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System for Scoring Severity of Acute Radiation Syndrome Response in Rhesus Macaques (Macaca mulatta)
Gregory L King1, David J Sandgren1, Jennifer M Mitchell2
1Departments of Scientific Research, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Abstract:
We developed a clinical assessment tool for use in an NHP radiation model to 1) quantify severity responses for subsyndromes of the acute radiation syndrome (ARS; that is, hematopoietic and others) and 2) identify animals that required enhanced monitoring. Our assessment tool was based primarily on the MEdical TREatment ProtocOLs for Radiation Accident Victims (METREPOL) scoring system but was adapted for NHP to include additional indices (for example, behaviors) for use in NHP studies involving limited medical intervention. Male (n = 16) and female (n = 12) rhesus macaques (Macaca mulatta; 5 groups: sham and 1.0, 3.5, 6.5, and 8.5 Gy; n = 6 per group) received sham- or bilateral Co γ-irradiation at approximately 0.6 Gy/mn. Clinical signs of ARS and blood analysis were obtained before and serially for clinical assessment during the period of 6 h to 60 d after sham or Co irradiation. Minimal supportive care (that is, supplemental nutrition, subcutaneous fluid, loperamide, acetaminophen, and topical antibiotic ointment) was prescribed based on clinical observations. Results from clinical signs and assays for assessment of relevant organ systems in individual animals were stratified into ARS severity scores of normal (0), mild (1), moderate (2), and severe (3 or 4). Individual NHP were scored for maximal subsyndrome ARS severity in multiple organ systems by using the proposed ARS scoring system to obtain an overall ARS response category. One NHP died unexpectedly. The multiple-parameter ARS severity scoring tool aided in the identification of animals in the high-dose (6.5 and 8.5 Gy) groups that required enhanced monitoring.
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