Radiobiology of the acute radiation syndrome.

PubMed

Macià I Garau, Miquel; Lucas Calduch, Anna; López, Enric Casanovas

2011-07-06

ACUTE RADIATION SYNDROME OR ACUTE RADIATION SICKNESS IS CLASSICALLY SUBDIVIDED INTO THREE SUBSYNDROMES: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. The time course and severity of clinical signs and symptoms are a function of the overall body volume irradiated, the inhomogeneity of dose exposure, the particle type, the absorbed dose and the dose rate. Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. Contemporaneously, many other radiation-induced effects has been described and all of them may lead to tissue injury with their corresponding signs and symptoms that can be expressed after short or long period of time. Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines.

Combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an LPA2 receptor-specific nonlipid agonist.

PubMed

Patil, Renukadevi; Szabó, Erzsébet; Fells, James I; Balogh, Andrea; Lim, Keng G; Fujiwara, Yuko; Norman, Derek D; Lee, Sue-Chin; Balazs, Louisa; Thomas, Fridtjof; Patil, Shivaputra; Emmons-Thompson, Karin; Boler, Alyssa; Strobos, Jur; McCool, Shannon W; Yates, C Ryan; Stabenow, Jennifer; Byrne, Gerrald I; Miller, Duane D; Tigyi, Gábor J

2015-02-19

Pharmacological mitigation of injuries caused by high-dose ionizing radiation is an unsolved medical problem. A specific nonlipid agonist of the type 2 G protein coupled receptor for lysophosphatidic acid (LPA2) 2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl]benzoic acid (DBIBB) when administered with a postirradiation delay of up to 72 hr reduced mortality of C57BL/6 mice but not LPA2 knockout mice. DBIBB mitigated the gastrointestinal radiation syndrome, increased intestinal crypt survival and enterocyte proliferation, and reduced apoptosis. DBIBB enhanced DNA repair by augmenting the resolution of γ-H2AX foci, increased clonogenic survival of irradiated IEC-6 cells, attenuated the radiation-induced death of human CD34(+) hematopoietic progenitors and enhanced the survival of the granulocyte/macrophage lineage. DBIBB also increased the survival of mice suffering from the hematopoietic acute radiation syndrome after total-body irradiation. DBIBB represents a drug candidate capable of mitigating acute radiation syndrome caused by high-dose γ-radiation to the hematopoietic and gastrointestinal system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute radiation syndrome and chronic radiation syndrome.

PubMed

Grammaticos, Philip; Giannoula, Evanthia; Fountos, George P

2013-01-01

Acute radiation syndrome (ARS) or sickness or poisoning or toxicity is induced after a whole body exposure of men to high doses of radiation between 1-12Gy. First symptoms are from the gastrointestinal system, which together with bone marrow are the most sensitive parts of our body. Chronic radiation syndrome (CRS) may be induced by smaller than 1Gy radiation doses or after a mild form of ARS. Prophylaxis and treatment suggestions are described. In cases of ARS, a large part of the exposed population after proper medical care may survive, while without medical care this part of the population will be lost. Prophylaxis may also save another part of the population.

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Hengwen; Yang, Shana; Li, Jianhua

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expressionmore » in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.« less

Loxoprofen--another NSAID associated with acute asthmatic death.

PubMed

Watanabe, T; Sakata, M; Shimabukuro, R; Sakata, K; Tabata, N; Azumi, J; Morita, M; Itaya, K

1993-01-01

Loxoprofen sodium (sodium 2[4-(2-oxocyclopentylmethyl) phenyl] dehydrate; CAS #68767-14-6) is a nonsteroidal, inflammatory drug marketed only in Japan. A case report describes its association with an acute asthmatic death with features resembling those evoked by similar drugs. The analytic methodology is reported. The blood levels of loxoprofen were in the therapeutic range. The tissue concentrations are reported.

Pharmacological countermeasures for the acute radiation syndrome.

PubMed

Xiao, Mang; Whitnall, Mark H

2009-01-01

The acute radiation syndrome (ARS) is defined as the signs and symptoms that occur within several months after exposure to ionizing radiation (IR). This syndrome develops after total- or partial-body irradiation at a relatively high dose (above about 1 Gy in humans) and dose rate. Normal tissue injuries induced by IR differ depending on the target organ and cell type. Organs and cells with high sensitivity to radiation include the skin, the hematopoietic system, the gut, the spermatogenic cells and the vascular system. Exposure to IR causes damage to DNA, protein, and lipids in mammalian cells, as well as increased mitochondria-dependent generation of reactive oxygen species (ROS), with subsequent cell cycle checkpoint arrest, apoptosis, and stress-related responses. DNA double strand breaks (DSBs) are a primary lethal lesion induced by IR. The cellular response to damage is complex and relies on simultaneous activation of a number of signaling networks. Among these, the activation of DNA non-homologous end-joining (NHEJ) and homologous recombination (HR), and signaling pathways containing ataxia telangiectasia mutated (ATM), play important roles. The transcription factor NFkappaB has emerged as a pro-survival actor in response to IR in ATM and p53-induced protein with a death domain (PIDD) cascades. Although radiation-induced ARS has been well documented at the clinical level, and mechanistic information is accumulating, successful prophylaxis and treatment for ARS is problematic, even with the use of supportive care and growth factors. There is a pressing need to develop radiation countermeasures that can be used both in the clinic, for small-scale incidents, and outside the clinic, in mass casualty scenarios. In this review we summarize recent information on intracellular and extracellular signaling pathways relevant to radiation countermeasure research.

Acute radiation syndrome (ARS) - treatment of the reduced host defense.

PubMed

Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

2012-01-01

The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. Review of the current literature. The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage's important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250-400 μg GM-CSF/m(2) or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14-21 days. The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary

GUCY2C Signaling Opposes the Acute Radiation-Induced GI Syndrome.

PubMed

Li, Peng; Wuthrick, Evan; Rappaport, Jeff A; Kraft, Crystal; Lin, Jieru E; Marszalowicz, Glen; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Waldman, Scott A

2017-09-15

High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. Eliminating GUCY2C signaling exacerbated RIGS, amplifying radiation-induced mortality, weight loss, mucosal bleeding, debilitation, and intestinal dysfunction. Durable expression of GUCY2C, guanylin, and uroguanylin mRNA and protein by intestinal epithelial cells was preserved following lethal irradiation inducing RIGS. Oral delivery of the heat-stable enterotoxin (ST), an exogenous GUCY2C ligand, opposed RIGS, a process requiring p53 activation mediated by dissociation from MDM2. In turn, p53 activation prevented cell death by selectively limiting mitotic catastrophe, but not apoptosis. These studies reveal a role for the GUCY2C paracrine hormone axis as a novel compensatory mechanism opposing RIGS, and they highlight the potential of oral GUCY2C agonists (Linzess; Trulance) to prevent and treat RIGS in cancer therapy and nuclear disasters. Cancer Res; 77(18); 5095-106. ©2017 AACR . ©2017 American Association for Cancer Research.

Sudden unexpected death under acute influence of cannabis.

PubMed

Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

2014-04-01

The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

NASA Astrophysics Data System (ADS)

Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

NASA Astrophysics Data System (ADS)

Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation.

PubMed

Sanzari, Jenine K; Cengel, Keith A; Wan, X Steven; Rusek, Adam; Kennedy, Ann R

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

PubMed Central

Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

2014-01-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Protective Role of Angiogenin Against Hematopoietic Syndrome of the Acute Radiation Syndrome

DTIC Science & Technology

2016-09-01

Syndrome of the Acute Radiation Syndrome PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Protective Role of Angiogenin Against Hematopoietic Syndrome of the Acute Radiation Syndrome 5b. GRANT NUMBER W81XWH-15...protective role against hematopoietic syndrome of the acute radiation syndrome (H-ARS) and is able to attenuate the effect of residual bone marrow

Inhibiting glycogen synthase kinase-3 mitigates the hematopoietic acute radiation syndrome in mice.

PubMed

Lee, Chang-Lung; Lento, William E; Castle, Katherine D; Chao, Nelson J; Kirsch, David G

2014-05-01

Exposure to a nuclear accident or radiological attack can cause death from acute radiation syndrome (ARS), which results from radiation injury to vital organs such as the hematopoietic system. However, the U.S. Food and Drug Administration (FDA) has not approved any medical countermeasures for this specific purpose. With growing concern over nuclear terrorism, there is an urgent need to develop small molecule deliverables that mitigate mortality from ARS. One emerging modulator of hematopoietic stem/progenitor cell (HSPC) activity is glycogen synthase kinase-3 (GSK-3). The inhibition of GSK-3 has been shown to augment hematopoietic repopulation in mouse models of bone marrow transplantation. In this study, we performed an in vitro screen using irradiated bone marrow mononuclear cells (BM-MNCs) to test the effects of four GSK-3 inhibitors: CHIR99021; 6-Bromoindirubin-3'-oxime (BIO); SB415286; and SB216763. This screen showed that SB216763 significantly increased the frequency of c-Kit(+) Lin(-) Sca1(+) (KLS) cells and hematopoietic colony-forming cells in irradiated BM-MNCs. Importantly, administration of a single dose of SB216763 to C57BL/6J mice by subcutaneous injection 24 h after total-body irradiation significantly improved hematopoietic recovery and mitigated hematopoietic ARS. Collectively, our results demonstrate that the GSK-3 inhibitor SB216763 is an effective medical countermeasure against acute radiation injury of the hematopoietic system.

Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.

Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100%more » mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.« less

Evidence for radiation-induced disseminated intravascular coagulation as a major cause of radiation-induced death in ferrets.

PubMed

Krigsfeld, Gabriel S; Savage, Alexandria R; Billings, Paul C; Lin, Liyong; Kennedy, Ann R

2014-03-15

The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute radiation nephritis. Its evolution on sequential bone imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palestro, C.; Fineman, D.; Goldsmith, S.J.

1988-11-01

Acute radiation nephritis typically affects the kidneys 3-12 months after radiation exposure and may occur with doses as low as 2500 rads. After an initial latent period, the affected portions of the kidneys become swollen and edematous, and develop multiple petechiae. Necrotizing vasculitis and interstitial hemorrhage occur, and the end stage is that of scarring. Two patients are presented in whom localized acute radiation nephritis developed, and whose kidneys demonstrated the characteristic sequential changes of this entity on serial bone imaging.

Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

PubMed

Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

2014-12-01

We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.

Acute radiation syndrome caused by accidental radiation exposure - therapeutic principles.

PubMed

Dörr, Harald; Meineke, Viktor

2011-11-25

Fortunately radiation accidents are infrequent occurrences, but since they have the potential of large scale events like the nuclear accidents of Chernobyl and Fukushima, preparatory planning of the medical management of radiation accident victims is very important. Radiation accidents can result in different types of radiation exposure for which the diagnostic and therapeutic measures, as well as the outcomes, differ. The clinical course of acute radiation syndrome depends on the absorbed radiation dose and its distribution. Multi-organ-involvement and multi-organ-failure need be taken into account. The most vulnerable organ system to radiation exposure is the hematopoietic system. In addition to hematopoietic syndrome, radiation induced damage to the skin plays an important role in diagnostics and the treatment of radiation accident victims. The most important therapeutic principles with special reference to hematopoietic syndrome and cutaneous radiation syndrome are reviewed.

Methylglyoxal-bis(guanylhydrazone), a polyamine analogue, sensitized γ-radiation-induced cell death in HL-60 leukemia cells Sensitizing effect of MGBG on γ-radiation-induced cell death.

PubMed

Kim, Jin Sik; Lee, Jin; Chung, Hai Won; Choi, Han; Paik, Sang Gi; Kim, In Gyu

2006-09-01

Methylglyoxal-bis(guanylhydrazone) (MGBG), a polyamine analogue, has been known to inhibit the biosynthesis of polyamines, which are important in cell proliferation. We showed that MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that polyamine depletion by MGBG treatment did not effectively protect against the chemical (OH) or physical damage to DNA caused by γ-radiation. Through in vitro experiment, we confirmed that DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of polyamines (spermine and spermidine) than in the absence of polyamines. MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and ataxia telangiectasia mutated, which is involved in the DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with MGBG. However, exogenous spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.

Incidence and predictors of in-hospital non-cardiac death in patients with acute heart failure.

PubMed

Wakabayashi, Kohei; Sato, Naoki; Kajimoto, Katsuya; Minami, Yuichiro; Mizuno, Masayuki; Keida, Takehiko; Asai, Kuniya; Munakata, Ryo; Murai, Koji; Sakata, Yasushi; Suzuki, Hiroshi; Takano, Teruo

2017-08-01

Patients with acute heart failure (AHF) commonly have multiple co-morbidities, and some of these patients die in the hospital from causes other than aggravated heart failure. However, limited information is available on the mode of death in patients with AHF. Therefore, the present study was performed to determine the incidence and predictors of in-hospital non-cardiac death in patients with AHF, using the Acute Decompensated Heart Failure Syndromes (ATTEND) registry Methods: The ATTEND registry included 4842 consecutive patients with AHF admitted between April 2007-September 2011. The primary endpoint of the present study was in-hospital non-cardiac death. A stepwise regression model was used to identify the predictors of in-hospital non-cardiac death. The incidence of all-cause in-hospital mortality was 6.4% ( n=312), and the incidence was 1.9% ( n=93) and 4.5% ( n=219) for non-cardiac and cardiac causes, respectively. Old age was associated with in-hospital non-cardiac death, with a 42% increase in the risk per decade (odds 1.42, p=0.004). Additionally, co-morbidities including chronic obstructive pulmonary disease (odds 1.98, p=0.034) and anaemia (odds 1.17 (per 1.0 g/dl decrease), p=0.006) were strongly associated with in-hospital non-cardiac death. Moreover, other predictors included low serum sodium levels (odds 1.05 (per 1.0 mEq/l decrease), p=0.045), high C-reactive protein levels (odds 1.07, p<0.001) and no statin use (odds 0.40, p=0.024). The incidence of in-hospital non-cardiac death was markedly high in patients with AHF, accounting for 30% of all in-hospital deaths in the ATTEND registry. Thus, the prevention and management of non-cardiac complications are vital to prevent acute-phase mortality in patients with AHF, especially those with predictors of in-hospital non-cardiac death.

Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation.

PubMed

Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun; Moon, Changjong; Kim, Sung-Ho

2010-03-01

This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.

Deaths, injuries, and evacuations from acute hazardous materials releases.

PubMed Central

Binder, S

1989-01-01

We examined reports from three surveillance systems of 587 acute releases of hazardous materials in 1986. These releases resulted in at least 115 deaths, 2,254 injuries, and 111 evacuations. Only eight (1 percent) of the 587 events were common to all three systems. Estimates of the public health consequences of hazardous materials releases could be improved by enforcing existing laws, modifying report forms, and validating collected information. PMID:2751024

Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

NASA Astrophysics Data System (ADS)

Kennedy, Ann; Cengel, Keith

2012-07-01

A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

Protective Role of Angiogenin Against Hematopoietic Syndrome of the Acute Radiation Syndrome

DTIC Science & Technology

2017-05-01

AWARD NUMBER: W81XWH-15-1-0207 TITLE: “Protective Role of Angiogenin Against Hematopoietic Syndrome of the Acute Radiation Syndrome ...SUBTITLE Protective Role of Angiogenin Against Hematopoietic Syndrome 5a. CONTRACT NUMBER of the Acute Radiation Syndrome 5b. GRANT NUMBER 5c...hematopoietic syndrome of the acute radiation syndrome (H-ARS) and is able to attenuate the effect of residual bone marrow damage (RBMD) after

Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation from selected severe 235U or 239Pu criticality accidents in USSR, United States, and Argentina.

PubMed

Barabanova, Tatyana; Wiley, Albert L; Bushmanov, Andrey

2012-04-01

Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.

Sudden Cardiac Death After Non-ST-Segment Elevation Acute Coronary Syndrome.

PubMed

Hess, Paul L; Wojdyla, Daniel M; Al-Khatib, Sana M; Lokhnygina, Yuliya; Wallentin, Lars; Armstrong, Paul W; Roe, Matthew T; Ohman, E Magnus; Harrington, Robert A; Alexander, John H; White, Harvey D; Van de Werf, Frans; Piccini, Jonathan P; Held, Claes; Aylward, Philip E; Moliterno, David J; Mahaffey, Kenneth W; Tricoci, Pierluigi

2016-04-01

In the current therapeutic era, the risk for sudden cardiac death (SCD) after non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been characterized completely. To determine the cumulative incidence of SCD during long-term follow-up after NSTE ACS, to develop a risk model and risk score for SCD after NSTE ACS, and to assess the association between recurrent events after the initial ACS presentation and the risk for SCD. This pooled cohort analysis merged individual data from 48 286 participants in 4 trials: the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2), Study of Platelet Inhibition and Patient Outcomes (PLATO), Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER), and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trials. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. Using competing risk and Cox proportional hazards models, clinical factors at baseline and after the index event that were associated with SCD after NSTE ACS were identified. Baseline factors were used to develop a risk model. Data were analyzed from January 2, 2014, to December 11, 2015. Sudden cardiac death. Of the initial 48 286 patients, 37 555 patients were enrolled after NSTE ACS (67.4% men; 32.6% women; median [interquartile range] age, 65 [57-72] years). Among these, 2109 deaths occurred after a median follow-up of 12.1 months. Of 1640 cardiovascular deaths, 513 (31.3%) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.79%, 1.65%, and 2.37%, respectively. Reduced left ventricular ejection fraction, older age, diabetes mellitus, lower estimated glomerular filtration rate, higher heart rate, prior myocardial infarction, peripheral artery disease, Asian race, male sex, and high Killip class were significantly associated with SCD. A model developed to

Acute radiation syndrome: assessment and management.

PubMed

Donnelly, Elizabeth H; Nemhauser, Jeffrey B; Smith, James M; Kazzi, Ziad N; Farfán, Eduardo B; Chang, Arthur S; Naeem, Syed F

2010-06-01

Primary care physicians may be unprepared to diagnose and treat rare, yet potentially fatal, illnesses such as acute radiation syndrome (ARS). ARS, also known as radiation sickness, is caused by exposure to a high dose of penetrating, ionizing radiation over a short period of time. The time to onset of ARS is dependent on the dose received, but even at the lowest doses capable of causing illness, this will occur within a matter of hours to days. This article describes the clinical manifestations of ARS, provides guidelines for assessing its severity, and makes recommendations for managing ARS victims.

Antiradiation Antitoxin IgG : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: High doses of radiation induce apoptotic necrosis of radio-sensitive cells. Mild doses of radiation induce apoptosis or controlled programmed death of radio-sensitive cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune IgG preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. 2.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD

Clinical presentation and in-hospital death in acute pulmonary embolism: does cancer matter?

PubMed

Casazza, Franco; Becattini, Cecilia; Rulli, Eliana; Pacchetti, Ilaria; Floriani, Irene; Biancardi, Marco; Scardovi, Angela Beatrice; Enea, Iolanda; Bongarzoni, Amedeo; Pignataro, Luigi; Agnelli, Giancarlo

2016-09-01

Cancer is one of the most common risk factors for acute pulmonary embolism (PE), but only few studies report on the short-term outcome of patients with PE and a history of cancer. The aim of the study was to assess whether a cancer diagnosis affects the clinical presentation and short-term outcome in patients hospitalized for PE who were included in the Italian Pulmonary Embolism Registry. All-cause and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451 (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer patients). Patients with and without cancer were similar concerning clinical status at presentation. Patients with cancer less commonly received thrombolytic therapy, and more often had an inferior vena cava filter inserted. Major or intracranial bleeding was not different between groups. In-hospital all-cause death occurred in 8.4 and 5.9 % of patients with and without cancer, respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27-3.98; P = 0.006) was an independent predictor of in-hospital death. Clinical instability, PE recurrence, age ≥75 years, recent bed rest ≥3 days, but not cancer, were independent predictors of in-hospital death due to PE. Cancer seems a weaker predictor of all-cause in-hospital death compared to other factors; the mere presence of cancer, without other risk factors, leads to a probability of early death of 2 %. In patients with acute PE, cancer increases the probability of in-hospital all-cause death, but does not seem to affect the clinical presentation or the risk of in-hospital PE-related death.

Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

PubMed

Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

2014-12-01

Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis. © 2014 by the Society for Experimental Biology and Medicine.

A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

DTIC Science & Technology

2016-08-01

Acronyms and Symbols ARA Applied Research Associates, Inc. ARS Acute radiation syndrome d Days DE Differential Evolution DTRA Defense Threat...04-08-2016 Technical Report A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures HDTRA1...epithelial cells to acute radiation alone. The model has been modified for improved radiation response, and an addition to the model allows for thermal injury

Pharmacological management of acute radiation morbidity.

