Document Detail


A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.
MedLine Citation:
PMID:  22929469     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.
Authors:
Ann M Farese; Melanie V Cohen; Barry P Katz; Cassandra P Smith; William Jackson; Daniel M Cohen; Thomas J MacVittie
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Health physics     Volume:  103     ISSN:  1538-5159     ISO Abbreviation:  Health Phys     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-08-29     Completed Date:  2012-11-05     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  2985093R     Medline TA:  Health Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  367-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acute Radiation Syndrome / etiology*,  physiopathology
Animals
Cell Survival / radiation effects
Dose-Response Relationship, Radiation
Hematopoietic Stem Cells / radiation effects*
Humans
Lethal Dose 50
Macaca mulatta
Male
Radiation Dosage
Radiation Injuries, Experimental / etiology*,  physiopathology
Survival Analysis
Survival Rate
Whole-Body Irradiation / adverse effects*
Grant Support
ID/Acronym/Agency:
N01AI50043/AI/NIAID NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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