The Acute Mortality Response of the Miniature Pig to Pulsed Mixed Gamma-Neutron Radiations

Wise, D.; Turbyfill, C. L.

doi:10.2307/3572840

Cited by 8 publications

(5 citation statements)

References 3 publications

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“…These conditions forecast the sparing of variable amounts of critical organ tissue that will define the severity of the ARS and DEARE. The sparing of BM, GI, lung, heart and/or kidney tissue, can have dramatic effects on the incidence, latency, severity, progression and resolution of organ-specific and organ-interactive sequelae (Ainsworth et al 1965;Cole et al 1967;Wise and Turbyfill 1968;Rauchwerger 1972;Monroy et al 1988;Mason et al 1989;Terry and Travis 1989;Geraci et al 1990;Guskova et al 1990;Geraci et al 1992;Liao et al 1995;Bertho et al 2005a;Novakova-Jiresova et al 2005;van Luijk et al 2007;Drouet et al 2008;Granton et al 2014;Boittin et al 2015). Non-uniform and/or heterogeneous exposure with or without medical management will change the organ-specific dose response relationships (DRR) for morbidity and mortality throughout the ARS and DEARE (Ainsworth et al 1965;Wise and Turbyfill 1968;Evans et al 1987;Baranov and Guskova 1990;Guskova et al 1990;Herodin et al 2007;MacVittie et al 2012a).…”

Section: Discussionmentioning

confidence: 99%

“…The ability of surviving BM hematopoietic progenitor cells (HPC), either localized to a marrow site or dispersed throughout the total marrow space, to accelerate hematopoietic recovery after highly myelosuppressive irradiation has been consistent and is model independent, be it partial-body with marrow shielding/sparing, or unilateral, non-uniform total-body exposure in several animal species (Maillie et al 1966;Cole et al 1967;Wise and Turbyfill 1968;Gidali and Lajtha 1972;Maloney and Patt 1972;Monroy et al 1988;Wang et al 1991;Geraci et al 1992;Bertho et al 2005a;Booth et al 2012;Herodin et al 2012;MacVittie et al 2012a;Drouet et al 2014;Boittin et al 2015). The critical condition is the differential dose distribution throughout the tissue and the basic assumptions that hematopoietic recovery from the H-ARS is dependent on the survival of a critical fraction of HPC that are equally distributed throughout the active marrow tissue, independent of location and equivalent in regenerative ability (Bond and Robinson 1967;Taketa et al 1970;Bond et al 1991;Campbell et al 2015).…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing

et al. 2019

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A nonhuman primate (NHP) model of acute, partial-body, high dose, irradiation with minimal (2.5%) bone marrow sparing (PBI/BM2.5) was used to assess the endogenous gastrointestinal and hematopoietic recovery and the ability of Neulasta ® (pegylated granulocyte colony stimulating factor [G-CSF]) or Neupogen ® (G-CSF) to enhance recovery from myelosuppression when administered at an increased interval between exposure and initiation of treatment. A secondary objective was to assess the effect of Neulasta ® or Neupogen ® on the mortality and morbidity due to the hematopoietic acute radiation syndrome (H-ARS) and concomitant acute gastrointestinal (GI)-ARS. NHP were exposed to 10.0 Gy 6 megavolt (MV) linear accelerator (LINAC)-derived photons delivered at 0.80 Gy min −1 . All NHP received subject-based medical management. NHP were dosed daily with control article (5% dextrose in water) initiated on day 1 post-exposure, or Neulasta ® (300 μg kg −1 ) administered on days 1 and 8 or days 3 and 10 post-exposure, or Neupogen ® (10 μg kg −1 ) administered daily post-exposure following its initiation on day 1 or day 3 until neutrophil recovery (absolute neutrophil count [ANC] ≥ 1,000 cells μL −1 for 3 consecutive days). Mortality in the irradiated-cohorts suggested that administration of Neulasta ® or Neupogen ® at either schedule did not affect mortality due to acute GI-ARS or mitigate mortality due to H-ARS (plus GI damage). Following 10.0 Gy PBI/BM2.5, the mean duration of neutropenia (absolute neutrophil count < 500 cells μL −1 ) was 22.4 days in the control cohort, versus 13.0 and 15.3 days in the Neulasta ® day 1-8 and day 3-10 cohorts relative to 16.2 and 17.4 days in the Neupogen ® cohorts initiated on day 1 and day 3, respectively. The absolute neutrophil count nadirs were 48 cells μL −1 in the controls, 117 cells μL −1 and 40 cells μL −1 in the Neulasta ® days 1, 8 and days 3, 10 cohorts, respectively, and 75 cells μL −1 , and 37 cells μL −1 in the Neupogen ® day 1 and day 3 cohorts, respectively. Therefore, the earlier administration of Neulasta ® or Neupogen ® was more effective in this model of marginal 2.5% BM sparing. The approximate 2.5% BM-sparing may approximate the threshold for efficacy of the lineage-specifc

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing

et al. 2019

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“…The relationship between supportive care and lethality over the H-ARS has been shown in canines but has not been established for NHP (Broerse and MacVittie 2001; MacVittie et al 2005). There have been a number of studies that established the DRR for NHP exposed to TBI with 250 kVp or 2Mev x-rays and mixed neutron and gamma (γ) radiation (Table 1) (Eldred and Trowbridge 1954; Stanley et al 1966; Wise and Turbyfill 1968; Henschke and Morton 1957; Haigh and Paterson 1956; Schlumberger and Vazquez 1954; Dalrymple et al 1965). Additionally, there is a single study describing the DRR for Co-60γ radiation-induced lethality in NHP performed in 1967 (Eltringham 1967).…”

Section: Introductionmentioning

confidence: 99%

A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

Farese¹,

Cohen²,

Katz³

et al. 2012

Health Physics

121

171

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The development of medical countermeasures against the hematopoietic sub-syndrome 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 the morbidity and mortality. Herein, we define these parameters for the 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 8.90Gy at 0.80Gy minute−1. Following irradiation animals were monitored for complete blood counts, body weight, temperature, diarrhea, and hydration status for 60 days. 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 days 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 7.06Gy, LD50/60 of 7.52Gy, and an LD70/60 of 7.99Gy 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.

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“…Rhesus macaques ( Macaca mulatta ) have been used as non‐human primate (NHP) models for a number of stress‐related situations including radiation injury and radiation‐induced sepsis [1, 4, 7, 17, 18, 25]. At the Armed Forces Radiobiology Research Institute (AFRRI) laboratory, the rhesus macaque has been used to evaluate promising radiation countermeasures and antimicrobials for efficacy prior to seeking human use approval.…”

Section: Introductionmentioning

confidence: 99%

Resident bacteria in a mixed population of rhesus macaque (Macaca mulatta) monkeys: a prevalence study

Carrier

Elliott

Ledney

2009

J of Medical Primatology

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The Acute Mortality Response of the Miniature Pig to Pulsed Mixed Gamma-Neutron Radiations

Cited by 8 publications

References 3 publications

Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing

Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing

A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

Resident bacteria in a mixed population of rhesus macaque (Macaca mulatta) monkeys: a prevalence study

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