PubMed

Zimmermann, J S; Kimmig, B

1998-11-01

The acute radiation morbidity may be a serious problem for the patient and may be decreased by pharmacological approaches. A database research (Medline, Cancerlit, DIMDI, etc.) was performed in order to obtain pharmacological approaches to decrease the acute radiation morbidity. The evaluation was focused on therapeutic principles but not on special drugs. Different approaches may be chosen to protect healthy tissues from the effects of ionizing radiation: 1. administration of cyto- or radioprotective agents prior to irradiation, 2. administration of agents to avoid additional secondary toxicity by inflammation or superinfection during the treatment cycle (supportive care) and 3. administration of rescue agents, such as bone marrow CSFs or hyperbaric oxygen (HBO), after therapy. For radioprotection, there are reports on cellular protection by vitamine E, vitamine C, beta carotene, ribose-cysteine, glutamine, Mgcl2/adenosine triphosphate and WR-2721 (amifostine). In general, preclinical studies show that the combination of pretreatment with amifostine, irradiation, and G-CSF after radiation enhances hematologic recovery. Assessment of these combined effects, including local supportive therapies, merits further clinical investigation. There are data from prospective studies as well as from empirical clinical experience, that radioprotection and clinical supportive care may reduce the treatment related morbidity by 10 to 30% either. A further improvement of the therapeutic ratio is to be expected by systemically combined application of radioprotectors, supportive care and rescue agents.

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats

PubMed Central

Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-de-la-Asuneión, J; Viña, J; Sastre, J

2006-01-01

Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor α production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. Experimental approach: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. Key results: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. Conclusions and Implications: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans. PMID:16953192

Impact of Acute Coronary Syndrome Complicated by Ventricular Fibrillation on Long-term Incidence of Sudden Cardiac Death.

PubMed

Álvarez-Álvarez, Belén; Bouzas-Cruz, Noelia; Abu-Assi, Emad; Raposeiras-Roubin, Sergio; López-López, Andrea; González Cambeiro, María Cristina; Peña-Gil, Carlos; García-Acuña, José María; González-Juanatey, José Ramón

2015-10-01

There is little information on the effect of acute coronary syndrome complicated by ventricular fibrillation on the long-term incidence of sudden cardiac death. We analyzed this effect in a contemporary cohort of patients with acute coronary syndrome. We studied 5302 consecutive patients with acute coronary syndrome between December 2003 and December 2012. We compared mortality during and after hospitalization according to the presence or absence of ventricular fibrillation. Ventricular fibrillation was observed in 163 (3.1%) patients, and was early onset in 72.4% of these patients. In-hospital mortality was 36.2% in the group with ventricular fibrillation and 4.7% in the group without (p<.001). After a mean follow-up of 4.7 years (standard deviation, 2.6 years), mortality was 30.7% in the ventricular fibrillation group and 24.7% in the other group (P=.23). After adjusting for confounding variables, the presence of ventricular fibrillation was not associated with an increased risk of death in the follow-up period (hazard ratio=1.29; 95% confidence interval, 0.90-1.87). The cause of death was established in 72% of patients. The incidence of sudden death was 12.9% in the ventricular fibrillation group and 11.9% in the other group (P=.71). Cardiovascular-cause mortality was also similar between the 2 groups (35.5% and 34.4%, respectively. Patients with acute coronary syndrome complicated by ventricular fibrillation who survive the in-hospital phase do not appear to be at an increased risk of sudden cardiac death or other cardiovascular-cause death. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Countermeasure development : Specific Immunoprophylaxis and Immunotherapy of Combined Acute Radiation Syndromes.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: Combined Acute Radiation Syndromes (CARS) are extremely severe injuries. Combination of Radiation and Thermal factors induce development of the acute pathologi-cal processes in irradiated mammals: systemic inflammatory response syndrome (SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMOD), toxic multiple organ failure (TMOF). Also, high doses of Radiation and Thermal injury induce for-mation of following Toxin groups: A. Specific Radiation Toxins; B. Specific Thermal Toxins; C. Nonspecific Histiogenic Pro-inflammatory and Inflammatory Toxins (NHIT). Specific Radi-ation Toxins (SRT) include four major group of Toxins: Cerebrovascular Radiation Toxins (Cv RT), Cardiovascular Radiation Toxins (Cr RT), Gastrointestinal Radiation Toxins (Gi RT), and Hematopoietic Radiation Toxins (Hp RT). CvRT, Cr RT, Gi RT groups of toxins are defined as Neurotoxins and Hp RT group is defined as Hematotoxins. Specific Thermal Toxins (STT) were isolated from the burned skin (Voul S., Colker I. 1972). The group of Nonspecific Histio-genic Inflammatory Toxins (NHIT) includes high amount of tissue toxins which are peptides with medium molecular weight. This group of polypeptides can be a significant factor as a part of developing of the general inflammation reaction. However, NHIT toxins can't induce many reactions and changes which are specific for radiation. Specific Radiation Toxins (SRT) can induce specific processes and reactions such as clonogenic cell death -programmed apoptotic necrosis. Although besides high doses of radiation, other forms of cell death such as Pyroptosis or Oncosis should be considered. We postulate that NHIT toxins are similar for high doses of radiation and thermal injury. Specific Radiation Toxins (SRT) are induced by high doses of radiation. Specific Thermal Toxins (STT) toxins which formation is induced by a Thermal Factor are different from SRT. Administration of STT toxins or NHIT toxins (IV or IM) to

Use of Proteomic and Hematology Biomarkers for Prediction of Hematopoietic Acute Radiation Syndrome Severity in Baboon Radiation Models.

PubMed

Blakely, William F; Bolduc, David L; Debad, Jeff; Sigal, George; Port, Matthias; Abend, Michael; Valente, Marco; Drouet, Michel; Hérodin, Francis

2018-07-01

Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.25 cGy min and 32 cGy min. Hematopoietic acute radiation syndrome severity levels determined by an analysis of blood count changes measured up to 60 d after irradiation were used to gauge overall hematopoietic acute radiation syndrome severity classifications. A panel of protein biomarkers was measured on plasma samples collected at 0 to 28 d after exposure using electrochemiluminescence-detection technology. The database was split into two distinct groups (i.e., "calibration," n = 11; "validation," n = 7). The calibration database was used in an initial stepwise regression multivariate model-fitting approach followed by down selection of biomarkers for identification of subpanels of hematopoietic acute radiation syndrome-responsive biomarkers for three time windows (i.e., 0-2 d, 2-7 d, 7-28 d). Model 1 (0-2 d) includes log C-reactive protein (p < 0.0001), log interleukin-13 (p < 0.0054), and procalcitonin (p < 0.0316) biomarkers; model 2 (2-7 d) includes log CD27 (p < 0.0001), log FMS-related tyrosine kinase 3 ligand (p < 0.0001), log serum amyloid A (p < 0.0007), and log interleukin-6 (p < 0.0002); and model 3 (7-28 d) includes log CD27 (p < 0.0012), log serum amyloid A (p < 0.0002), log erythropoietin (p < 0.0001), and log CD177 (p < 0.0001). The predicted risk of radiation injury categorization values, representing the hematopoietic acute radiation syndrome severity outcome for the three models, produced least squares multiple regression fit confidences of R = 0.73, 0.82, and 0.75, respectively. The resultant algorithms support the proof of concept that plasma proteomic biomarkers can supplement

Association of Radon Background and Total Background Ionizing Radiation with Alzheimer's Disease Deaths in U.S. States.

PubMed

Lehrer, Steven; Rheinstein, Peter H; Rosenzweig, Kenneth E

2017-01-01

Exposure of the brain to ionizing radiation might promote the development of Alzheimer's disease (AD). Analysis of AD death rates versus radon background radiation and total background radiation in U.S. states. Total background, radon background, cosmic and terrestrial background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States and Report No. 160 - Ionizing Radiation Exposure of the Population of the United States. 2013 AD death rates by U.S. state are from the Alzheimer's Association. Radon background ionizing radiation was significantly correlated with AD death rate in 50 states and the District of Columbia (r = 0.467, p = 0.001). Total background ionizing radiation was also significantly correlated with AD death rate in 50 states and the District of Columbia (r = 0.452, p = 0.001). Multivariate linear regression weighted by state population demonstrated that AD death rate was significantly correlated with radon background (β= 0.169, p < 0.001), age (β= 0.231, p < 0.001), hypertension (β= 0.155, p < 0.001), and diabetes (β= 0.353, p < 0.001). Our findings, like other studies, suggest that ionizing radiation is a risk factor for AD. Intranasal inhalation of radon gas could subject the rhinencephalon and hippocampus to damaging radiation that initiates AD. The damage would accumulate over time, causing age to be a powerful risk factor.

Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

PubMed

Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

2009-10-01

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Cell Death and DAMPs in Acute Pancreatitis

PubMed Central

Kang, Rui; Lotze, Michael T; Zeh, Herbert J; Billiar, Timothy R; Tang, Daolin

2014-01-01

Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP. Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP. DAMPs might be an attractive therapeutic target in AP. PMID:25105302

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

PubMed

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

The acute gastrointestinal subsyndrome of the acute radiation syndrome: a rhesus macaque model.

PubMed

MacVittie, Thomas J; Farese, Ann M; Bennett, Alexander; Gelfond, Daniel; Shea-Donohue, Terez; Tudor, Gregory; Booth, Catherine; McFarland, Emylee; Jackson, William

2012-10-01

The development of medical countermeasures against the acute gastrointestinal subsyndrome of the acute radiation syndrome in humans requires well characterized and validated animal models. These models must adhere to the criteria of the U.S. Food and Drug Administration's Animal Rule and consider the natural history and clinical context of the human radiation response and treatment in the nuclear terrorist scenario. The models must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity, including concurrent damage in other organs, such as the bone marrow, that may contribute to the overall mortality and morbidity. There are no such models of the gastrointestinal syndrome in response to total-body irradiation in the nonhuman primate. Herein, these parameters are defined for the rhesus macaque exposed to potentially lethal doses of radiation and administered medical management. Rhesus macaques (n = 69) were exposed bilaterally to 6 MV linear accelerator-derived photon total body irradiation to midline tissue (thorax) doses ranging from 10.0 to 14.0 Gy at 0.80 Gy min(-1). Following irradiation, all animals were administered supportive care consisting of fluids, anti-emetics, anti-diarrheal medication, antibiotics, blood transfusions, analgesics, and nutrition. The primary endpoint was survival at 15 d post-irradiation. Secondary endpoints included indices of dehydration, diarrhea, weight loss, hematological parameters, cellular histology of the small and large intestine, and mean survival time of decedents. Mortality within the 15-d in vivo study defined the acute gastrointestinal syndrome and provided an LD30/15 of 10.76 Gy, LD50/15 of 11.33 Gy, and an LD70/15 of 11.90 Gy. Intestinal crypt and villus loss were dose- and time-dependent with an apparent nadir 7 d post-irradiation and recovery noted thereafter. Severe myelosuppression and thrombocytopenia were noted in all animals, requiring the administration of

[Sudden death secondary to acute aortic syndromes in the North of Portugal: medico-legal study].

PubMed

Moreira, Pedro Costa; Santos, Agostinho

2013-01-01

An evaluation is presented on the clinical, pathological and sociodemographic characteristics of a sample of sudden death victims secondary to an Acute Aortic Syndrome (AAS) in the north of Portugal, submitted to medico-legal autopsy, during the period between January 2008 and December 2012. Autopsy reports were analyzed in which, through necropsy and histological examination, the confirmed cause of death was an Acute Aortic Syndrome. From the studied cases, 70.3% of the victims were male. The median age was 65,19 ± 14,35 years (minimum of 27 years and maximum of 88 years). Death occurred mainly at home (40,5%) and during the normal activities of daily living (43,1%). There was an history of prodromes in 64,9% of the cases, mainly syncope and pain or respiratory symptoms. In 62,2% of the cases no pain history was reported. In the internal examination three presentation forms were identified: cardiac tamponade (51,4%); hemotorax (16,2%) and intra-abdominal bleeding (32,4%). The occurence of an Acute Aortic Syndrome was related to an aneurysmatic formation in 81% of the cases. Atherosclerotic plaques were identified in 51,4% of the cases and left ventricular hypertrophy was identified in 54,1%. None of the victims had a family history of aortic pathology and 54,1% of them presented a history of arterial hypertension. Necropsy data analysis of sudden death victims allows a better understanding of the AAS presentation, thus complementing the existent clinical studies. This work reveals how forensic medicine can be a privileged medium for articulation with clinical practice.

Mitigation Strategies for Acute Radiation Exposure during Space Flight

NASA Technical Reports Server (NTRS)

Hamilton, Douglas R.; Epelman, Slava

2006-01-01

While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 grams per square centimeters would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.

Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

DTIC Science & Technology

2016-10-01

MV, Katz BP, Smith CP, Jackson W 3rd, Cohen DM, et al. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management...subsyndrome of the acute radiation syndrome : a rhesus macaque model. Health Phys 2012; 103:411–26. 32. Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler...AD______________ AWARD NUMBER: W81XWH-15-1-0574 TITLE: Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

PubMed

Kolbe, Scott C; van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F; Kilpatrick, Trevor J

2016-01-01

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis

PubMed Central

van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F.; Kilpatrick, Trevor J.

2016-01-01

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = −0.428, p = 0.009; MD: R = −0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage. PMID:27555964

DEATH, DYING AND NEAR DEATH EXPERIENCE

PubMed Central

Singh, Ajai R.; Bagadia, V.N.; Pradhan, P.V.; Acharya, V.N.

1988-01-01

SUMMARY Psychology of deaths due to acute medical emergencies is under-researched. Most studies till now have concentrated on extended-death situations like malignancy. This open pilot study of twenty five patients examines the psychological state of patients during a life threatening acute medical illness (Group A, ten patients) and of those who survive such an experience (Group B, fifteen patients). The study finds psychological exploration both possible and necessary if carried out in a discreet manner. Salient features of the interview technique are discussed. The study finds out whether patients are aware of the possibility of terminality. The psychological disturbances manifest and nature of care expected are also discussed. Near Death Experiences of those who acknowledge their occurence are reported. Some nuances of thanatological research are high-lighted: What are the abilities needed in an interviewer? Can such exploration increase psychological distress in a patient already prone to it because of serious medical sickness? What impact such research can have on the interviewer himself? The paper answers some of these common questions while developing the method of thanatological study in acute medical death-situations. PMID:21927325

Abnormal intra-aural pressure waves associated with death in African children with acute nontraumatic coma.

PubMed

Gwer, Samson; Kazungu, Michael; Chengo, Eddie; Ohuma, Eric O; Idro, Richard; Birch, Tony; Marchbanks, Robert; Kirkham, Fenella J; Newton, Charles R

2015-07-01

We explored the relationship between tympanic membrane displacement (TMD) measurements, a tool to monitor intracranial pressure noninvasively, and clinical features and death in children with acute coma in Kilifi, Kenya. Between November 2007 and September 2009, we made serial TMD measurements and clinical observations on children with acute coma (Blantyre coma score (BCS) ≤ 2) on the pediatric high dependency unit of Kilifi District Hospital, and on well children presenting to the hospital's outpatient department for routine follow-up. We examined middle ear function using tympanometry and measured cardiac pulse (CPA) and respiratory pulse pressure amplitudes (RPA) using the TMD analyzer. We recruited 75 children (32 (43%) females; median age 3.3 (IQR: 2.0, 4.3) years). Twenty-one (28%) children died. Higher TMD measurements predicted death. Adjusting for diagnosis, every 50 nl rise in both semirecumbent and recumbent CPA was associated with increased odds of death associated with intracranial herniation (OR: 1.61, 95% confidence interval (CI): 1.07, 2.41; P = 0.02 and OR: 1.35, 95% CI: 1.10, 1.66; P ≤ 0.01 respectively). Raised TMD pulse pressure measurements are associated with death and may be useful in detecting and monitoring risk of intracranial herniation and intracranial pressure in childhood coma.

Effect of blue light radiation on curcumin-induced cell death of breast cancer cells

NASA Astrophysics Data System (ADS)

Zeng, X. B.; Leung, A. W. N.; Xia, X. S.; Yu, H. P.; Bai, D. Q.; Xiang, J. Y.; Jiang, Y.; Xu, C. S.

2010-06-01

In the present study, we have successfully set up a novel blue light source with the power density of 9 mW/cm2 and the wavelength of 435.8 nm and then the novel light source was used to investigate the effect of light radiation on curcumin-induced cell death. The cytotoxicity was investigated 24 h after the treatment of curcumin and blue light radiation together using MTT reduction assay. Nuclear chromatin was observed using a fluorescent microscopy with Hoechst33258 staining. The results showed blue light radiation could significantly enhance the cytotoxicity of curcumin on the MCF-7 cells and apoptosis induction. These findings demonstrated that blue light radiation could enhance curcumin-induced cell death of breast cancer cells, suggesting light radiation may be an efficient enhancer of curcumin in the management of breast cancer.

Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

Evaluation of acute radiation optic neuropathy by B-scan ultrasonography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lovato, A.A.; Char, D.H.; Quivey, J.M.

1990-09-15

We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography.more » In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.« less

Risk of acute myocardial infarction after the death of a significant person in one's life: the Determinants of Myocardial Infarction Onset Study.

PubMed

Mostofsky, Elizabeth; Maclure, Malcolm; Sherwood, Jane B; Tofler, Geoffrey H; Muller, James E; Mittleman, Murray A

2012-01-24

Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied. We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patient's control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1-34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk. Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk.

[Hematopoiesis during remote period after acute radiation syndrome].

PubMed

Kotenko, K V; Bushmanov, A Iu; Suvorova, L A; Galstian, I A; Nadezhina, N M; Nugis, V Iu

2011-01-01

Based on the long (19.7 +/- 1.8 year) hemopoiesis follow-up study in 152 patients after acute radiation syndrome (ARS) as a result of exposure to gamma-, gamma-beta and gamma-eta radiation in a wide dose range (1.2-9.8 Gy) it was detected that cytopenia appears in the late consequences period: thrombocytopenia was found in 26.9% cases, leukocytopenia, neutropenia and lymphocytopenia--in 13.1% patients. A higher ARS degree causes the increase of various disorders (cytopenia and cytosis) in the late period. It reflects a tight interrelation between blood cell contents and radiation dose. Frequency of cytopenias increases if such somatic disorders: persistent hepatitis, hepatic cirrhosis and late radiation ulcers as appear.

Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity

PubMed Central

Liu, Yong; Chen, Xiao-Dong; Yu, Jiang; Chi, Jun-Lin; Long, Fei-Wu; Yang, Hong-Wei; Chen, Ke-Ling; Lv, Zhao-Ying; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

2017-01-01

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that

Emetic Mechanism in Acute Radiation Sickness

DTIC Science & Technology

1987-08-20

humans renders the subjects refractory to a wide variety of chemical emetic agents, now numbering more than 25 substances of both exogenous and endogenous...tractus solitarius with each of three neurons (shown as large triangles) in the nucleus of the tractus solitarius (NTS). These hells of NTS connect...Outputs are innervated through autonomic ganglia or by direct efferent connections. I4 Acute radiation-induced vomiting is generally typified by the

Interferon-gamma enhances radiation-induced cell death via downregulation of Chk1

PubMed Central

Kim, Kwang Seok; Choi, Kyu Jin; Bae, Sangwoo

2012-01-01

Interferon-gamma (IFNγ) is a cytokine with roles in immune responses as well as in tumor control. Interferon is often used in cancer treatment together with other therapies. Here we report a novel approach to enhancement of cancer cell killing by combined treatment of IFNγ with ionizing radiation. We found that IFNγ treatment alone in HeLa cells induced phosphorylation of Chk1 in a time- and dose-dependent manner, and resulted in cell arrest. Moreover IFNγ treatment was correlated with attenuation of Chk1 as the treatment shortened protein half-life of Chk1. As Chk1 is an essential cell cycle regulator for viability after DNA damage, attenuation of Chk1 by IFNγ pre-treatment in HeLa cells resulted in increased cell death following ionizing radiation about 2-folds than ionizing radiation treatment alone whereas IFNγ treatment alone had little effect on cell death. X-linked inhibitor of apoptosis-associated factor 1 (XAF1), an IFN-induced gene, seems to partly regulate IFNγ-induced Chk1 destabilization and radiation sensitivity because transient depletion of XAF1 by siRNA prevented IFNγ-induced Chk1 attenuation and partly protected cells from IFNγ-enhanced radiation cell killing. Therefore the results provide a novel rationale to combine IFNγ pretreatment and DNA-damaging anti-cancer drugs such as ionizing radiation to enhance cancer cell killing. PMID:22825336

One in Five Maternal Deaths in Bangladesh Associated with Acute Jaundice: Results from a National Maternal Mortality Survey

PubMed Central

Shah, Rupal; Nahar, Quamrun; Gurley, Emily S.

