcertainly have had less than 0.75 Gy of whole-bodyexposure. Hospitalization is generally unnecessary if exposure is less than 2 Gy (200 rads).Management of ARS (dose less than 2 Gy):• Observation and frequent CBC with differential.• Outpatient management may be appropriate.• Provide instructions regarding home care. 4
  • 5. Acute Radiation Syndrome: Exposure Greater than 2 Gy (200 rads)• Prevention and treatment of infections.• Stimulation of hematopoiesis (use of growth factors, i.e., GCSF, GMCSF, interleukin 11).• Stem cell transfusions: cord blood, peripheral blood, or bone marrow. Platelet transfusions if bleeding occurs or if platelet count too low.• Psychological support.• Observe carefully for erythema, hair loss, skin injury, mucositis, parotitis, weight loss, and/or FEVER.• Consultation with experts in radiation accident management is encouraged. 5
  • 6. Hematopoietic Syndrome:• Prodromal phase: nausea, vomiting and anorexia within a few hours at the higher dose levels, lasts 24 to 48 hours• Latent Phase: lasts a few days to 2-3 weeks depending on dose. Exhibits lymphocyte depression, and gradual decline of neutrophil and platelet counts• Bone Marrow Depression Phase: Infection and hemorrhage can occur when white cell and platelet become critically low• Depending on exposure, Hematopoietic support can become critical within several days to three weeks 6
  • 7. Chernobyl: A Harsh Lesson• At Chernobyl, some victims received bone marrow that was HLA matched or partially matched. However, donor marrows were difficult to obtain in adequate numbers.• After exposure to between 2 to 16 Gy, 28 of 34 service personnel died of acute bone-marrow failure, GVHD, or gastro-intestinal infection.• Human umbilical cord blood, now considered an excellent source of hematopoietic stem cells, was not used at Chernobyl. 7
  • 8. Bone Marrow Transplantation: practical limitations and clinical hurdles• Finding matched donors for numerous casualties on short notice• Rejection of donor marrow by residual immune functions• Graft Versus Host Disease (GVHD): transplanted cells attack the host• Increased risk of infection through immunosuppression. 8
  • 9. Cord Blood for Hematopoietic Syndrome: Benefits• Greater genetic diversity and availability• Reduced need for HLA-matching• Less prone to GVHD, or host rejection• Reduced need for immunosuppression• Extensive clincial experience (for hematopoietic restoration following radiation and/or chemo for cancer)• Easy to collect, analyze, store, and use 9
  • 10. Unique Points Single units of cord blood engraft more slowly than bone marrow from an HLA-matched bone marrow donor, however…• Cord blood’s speed of engraftment and event-free success is directly related to the number of transplanted nucleated cells.• Pooling unmatched units of cord blood increases densities of nucleated blood cells, primitive (Berashis) stem cells, CD34, CD117, and GPA cells, and increases mitotic activity• Without raising risks of rejection, pooling unmatched cord blood substancially reduces reactivity of CB responder cells to fresh allogenic CB stimulator cells, likewise reducing CB responder cell reactivity to host stimulator cells (GVHD)• In addition to offering replacement of hematopoietic systems destroyed by radiation, cord blood-derived hematopoietic cells co-exist with surviving marrow cells, encouraging endogenous hematopoietic recovery, while providing transitional support 10
  • 11. Human evidence suggestive of the previous points“Four patients with advanced solid tumors weretreated by means of high-dose chemotherapy andHLA-mismatched and unrelated multi-cord bloodtransfusion. Of these patients, three achievedcomplete remission and one achieved a partialremission. Little or no graft vs. host disease (GVHD)was observed. These results suggest the possibilitythat HLA-mismatched and unrelated multi-cordblood transfusion may engraft with little or no GVHDand hasten recovery from marrow suppression.” Shen B.-J. et.al., Blood Cells Volume 20, Issue 2-3 , 1994, Pages 285-292 11
