title: Significance of Bioindicators for Early Predictions on Diagnosis and Therapy of Irradiated Minipigs.
abstract: Decisions on whether to start a therapeutic intervention for management of the Acute Radiation Syndrome (ARS) should be made early after exposure, and it should be based on readily available clinical signs and laboratory parameters. Here, the authors use the minipig to assess if early prediction of the later developing clinical outcome and necessity of therapeutic interventions can be determined within the first 3 d after exposure and whether it is comparable to human data. Retrospective analysis of data accumulated in the period 2009-2012 was used. Male Göttingen minipigs (age 4-5 mo, weight 9-10 kg) were irradiated (or sham-irradiated) bilaterally with gamma-photons (Co, 0.5-0.6 Gy min) in the dose range of 1.6-12 Gy. Complete blood counts, serum chemistry, and clinical symptoms were collected up to 60 d after irradiation in untreated minipigs. Changes in these early parameters (up to 3 d after exposure) were correlated with later occurrence (10-60 d after irradiation) of (1) hematological severity scores, (2) severe thrombocytopenia, (3) severe neutropenia, as well as need for (4) therapeutic intervention, (5) administration of cytokines/antibiotics, or (6) thrombocyte transfusions. Binary endpoints were analyzed using logistic regression analysis and calculating receiver operating characteristic (ROC) curves. Most predictive were decreased lymphocyte counts and increases in body temperature at 3 h after irradiation. These data corroborate earlier findings performed on human radiation victims suffering from severe hematological syndrome and provide further evidence for the suitability of the minipig model as a potential alternative non-rodent animal model.
authors.affiliation: *Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD; †Bundeswehr Institute of Radiobiology affiliated to the University Ulm, Munich, Germany; ‡The Henry M. Jackson Foundation, Bethesda, MD 20817; §Veterinary Science Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda MD.
authors.forename: Maria
authors.initials: M
authors.lastname: Moroni
authors.forename: Matthias
authors.initials: M
authors.lastname: Port
authors.forename: Jatinder
authors.initials: J
authors.lastname: Gulani
authors.forename: Mark
authors.initials: M
authors.lastname: Chappell
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
mesh_terms: D054508:Acute Radiation Syndrome / Q000097:blood / Q000000981:diagnostic imaging* / Q000628:therapy*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001772:Blood Cell Count; D020000:Decision Support Systems, Clinical; D042241:Early Diagnosis; D008297:Male; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine; D013556:Swine, Miniature; D063189:Symptom Assessment / Q000379:methods*; D015599:Trauma Severity Indices; D014916:Whole-Body Irradiation
chemical_list: D015415:Biomarkers