2016-01-01

We estimated the proportion of maternal deaths in Bangladesh associated with acute onset of jaundice. We used verbal autopsy data from a nationally representative maternal mortality survey to calculate the proportion of maternal deaths associated with jaundice and compared it to previously published estimates. Of all maternal deaths between 2008 and 2010, 23% were associated with jaundice, compared with 19% from 1998 to 2001. Approximately one of five maternal deaths was preceded by jaundice, unchanged in 10 years. Our findings highlight the need to better understand the etiology of these maternal deaths in Bangladesh. PMID:26755563

One in Five Maternal Deaths in Bangladesh Associated with Acute Jaundice: Results from a National Maternal Mortality Survey.

PubMed

Shah, Rupal; Nahar, Quamrun; Gurley, Emily S

2016-03-01

We estimated the proportion of maternal deaths in Bangladesh associated with acute onset of jaundice. We used verbal autopsy data from a nationally representative maternal mortality survey to calculate the proportion of maternal deaths associated with jaundice and compared it to previously published estimates. Of all maternal deaths between 2008 and 2010, 23% were associated with jaundice, compared with 19% from 1998 to 2001. Approximately one of five maternal deaths was preceded by jaundice, unchanged in 10 years. Our findings highlight the need to better understand the etiology of these maternal deaths in Bangladesh. © The American Society of Tropical Medicine and Hygiene.

MRI assessment of local acute radiation syndrome.

PubMed

Weber-Donat, G; Amabile, J-C; Lahutte-Auboin, M; Potet, J; Baccialone, J; Bey, E; Teriitehau, C; Laroche, P

2012-12-01

To describe local acute radiation syndrome and its radiological imaging characteristics. We performed a retrospective study of patients who had suffered skin and deeper radiation damage who were investigated by magnetic resonance imaging (MRI). We compared the clinical findings, C-reactive protein (CRP) levels and MRI results. A total of 22 MRI examinations were performed between 2005 and 2010 in 7 patients; 6 patients had increased CRP levels and MRI abnormalities. They were treated by surgery and local cellular therapy. One patient had no CRP or MRI abnormalities, and had a spontaneous good outcome. Eighteen abnormal MR examinations demonstrated high STIR signal and/or abnormal enhancement in the dermis and muscle tissues. Three MRI examinations demonstrated skeletal abnormalities, consistent with radionecrosis. The four normal MRI examinations were associated only with minor clinical manifestations such as pain and pigmentation disorders. MRI seems to be a useful and promising imaging investigation in radiation burns management i.e. initial lesion evaluation, treatment evaluation and complication diagnosis. MRI findings correlated perfectly with clinical stage and no false negative examinations were obtained. In particular, the association between normal MRI and low CRP level seems to be related to good outcome without specific treatment. Local acute radiation syndrome (radioepidermitis) mainly affects the skin and superficial tissues. MRI findings correspond with clinical stage (with a strong negative predictive value). MRI outperformed X-ray examination for the diagnosis of bone radionecrosis. Diffusion-weighted imaging shows low ADC in bone and soft tissue necrosis. Perfusion sequence allows assessment of tissue microcirculation impairment.

Acute changes in community violence and increases in hospital visits and deaths from stress-responsive diseases.

PubMed

Ahern, Jennifer; Matthay, Ellicott C; Goin, Dana E; Farkas, Kriszta; Rudolph, Kara E

2018-06-06

Community violence may affect a broad range of health outcomes through physiologic stress responses and changes in health behaviors among residents. However, existing research on the health impacts of community violence suffers from problems with bias. We examined the relations of acute changes in community violence with hospital visits and deaths due to stress-responsive diseases (mental, respiratory, and cardiac conditions) in statewide data from California 2005-2013. The community violence exposure was measured as both binary spikes and continuous acute changes. We applied a combined fixed-effects and time-series design that separates the effects of violence from those of community- and individual-level confounders more effectively than past research. Temporal patterning was removed from community violence rates and disease rates in each place using a Kalman smoother, resulting in residual rates. We used linear regression with place fixed-effects to examine within-place associations of acute changes in community violence with residual rates of each outcome, controlling for local time-varying covariates. We found acute increases in hospital visits and deaths due to anxiety disorders (0.31 per 100,000; 95% Confidence Interval (CI) 0.02,0.59), substance use (0.47 per 100,000; 95%CI 0.14,0.80), asthma (0.56 per 100,000; 95%CI 0.16,0.95), and fatal acute myocardial infarction (0.09 per 100,000; 95%CI 0.00,0.18) co-occurring with violence spikes. The pattern of findings was similar for the exposure of continuous acute violence changes. Although the associations were small, the identified increases in stress-responsive conditions suggest the possibility of health impacts of acute changes in community violence.

Gastrointestinal acute radiation syndrome in Göttingen minipigs (Sus scrofa domestica).

PubMed

Elliott, Thomas B; Deutz, Nicolaas E; Gulani, Jatinder; Koch, Amory; Olsen, Cara H; Christensen, Christine; Chappell, Mark; Whitnall, Mark H; Moroni, Maria

2014-12-01

In the absence of supportive care, exposing Göttingen minipigs to γ-radiation doses of less than 2 Gy achieves lethality due to hematopoietic acute radiation syndrome. Doses of 2 to 5 Gy are associated with an accelerated hematopoietic syndrome, characterized by villus blunting and fusion, the beginning of sepsis, and a mild transient reduction in plasma citrulline concentration. We exposed male Göttingen minipigs (age, 5 mo; weight, 9 to 11 kg) to γ-radiation doses of 5 to 12 Gy (total body; (60)Co, 0.6 Gy/min) to test whether these animals exhibit classic gastrointestinal acute radiation syndrome (GI-ARS). After exposure, the minipigs were monitored for 10 d by using clinical signs, CBC counts, and parameters associated with the development of the gastrointestinal syndrome. Göttingen minipigs exposed to γ radiation of 5 to 12 Gy demonstrate a dose-dependent occurrence of all parameters classically associated with acute GI-ARS. These results suggest that Göttingen minipigs may be a suitable model for studying GI-ARS after total body irradiation, but the use of supportive care to extend survival beyond 10 d is recommended. This study is the first step toward determining the feasibility of using Göttingen minipigs in testing the efficacy of candidate drugs for the treatment of GI-ARS after total body irradiation.

Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

PubMed Central

Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

2014-01-01

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, p<0.0001), reached a minimum value after 3 days (86% reduction, p<0.0001), and partially rebounded by 14 days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, p<0.0001), and 530% (14 days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure

Non-arrhythmic therapy of ventricular tachyarrhythmias and sudden cardiac death after acute myocardial infarction.

PubMed

Schweitzer, P

2006-12-01

The management of ventricular tachyarrhythmias and prevention of sudden cardiac death after acute myocardial infarction (AMI) underwent important evolution. In the CAST study, encanaide and other antiarrhythmic drugs were not only ineffective but also increased mortality after myocardial infarction. Amiodarone had some beneficial effect on arrhythmic events without improving survival, and ICDs failed to improve outcome early after AMI. In comparison, short and long term survival benefits of beta blockers, angiotensine converting enzyme inhibitors and aldosterone antagonists after AMI is well established. This review discusses the role of non-arrhythmic therapy in the prevention of ventricular tachyarrhythmia's and sudden cardiac death after AMI.

Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

NASA Technical Reports Server (NTRS)

Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael C.

2007-01-01

Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and

Filgrastim for the treatment of hematopoietic acute radiation syndrome.

PubMed

Farese, A M; MacVittie, T J

2015-09-01

The U.S. Food and Drug Administration (FDA) recently approved Neupogen(®) (filgrastim) for the treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident. It is the first medical countermeasure currently approved by the FDA for this indication under the criteria of the FDA "animal rule". This article summarizes the consequences of high-dose radiation exposure, a description of the hematopoietic acute radiation syndrome (H-ARS), the use of hematopoietic growth factors in radiation accident victims and current available treatments for H-ARS with an emphasis on the use of Neupogen in this scenario. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

In-hospital death according to dementia diagnosis in acutely ill elderly patients: the REPOSI study.

PubMed

Marengoni, A; Corrao, S; Nobili, A; Tettamanti, M; Pasina, L; Salerno, F; Iorio, A; Marcucci, M; Bonometti, F; Mannucci, P M

2011-09-01

The aim of the study was to explore the association of dementia with in-hospital death in acutely ill medical patients. Thirty-four internal medicine and 4 geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI-study during 2008. One thousand three hundred and thirty two in-patients aged 65 years or older were enrolled. Logistic regression models were used to evaluate the association of dementia with in-hospital death. Socio-demographic characteristics, morbidity (single diseases and the Charlson Index), number of drugs, and adverse clinical events during hospitalization were considered as potential confounders. One hundred and seventeen participants were diagnosed as being affected by dementia. Patients with dementia were more likely to be women, older, to have cerebrovascular diseases, pneumonia, and a higher number of adverse clinical events during hospitalization. The percentage of patients affected by dementia who died during hospitalization was higher than that of patients without dementia (9.4 versus 4.9%). After multiadjustment, the diagnosis of dementia was associated with in-hospital death (OR = 2.1; 95% CI = 1.0-4.5). Having dementia and at least one adverse clinical event during hospitalization showed an additive effect on in-hospital mortality (OR = 20.7; 95% CI = 6.9-61.9). Acutely ill elderly patients affected by dementia are more likely to die shortly after hospital admission. Having dementia and adverse clinical events during hospital stay increases the risk of death. Copyright © 2010 John Wiley & Sons, Ltd.

Estimating Risk of Hematopoietic Acute Radiation Syndrome in Children.

PubMed

Adams, Tim G; Sumner, Louise E; Casagrande, Rocco

2017-12-01

Following a radiological terrorist attack or radiation accident, the general public may be exposed to radiation. Historically, modeling efforts have focused on radiation effects on a "reference man"-a 70-kg, 180-cm-tall, 20- to 30-y-old male-which does not adequately reflect radiation hazard to special populations, particularly children. This work examines the radiosensitivity of children with respect to reference man to develop a set of parameters for modeling hematopoetic acute radiation syndrome in children. This analysis was performed using animal studies and the results verified using data from medical studies. Overall, the hematopoietic system in children is much more radiosensitive than that in adults, with the LD50 for children being 56% to 91% of the LD50 of adults, depending on age.

Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma.

PubMed

Redjal, Navid; Agarwalla, Pankaj K; Dietrich, Jorg; Dinevski, Nikolaj; Stemmer-Rachamimov, Anat; Nahed, Brian V; Loeffler, Jay S

2015-08-01

We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential for a pluripotent adult stem cell treatment for acute radiation sickness

PubMed Central

Rodgerson, Denis O; Reidenberg, Bruce E; Harris, Alan G; Pecora, Andrew L

2012-01-01

Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ionizing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung. PMID:24520532

Protracted low-dose radiation priming and response of liver to acute gamma and proton radiation.

PubMed

Gridley, D S; Mao, X W; Cao, J D; Bayeta, E J M; Pecaut, M J

2013-10-01

This study evaluated liver from C57BL/6 mice irradiated with low-dose/low-dose-rate (LDR) γ-rays (0.01 Gy, 0.03 cGy/h), with and without subsequent exposure to acute 2 Gy gamma or proton radiation. Analyses were performed on day 56 post-exposure. Expression patterns of apoptosis-related genes were strikingly different among irradiated groups compared with 0 Gy (p < 0.05). Two genes were affected in the Gamma group, whereas 10 were modified in the LDR + Gamma group. In Proton and LDR + Proton groups, there were six and 12 affected genes, respectively. Expression of genes in the Gamma (Traf3) and Proton (Bak1, Birc2, Birc3, Mcl1) groups was no longer different from 0 Gy control group when mice were pre-exposed to LDR γ-rays. When each combined regimen was compared with the corresponding group that received acute radiation alone, two genes in the LDR + Gamma group and 17 genes in the LDR + Proton group were modified; greatest effect was on Birc2 and Nol3 (> 5-fold up-regulated by LDR + Protons). Oxygen radical production in livers from the LDR + Proton group was higher in LDR, Gamma, and LDR + Gamma groups (p < 0.05 vs. 0 Gy), but there were no differences in phagocytosis of E. coli. Sections stained with hematoxylin and eosin (H&E) suggested more inflammation, with and without necrosis, in some irradiated groups. The data demonstrate that response to acute radiation is dependent on radiation quality and regimen and that some LDR γ-ray-induced modifications in liver response were still evident nearly 2 months after exposure.

Association of Hematological Nadirs and Survival in a Nonhuman Primate Model of Hematopoietic Syndrome of Acute Radiation Syndrome.

PubMed

Gluzman-Poltorak, Zoya; Vainstein, Vladimir; Basile, Lena A

2015-08-01

Recombinant human interleukin-12 (rHuIL-12) mitigates the hematopoietic subsyndrome of acute radiation syndrome (HSARS) after total body irradiation (TBI) in a nonhuman primate (NHP) model of HSARS. The mechanism for this effect appears to involve multiple effects of rHuIL-12 on hematopoiesis. We conducted a meta-analysis to examine hematological nadirs and survival across our three NHP completed studies. Animals were irradiated (700 cGy) and treated with a single subcutaneous injection of vehicle (n = 64) or rHuIL-12 (50-500 ng/kg; n = 108) 24-25 h after irradiation, or with daily subcutaneous injections of granulocyte-colony stimulating factor (G-CSF; 10 μg/kg/day) for 18 days starting 24-25 h after exposure (n = 26). Blood samples were obtained at various time points up to day 60 after TBI. Lymphocytes, neutrophils and platelets were significantly lower in nonsurvivors than in survivors in the overall sample and in each treatment group (P < 0.001 for each comparison, Wilcoxon rank-sum test). Lymphocyte nadir was the strongest and most consistent predictor of death by Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis of death and threshold hematologic nadir values (where nadir values less than or equal the threshold are predictive of death) showed that a threshold of 0.08 × 10(9)/L for lymphocytes had the largest positive predictive value of death (97.2% and 92.5% for the control and rHuIL-12 groups, respectively) and high sensitivity (76.1% and 62.7%, respectively), consistent with human radiation victims data. The current findings suggest that enhanced early bone marrow regeneration resulting in increases in nadir values for all major blood cell types may be the main mechanism of action by which rHuIL-12 mitigates the lethality of HSARS.

Mesenchymal Stem Cell Therapy for Acute Radiation Syndrome: Innovative Medical Approaches in Military Medicine

DTIC Science & Technology

2015-01-30

mesenchymal stem cells . Cytokine Growth Factor Rev. 2009;20:419–27. 8. Wang L, Li Y, Chen X, Chen J, Gautam SC, Xu Y, et al. MCP...Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Mesenchymal stem cell therapy for acute radiation syndrome: innovative medical...Independent Research Program 14. ABSTRACT See reprint. 15. SUBJECT TERMS Acute radiation syndrome, Mesenchymal stem cell , cell therapy,

Targeting Extracellular Histones with Novel RNA Bio drugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

organ involved in MODS is the lung (referred to as acute respiratory distress syndrome or ARDS). Trauma, smoke inhalation, burns, radiation , severe...and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome (MODS/ARDS) and ALI that can be easily delivered in combat...MODS, the risk of death is 40%. The most common organ involved in MODS is the lungs (referred to as acute respiratory distress syndrome or ARDS

Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

PubMed

Burman, P; Mattsson, A F; Johannsson, G; Höybye, C; Holmer, H; Dahlqvist, P; Berinder, K; Engström, B E; Ekman, B; Erfurth, E M; Svensson, J; Wahlberg, J; Karlsson, F A

2013-04-01

Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant

Characterization of a novel epigenetic effect of ionizing radiation: the death-inducing effect

NASA Technical Reports Server (NTRS)

Nagar, Shruti; Smith, Leslie E.; Morgan, William F.

2003-01-01

The detrimental effects associated with exposure to ionizing radiation have long been thought to result from the direct targeting of the nucleus leading to DNA damage; however, the emergence of concepts such as radiation-induced genomic instability and bystander effects have challenged this dogma. After cellular exposure to ionizing radiation, we have isolated a number of clones of Chinese hamster-human hybrid GM10115 cells that demonstrate genomic instability as measured by chromosomal destabilization. These clones show dynamic and persistent generation of chromosomal rearrangements multiple generations after the original insult. We hypothesize that these unstable clones maintain this delayed instability phenotype by secreting factors into the culture medium. To test this hypothesis we transferred filtered medium from unstable cells to unirradiated GM10115 cells. No GM10115 cells were able to survive this medium. This phenomenon by which GM10115 cells die when cultured in medium from chromosomally unstable GM10115 clones is the death-inducing effect. Medium transfer experiments indicate that a factor or factors is/are secreted by unstable cells within 8 h of growth in fresh medium and result in cell killing within 24 h. These factors are stable at ambient temperature but do not survive heating or freezing, and are biologically active when diluted with fresh medium. We present the initial description and characterization of the death-inducing effect. This novel epigenetic effect of radiation has implications for radiation risk assessment and for health risks associated with radiation exposure.

Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients.

PubMed

Levitsky, Josh; Goldberg, David; Smith, Abigail R; Mansfield, Sarah A; Gillespie, Brenda W; Merion, Robert M; Lok, Anna S F; Levy, Gary; Kulik, Laura; Abecassis, Michael; Shaked, Abraham

2017-04-01

Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors. We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors. At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. Contrary to previous data, acute rejection after liver transplant is associated with significantly increased

CD47-ligation induced cell death in T-acute lymphoblastic leukemia.

PubMed

Leclair, Pascal; Liu, Chi-Chao; Monajemi, Mahdis; Reid, Gregor S; Sly, Laura M; Lim, Chinten James

2018-05-10

CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue for targeted cancer therapies involves neutralizing the anti-phagocytic function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of CD47 receptor ligation is the direct induction of tumour cell death. While several mAbs and their derivatives with this property have been studied, the best characterized is the commercially available mAb B6H12, which requires immobilization for induction of cell death. Here, we describe a commercially available mAb, CC2C6, which induces T-cell acute lymphoblastic leukemia (ALL) cell death in soluble form. Soluble CC2C6 induces CD47-dependent cell death in a manner consistent with immobilized B6H12, which is characterized by mitochondrial deficiencies but is independent of caspase activation. Titration studies indicated that CC2C6 shares a common CD47-epitope with B6H12. Importantly, CC2C6 retains the anti-phagocytic neutralizing function, thus possessing dual anti-tumour properties. Although CD47-ligation induced cell death occurs in a caspase-independent manner, CC2C6 was found to stimulate increases in Mcl-1 and NOXA levels, two Bcl-2 family proteins that govern the intrinsic apoptosis pathway. Further analysis revealed that the ratio of Mcl-1:NOXA were minimally altered for cells treated with CC2C6, in comparison to cells treated with agents that induced caspase-dependent apoptosis which alter this ratio in favour of NOXA. Finally, we found that CC2C6 can synergize with low dose chemotherapeutic agents that induce classical apoptosis, giving rise to the possibility of an effective combination treatment with reduced long-term sequelae associated with high-dose chemotherapies in childhood ALL.

Serum Acylcarnitines and Risk of Cardiovascular Death and Acute Myocardial Infarction in Patients With Stable Angina Pectoris.

PubMed

Strand, Elin; Pedersen, Eva R; Svingen, Gard F T; Olsen, Thomas; Bjørndal, Bodil; Karlsson, Therese; Dierkes, Jutta; Njølstad, Pål R; Mellgren, Gunnar; Tell, Grethe S; Berge, Rolf K; Svardal, Asbjørn; Nygård, Ottar

2017-02-03

Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl-, octanoyl-, palmitoyl-, propionyl-, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry. Hazard ratios (HRs) and 95% CIs for quartile 4 versus quartile 1 are reported. The multivariable model included age, sex, body mass index, fasting status, current smoking, diabetes mellitus, apolipoprotein A1, apolipoprotein B, creatinine, left ventricular ejection fraction, extent of coronary artery disease, study center, and intervention with folic acid or vitamin B6. During median 10.2 years of follow-up, 10.0% of the patients died of cardiovascular disease and 12.8% suffered a fatal or nonfatal acute myocardial infarction. Higher levels of the even-chained acetyl-, octanoyl-, and palmitoyl-carnitines were significantly associated with elevated risk of cardiovascular death, also after multivariable adjustments (HR [95% CI]: 1.52 [1.12, 2.06]; P=0.007; 1.73 [1.23, 2.44]; P=0.002; and 1.61 [1.18, 2.21]; P=0.003, respectively), whereas their associations with acute myocardial infarction were less consistent. Among patients with suspected stable angina pectoris, elevated serum even-chained acylcarnitines were associated with increased risk of cardiovascular death and, to a lesser degree with acute myocardial infarction, independent of traditional risk factors. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Immunotherapy of acute radiation syndromes with antiradiation gamma G globulin.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Vecheslav; Casey, Rachael; Jones, Jeffrey; Kedar, Prasad

Introduction: If an immunotherapy treatment approach to treatment of acute radiation syndromes (ARS) were to be developed; consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants- SRD) by specific antiradiation antibodies. To accomplish this objective, irradiated animals were injected with a preparation of antiradiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-indeced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic and enterotoxic) characteristics as well as specific antigenic properties that combined with the direct physiochemical direct radiation damage, induce the development of many of the pathological processes associated with ARS. We tested several specific hyperimmune IgG preparations against these radiation toxins and observed that their toxic properties were neutralized by specific antiradiation IgGs. Material and Methods: Rabbits were inoculated with SRD radiation toxins to induce hyperimmune serum. The hyperimmune serum was pooled from several animals, purified, and concentrated. Enzyme-linked immunosorbent assays of the hyperimmune serum revealed high titers of IgG with specific binding to radiation toxins. The antiradiation IgG preparation was injected into laboratory animals one hour before and three hours after irradiation, and was evaluated for its ability to protect inoculated animals against the development of acute radiation syndromes. Results: Animals that were inoculated with specific antiradiation antibodies before receiving lethal irradiation at LD 100/30 exhibited 60-75% survival rate at 30 days, whereas all control animals expired by 30 days following exposure. These inoculated animals also exhibited markedly reduced clinical symptoms of ARS, even those that did not survive irradiation. Discussion: The results of our experiments demonstrate that rabbit hyperimmune serum directed against SRD toxins afford significant, albeit

Mitigation effect of an FGF-2 peptide on acute gastrointestinal syndrome after high-dose ionizing radiation.