  • 12. Cord Blood –Treated Radiation Casualty Japanese Tokaimura Facility “Although the transplanted cord bloodcells engrafted, the patient’s bone marrowfunctions eventually returned two monthslater. During this period, there existed amixed chimerism between donor cells andrecipient cells.” From: Radiation-Accident Preparedness: The Clinical Care of Victims, Fourth International REAC/TS Conference on the Medical Basis for Radiation Accident Preparedness, March 2001, Orlando FL 12
  • 13. Cord Blood vs. Bone Marrow68 adult human study using single units of mismatched cord blood compared to HLA-matched bone marrow use: Cord Blood Bone Marrow Engraftement 90% 92% success: Acute severe GVHD: 20% 35-55% Chronic GVHD: 38% 55-75% M. J. Laughlin, M.D., et.al., Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical Cord Blood from Unrelated Donors. New England Journal of Medicine Volume 344:1815-1822 June 14, 2001 Number 24 13
  • 14. In Conclusion: “In the event of large-scale exposure,some persons are likely to be exposed to adose of total-body radiation (approximately 6to 15 Gy) that would result in death frombone marrow failure without other life-threatening complications. The only effectivetreatment for bone marrow failure caused bylethal doses of radiation is hematopoietic-cell transplantation.” Continued… 14
  • 15. “Units of cryopreserved umbilical-cordblood can be identified in registries andmade available for transplantation withindays. When umbilical-cord blood is used,less stringent HLA matching is required. Abank of approximately 200,000 units couldprovide 90 percent of the population withcord blood matched at four or five of six HLAloci — the type of matches most commonlyused in cord-blood transplantation.” Continued… 15
  • 16. “Shortening the turnaround time for searching donor registries, providing an umbilical-cord–blood bank of appropriate size, and developing a consortium of transplantation programs should be part of the plan for national preparedness for radiological disaster.” Stephen J. Forman, M.D. Lawrence D. Petz, M.D. Major Radiation Exposure, Letters; New England Journal ofMedicine, Volume 347:944-947 September 19, 2002 Number 12 16
  • 17. Referenced Literature:Ricks RC, Berger ME, O’Hara FM Jr., Radiation-Accident Preparedness: TheClinical Care of Victims, Fourth International REAC/TS Conference on the MedicalBasis for Radiation Accident Preparedness, March 2001, Orlando FLRubinstein, et.al., Outcomes among 562 Recipients of Placental-Blood Transplantsfrom unrelated donors. New England Journal of Medicine, Vol. 339, Nov. 26th,1998, no.22 1565-77Laughlin, et.al., Hematopoietic Engraftment and survival in adult recipients ofumbilical cord blood from unrelated donors. New England Journal of MedicineVolume 344:1815-1822 June 14, 2001 Number 24Ende, et.al., Potential effectiveness of stored cord blood (non-frozen) foremergency use. The Journal of Emergency Medicine Vol 14, no.6, pp673-677 (1996)Ende, et.al., Pooled umbilical cord blood as a possible universal donor for marrowreconstitution and use in nuclear accidents. Life Sciences 69 (2001) 1531-1539`Shen et.al., Unrelated, HLA-mismatched multiple human umbilical cord bloodtransfusion in four cases with advanced solid tumors: Initial studies. Blood CellsVolume 20, Issue 2-3 , 1994, Pages 285-292 17
  • 18. Ende et.al., The feasibility of using blood bank-stored (4°C) cord blood,unmatched for HLA for marrow transplantation. Am J. Clin. Pathol. (1999) 111;6: 773-781.Gluckman, Hematopoietic Stem-Cell Transplants using umbilical-cord blood, TheNew England Journal of Medicine, Vol. 344, No. 24; June 14, 2001, pg. 1860-61Ende, et.al., Murine survival of lethal irradiation with the use of humanumbilical cord blood. Life Sci. 51:1249-1253. (1992)Ende, N. Use of human umbilical cord blood for stem-cell transplantation (HLA-matched, unmatched. Clinical, ethical, and legal aspects). In: HematopoieticStem Cells. (1995) Edited by: D. Levitt and Mertelsmann. 333-347.Ende et.al., The effect of human cord blood on SJL/J mice after chemoablationand irradiation and its possible clinical significance Immunological InvestigationsVolume 24, Issue 6 , November 1995, Pages 999-1012Gluckman et.al., Clinical applications of stem cell transfusion from cord bloodand rationale for cord blood banking Bone Marrow Transplantation Volume 9,Supplement 1 , 1992, Pages 114-117Guidance for Radiation Accident Management: Radiation Emergency AssistanceCenter/Training Site REAC/TS 18