PubMed

Zhang, Lurong; Sun, Weimin; Wang, Jianjun; Zhang, Mei; Yang, Shanmin; Tian, Yeping; Vidyasagar, Sadasivan; Peña, Louis A; Zhang, Kunzhong; Cao, Yongbing; Yin, Liangjie; Wang, Wei; Zhang, Lei; Schaefer, Katherine L; Saubermann, Lawrence J; Swarts, Steven G; Fenton, Bruce M; Keng, Peter C; Okunieff, Paul

2010-05-01

Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and their proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. The study data support pursuing FGF-P as a mitigator for AGS.

National trends in rates of death and hospital admissions related to acute myocardial infarction, heart failure and stroke, 1994–2004

PubMed Central

Tu, Jack V.; Nardi, Lorelei; Fang, Jiming; Liu, Juan; Khalid, Laila; Johansen, Helen

2009-01-01

Background Rates of death from cardiovascular and cerebrovascular diseases have been steadily declining over the past few decades. Whether such declines are occurring to a similar degree for common disorders such as acute myocardial infarction, heart failure and stroke is uncertain. We examined recent national trends in mortality and rates of hospital admission for these 3 conditions. Methods We analyzed mortality data from Statistic Canada’s Canadian Mortality Database and data on hospital admissions from the Canadian Institute for Health Information’s Hospital Morbidity Database for the period 1994–2004. We determined age- and sex-standardized rates of death and hospital admissions per 100 000 population aged 20 years and over as well as in-hospital case-fatality rates. Results The overall age- and sex-standardized rate of death from cardiovascular disease in Canada declined 30.0%, from 360.6 per 100 000 in 1994 to 252.5 per 100 000 in 2004. During the same period, the rate fell 38.1% for acute myocardial infarction, 23.5% for heart failure and 28.2% for stroke, with improvements observed across most age and sex groups. The age- and sex-standardized rate of hospital admissions decreased 27.6% for stroke and 27.2% for heart failure. The rate for acute myocardial infarction fell only 9.2%. In contrast, the relative decline in the inhospital case-fatality rate was greatest for acute myocardial infarction (33.1%; p < 0.001). Much smaller relative improvements in case-fatality rates were noted for heart failure (8.1%) and stroke (8.9%). Interpretation The rates of death and hospital admissions for acute myocardial infarction, heart failure and stroke in Canada changed at different rates over the 10-year study period. Awareness of these trends may guide future efforts for health promotion and health care planning and help to determine priorities for research and treatment. PMID:19546444

Optimizing the time-frame for the definition of bleeding-related death after acute variceal bleeding in cirrhosis.

PubMed

Merkel, C; Gatta, A; Bellumat, A; Bolognesi, M; Borsato, L; Caregaro, L; Cavallarin, G; Cielo, R; Cristina, P; Cucci, E; Donada, C; Donadon, V; Enzo, E; Martin, R; Mazzaro, C; Sacerdoti, D; Torboli, P

1996-01-01

To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. Eight medical departments in seven hospitals in north-eastern Italy. Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.

Acute pulmonary emphysema in death by hanging: a morphometric digital study.

PubMed

Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

2016-09-01

Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice.

Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome

PubMed Central

Gorbunov, Nikolai V.; Sharma, Pushpa

2015-01-01

The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as “two-hit phenomenon” where the “first hit” is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the “second hit” derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant

Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome.

PubMed

Gorbunov, Nikolai V; Sharma, Pushpa

2015-02-27

The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as "two-hit phenomenon" where the "first hit" is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the "second hit" derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant mesenchymal

Creation of a Scorecard to Predict In-Hospital Death in Patients Undergoing Operations for Acute Type A Aortic Dissection.

PubMed

Leontyev, Sergey; Légaré, Jean-Francois; Borger, Michael A; Buth, Karen J; Funkat, Anne K; Gerhard, Jochann; Mohr, Friedrich W

2016-05-01

This study evaluated preoperative predictors of in-hospital death for the surgical treatment of patients with acute type A aortic dissection (Type A) and created an easy-to-use scorecard to predict in-hospital death. We reviewed retrospectively all consecutive patients who underwent operations for acute Type A between 1996 and 2011 at 2 tertiary care institutions. A logistic regression model was created to identify independent preoperative predictors of in-hospital death. The results were used to create a scorecard predicting operative risk. Emergency operations were performed in 534 consecutive patients for acute Type A. Mean age was 61 ± 14 years and 36.3% were women. Critical preoperative state was present in 31% of patients and malperfusion of one or more end organs in 36%. Unadjusted in-hospital mortality was 18.7% and not significantly different between institutions. Independent predictors of in-hospital death were age 50 to 70 years (odds ratio [OR], 3.8; p = 0.001), age older than 70 years (OR, 2.8; p = 0.03), critical preoperative state (OR, 3.2; p < 0.001), visceral malperfusion (OR, 3.0; p = 0.003), and coronary artery disease (OR, 2.2; p = 0.006). Age younger than 50 years (OR, 0.3; p = 0.01) was protective for early survival. Using this information, we created an easily usable mortality risk score based on these variables. The patients were stratified into four risk categories predicting in-hospital death: less than 10%, 10% to 25%, 25% to 50%, and more than 50%. This represents one of the largest series of patients with Type A in which a risk model was created. Using our approach, we have shown that age, critical preoperative state, and malperfusion syndrome were strong independent risk factors for early death and could be used for the preoperative risk assessment. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

El Kaffas, Ahmed; Sadeghi-Naini, Ali; Falou, Omar

Purpose: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. Methods: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit tomore » the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. Results: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R{sup 2} of 0.9 was observed when quantified cell death was correlated with changes in midband fit. Conclusions: Results from QUS

Acute Radiation Risk and BRYNTRN Organ Dose Projection Graphical User Interface

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Hu, Shaowen; Nounu, Hateni N.; Kim, Myung-Hee

2011-01-01

The integration of human space applications risk projection models of organ dose and acute radiation risk has been a key problem. NASA has developed an organ dose projection model using the BRYNTRN with SUM DOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUM DOSE are a Baryon transport code and an output data processing code, respectively. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN. A GUI for the ARR and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. BRYNTRN code operation requires extensive input preparation. Only a graphical user interface (GUI) can handle input and output for BRYNTRN to the response models easily and correctly. The purpose of the GUI development for ARRBOD is to provide seamless integration of input and output manipulations for the operations of projection modules (BRYNTRN, SLMDOSE, and the ARR probabilistic response model) in assessing the acute risk and the organ doses of significant Solar Particle Events (SPEs). The assessment of astronauts radiation risk from SPE is in support of mission design and operational planning to manage radiation risks in future space missions. The ARRBOD GUI can identify the proper shielding solutions using the gender-specific organ dose assessments in order to avoid ARR symptoms, and to stay within the current NASA short-term dose limits. The quantified evaluation of ARR severities based on any given shielding configuration and a specified EVA or other mission

Supplemental vitamin A prevents the acute radiation-induced defect in wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levenson, S.M.; Gruber, C.A.; Rettura, G.

Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet (which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)) was supplemented with 150,000 IU vit. A/kg dietmore » beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental vitamin A is due to its enhancing the early inflammatory reaction to wounding, including increasing the number of monocytes and macrophages at the wound site; possible effect on modulating collagenase activity; effect on epithelial cell (and possible mesenchymal cell) differentiation; stimulation of immune responsiveness; and lessening of the adverse effects of radiation.« less

Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Lurong; Sun Weimin; Wang Jianjun

Purpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. Methods and Materials: A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and theirmore » proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Results: Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. Conclusions: The study data support pursuing FGF-P as a mitigator for AGS.« less

How many deaths will it take? A death from asthma associated with work-related environmental tobacco smoke.

PubMed

Stanbury, Martha; Chester, Debra; Hanna, Elizabeth A; Rosenman, Kenneth D

2008-02-01

Despite epidemiologic, experimental and observational data on the association of environmental tobacco smoke (ETS) and adverse health effects, bar and restaurant workers remain exposed to ETS in the majority of states and countries. Three public health surveillance systems were used to identify and conduct a follow-up investigation of a reported acute asthma death of a young waitress in a bar. The waitress collapsed at the bar where she worked and was declared dead shortly thereafter. Evaluation of the circumstances of her death and her medical history concluded that her death was from acute asthma due to environmental tobacco smoke at work. This is the first reported acute asthma death associated with work-related ETS. Recent studies of asthma among bar and restaurant workers before and after smoking bans support this association. This death dramatizes the need to enact legal protections for workers in the hospitality industry from secondhand smoke.

The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Seon Young; Chung, Hee-Yong

2005-10-21

In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents inmore » bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.« less

Acute myeloid leukemia-targeted toxin activates both apoptotic and necroptotic death mechanisms.

PubMed

Horita, Henrick; Frankel, Arthur E; Thorburn, Andrew

2008-01-01

Acute myelogenous leukemia (AML) is the second most common leukemia with approximately 13,410 new cases and 8,990 deaths annually in the United States. A novel fusion toxin treatment, diphtheria toxin GM-CSF (DT-GMCSF) has been shown to selectively eliminate leukemic repopulating cells that are critical for the formation of AML. We previously showed that DT-GMCSF treatment of U937 cells, an AML cell line, causes activation of caspases and the induction of apoptosis. In this study we further investigate the mechanisms of cell death induced by DT-GMCSF and show that, in addition to the activation of caspase-dependent apoptosis, DT-GMCSF also kills AML cells by simultaneously activating caspase-independent necroptosis. These mechanisms depend on the ability of the targeted toxin to inhibit protein synthesis, and are not affected by the receptor that is targeted or the mechanism through which protein synthesis is blocked. We conclude that fusion toxin proteins may be effective for treating AML cells whether or not they are defective in apoptosis.

[Leading causes of death during the induction therapy in pediatric patients with acute lymphoblastic leukemia].

PubMed

Aguilar-Hernández, Máximo; Fernández-Castillo, Gabriela; Núñez-Villegas, Nora Nancy; Pérez-Casillas, Ruy Xavier; Núñez-Enríquez, Juan Carlos

2017-01-01

Leukemias are the leading cause of childhood cancer. In most developed countries 1-2% of patients die during remission induction; however, in developing countries, this figure is higher and the causes of death apparently vary among the populations studied. The aim was to determine the cause of death during remission induction in pediatric patients with acute lymphoblastic leukemia (ALL) in the hospital "Dr. Gaudencio González Garza" of Centro Médico Nacional La Raza from January 1, 2009, to December 31, 2014. A retrospective cohort study was carried out and a descriptive statistical analysis was performed. During the study period, a total of 463 patients with ALL were diagnosed, out of which 5.4% died (n = 25). Among the patients who died, 64% (n = 16) were female and 60% had high-risk clinical features at diagnosis. The main causes of death were septic shock and bleeding. Early mortality was five times higher than the one reported for developed countries, while the causes of death did not differ. Close monitoring is necessary to detect and promptly treat complications secondary to chemotherapy toxicity in Mexican pediatric patients with ALL.

ASEPTIC INFLAMMATION IN THE LUNGS IN ACUTE RADIATION SICKNESS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanov, A.E.

1963-09-01

Inflammation in the lungs of irradiated rabbits at the site of turpentine injection has much in common with the inflammatory changes arising in other tissues and organs during local irradiation or acute radiation sickness. The fact that the inflammatory changes under different conditions of irradiation are similar in type regardless of the character of the inflammatory agent suggests that the phenomenon has a common mechanism. The absence of polymorphonuclear (eosinophtlic) leukocytes from inflammatory foci in irradiated rabbits is due not only to the developing leukopenia, but also to a disturbance of the leukocyte emigration process into the inflammatory focus. Inmore » irradiated rabbits in cortrast to the controls, the normal arrangement of the fibrous structures is preserved in the necrotic lung tissue at the site of turpentine injection. In animals with severe acute radiation sickness induced by external irradiation in sublethal doses, the ability of the organism to respond to introduction of an inflammatory agent by an increase in the number of leukocytes in the blood and by a rise of the body temperature is to some extent preserved. (auth)« less

CHANGES OF ARTERIAL BLOOD PRESSURE IN ACUTE RADIATION DISEASE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryzewski, J.

1962-12-01

Acute experiments were done in cats and chronic experiments in dogs. The cats were subjected to whole-body x irradiation with a dose of 1500 r, and were examined on the third day after irradiation, when radiation disease was fully developed. Reflexes from the baro- and chemoreceptors were investigated, and arterial blood pressure was recorded in the irradiated cats after intravenous administration of adrenaline, noradrenaline, serotonin, acetylcholine, histamine, Regitine, atropine, or Pendiomid. Dogs were subjected to whole-body irradiation with 800 r,; changes in arterial blood pressure, which occurred after the administration of neurohormones, were investigated before and after irradiation. Pressor reflexesmore » in irradiated cats, elicited by clamping and unclamping of both common carotid arteries, corresponded to a rise from 129.6 to 141.4 mm Hg, as compared to pressor reflexes in nonirradiated cats from 106.6 to 146. Reflexes from carotid sinus chemoreceptors evoked by 0.5% KCl were also weaker in irradiated cats. The results of both the acute and chronic experiments indicate that circulatory changes occur in radiation disease. The changes mainly involve responses of the circulatory system to neurohormones and stimulation of vascular baro- and chemoreceptors. (TCO)« less

Micro RNA responses to chronic or acute exposures to low dose ionizing radiation

PubMed Central

Chaudhry, M. Ahmad; Omaruddin, Romaica A.; Kreger, Bridget; de Toledo, Sonia M.; Azzam, Edouard I.

2014-01-01

Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose c-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of 137Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate c-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation. PMID:22367372

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.

PubMed

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong Choon; Kang, Seong Soo; Bae, Chun-Sik; Shin, Taekyun; Jin, Jae-Kwang; Kim, Sung Ho; Wang, Hongbing; Moon, Changjong

2008-09-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.

Correlated Uncertainties in Radiation Shielding Effectiveness

NASA Technical Reports Server (NTRS)

Werneth, Charles M.; Maung, Khin Maung; Blattnig, Steve R.; Clowdsley, Martha S.; Townsend, Lawrence W.

2013-01-01

The space radiation environment is composed of energetic particles which can deliver harmful doses of radiation that may lead to acute radiation sickness, cancer, and even death for insufficiently shielded crew members. Spacecraft shielding must provide structural integrity and minimize the risk associated with radiation exposure. The risk of radiation exposure induced death (REID) is a measure of the risk of dying from cancer induced by radiation exposure. Uncertainties in the risk projection model, quality factor, and spectral fluence are folded into the calculation of the REID by sampling from probability distribution functions. Consequently, determining optimal shielding materials that reduce the REID in a statistically significant manner has been found to be difficult. In this work, the difference of the REID distributions for different materials is used to study the effect of composition on shielding effectiveness. It is shown that the use of correlated uncertainties allows for the determination of statistically significant differences between materials despite the large uncertainties in the quality factor. This is in contrast to previous methods where uncertainties have been generally treated as uncorrelated. It is concluded that the use of correlated quality factor uncertainties greatly reduces the uncertainty in the assessment of shielding effectiveness for the mitigation of radiation exposure.

Non-cancer effects in acute radiation syndrome survivors in Ukraine.

PubMed

Belyi, David; Kovalenko, Aleksander; Bazyka, Dmitrij; Bebeshko, Vladimir

2010-06-01

The 1986 Chernobyl Nuclear Power Plant accident that occurred is known as the most severe nuclear disaster in the history of humankind. Acute radiation syndrome (ARS) was diagnosed in 237 persons but only 134 of those were confirmed, including 28 patients who died due to lethal total-body gamma-irradiation and severe skin injuries caused by beta/gamma-emitting radionuclides. A small group of ARS survivors offers an interesting observational insight pertinent to the on-going discussions about long-term non-cancer effects of ionizing radiation. This descriptive study summarizes more than 20 y of follow-up, makes attempts to offer a prognosis for the Chernobyl ARS survivors' health, and explores the link between the outcomes of interest and radiation exposure.

Risk factors for death in children during inpatient treatment of severe acute malnutrition: a prospective cohort study.

PubMed

Rytter, Maren Jh; Babirekere-Iriso, Esther; Namusoke, Hanifa; Christensen, Vibeke B; Michaelsen, Kim F; Ritz, Christian; Mortensen, Charlotte G; Mupere, Ezekiel; Friis, Henrik

2017-02-01

Children who receive in-hospital treatment of severe acute malnutrition often have high mortality rates, and the reasons are not well understood. We assessed risk factors for death in children who were treated for malnutrition in a hospital. In a prospective observational study of 120 children who were receiving in-hospital treatment of severe acute malnutrition in Uganda with therapeutic formulas F-75 and F-100, we collected data on symptoms, clinical findings, plasma markers of refeeding syndrome (electrolytes and phosphate), and acute phase reactants, and recorded the nutritional therapy given in hospital. Seventeen children (14%) died. Clinical risk factors for death were the presence of oral thrush (HR: 5.0; 95% CI: 1.6, 15.2), a caretaker-reported severity of illness on a visual analog scale (HR: 1.7; 95% CI: 1.1, 2.6), impaired consciousness (HR: 16.7; 95% CI: 3.1, 90.4), and a capillary refill time >2 s (HR: 3.9; 95% CI: 1.4, 11.3). HIV infection was not associated with mortality (HR: 3.0; 95% CI: 0.7, 12.4), which was most likely due to low power. Biochemical risk factors were a plasma C-reactive protein concentration >15 mg/L on admission and low plasma phosphate that was measured on day 2 (HR: 8.7; 95% CI: 2.5, 30.1), particularly in edematous children. The replacement of F-75 with unfortified rice porridge to ameliorate diarrhea was associated with a higher risk of death, particularly if given during the first 2 d (HR: 5.0; 95% CI: 1.9, 13.3), which was an association that remained after adjustment for potential confounders (HR: 69.5; 95% CI: 7.0, 694.6). Refeeding syndrome may occur in children who are treated for malnutrition, even with moderately low plasma phosphate, and, in particular, in children with edematous malnutrition. The replacement of F-75 with unfortified rice porridge is associated with increased risk of death, which is possibly mediated by lowering plasma phosphate. The identified clinical risk factors may potentially improve the

Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death.

PubMed

Nagar, Himanshu; Yan, Weisi; Christos, Paul; Chao, K S Clifford; Nori, Dattatreyudu; Ravi, Akkamma

2017-06-01

Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0

A possible approach to large-scale laboratory testing for acute radiation sickness after a nuclear detonation.

PubMed

Adalja, Amesh A; Watson, Matthew; Wollner, Samuel; Toner, Eric

2011-12-01

After the detonation of an improvised nuclear device, several key actions will be necessary to save the greatest number of lives possible. Among these tasks, the identification of patients with impending acute radiation sickness is a critical problem that so far has lacked a clear solution in national planning. We present one possible solution: the formation of a public-private partnership to augment the capacity to identify those at risk for acute radiation sickness. © Mary Ann Liebert, Inc.

The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Stegelmeier, B L; Green, B T; Pfister, J A; Cook, D

2011-05-01

Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for

Animal models for acute radiation syndrome drug discovery.

PubMed

Singh, Vijay K; Newman, Victoria L; Berg, Allison N; MacVittie, Thomas J

2015-05-01

Although significant scientific advances have been made over the past six decades in developing safe, nontoxic and effective radiation/medical countermeasures (MCMs) for acute radiation syndrome (ARS), no drug has been approved by the US FDA. The availability of adequate animal models is a prime requisite under the criteria established by the FDA 'animal rule' for the development of novel MCMs for ARS and the discovery of biomarkers for radiation exposure. This article reviews the developments of MCMs to combat ARS, with particular reference to the various animal models (rodents: mouse and rat; canine: beagle; minipigs and nonhuman primates [NHPs]) utilized for the in-depth evaluation. The objective, pathways and challenges of the FDA Animal Efficacy Rule are also discussed. There are a number of well-defined animal models, the mouse, canine and NHP, that are being used for the development of MCMs. Additional animal models, such as the minipig, are under development to further assist in the identification, efficacy testing and approval of MCMs under the FDA Animal Efficacy Rule.

Medical management of the acute radiation syndrome.

PubMed

López, Mario; Martín, Margarita

2011-07-13

The acute radiation syndrome (ARS) occurs after whole-body or significant partial-body irradiation (typically at a dose of >1 Gy). ARS can involve the hematopoietic, cutaneous, gastrointestinal and the neurovascular organ systems either individually or in combination. There is a correlation between the severity of clinical signs and symptoms of ARS and radiation dose. Radiation induced multi-organ failure (MOF) describes the progressive dysfunction of two or more organ systems over time. Radiation combined injury (RCI) is defined as radiation injury combined with blunt or penetrating trauma, burns, blast, or infection. The classic syndromes are: hematopoietic (doses >2-3 Gy), gastrointestinal (doses 5-12 Gy) and cerebrovascular syndrome (doses 10-20 Gy). There is no possibility to survive after doses >10-12 Gy. The Phases of ARS are-prodromal: 0-2 days from exposure, latent: 2-20 days, and manifest illness: 21-60 days from exposure. Granulocyte-colony stimulating factor (G-CSF) at a dose of 5 μg/kg body weight per day subcutaneously has been recommended as treatment of neutropenia, and antibiotics, antiviral and antifungal agents for prevention or treatment of infections. If taken within the first hours of contamination, stable iodine in the form of nonradioactive potassium iodide (KI) saturates iodine binding sites within the thyroid and inhibits incorporation of radioiodines into the gland. Finally, if severe aplasia persists under cytokines for more than 14 days, the possibility of a hematopoietic stem cell (HSC) transplantation should be evaluated. This review will focus on the clinical aspects of the ARS, using the European triage system (METREPOL) to evaluate the severity of radiation injury, and scoring groups of patients for the general and specific management of the syndrome.

Single-centre experience of radiation exposure in acute surgical patients: assessment of therapeutic impact and future recommendations.

PubMed

Fitzmaurice, Gerard J; Brown, Robin; Cranley, Brian; Conlon, Enda F; Todd, R Alan J; O'Donnell, Mark E

2010-09-01

Radiological investigations have become a key adjunct in patient management and consequently radiation exposure to patients is increasing. The study objectives were to examine the use of radiological investigations in the management of acute surgical patients and to assess whether a guideline-based radiation exposure risk/benefit analysis can aid in the choice of radiological investigation used. A prospective observational study was completed over a 12-week period from April to July 2008 for all acute surgical admissions. Data recorded included demographics, clinical presentation, differential diagnosis, investigations, surgical interventions, and final clinical outcome. The use of radiological investigative modalities as an adjunct to clinical assessment was then evaluated against The Royal College of Radiologists (RCR) guidelines. A total of 380 acute surgical admissions (M = 174, F = 185, children = 21) were assessed during the study period. Seven hundred thirty-four radiological investigations were performed with a mean of 1.93 investigations per patient. Based on the RCR guidelines, 680 (92.6%) radiological investigations were warranted and included 142 CT scans (19.3%), 129 chest X-rays (17.6%), and 85 abdominal X-rays (11.6%). Clinically, radiological imaging complemented surgical management in 326 patients (85.8%) and the management plan remained unchanged for the remaining 54 patients (14.2%). This accounted for an average radiation dose of 4.18 millisievert (mSv) per patient or 626 days of background radiation exposure. CT imaging was responsible for the majority of the radiation exposure, with a total of 1310 mSv (82.6%) of the total radiation exposure being attributed to CT imaging in 20.8% of acute admissions. Subgroup analysis demonstrated that 92.8% of the CT scans performed were appropriate. Radiation exposure was generally low for the majority of acute surgical admissions. However, it is recommended that CT imaging requests be evaluated carefully

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries

[Medium-term forecast of solar cosmic rays radiation risk during a manned Mars mission].

PubMed

Petrov, V M; Vlasov, A G

2006-01-01

Medium-term forecasting radiation hazard from solar cosmic rays will be vital in a manned Mars mission. Modern methods of space physics lack acceptable reliability in medium-term forecasting the SCR onset and parameters. The proposed estimation of average radiation risk from SCR during the manned Mars mission is made with the use of existing SCR fluence and spectrum models and correlation of solar particle event frequency with predicted Wolf number. Radiation risk is considered an additional death probability from acute radiation reactions (ergonomic component) or acute radial disease in flight. The algorithm for radiation risk calculation is described and resulted risk levels for various periods of the 23-th solar cycle are presented. Applicability of this method to advance forecasting and possible improvements are being investigated. Recommendations to the crew based on risk estimation are exemplified.

The phenoptosis problem: what is causing the death of an organism? Lessons from acute kidney injury.

PubMed

Zorov, D B; Plotnikov, E Y; Jankauskas, S S; Isaev, N K; Silachev, D N; Zorova, L D; Pevzner, I B; Pulkova, N V; Zorov, S D; Morosanova, M A

2012-07-01

Programmed execution of various cells and intracellular structures is hypothesized to be not the only example of elimination of biological systems - the general mechanism can also involve programmed execution of organs and organisms. Modern rating of programmed cell death mechanisms includes 13 mechanistic types. As for some types, the mechanism of actuation and manifestation of cell execution has been basically elucidated, while the causes and intermediate steps of the process of fatal failure of organs and organisms remain unknown. The analysis of deaths resulting from a sudden heart arrest or multiple organ failure and other acute and chronic pathologies leads to the conclusion of a special role of mitochondria and oxidative stress activating the immune system. Possible mechanisms of mitochondria-mediated induction of the signaling cascades involved in organ failure and death of the organism are discussed. These mechanisms include generation of reactive oxygen species and damage-associated molecular patterns in mitochondria. Some examples of renal failure-induced deaths are presented with mechanisms and settings determined by some hypothetical super system rather than by the kidneys themselves. This system plays the key role in the process of physiological senescence and termination of an organism. The facts presented suggest that it is the immune system involved in mitochondrial signaling that can act as the system responsible for the organism's death.

Linking Doses with Clinical Scores of Hematopoietic Acute Radiation Syndrome.

PubMed

Hu, Shaowen

2016-10-01

In radiation accidents, determining the radiation dose the victim received is a key step for medical decision making and patient prognosis. To reconstruct and evaluate the absorbed dose, researchers have developed many physical devices and biological techniques during the last decades. However, using the physical parameter "absorbed dose" alone is not sufficient to predict the clinical development of the various organs injured in an individual patient. In operational situations for radiation accidents, medical responders need more urgently to classify the severity of the radiation injury based on the signs and symptoms of the patient. In this work, the author uses a unified hematopoietic model to describe dose-dependent dynamics of granulocytes, lymphocytes, and platelets, and the corresponding clinical grading of hematopoietic acute radiation syndrome. This approach not only visualizes the time course of the patient's probable outcome in the form of graphs but also indirectly gives information of the remaining stem and progenitor cells, which are responsible for the autologous recovery of the hematopoietic system. Because critical information on the patient's clinical evolution can be provided within a short time after exposure and only peripheral cell counts are required for the simulation, these modeling tools will be useful to assess radiation exposure and injury in human-involved radiation accident/incident scenarios.

Obesity in pediatric kidney transplant recipients and the risks of acute rejection, graft loss and death.

PubMed

Ladhani, Maleeka; Lade, Samantha; Alexander, Stephen I; Baur, Louise A; Clayton, Philip A; McDonald, Stephen; Craig, Jonathan C; Wong, Germaine

2017-08-01

Obesity is prevalent in children with chronic kidney disease (CKD), but the health consequences of this combination of comorbidities are uncertain. The aim of this study was to evaluate the impact of obesity on the outcomes of children following kidney transplantation. Using data from the ANZDATA Registry (1994-2013), we assessed the association between age-appropriate body mass index (BMI) at the time of transplantation and the subsequent development of acute rejection (within the first 6 months), graft loss and death using adjusted Cox proportional hazards models. Included in our analysis were 750 children ranging in age from 2 to 18 (median age 12) years with a total of 6597 person-years of follow-up (median follow-up 8.4 years). Overall, at transplantation 129 (17.2%) children were classified as being overweight and 61 (8.1%) as being obese. Of the 750 children, 102 (16.2%) experienced acute rejection within the first 6 months of transplantation, 235 (31.3%) lost their allograft and 53 (7.1%) died. Compared to children with normal BMI, the adjusted hazard ratios (HR) for graft loss in children who were underweight, overweight or diagnosed as obese were 1.05 [95% confidence interval (CI) 0.70-1.60], 1.03 (95% CI 0.71-1.49) and 1.61 (95% CI 1.05-2.47), respectively. There was no statistically significant association between BMI and acute rejection [underweight: HR 1.07, 95% CI 0.54-2.09; overweight: HR 1.42, 95% CI 0.86-2.34; obese: HR 1.83, 95% CI 0.95-3.51) or patient survival (underweight: HR 1.18, 95% CI 0.54-2.58, overweight: HR 0.85, 95% CI 0.38-1.92; obese: HR 0.80, 95% CI 0.25-2.61). Over 10 years of follow-up, pediatric transplant recipients diagnosed with obesity have a substantially increased risk of allograft failure but not acute rejection of the graft or death.

Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer.

PubMed

Zhao, Yaqin; Chen, Lu; Zhang, Shu; Wu, Qiang; Jiang, Xiaoqin; Zhu, Hong; Wang, Jin; Li, Zhiping; Xu, Yong; Zhang, Ying Jie; Bai, Sen; Xu, Feng

2015-01-01

Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD ≥ 12 Gy, and V30 ≥ 13% are significantly correlated with an increased risk of RP. Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning.

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.

2005-12-01

Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo andmore » the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.« less

DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

NASA Technical Reports Server (NTRS)

Viger, Louise; Ponomarev, Artem L.; Plante, Ianik; Evain, Trevor; Penninckx, Sebastien; Blattnig, Steve R.; Costes, Sylvain V.

2017-01-01

Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from 10 to 2,400 keV/µm. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with

Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

PubMed

Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

2016-11-01

The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

PubMed

Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

2017-01-01

Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy.

PubMed

Vano-Galvan, S; Fernandez-Lizarbe, E; Truchuelo, M; Diaz-Ley, B; Grillo, E; Sanchez, V; Ríos-Buceta, L; Paoli, J; Sancho, S; Montero, A; Hernanz, R; Ramos, A; Jaen, P; Gonzalez, S

2013-09-01

A better knowledge of the dynamic biological changes that the skin undergoes in response to ionizing radiation is advisable to improve the management of radiation dermatitis, allowing selection of patients needing treatment or close monitoring. To describe the evolution of the skin in response to ionizing radiation through the reflectance confocal microscopy (RCM) features of acute radiation dermatitis. In this prospective descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included in the study through consecutive sampling. Clinical, dermoscopic and RCM evaluation of the skin were performed prior to treatment and on days 1, 15, 30 and 45 after radiotherapy. While clinical features of radiation dermatitis emerged after 30 days on average, histopathological changes were detectable by RCM after a mean time of 15 days. The main RCM features included initial appearance of spongiosis, exocytosis and inflammatory cells followed by the presence of dendritic-shaped cells, 'streaming-like figures', 'broken geographic papillae', epidermal architectural disarray, effacement of rete ridges, melanophages and, finally, hyperpigmentation of the basal layer. RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

NASA Technical Reports Server (NTRS)

2014-01-01

The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

[Effects of radiation exposure on human body].

PubMed

Kamiya, Kenji; Sasatani, Megumi

2012-03-01

There are two types of radiation health effect; acute disorder and late on-set disorder. Acute disorder is a deterministic effect that the symptoms appear by exposure above a threshold. Tissues and cells that compose the human body have different radiation sensitivity respectively, and the symptoms appear in order, from highly radiosensitive tissues. The clinical symptoms of acute disorder begin with a decrease in lymphocytes, and then the symptoms appear such as alopecia, skin erythema, hematopoietic damage, gastrointestinal damage, central nervous system damage with increasing radiation dose. Regarding the late on-set disorder, a predominant health effect is the cancer among the symptoms of such as cancer, non-cancer disease and genetic effect. Cancer and genetic effect are recognized as stochastic effects without the threshold. When radiation dose is equal to or more than 100 mSv, it is observed that the cancer risk by radiation exposure increases linearly with an increase in dose. On the other hand, the risk of developing cancer through low-dose radiation exposure, less 100 mSv, has not yet been clarified scientifically. Although uncertainty still remains regarding low level risk estimation, ICRP propound LNT model and conduct radiation protection in accordance with LNT model in the low-dose and low-dose rate radiation from a position of radiation protection. Meanwhile, the mechanism of radiation damage has been gradually clarified. The initial event of radiation-induced diseases is thought to be the damage to genome such as radiation-induced DNA double-strand breaks. Recently, it is clarified that our cells could recognize genome damage and induce the diverse cell response to maintain genome integrity. This phenomenon is called DNA damage response which induces the cell cycle arrest, DNA repair, apoptosis, cell senescence and so on. These responses act in the direction to maintain genome integrity against genome damage, however, the death of large number of

The PLAN score: a bedside prediction rule for death and severe disability following acute ischemic stroke.

PubMed

O'Donnell, Martin J; Fang, Jiming; D'Uva, Cami; Saposnik, Gustavo; Gould, Linda; McGrath, Emer; Kapral, Moira K

2012-11-12

We sought to develop and validate a simple clinical prediction rule for death and severe disability after acute ischemic stroke that can be used by general clinicians at the time of hospital admission. We analyzed data from a registry of 9847 patients (4943 in the derivation cohort and 4904 in the validation cohort) hospitalized with acute ischemic stroke and included in the Registry of the Canadian Stroke Network (July 1, 2003, to March 31, 2008; 11 regional stroke centers in Ontario, Canada). Outcome measures were 30-day and 1-year mortality and a modified Rankin score of 5 to 6 at discharge. Overall 30-day mortality was 11.5% (derivation cohort) and 13.5% (validation cohort). In the final multivariate model, we included 9 clinical variables that could be categorized as preadmission comorbidities (5 points for preadmission dependence [1.5], cancer [1.5], congestive heart failure [1.0], and atrial fibrillation [1.0]), level of consciousness (5 points for reduced level of consciousness), age (10 points, 1 point/decade), and neurologic focal deficit (5 points for significant/total weakness of the leg [2], weakness of the arm [2], and aphasia or neglect [1]). Maximum score is 25. In the validation cohort, the PLAN score (derived from preadmission comorbidities, level of consciousness, age, and neurologic deficit) predicted 30-day mortality (C statistic, 0.87), death or severe dependence at discharge (0.88), and 1-year mortality (0.84). The PLAN score also predicted favorable outcome (modified Rankin score, 0-2) at discharge (C statistic, 0.80). The PLAN clinical prediction rule identifies patients who will have a poor outcome after hospitalization for acute ischemic stroke. The score comprises clinical data available at the time of admission and may be determined by nonspecialist clinicians. Additional studies to independently validate the PLAN rule in different populations and settings are required.

Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in IMRT for Nasopharyngeal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Victor H.F., E-mail: vhflee@hku.hk; Ng, Sherry C.Y.; Leung, T.W.

Purpose: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). Methods and Materials: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR).more » A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. Results: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. Conclusions: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive

Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

NASA Technical Reports Server (NTRS)

Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

2016-01-01

Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

Low-dose radiation modifies skin response to acute gamma-rays and protons.

PubMed

Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

2013-01-01

The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (p<0.05) increases in immunoreactivity in the Gamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

Death following acute poisoning by moclobemide.

PubMed

Giroud, Christian; Horisberger, Beat; Eap, Chin; Augsburger, Marc; Ménétrey, Annick; Baumann, Pierre; Mangin, Patrice

2004-02-10

A fatality due to ingestion of a reversible inhibitor of monoamine-oxidase A (MAO-A) is reported. Moclobemide is generally considered as a safe drug far less toxic than tricyclic anti-depressants. However, severe intoxications may result from interactions with other drugs and food such as selective serotonin reuptake inhibitors (SSRIs), anti-Parkinsonians of the MAOI-type (e.g. selegiline) or tyramine from ripe cheese or other sources. In the present case, high levels of moclobemide were measured in peripheral blood exceeding toxic values reported so far in the scientific literature. The body fluid concentrations of moclobemide were of 498 mg/l in peripheral whole blood, 96.3 mg/l in urine while an amount of approximately 33 g could be recovered from gastric contents. The other xenobiotics were considered of little toxicological relevance. The victim (male, 48-year-old) had a past history of depression and committed one suicide attempt 2 years before death. Autopsy revealed no evidence of significant natural disease or injury. It was concluded that the manner of death was suicide and that the unique cause of death was massive ingestion of moclobemide.

Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death.

PubMed

Heo, Sook-Kyoung; Noh, Eui-Kyu; Kim, Jeong Yi; Jeong, Yoo Kyung; Jo, Jae-Cheol; Choi, Yunsuk; Koh, SuJin; Baek, Jin Ho; Min, Young Joo; Kim, Hawk

2017-11-10

Dasatinib and radotinib are oral BCR-ABL tyrosine kinase inhibitors that were developed as drugs for the treatment of chronic myeloid leukemia. We report here that the c-KIT (CD117) targeting with dasatinib and radotinib promotes acute myeloid leukemia (AML) cell death, and c-KIT endocytosis is essential for triggering c-KIT-positive AML cell death by dasatinib and radotinib during the early stages. In addition, dasatinib and radotinib reduce heat shock protein 90β (HSP90β) expression and release Apaf-1 in c-KIT-positive AML cells. Finally, this activates a caspase-dependent apoptotic pathway in c-KIT-positive AML cells. Moreover, the inhibition of c-KIT endocytosis by dynamin inhibitor (DY) reversed cell viability and c-KIT expression by dasatinib and radotinib. HSP90β expression was recovered by DY in c-KIT-positive AML cells as well. Furthermore, the effect of radotinib on c-KIT and HSP90β showed the same pattern in a xenograft animal model using HEL92.1.7 cells. Therefore, dasatinib and radotinib promote AML cell death by targeting c-KIT. Taken together, these results indicate that dasatinib and radotinib treatment have a potential role in anti-leukemic therapy on c-KIT-positive AML cells.

Risk Factors for Death and Major Morbidity in Guatemalan Children with Acute Bacterial Meningitis.

PubMed

Olson, Daniel; Lamb, Molly M; Gaensbauer, James T; Todd, James K; Halsey, Neal A; Asturias, Edwin J

2015-07-01

Acute bacterial meningitis (ABM) remains a significant cause of pediatric illness and death in low and middle income countries. Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcomes. Data from a prospective surveillance study for ABM in children aged 0-59 months admitted to 3 referral hospitals in Guatemala City from 2000 to 2007 were analyzed. ABM was defined as positive cerebrospinal fluid (CSF) culture, positive latex agglutination or CSF white blood cell greater than 100 cells/mL. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed, along with validation of the predictive Herson-Todd score (HTS). Of 809 children with ABM episodes, 221 (27.3%) survived with major morbidity and 192 (23.7%) died. Among 383 children with nonmissing data, the most significant multivariate predictors for death or major morbidity were seizure [odds ratio (OR), 101.5; P < 0.001], CSF glucose less than 20 mg/dL (OR, 5.3; P = 0.0004), symptom duration more than 3 days (OR, 3.7; P = 0.003) and coma (OR, 6.3; P = 0.004). Of 221 children with a HTS greater than 5, 204 (92%) died or suffered major morbidity (OR, 10.3; P < 0.0001). ABM is a cause of considerable morbidity and mortality in Guatemala. Several clinical risk factors and the composite HTS predicted death or major morbidity. These predictors could help clinicians in low and middle income country guide medical care for ABM and could contribute to the public health impact assessment in preventing meningitis with vaccines.

Long-term survival and causes of death in patients with ST-elevation acute coronary syndrome without obstructive coronary artery disease.

PubMed

Andersson, Hedvig Bille; Pedersen, Frants; Engstrøm, Thomas; Helqvist, Steffen; Jensen, Morten Kvistholm; Jørgensen, Erik; Kelbæk, Henning; Räder, Sune Bernd Emil Werner; Saunamäki, Kari; Bates, Eric; Grande, Peer; Holmvang, Lene; Clemmensen, Peter

2018-01-07

We aimed to study survival and causes of death in patients with ST-elevation acute coronary syndrome (STE-ACS) with and without obstructive coronary artery disease (CAD). We included 4793 consecutive patients with STE-ACS triaged for acute coronary angiography at a large cardiac invasive centre (2009-2014). Of these, 88% had obstructive CAD (stenosis ≥50%), 6% had non-obstructive CAD (stenosis 1-49%), and 5% had normal coronary arteries. Patients without obstructive CAD were younger and more often female with fewer cardiovascular risk factors. Median follow-up time was 2.6 years. Compared with patients with obstructive CAD, the short-term hazard of death (≤30 days) was lower in both patients with non-obstructive CAD [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.27-0.89, P = 0.018] and normal coronary arteries (HR 0.31, 95% CI 0.11-0.83, P = 0.021). In contrast, the long-term hazard of death (>30 days) was similar in patients with non-obstructive CAD (HR 1.15, 95% CI 0.77-1.72, P = 0.487) and higher in patients with normal coronary arteries (HR 2.44, 95% CI 1.58-3.76, P < 0.001), regardless of troponin levels. Causes of death were cardiovascular in 70% of patients with obstructive CAD, 38% with non-obstructive CAD, and 32% with normal coronary arteries. Finally, patients without obstructive CAD had lower survival compared with an age and sex matched general population. STE-ACS patients without obstructive CAD had a long-term risk of death similar to or higher than patients with obstructive CAD. Causes of death were less often cardiovascular. This suggests that STE-ACS patients without obstructive CAD warrant medical attention and close follow-up. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

INTUSSUSCEPTION AS A COMPLICATION OF RADIATION SICKNESS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuikova, E.A.; Kasyanov, I.

1957-01-01

The digestive tract is highly sensitive to ionizing radiation, and the changes taking place in it have a promi nent place in the clinical picture of the radiation sickness. The secreting function of the digestive glands is upset, as well as the processes of digestion and absorption. The intestinal wall becomes extremely permeable. Motor function disorders are accompanied by peristaltic contractions, tenesmus. This finds its clinical expression in nausea, vomiting, colicky pains, and diarrhea Marked disorders of the motor function can lead to intussusception, which complicates considerably the subsequent evolution of the radiation sickness. Three cases of thususception of themore » thin and lange bowels in dogs who had received a total x-ray dose of 500 r are descrtbed. Acute radiation sickness in these animals ran a more severe and rapid course than in the controls. All cases ended in death on the 6 to lOth day after irrakiation with symptoms of intestinal obstruction. Morphological changes in the dead animals were typical of acute radiation sickness and differed from the irrakiated control cases by more marked dystrophic changes In the liver, kidneys, and heart. (tr-auth)« less

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okunieff, Paul; Xu Jianhua; Hu Dongping

2006-07-01

Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to themore » hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.« less

Aml1 gene rearrangements and mutations in radiation-associated acute myeloid leukemia and myelodysplastic syndromes.

PubMed

Klymenko, Sergiy; Trott, Klaus; Atkinson, Michael; Bink, Karin; Bebeshko, Vladimir; Bazyka, Dimitry; Dmytrenko, Iryna; Abramenko, Iryna; Bilous, Nadia; Misurin, Andrei; Zitzelsberger, Horst; Rosemann, Michael

2005-06-01

Several studies suggested a causal link between AML1 gene rearrangements and both radiation-induced acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Fifty-three AML samples were analyzed for the presence of AML1 abnormalities using fluorescent in-situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). Of these patients, 24 had experienced radiation exposure due to the Chernobyl accident, and 29 were non-irradiated spontaneous AML cases and served as controls. AML1/ETO translocations were found in 9 of 29 spontaneous AML but only in 1 of 24 radiation-associated AML cases. This difference between translocation frequencies is statistically significant in the age-unstratified cohorts (p=0.015). Following age stratification, the difference becomes less pronounced but remains on borderline significance (p=0.053). AML1 mutation status was assessed in 5 clean-up workers at Chernobyl NPP with MDS, or AML following MDS, by direct sequencing of genomic DNA from the coding region (exon 3 through 8). In one patient who developed MDS following an acute radiation syndrome, a hexanucleotide duplication of CGGCAT in exon 8 was found, inserted after base position 1502. Our results suggest that AML1 gene translocations are infrequent in radiation-induced leukemogenesis but are consistent with the idea that radiation may contribute to the development of MDS through AML1 gene mutation.

Granulocyte colony-stimulating factor in the treatment of acute radiation syndrome: a concise review.

PubMed

Hofer, Michal; Pospíšil, Milan; Komůrková, Denisa; Hoferová, Zuzana

2014-04-16

This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF), in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.

PubMed

DeBo, Ryne J; Register, Thomas C; Caudell, David L; Sempowski, Gregory D; Dugan, Gregory; Gray, Shauna; Owzar, Kouros; Jiang, Chen; Bourland, J Daniel; Chao, Nelson J; Cline, J Mark

2015-06-01

The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques. Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses. Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP-1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals. Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation.

Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study

PubMed Central

Bateman, Brian T; Kim, Dae Hyun; Hernandez-Diaz, Sonia; Patorno, Elisabetta; Glynn, Robert J; Mogun, Helen; Huybrechts, Krista F

2018-01-01

Abstract Objective To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction. Design Cohort study using a healthcare database. Setting Nationwide sample of patient data from more than 700 hospitals across the United States. Participants 6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014. Main outcome measure In-hospital mortality during seven days of follow-up from treatment initiation. Results Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted

A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death.

PubMed

Cho, Jong Tae; Han, Jin Hyung

2016-07-01

Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis.

[Sudden death due to acute coronary insufficiency].

PubMed

Mazur, N A; Zhukov, V N

1976-01-01

The study was conducted in the course of 2 years in accordance with the programme of myocardial infarction register of all mortality cases among the inhabitants of one of the Moscow districts. In conformity with the criteria recommended by the WHO Expert Committee, general figures of sudden death incidence at the age of 20 to 64 years comprised 80.3--76.2 and 32.7--34.5 per 100,000 males and females, respectively, during the 1st and 2nd year of observation. Autopsies performed in 89.5% of the mortality cases established that only in 39.8% of the cases death ensued in the presence of fresh foci of necrosis in the myocardium, while in the rest no myocardial infarction was found. In an overwhelming majority of the dying patients severe stenoses or occlusions of the coronary arteries were seen, and only 13% had no stenoses. However, the latter group showed fresh necroses or postinfarction cicatrices in the myocardium. The obtained data indicate that sudden death occupies an important place in the structure of mortality in ischaemic heart disease. It has been demonstrated that no reduction of general mortality due to myocardial infarction is possible without effective measures against this kind of death.

Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome

PubMed Central

Kindekov, Ivan; Mileva, Milka; Krastev, Dimo; Vassilieva, Vladimira; Raynova, Yuliana; Doumanova, Lyuba; Aljakov, Mitko; Idakieva, Krassimira

2014-01-01

The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 – dose that kills 100% of the mice at 30 days) from 137Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery. PMID:26019540

Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome.

PubMed

Kindekov, Ivan; Mileva, Milka; Krastev, Dimo; Vassilieva, Vladimira; Raynova, Yuliana; Doumanova, Lyuba; Aljakov, Mitko; Idakieva, Krassimira

2014-05-04

The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 - dose that kills 100% of the mice at 30 days) from 137 Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery.

The impact of Massachusetts' smoke-free workplace laws on acute myocardial infarction deaths.

PubMed

Dove, Melanie S; Dockery, Douglas W; Mittleman, Murray A; Schwartz, Joel; Sullivan, Eileen M; Keithly, Lois; Land, Thomas

2010-11-01

We examined the rate of acute myocardial infarction (AMI) deaths in Massachusetts before and after the implementation of a comprehensive smoke-free workplace law in July 2004. We used Poisson regression models to examine the impact of the state law in cities and towns with and without previous local smoking bans and the effect of the local laws for the period of 1999 through 2006. The AMI mortality rate decreased by 7.4% (95% confidence interval [CI] = 3.3%, 11.4%) after implementation of the state law. The state ban had an impact in cities and towns with no prior local smoking ban (9.2% decrease; P < .001) but not cities and towns with a prior local smoking ban. However, there was a nonsignificant 4.9% (95% CI = -5.0%, 13.9%) decrease associated with the local smoking ban that preceded the effect of the state ban. The effect of the state ban was modest (-1.6%) in the first 12 months after implementation but much larger after the first 12 months (-18.6%; P < .001). Comprehensive statewide smoke-free workplace laws in Massachusetts were associated with an estimated 270 fewer AMI deaths per year. These results add to the evidence suggesting that smoke-free air laws are associated with lower rates of AMI.

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca; Fortin, Andre; Wang, Chang Shu

2012-03-15

Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, andmore » the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting

PEGylated IL-11 (BBT-059): A Novel Radiation Countermeasure for Hematopoietic Acute Radiation Syndrome.

PubMed

Kumar, Vidya P; Biswas, Shukla; Sharma, Neel K; Stone, Sasha; Fam, Christine M; Cox, George N; Ghosh, Sanchita P

2018-07-01

Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin-11 (BBT-059), developed by Bolder Biotechnology, Inc., exhibited a longer half-life in rodents and induced longer-lasting increases in hematopoietic cells than interleukin-11. A single dose of 1.2 mg kg of BBT-059, administered subcutaneously to CD2F1 mice (12-14 wk, male) was found to be safe in a 14 d toxicity study. The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to Co gamma total-body irradiation. A single dose of 0.3 mg kg, administered either 24 h pre-, 4 h post-, or 24 h postirradiation increased the survival of mice to 70-100% from lethal doses of radiation. Preadministration (-24 h) of the drug conferred a significantly (p < 0.05) higher survival compared to 24 h post-total-body irradiation. There was significantly accelerated recovery from radiation-induced peripheral blood neutropenia and thrombocytopenia in animals pretreated with BBT-059. The drug also increased bone marrow cellularity and megakaryocytes and accelerated multilineage hematopoietic recovery. In addition, BBT-059 inhibited the induction of radiation-induced hematopoietic biomarkers, thrombopoietin, erythropoietin, and Flt-3 ligand. These results indicate that BBT-059 is a promising radiation countermeasure, demonstrating its potential to be used both pre- and postirradiation for hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.

Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells.

PubMed

Yuan, Guang-Jin; Deng, Jun-Jian; Cao, De-Dong; Shi, Lei; Chen, Xin; Lei, Jin-Ju; Xu, Xi-Ming

2017-08-14

To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism. Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe DCFH-DA. Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation. Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

Infection and acute respiratory distress syndrome during pregnancy: a case series of preventable maternal deaths from southern India.

PubMed

Vasudeva, Akhila; Bhat, Rajeshwari G; Ramachandran, Amar; Kumar, Pratap

2013-02-01

Acute respiratory distress syndrome (ARDS) is common among women admitted to obstetric intensive care units, and it contributes significantly, both directly and indirectly, to maternal deaths. We present a case series of ARDS in pregnant women caused by non-obstetric causes. The women were treated at a tertiary hospital in southern India. The striking features were delayed referral from the primary care unit and the lack of a primary diagnosis or treatment. Undiagnosed rheumatic heart disease, anemia, and malaria and H1N1 epidemics contributed to these cases of ARDS and maternal death. It is necessary to increase the awareness of evidence-based uniform protocols to tackle common medical complaints during pregnancy. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Chromosome aberrations and cell death by ionizing radiation: Evolution of a biophysical model

NASA Astrophysics Data System (ADS)

Ballarini, Francesca; Carante, Mario P.

2016-11-01

The manuscript summarizes and discusses the various versions of a radiation damage biophysical model, implemented as a Monte Carlo simulation code, originally developed for chromosome aberrations and subsequently extended to cell death. This extended version has been called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations). According to the basic assumptions, complex double-strand breaks (called ;Cluster Lesions;, or CLs) produce independent chromosome free-ends, mis-rejoining within a threshold distance d (or un-rejoining) leads to chromosome aberrations, and ;lethal aberrations; (i.e., dicentrics plus rings plus large deletions) lead to clonogenic cell death. The mean number of CLs per Gy and per cell is an adjustable parameter. While in BIANCA the threshold distance d was the second parameter, in a subsequent version, called BIANCA II, d has been fixed as the mean distance between two adjacent interphase chromosome territories, and a new parameter, f, has been introduced to represent the chromosome free-end un-rejoining probability. Simulated dose-response curves for chromosome aberrations and cell survival obtained by the various model versions were compared with literature experimental data. Such comparisons provided indications on some open questions, including the role of energy deposition clustering at the nm and the μm level, the probability for a chromosome free-end to remain un-rejoined, and the relationship between chromosome aberrations and cell death. Although both BIANCA and BIANCA II provided cell survival curves in general agreement with human and hamster fibroblast survival data, BIANCA II allowed for a better reproduction of dicentrics, rings and deletions considered separately. Furthermore, the approach adopted in BIANCA II for d is more consistent with estimates reported in the literature. After testing against aberration and survival data, BIANCA II was applied to investigate the depth-dependence of the radiation

A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.

PubMed

Farese, Ann M; Cohen, Melanie V; Katz, Barry P; Smith, Cassandra P; Jackson, William; Cohen, Daniel M; MacVittie, Thomas J

2012-10-01

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.

Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu; Corbin, Kimberly S.; Al-Hallaq, Hania

Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetricmore » parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women

Acute Lymphocytic Leukemia

MedlinePlus

... radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing acute lymphocytic leukemia. Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of acute ...

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Chang W., E-mail: songx001@umn.edu; Korea Institute of Radiological and Medical Sciences, Seoul; Lee, Yoon-Jin

Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 daysmore » and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.« less

A basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes.

PubMed

Casey-Sawicki, Kate; Zhang, Mei; Kim, Sunghee; Zhang, Amy; Zhang, Steven B; Zhang, Zhenhuan; Singh, Ravi; Yang, Shanmin; Swarts, Steven; Vidyasagar, Sadasivan; Zhang, Lurong; Zhang, Aiguo; Okunieff, Paul

2014-06-01

The effects of fibroblast growth factors and their potential as broad-spectrum agents to treat and mitigate radiation injury have been studied extensively over the past two decades. This report shows that a peptide mimetic of basic fibroblast growth factor (FGF-P) protects and mitigates against acute radiation syndromes. FGF-P attenuates both sepsis and bleeding in a radiation-induced bone marrow syndrome model and reduces the severity of gastrointestinal and cutaneous syndromes; it should also mitigate combined injuries. FGF-2 and FGF-P induce little or no deleterious inflammation or vascular leakage, which distinguishes them from most other growth factors, angiogenic factors, and cytokines. Although recombinant FGFs have proven safe in several ongoing clinical trials, they are expensive to synthesize, can only be produced in limited quantity, and have limited shelf life. FGF-P mimics the advantageous features of FGF-2 without these disadvantages. This paper shows that FGF-P not only has the potential to be a potent yet safe broad-spectrum medical countermeasure that mitigates acute radiotoxicity but also holds promise for thermal burns, ischemic wound healing, tissue engineering, and stem-cell regeneration.

Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

PubMed

Ozasa, K; Sakata, R; Cullings, H M; Grant, E J

2016-06-01

Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes.

Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Hu, Shaowen; Nounu, Hatem N.; Cucinotta, Francis A.

2010-01-01

Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts, because organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. Assessment of astronauts organ doses and ARS from the exposure to historically large SPEs is in support of mission design and operation planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI product, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance

PubMed Central

Luedde, Tom; Kaplowitz, Neil; Schwabe, Robert F.

2015-01-01

Summary Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets. PMID:25046161

The impact of community-based palliative care on acute hospital use in the last year of life is modified by time to death, age and underlying cause of death. A population-based retrospective cohort study

PubMed Central

Rosenwax, Lorna; Arendts, Glenn; Semmens, James B.

2017-01-01

Objective Community-based palliative care is known to be associated with reduced acute care health service use. Our objective was to investigate how reduced acute care hospital use in the last year of life varied temporally and by patient factors. Methods A retrospective cohort study of the last year of life of 12,763 Western Australians who died from cancer or one of seven non-cancer conditions. Outcome measures were rates of hospital admissions and mean length of hospital stays. Multivariate analyses involved time-to-event and population averaged log-link gamma models. Results There were 28,939 acute care overnight hospital admissions recorded in the last year of life, an average of 2.3 (SD 2.2) per decedent and a mean length of stay of 9.2 (SD 10.3) days. Overall, the rate of hospital admissions was reduced 34% (95%CI 1–66) and the mean length of stay reduced 6% (95%CI 2–10) during periods of time decedents received community-based palliative care compared to periods of time not receiving this care. Decedents aged <70 years receiving community-based palliative care showed a reduced rate of hospital admission around five months before death, whereas for older decedents the reduction in hospital admissions was apparent a year before death. All decedents who were receiving community-based palliative care tended towards shorter hospital stays in the last month of life. Decedents with neoplasms had a mean length of stay three weeks prior to death while not receiving community-based palliative care of 9.6 (95%CI 9.3–9.9) days compared to 8.2 (95% CI 7.9–8.7) days when receiving community-based palliative care. Conclusion Rates of hospital admission during periods of receiving community-based palliative care were reduced with benefits evident five months before death and even earlier for older decedents. The mean length of hospital stay was also reduced while receiving community-based palliative care, mostly in the last month of life. PMID:28934324

The impact of community-based palliative care on acute hospital use in the last year of life is modified by time to death, age and underlying cause of death. A population-based retrospective cohort study.

PubMed

Spilsbury, Katrina; Rosenwax, Lorna; Arendts, Glenn; Semmens, James B

2017-01-01

Community-based palliative care is known to be associated with reduced acute care health service use. Our objective was to investigate how reduced acute care hospital use in the last year of life varied temporally and by patient factors. A retrospective cohort study of the last year of life of 12,763 Western Australians who died from cancer or one of seven non-cancer conditions. Outcome measures were rates of hospital admissions and mean length of hospital stays. Multivariate analyses involved time-to-event and population averaged log-link gamma models. There were 28,939 acute care overnight hospital admissions recorded in the last year of life, an average of 2.3 (SD 2.2) per decedent and a mean length of stay of 9.2 (SD 10.3) days. Overall, the rate of hospital admissions was reduced 34% (95%CI 1-66) and the mean length of stay reduced 6% (95%CI 2-10) during periods of time decedents received community-based palliative care compared to periods of time not receiving this care. Decedents aged <70 years receiving community-based palliative care showed a reduced rate of hospital admission around five months before death, whereas for older decedents the reduction in hospital admissions was apparent a year before death. All decedents who were receiving community-based palliative care tended towards shorter hospital stays in the last month of life. Decedents with neoplasms had a mean length of stay three weeks prior to death while not receiving community-based palliative care of 9.6 (95%CI 9.3-9.9) days compared to 8.2 (95% CI 7.9-8.7) days when receiving community-based palliative care. Rates of hospital admission during periods of receiving community-based palliative care were reduced with benefits evident five months before death and even earlier for older decedents. The mean length of hospital stay was also reduced while receiving community-based palliative care, mostly in the last month of life.

Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study.

PubMed

Park, Yoonyoung; Bateman, Brian T; Kim, Dae Hyun; Hernandez-Diaz, Sonia; Patorno, Elisabetta; Glynn, Robert J; Mogun, Helen; Huybrechts, Krista F

2018-03-28

To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction. Cohort study using a healthcare database. Nationwide sample of patient data from more than 700 hospitals across the United States. 6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014. In-hospital mortality during seven days of follow-up from treatment initiation. Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were 1.90 (1.43 to 2.53) and 1.93 (1.34 to 2

Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk; Zain, Zakiyah; Wood, Lisa

Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MFmore » than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.« less

Effects of radiation quality and oxygen on clustered DNA lesions and cell death.

PubMed

Stewart, Robert D; Yu, Victor K; Georgakilas, Alexandros G; Koumenis, Constantinos; Park, Joo Han; Carlson, David J

2011-11-01

Radiation quality and cellular oxygen concentration have a substantial impact on DNA damage, reproductive cell death and, ultimately, the potential efficacy of radiation therapy for the treatment of cancer. To better understand and quantify the effects of radiation quality and oxygen on the induction of clustered DNA lesions, we have now extended the Monte Carlo Damage Simulation (MCDS) to account for reductions in the initial lesion yield arising from enhanced chemical repair of DNA radicals under hypoxic conditions. The kinetic energy range and types of particles considered in the MCDS have also been expanded to include charged particles up to and including (56)Fe ions. The induction of individual and clustered DNA lesions for arbitrary mixtures of different types of radiation can now be directly simulated. For low-linear energy transfer (LET) radiations, cells irradiated under normoxic conditions sustain about 2.9 times as many double-strand breaks (DSBs) as cells irradiated under anoxic conditions. New experiments performed by us demonstrate similar trends in the yields of non-DSB (Fpg and Endo III) clusters in HeLa cells irradiated by γ rays under aerobic and hypoxic conditions. The good agreement among measured and predicted DSBs, Fpg and Endo III cluster yields suggests that, for the first time, it may be possible to determine nucleotide-level maps of the multitude of different types of clustered DNA lesions formed in cells under reduced oxygen conditions. As particle LET increases, the MCDS predicts that the ratio of DSBs formed under normoxic to hypoxic conditions by the same type of radiation decreases monotonically toward unity. However, the relative biological effectiveness (RBE) of higher-LET radiations compared to (60)Co γ rays (0.24 keV/μm) tends to increase with decreasing oxygen concentration. The predicted RBE of a 1 MeV proton (26.9 keV/μm) relative to (60)Co γ rays for DSB induction increases from 1.9 to 2.3 as oxygen concentration

UV-Induced cell death in plants.

PubMed

Nawkar, Ganesh M; Maibam, Punyakishore; Park, Jung Hoon; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

2013-01-14

Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400-700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280-320 nm) and UV-A (320-390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD).

Medical Management of Acute Radiation Syndromes : Immunoprophylaxis by Antiradiation Vaccine

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael; Kedar, Prasad

Introduction: Traditionally, the treatment of Acute Radiation Syndrome (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and even stem cell transplantation. Recommendations for ARS treatment are based on clinical symptoms, laboratory results, radiation exposure doses and information received from medical examinations. However, the current medical management of ARS does not include immune prophylaxis based on antiradiation vaccines or immune therapy with hyperimmune antiradiation serum. Immuneprophylaxis of ARS could result from stimulating the immune system via immunization with small doses of radiation toxins (Specific Radiation Determinants-SRD) that possess significant immuno-stimulatory properties. Methods: Principles of immuno-toxicology were used to derive this method of immune prophylaxis. An antiradiation vaccine containing a mixture of Hematotoxic, Neurotoxic and Non-bacterial (GI) radiation toxins, underwent modification into a toxoid forms of the original SRD radiation toxins. The vaccine was administered to animals at different times prior to irradiation. The animals were subjected to lethal doses of radiation that induced different forms of ARS at LD 100/30. Survival rates and clinical symptoms were observed in both control and vaccine-treated animals. Results: Vaccination with non-toxic doses of Radiation toxoids induced immunity from the elaborated Specific Radiation Determinant (SRD) toxins. Neutralization of radiation toxins by specific antiradiation antibodies resulted in significantly improved clinical symptoms in the severe forms of ARS and observed survival rates of 60-80% in animals subjected to lethal doses of radiation expected to induce different forms of ARS at LD 100/30. The most effective vaccination schedule for the antiradiation vaccine consisted of repeated injections 24 and 34 days before irradiation. The vaccine remained effective for the next two years, although the specific immune memory probably

Development of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Hu, Shaowen; Nounu, Hatem N.; Cucinotta, Francis A.

2010-01-01

The space radiation environment, particularly solar particle events (SPEs), poses the risk of acute radiation sickness (ARS) to humans; and organ doses from SPE exposure may reach critical levels during extra vehicular activities (EVAs) or within lightly shielded spacecraft. NASA has developed an organ dose projection model using the BRYNTRN with SUMDOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUMDOSE, written in FORTRAN, are a Baryon transport code and an output data processing code, respectively. The ARR code is written in C. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. BRYNTRN code operation requires extensive input preparation. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN in friendly way. A GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. The ARRBOD GUI will serve as a proof-of-concept example for future integration of other human space applications risk projection models. The current version of the ARRBOD GUI is a new self-contained product and will have follow-on versions, as options are added: 1) human geometries of MAX/FAX in addition to CAM/CAF; 2) shielding distributions for spacecraft, Mars surface and atmosphere; 3) various space environmental and biophysical models; and 4) other response models to be connected to the BRYNTRN. The major components of the overall system, the subsystem interconnections, and external interfaces are described in this

γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.

PubMed

Yashavarddhan, M H; Shukla, Sandeep K; Srivastava, Nitya N; Suar, Mrutyunjay; Dutta, Sangeeta; Kalita, Bhargab; Ranjan, Rajiv; Singh, Abhinav; Bajaj, Sania; Gupta, Manju L

2016-07-01

DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS): an international cohort study.

PubMed

Leuraud, Klervi; Richardson, David B; Cardis, Elisabeth; Daniels, Robert D; Gillies, Michael; O'Hagan, Jacqueline A; Hamra, Ghassan B; Haylock, Richard; Laurier, Dominique; Moissonnier, Monika; Schubauer-Berigan, Mary K; Thierry-Chef, Isabelle; Kesminiene, Ausrele

2015-07-01

There is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low-dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA. We assembled a cohort of 308,297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8.22 million person-years. We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality. Doses were accrued at very low rates (mean 1.1 mGy per year, SD 2.6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2.96 per Gy (90% CI 1.17-5.21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10.45, 90% CI 4.48-19.65). This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia. Centers for Disease Control and Prevention, Ministry of Health, Labour and Welfare of Japan, Institut de Radioprotection et de Sûreté Nucléaire, AREVA, Electricité de France, National Institute for Occupational Safety and Health, US Department of Energy, US Department of Health and Human Services, University of North Carolina, Public Health England. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of low larkspur (Delphinium spp.) co-administration on the acute toxicity of death camas (Zigadenus spp.) in sheep.

PubMed

Welch, K D; Green, B T; Gardner, D R; Stonecipher, C A; Panter, K E; Pfister, J A; Cook, D

2013-12-15

In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in the same area. Two poisonous plants that are often found growing simultaneously in the same location are death camas (Zigadenus spp.) and low larkspur (Delphinium spp.). Sheep are known to be susceptible to death camas poisoning while they are thought to be resistant to larkspur. The objective of this study was to determine if co-administration of low larkspur would exacerbate the toxicity of death camas in sheep. A dose finding study was performed to find a dose of death camas that caused minimal clinical signs of poisoning. Sheep were observed for clinical signs of poisoning as well as changes in heart rate and muscle fatigue. Sheep dosed with 1.14 g of death camas per kg BW showed slight frothing and lethargy, whereas sheep dosed with death camas and low larkspur showed slightly more noticeable clinical signs of poisoning. Sheep dosed with only low larkspur, at 7.8 g/kg BW, showed no signs of poisoning. Although we observed a qualitative difference in clinical signs of intoxication in sheep co-treated with death camas and low larkspur we did not detect any quantitative differences in heart rate, exercise-induced muscle fatigue, or differences in serum zygacine kinetics. Consequently, the results from this study suggest that low larkspur does not affect the toxicity of death camas in sheep. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas and low larkspur in sheep. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to other livestock species. Published by Elsevier Ltd.

[Low dose volume histogram analysis of the lungs in prediction of acute radiation pneumonitis in patients with esophageal cancer treated with three-dimensional conformal radiotherapy].

PubMed

Shen, Wen-bin; Zhu, Shu-chai; Gao, Hong-mei; Li, You-mei; Liu, Zhi-kun; Li, Juan; Su, Jing-wei; Wan, Jun

2013-01-01

To investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP. Two hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria. The acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group. The low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the

Acute pesticide poisoning related deaths in Tehran during the period 2003-2004.

PubMed

Soltaninejad, Kambiz; Faryadi, Mansoor; Sardari, Fariba

2007-08-01

Acute pesticide poisoning is an important cause of morbidity and mortality in Iran and worldwide. Determination of inducing factors in pesticide poisoning is very important parameter for planning of preventive and controlling programs. The aim of present study is assessing of effects of epidemiological variables on fatal pesticide poisoning. Data was obtained from autopsies on suspected pesticide poisoning deaths were performed in the Tehran Legal Medicine Center between 2003 and 2004. Among these medicolegal autopsies, fatal poisoning cases were evaluated retrospectively by reports of toxicological analysis. The variables such as age, sex, job, residential location, educational level, type of pesticide and cause of poisoning were reviewed. From total of 3885 autopsies referred to forensic toxicology laboratory for pesticide toxicology analysis, 51 (1.31%) deaths were due to pesticide poisoning. The age of cases was 32+/-17 years old. 63.3% of cases were male and 36.7% of them were female. The majority of cases (31.4%) were housekeeper and 23.5% were student. 66.7% of cases were lived in urban and 33.3% were lived in rural area. The most common type of poisoning was suicide (52.9%). 33.3% of cases had primary education. The common type of pesticide in this study was aluminum phosphide 18 (35.8%) and organophosphates 17 (33.3%). According to fatal aluminum phosphide poisoning, more stringent legislation and enforcement regarding the sale and distribution of this toxic substance is needed. Thus substitution of this pesticide with safer agents is necessary.

Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia.

PubMed

Harada, Masako; Pokrovskaja-Tamm, Katja; Söderhäll, Stefan; Heyman, Mats; Grander, Dan; Corcoran, Martin

2012-10-01

Analysis of the microRNA transcriptome following dexa- methasone treatment of the acute lymphocytic leukemia (ALL) cell line RS4;11 showed a global down-regulation of microRNA levels. MIR17HG was rapidly down-regulated following treatment, with chromatin immunoprecipitation (ChIP) analysis demonstrating the promoter to be a direct target of glucocorticoid (GC)-transcriptional repression and revealing the miR17-92 cluster as a prime target for dexamethasone-induced repression. The loss of miR17 family expression and concomitant increases in the miR17 target Bim occurred in an additional ALL cell line SUP-B15 but not in the dexamethasone-resistant REH. Alteration of miR17 levels through up-regulation or inhibition resulted in an decrease and increase, respectively, in Bim protein levels and dexamethasone-induced cell death. Primary ex vivo ALL cells that underwent apoptosis induced by dexamethasone also down-regulated miR17 levels. Thus, down-regulation of miR17 plays an important role in glucocorticoid-induced cell death suggesting that targeting miR17 may improve the current ALL combination therapy.

Space Radiation Hazards on Human Missions to the Moon and Mars

NASA Astrophysics Data System (ADS)

Townsend, L.

2004-12-01

One of the most significant health risks for humans exploring Earth's moon and Mars is exposure to the harsh space radiation environment. Crews on these exploration missions will be exposed to a complex mixture of very energetic particles. Chronic exposures to the ever-present background galactic cosmic ray (GCR) spectrum consisting of various fluxes of all naturally - occurring chemical elements are combined with infrequent, possibly acute exposures to large fluxes of solar energetic particles, consisting of protons and heavier particles. The GCR environment is primarily a concern for stochastic effects, such as the induction of cancer, with subsequent mortality in many cases, and late deterministic effects, such as cataracts and possible damage to the central nervous system. An acute radiation syndrome response ("radiation sickness") is not possible from the GCR environment since the organ doses are well below levels of concern. Unfortunately, the actual risks of cancer induction and mortality for the very important high-energy heavy ion component of the GCR spectrum are essentially unknown. The sporadic occurrence of extremely large solar energetic particle events, usually associated with intense solar activity, is also a major concern for Lunar and Mars missions because of the possible manifestation of acute effects from the accompanying high doses of such radiations, especially acute radiation syndrome effects such as nausea, emesis, hemorrhaging or possibly even death. Large solar energetic particle events can also contribute significantly to crew risks from cancer mortality. In this presentation an overview of current estimates of critical organ doses and equivalent doses for crews of Lunar and Mars bases and on those on transits between Earth and Mars is presented. Possible methods of mitigating these radiation exposures by shielding, thereby reducing the associated health risks to crews, are also described.

Cell death monitoring using quantitative optical coherence tomography methods

NASA Astrophysics Data System (ADS)

Farhat, Golnaz; Yang, Victor X. D.; Kolios, Michael C.; Czarnota, Gregory J.

2011-03-01

Cell death is characterized by a series of predictable morphological changes, which modify the light scattering properties of cells. We present a multi-parametric approach to detecting changes in subcellular morphology related to cell death using optical coherence tomography (OCT). Optical coherence tomography data were acquired from acute myeloid leukemia (AML) cells undergoing apoptosis over a period of 48 hours. Integrated backscatter (IB) and spectral slope (SS) were computed from OCT backscatter spectra and statistical parameters were extracted from a generalized gamma (GG) distribution fit to OCT signal intensity histograms. The IB increased by 2-fold over 48 hours with significant increases observed as early as 4 hours. The SS increased in steepness by 2.5-fold with significant changes at 12 hours, while the GG parameters were sensitive to apoptotic changes at 24 to 48 hours. Histology slides indicated nuclear condensation and fragmentation at 24 hours, suggesting the late scattering changes could be related to nuclear structure. A second series of measurements from AML cells treated with cisplatin, colchicine or ionizing radiation suggested that the GG parameters could potentially differentiate between modes of cell death. Distinct cellular morphology was observed in histology slides obtained from cells treated under each condition.

Acute infection contributes to racial disparities in stroke mortality.

PubMed

Levine, Deborah A; Langa, Kenneth M; Rogers, Mary A M

2014-03-18

It is unknown whether racial differences in exposure to acute precipitants of stroke, specifically infection, contribute to racial disparities in stroke mortality. Among participants in the nationally representative Health and Retirement Study with linked Medicare data (1991-2007), we conducted a case-crossover study employing within-person comparisons to study racial/ethnic differences in the risks of death and hospitalization from ischemic stroke following acute infection. There were 964 adults hospitalized for ischemic stroke. Acute infection increased the 30-day risks of ischemic stroke death (5.82-fold) and ischemic stroke hospitalization (1.87-fold). Acute infection was a more potent trigger of acute ischemic stroke death in non-Hispanic blacks (odds ratio [OR] 39.21; 95% confidence interval [CI] 9.26-166.00) than in non-Hispanic whites (OR 4.50; 95% CI 3.14-6.44) or Hispanics (OR 5.18; 95% CI 1.34-19.95) (race-by-stroke interaction, p = 0.005). When adjusted for atrial fibrillation, infection remained more strongly associated with stroke mortality in blacks (OR 34.85) than in whites (OR 3.58) and Hispanics (OR 3.53). Acute infection increased the short-term risk of incident stroke similarly across racial/ethnic groups. Infection occurred often before stroke death in non-Hispanic blacks, with 70% experiencing an infection in the 30 days before stroke death compared to a background frequency of 15%. Acute infection disproportionately increases the risk of stroke death for non-Hispanic blacks, independently of atrial fibrillation. Stroke incidence did not explain this finding. Acute infection appears to be one factor that contributes to the black-white disparity in stroke mortality.

Factors associated with maternal death in an intensive care unit

PubMed Central

Saintrain, Suzanne Vieira; de Oliveira, Juliana Gomes Ramalho; Saintrain, Maria Vieira de Lima; Bruno, Zenilda Vieira; Borges, Juliana Lima Nogueira; Daher, Elizabeth De Francesco; da Silva Jr, Geraldo Bezerra

2016-01-01

Objective To identify factors associated with maternal death in patients admitted to an intensive care unit. Methods A cross-sectional study was conducted in a maternal intensive care unit. All medical records of patients admitted from January 2012 to December 2014 were reviewed. Pregnant and puerperal women were included; those with diagnoses of hydatidiform mole, ectopic pregnancy, or anembryonic pregnancy were excluded, as were patients admitted for non-obstetrical reasons. Death and hospital discharge were the outcomes subjected to comparative analysis. Results A total of 373 patients aged 13 to 45 years were included. The causes for admission to the intensive care unit were hypertensive disorders of pregnancy, followed by heart disease, respiratory failure, and sepsis; complications included acute kidney injury (24.1%), hypotension (15.5%), bleeding (10.2%), and sepsis (6.7%). A total of 28 patients died (7.5%). Causes of death were hemorrhagic shock, multiple organ failure, respiratory failure, and sepsis. The independent risk factors associated with death were acute kidney injury (odds ratio [OR] = 6.77), hypotension (OR = 15.08), and respiratory failure (OR = 3.65). Conclusion The frequency of deaths was low. Acute kidney injury, hypotension, and respiratory insufficiency were independent risk factors for maternal death. PMID:28099637

UV-Induced Cell Death in Plants

PubMed Central

Nawkar, Ganesh M.; Maibam, Punyakishore; Park, Jung Hoon; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

2013-01-01

Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280–320 nm) and UV-A (320–390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD). PMID:23344059

[Psychological stress and sudden death].

PubMed

Pignalberi, Carlo; Ricci, Renato; Santini, Massimo

2002-10-01

Recent studies provide relevant evidence that psychological stress significantly influences the pathogenesis of sudden cardiac death. Psychological stress expresses a situation of imbalance, derived from a real or perceived disparity between environmental demands and the individual's ability to cope with these demands. A situation of psychological stress may include different components: personality factors and character traits, anxiety and depression, social isolation and acute or chronic adverse life events. In particular, it has been documented that a sudden extremely hard event, such as an earthquake or a war strike, can significantly increase the incidence of sudden death. Nevertheless, each one of these factors, if not present, can balance a partially unfavorable situation; this overview suggests a multifactorial situation where almost all elements are present and in which the relative influence of each one varies according to the individual examined. Sudden death occurs when a transient disruption (such as acute myocardial ischemia, platelet activation or neuroendocrine variations), occurring in a patient with a diseased myocardium (such as one with a post-necrotic scar or hypertrophy), triggers a malignant arrhythmia. Psychological stress acts at both levels: by means of a "chronic" action it contributes to create the myocardial background, while by means of an acute action it can create the transient trigger precipitating sudden death. In the chronic action two possible mechanisms can be detected: the first is a direct interaction, which contributes to cause a hypertension status or to exacerbate coronary atherosclerosis consequent to endothelial dysfunction; the second one acts through adverse health behaviors, such as a poor diet, alcohol consumption or smoking. In case of acute psychological stress, the mechanisms involved are mainly the ability to trigger myocardial ischemia, to promote arrhythmogenesis, to stimulate platelet function, and to increase

Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

PubMed

Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

2017-12-01

Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective.

PubMed

Goldberg, Robert J; Spencer, Frederick A; Gore, Joel M; Lessard, Darleen; Yarzebski, Jorge

2009-03-10

Limited information is available about potentially changing and contemporary trends in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction. The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the incidence rates of cardiogenic shock complicating acute myocardial infarction, patient characteristics and treatment practices associated with this clinical complication, and hospital death rates in residents of a large central New England community hospitalized with acute myocardial infarction at all area medical centers. The study population consisted of 13 663 residents of the Worcester (Mass) metropolitan area hospitalized with acute myocardial infarction at all greater Worcester medical centers during 15 annual periods between 1975 and 2005. Overall, 6.6% of patients developed cardiogenic shock during their index hospitalization. The incidence rates of cardiogenic shock remained stable between 1975 and the late 1990s but declined in an inconsistent manner thereafter. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (65.4%) than those who did not develop cardiogenic shock (10.6%) (P<0.001). Encouraging increases in hospital survival in patients with cardiogenic shock, however, were observed from the mid-1990s to our most recent study years. Several patient demographic and clinical characteristics were associated with an increased risk for developing cardiogenic shock. Our findings indicate improving trends in the hospital prognosis associated with cardiogenic shock. Given the high death rates associated with this clinical complication, monitoring future trends in the incidence and death rates and the factors associated with an increased risk for developing cardiogenic shock remains warranted.

Space Radiation

NASA Technical Reports Server (NTRS)

Wu, Honglu

2006-01-01

Astronauts receive the highest occupational radiation exposure. Effective protections are needed to ensure the safety of astronauts on long duration space missions. Increased cancer morbidity or mortality risk in astronauts may be caused by occupational radiation exposure. Acute and late radiation damage to the central nervous system (CNS) may lead to changes in motor function and behavior, or neurological disorders. Radiation exposure may result in degenerative tissue diseases (non-cancer or non-CNS) such as cardiac, circulatory, or digestive diseases, as well as cataracts. Acute radiation syndromes may occur due to occupational radiation exposure.

The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice.

PubMed

Goldman, Devorah C; Alexeev, Vitali; Lash, Elizabeth; Guha, Chandan; Rodeck, Ulrich; Fleming, William H

2015-03-01

Bone marrow suppression due to exposure to ionizing radiation is a significant clinical problem associated with radiation therapy as well as with nonmedical radiation exposure. Currently, there are no small molecule agents available that can enhance hematopoietic regeneration after radiation exposure. Here, we report on the effective mitigation of acute hematopoietic radiation syndrome in mice by the synthetic triterpenoid, RTA 408. The administration of a brief course of RTA 408 treatment, beginning 24 h after lethal doses of radiation to bone marrow, significantly increased overall survival. Importantly, treatment with RTA 408 led to the full recovery of steady state hematopoiesis with normalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cells from RTA 408-mitigated mice showed lineage-balanced, long-term, multilineage potential in serial transplantation assays, indicative of their normal self-renewal activity. The potency of RTA 408 in mitigating radiation-induced bone marrow suppression makes it an attractive candidate for potential clinical use in treating both therapy-related and unanticipated radiation exposure.

Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Langhe, Sofie, E-mail: Sofie.DeLanghe@UGent.be; De Ruyck, Kim; Ost, Piet

2013-02-01

Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancermore » patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.« less

Acute infection contributes to racial disparities in stroke mortality

PubMed Central

Langa, Kenneth M.; Rogers, Mary A.M.

2014-01-01

Objective: It is unknown whether racial differences in exposure to acute precipitants of stroke, specifically infection, contribute to racial disparities in stroke mortality. Methods: Among participants in the nationally representative Health and Retirement Study with linked Medicare data (1991–2007), we conducted a case-crossover study employing within-person comparisons to study racial/ethnic differences in the risks of death and hospitalization from ischemic stroke following acute infection. Results: There were 964 adults hospitalized for ischemic stroke. Acute infection increased the 30-day risks of ischemic stroke death (5.82-fold) and ischemic stroke hospitalization (1.87-fold). Acute infection was a more potent trigger of acute ischemic stroke death in non-Hispanic blacks (odds ratio [OR] 39.21; 95% confidence interval [CI] 9.26–166.00) than in non-Hispanic whites (OR 4.50; 95% CI 3.14–6.44) or Hispanics (OR 5.18; 95% CI 1.34–19.95) (race-by-stroke interaction, p = 0.005). When adjusted for atrial fibrillation, infection remained more strongly associated with stroke mortality in blacks (OR 34.85) than in whites (OR 3.58) and Hispanics (OR 3.53). Acute infection increased the short-term risk of incident stroke similarly across racial/ethnic groups. Infection occurred often before stroke death in non-Hispanic blacks, with 70% experiencing an infection in the 30 days before stroke death compared to a background frequency of 15%. Conclusions: Acute infection disproportionately increases the risk of stroke death for non-Hispanic blacks, independently of atrial fibrillation. Stroke incidence did not explain this finding. Acute infection appears to be one factor that contributes to the black–white disparity in stroke mortality. PMID:24510494

Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions.

PubMed

McDonnell, Bronagh M; Buchanan, Paul J; Prise, Kevin M; McCloskey, Karen D

2018-01-01

Radiation-induced bladder toxicity is associated with radiation therapy for pelvic malignancies, arising from unavoidable irradiation of neighbouring normal bladder tissue. This study aimed to investigate the acute impact of ionizing radiation on the contractility of bladder strips and identify the radiation-sensitivity of the mucosa vs the detrusor. Guinea-pig bladder strips (intact or mucosa-free) received ex vivo sham or 20Gy irradiation and were studied with in vitro myography, electrical field stimulation and Ca2+-fluorescence imaging. Frequency-dependent, neurogenic contractions in intact strips were reduced by irradiation across the force-frequency graph. The radiation-difference persisted in atropine (1μM); subsequent addition of PPADs (100μM) blocked the radiation effect at higher stimulation frequencies and decreased the force-frequency plot. Conversely, neurogenic contractions in mucosa-free strips were radiation-insensitive. Radiation did not affect agonist-evoked contractions (1μM carbachol, 5mM ATP) in intact or mucosa-free strips. Interestingly, agonist-evoked contractions were larger in irradiated mucosa-free strips vs irradiated intact strips suggesting that radiation may have unmasked an inhibitory mucosal element. Spontaneous activity was larger in control intact vs mucosa-free preparations; this difference was absent in irradiated strips. Spontaneous Ca2+-transients in smooth muscle cells within tissue preparations were reduced by radiation. Radiation affected neurogenic and agonist-evoked bladder contractions and also reduced Ca2+-signalling events in smooth muscle cells when the mucosal layer was present. Radiation eliminated a positive modulatory effect on spontaneous activity by the mucosa layer. Overall, the findings suggest that radiation impairs contractility via mucosal regulatory mechanisms independent of the development of radiation cystitis.

Impact of Radiation Therapy on Aggressive Care and Quality of Life near Death

PubMed Central

Li, David; Prigerson, Holly G.; Kang, Josephine; Maciejewski, Paul K.

2016-01-01

Context Radiation therapy (RT) is used with palliative intent in patients with advanced stage cancer. Prior studies, primarily in patients with poor performance status (PS), suggest that RT is associated with aggressive medical care, which may impact patients’ quality of life near death (QoD) adversely. Objective This study examines associations between RT use and patients’ receipt of aggressive care and QoD based on patients’ PS. Methods Multi-institutional, prospective cohort study of patients with end-stage cancers (N=312) and identified as terminally ill at study enrollment. RT use (n=24; 7.7%) and Eastern Cooperative Oncology Group (ECOG) PS were assessed at study entry (median = 3.8 months before death). Aggressive care near death was operationalized as use of mechanical ventilation and/or resuscitation in the last week of life. QoD was determined using validated caregiver ratings of patients’ physical and mental distress in their final week. Results RT use was associated with higher QoD (8/8, 100.0%, versus 58/114, 50.9%; p=0.006) among patients with good PS (ECOG=1), more aggressive care near death (3/9, 33.3%, versus 6/107, 5.6%; p=0.020) among patients with moderate PS (ECOG=2), and lower QoD (1/7, 14.3%, versus 28/51, 54.9%; p=0.046) among patients with poor PS (ECOG=3). Conclusions Targeted use of RT in end-of-life cancer care may benefit patients with good PS, but its use may adversely affect patients with poorer PS. Decisions about RT use in this setting should consider likely end-of-life outcomes based on patients’ current PS. PMID:27720786

The cell cycle and acute kidney injury

PubMed Central

Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

2009-01-01

Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute kidney injury. PMID:19536080

Admission Glycaemia and Acute Insulin Resistance in Heart Failure Complicating Acute Coronary Syndrome.

PubMed

Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; D'Alfonso, Maria Grazia; Spini, Valentina; Angelotti, Paola; Gensini, Gian Franco

2015-11-01

Few data are so far available on the relation between increased glucose values and insulin resistance and mortality at short-term in patients with acute heart failure (AHF). The present investigation, performed in 409 consecutive patients with AHF complicating acute coronary syndrome (ACS), was aimed at assessing the prognostic role of admission glycaemia and acute insulin resistance (as indicated by the Homeostatic Model Assessment - HOMA index) for death during Intensive Cardiac Care (ICCU) stay. Admission glucose tertiles were considered. In our series, diabetic patients accounted for the 33%. Patients in the third glucose tertiles exhibited the lowest LVEF (both on admission and at discharge), a higher use of mechanical ventilation, intra-aortic balloon pump and inotropic drugs and the highest in-ICCU mortality rate. In the overall population, hyperglycaemic patients (both diabetic and non diabetic) were 227 (227/409, 55.5%). Admission glycaemia was an independent predictor of in-ICCU mortality, together with admission LVEF and eGFR, while acute insulin resistance (as indicated by HOMA-index) was not associated with early death. The presence of admission hyperglycaemia in non-diabetic patients was independently associated with in-ICCU death while hyperglycaemia in diabetic patients was not. According to our results, hyperglycaemia is a common finding in patients with ACS complicated by AHF and it is an independent predictor of early death. Non-diabetic patients with hyperglycaemia are the subgroup with the highest risk of early death. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

PubMed

Li, Guang-hui; Wang, Dong-lin; Hu, Yi-de; Pu, Ping; Li, De-zhi; Wang, Wei-dong; Zhu, Bo; Hao, Ping; Wang, Jun; Xu, Xian-qiong; Wan, Jiu-qing; Zhou, Yi-bing; Chen, Zheng-tang

2010-09-01

Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

Angiotensin converting enzyme DD genotype is associated with acute coronary syndrome severity and sudden cardiac death in Taiwan: a case-control emergency room study.

PubMed

Chen, Ying-Hsin; Liu, Jui-Ming; Hsu, Ren-Jun; Hu, Sheng-Chuan; Harn, Horng-Jyh; Chen, Shee-Ping; Jeng, Jing-Ren; Wu, Chieh-Lin; Ho, Jar-Yi; Yu, Cheng-Ping

2012-02-15

Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined. The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046). This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype.

Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database.

PubMed

Gharzai, Laila; Verma, Vivek; Denniston, Kyle A; Bhirud, Abhijeet R; Bennion, Nathan R; Lin, Chi

2016-01-01

Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973-2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255-367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03-1.47, HR 1.961, 95% CI 1.466-2.624). Lower esophageal subsite (33-40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death could potentially be a causative effect.

Brachial-ankle PWV for predicting clinical outcomes in patients with acute stroke.

PubMed

Ahn, Kye Taek; Jeong, Jin-Ok; Jin, Seon-Ah; Kim, Mijoo; Oh, Jin Kyung; Choi, Ung-Lim; Seong, Seok-Woo; Kim, Jun Hyung; Choi, Si Wan; Jeong, Hye Seon; Song, Hee-Jung; Kim, Jei; Seong, In-Whan

2017-08-01

Although brachial-ankle pulse wave velocity (baPWV) is well-known for predicting the cardiovascular mortality and morbidity, its anticipated value is not demonstrated well concerning acute stroke. Total 1557 patients with acute stroke who performed baPWV were enrolled. We evaluated the prognostic value of baPWV predicting all-cause death and vascular death in patients with acute stroke Results: Highest quartile of baPWV was ≥23.64 m/s. All-caused deaths (including vascular death; 71) were 109 patients during follow-up periods (median 905 days). Multivariate Cox regression analysis revealed that patients with the highest quartile of baPWV had higher risk for vascular death when they are compared with patients with all other three quartiles of baPWV (Hazard ratio with 95% confidence interval [CI] 1.879 [1.022-3.456], p = .042 for vascular death). High baPWV was a strong prognostic value of vascular death in patients with acute stroke.

Radiation toxins: molecular mechanisms of action and radiomimetic properties .

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Vecheslav

Introduction: Acute Radiation Disease (ARD) or Acute Radiation Syndromes (ARS) were defined as a toxic poisonous with development of the acute pathological processes in irradi-ated animals: systemic inflammatory response syndrome(SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMOD), toxic multiple organ failure (TMOF). However, the nature of radiation toxins, their mechanisms of formation, molecular structure, and mechanism of actions remain uncertain. Moderate and high doses of radiation induce apoptotic necrosis of radiosensitive cells with formation of Radiation Toxins and in-flammation development. Mild doses of radiation induce apoptosis or controlled programmed death of radiosensitive cells without Radiation Toxins formation and development of inflam-mation processes. Only radiation induced apoptotic necrosis initiates formation of Radiation Toxins(RT). Radiation Toxins are playing an important role as the trigger mechanisms for in-flammation development and cell lysis. The systemic inflammatory response syndrome after radiation involves an influence of various endogenous agents and mediators of inflammation such as bradykinin, histamine, serotonin and phospholipases activation, prostaglandins biosyn-thesis. Although, formation of non-specific toxins such as Reactive Oxygen Species (ROS) is an important pathological process at mild or high doses of radiation. Reactive Oxygen Species play an important role in molecules damage and development of peroxidation of lipids and pro-teins which are the structural parts of cell and mitochondrial membranes. ROS and bio-radicals induce damage of DNA and RNA and peroxidation of their molecules. But high doses of radia-tion, severe and extremely severe physiological stress, result in cells death by apoptotic necrosis and could be defined as the neuroimmune acute disease. Excitotoxicity is an important patho-logical mechanism which damages the central nervous system. We postulate that

[Administration of Palonosetron and Phenotropil for Prophylaxis of the N-V-D Stage of Acute Radiation Syndrome].

PubMed

Drachouv, I S; Bykov, V N; Seleznev, A B

2016-01-01

Experiments on small (rats) and large (dogs) animals have shown that a sequential administration of Palonosetron and Phenotropil decreases the intensity of the main manifestations of the N-V-D stage of acute radiation syndrome. These data show the appropriateness of a combined administration of Palonosetron and Phenotropil to prevent a reduced work capacity in the individuals participating in elimination of the consequences of accidents associated with overexposure to radiation.

Acute empathy decline among resident physician trainees on a hematology-oncology ward: an exploratory analysis of house staff empathy, distress, and patient death exposure.

PubMed

McFarland, Daniel C; Malone, Adriana K; Roth, Andrew

2017-05-01

A reason for empathy decline during medical training has not been fully elucidated. Empathy may decrease acutely during an inpatient hematology-oncology rotation because of the acuity of death exposures. This study aimed to explore physician trainee empathy, distress, death exposures, and their attributed meaning for the trainee. Internal medicine interns and residents at a single academic center were evaluated before and after hematology-oncology ward rotations using Interpersonal Reactivity Index for empathy, previously cited reasons for empathy decline, Impact of Event Scale-Revised for distress, death exposures (no. of dying patients cared for) and attributed sense of meaning (yes/no) (post-rotation). Fifty-six trainees completed both pre-rotation and post-rotation questionnaires (58% response). Empathy averaged 58.9 (SD 12.0) before and 56.8 (SD 11.1) after the rotation (2.1 point decrease) (p = 0.018). Distress was elevated but did not change significantly during the rotation. Residents cared for 4.28 dying patients. Seventy-three percent reported that death was the most stressful event during the rotation, yet 68% reported that they derived a sense of meaning from caring for dying patients. Empathy and distress scales were positively correlated before the rotation (r = 0.277, p = 0.041) but not after (r = .059, p = 0.69). This study suggests that an acute drop in empathy can occur over several weeks in residents rotating through inpatient hematology-oncology, similar to empathy decline associated with years of training in other studies. Empathy decline may be associated with elevated distress and death exposures on the hematology-oncology ward and should be explored further in other medical training environments. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A preclinical rodent model of acute radiation-induced lung injury after ablative focal irradiation reflecting clinical stereotactic body radiotherapy.

PubMed

Hong, Zhen-Yu; Lee, Hae-June; Choi, Won Hoon; Lee, Yoon-Jin; Eun, Sung Ho; Lee, Jung Il; Park, Kwangwoo; Lee, Ji Min; Cho, Jaeho

2014-07-01

In a previous study, we established an image-guided small-animal micro-irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The goal of this study was to develop a rodent model of acute phase lung injury after ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice using a small animal stereotactic irradiator. At days 1, 3, 5, 7, 9, 11 and 14 after irradiation, the lungs were perfused with formalin for fixation and paraffin sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome. At days 7 and 14 after irradiation, micro-computed tomography (CT) images of the lung were taken and lung functional measurements were performed with a flexiVent™ system. Gross morphological injury was evident 9 days after irradiation of normal lung tissues and dynamic sequential events occurring during the acute phase were validated by histopathological analysis. CT images of the mouse lungs indicated partial obstruction located in the peripheral area of the left lung. Significant alteration in inspiratory capacity and tissue damping were detected on day 14 after irradiation. An animal model of radiation-induced lung injury (RILI) in the acute phase reflecting clinical stereotactic body radiotherapy was established and validated with histopathological and functional analysis. This model enhances our understanding of the dynamic sequential events occurring in the acute phase of radiation-induced lung injury induced by ablative dose focal volume irradiation.

Biologics as countermeasures for acute radiation syndrome: where are we now?

PubMed

Singh, Vijay K; Romaine, Patricia L P; Newman, Victoria L

2015-04-01

Despite significant scientific advances toward the development of a safe, nontoxic and effective radiation countermeasure for acute radiation syndrome (ARS) over the past six decades, no drug has been approved by the US FDA. Several biologics are currently under development as radiation countermeasures for ARS, of which three have received FDA Investigational New Drug (IND) status for clinical investigation. Presently, two of these agents, entolimod (CBLB502) and HemaMax (recombinant human IL-12) are progressing with large animal studies and clinical trials. Neupogen (G-CSF, filgrastim) has recently been recommended for approval by an FDA Advisory Committee. Filgrastim, GM-CSF (Leukine, sargramostim), and PEGylated G-CSF (Neulasta) have high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the FDA in the future. The former two biologics are available in the US Strategic National Stockpile (SNS) for use in the event of nuclear or radiological emergency. The Emergency Use Authorization (EAU) application for entolimod may be filed soon with the FDA. Biologics are attractive agents that are progressing along the path for FDA approval, to fill the unmet need for ARS countermeasures.

Minimally Invasive Radiation Biodosimetry and Evaluation of Organ Responses

DTIC Science & Technology

2016-10-01

radiation exposure, potentially leading to Acute Radiation Syndromes (ARS) and Delayed Effects of Acute ...underlying conditions and inherent variations. 2. KEYWORDS Radiation Biodosimetry, Radiation Biomarkers, microRNA, Acute Radiation Syndromes ... syndromes and delayed effects of acute radiation exposure. We expect to identify the circulating miRNA biomarkers as early predictors of late effects

Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

PubMed

Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

2011-06-01

Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin

Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by whichmore » ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.« less

Childhood diarrhoeal deaths in seven low- and middle-income countries

PubMed Central

Rahman, Ahmed Ehsanur; Moinuddin, Md; Molla, Mitike; Worku, Alemayehu; Hurt, Lisa; Kirkwood, Betty; Mohan, Sanjana Brahmawar; Mazumder, Sarmila; Bhutta, Zulfiqar; Raza, Farrukh; Mrema, Sigilbert; Masanja, Honorati; Kadobera, Daniel; Waiswa, Peter; Bahl, Rajiv; Zangenberg, Mike

2014-01-01

Abstract Objective To investigate the clinical characteristics of children who died from diarrhoea in low- and middle-income countries, such as the duration of diarrhoea, comorbid conditions, care-seeking behaviour and oral rehydration therapy use. Methods The study included verbal autopsy data on children who died from diarrhoea between 2000 and 2012 at seven sites in Bangladesh, Ethiopia, Ghana, India, Pakistan, Uganda and the United Republic of Tanzania, respectively. Data came from demographic surveillance sites, randomized trials and an extended Demographic and Health Survey. The type of diarrhoea was classified as acute watery, acute bloody or persistent and risk factors were identified. Deaths in children aged 1 to 11 months and 1 to 4 years were analysed separately. Findings The proportion of childhood deaths due to diarrhoea varied considerably across the seven sites from less than 3% to 30%. Among children aged 1–4 years, acute watery diarrhoea accounted for 31–69% of diarrhoeal deaths, acute bloody diarrhoea for 12–28%, and persistent diarrhoea for 12–56%. Among infants aged 1–11 months, persistent diarrhoea accounted for over 30% of diarrhoeal deaths in Ethiopia, India, Pakistan, Uganda and the United Republic of Tanzania. At most sites, more than 40% of children who died from persistent diarrhoea were malnourished. Conclusion Persistent diarrhoea remains an important cause of diarrhoeal death in young children in low- and middle-income countries. Research is needed on the public health burden of persistent diarrhoea and current treatment practices to understand why children are still dying from the condition. PMID:25378757

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke

PubMed Central

Nevatte, Tracy; Sim, Julius; Bishop, Jon; Ives, Natalie; Ferdinand, Phillip; Gray, Richard

2017-01-01

Importance Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. Objective To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. Design, Setting, and Participants In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Interventions Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. Main Outcomes and Measures The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement. Results A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National

MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury

PubMed Central

Thomasova, Dana; Ebrahim, Martrez; Fleckinger, Kristina; Li, Moying; Molnar, Jakob; Popper, Bastian; Liapis, Helen; Kotb, Ahmed M; Siegerist, Florian; Endlich, Nicole; Anders, Hans-Joachim

2016-01-01

Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the zebrafish model demonstrated that the tubulus cells of the larvae undergo cell death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute kidney injury with increased plasma creatinine and blood urea nitrogen and sharp decline of glomerular filtration rate. Histological analysis showed massive swelling of renal tubular cells and later their loss and extensive tubular dilation, markedly in proximal tubules. Ultrastructural changes of tubular epithelial cells included swelling of the cytoplasm and mitochondria with the loss of cristae and their transformation in the vacuoles. The pathological phenotype of the tubular cell-specific MDM2-knockout mouse model was completely rescued by co-deletion of p53. Tubular epithelium compensates only partially for the cell loss caused by MDM2 depletion by proliferation of surviving tubular cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We conclude that MDM2 is a non-redundant survival factor for proximal tubular cells by protecting them from spontaneous p53 overexpression-related cell death. PMID:27882940

Three case reports of radiation-induced glioblastoma after complete remission of acute lymphoblastic leukemia.

PubMed

Kajitani, Takumi; Kanamori, Masayuki; Saito, Ryuta; Watanabe, Yuko; Suzuki, Hiroyoshi; Watanabe, Mika; Kure, Shigeo; Tominaga, Teiji

2018-04-01

Radiation therapy is sometimes performed to control intracranial acute lymphoblastic leukemia (ALL), but may lead to radiation-induced malignant glioma. The clinical, radiological, histological, and molecular findings are described of three cases of radiation-induced glioblastoma after the treatment for ALL. They received radiation therapy at age 6-8 years. The latency from radiation therapy to the onset of radiation-induced glioblastoma was 5-10 years. Magnetic resonance imaging demonstrated diffuse lesions with multiple small enhanced lesions in all cases. Histological examination showed that the tumors consisted of mainly small round astrocytic atypical cells in one case, and astrocytic atypical cells with elongated cytoplasm and nuclear pleomorphism with small cell component in two cases. Microvascular proliferation was present in all cases. Immunohistochemical analysis for B-Raf V600E, and mutational analysis for the isocitrate dehydrogenase (IDH) 1, IDH2, and H3F3A gene revealed the wild-type alleles in all three cases. The integrated diagnoses were IDH wild-type glioblastoma, and local irradiation and concomitant temozolomide were performed. After the initial treatment, significant shrinkage of the diffuse lesion and enhanced lesion was found in all cases. Radiation-induced glioblastoma occurring after the treatment for ALL had unique clinical, radiological, histological, and molecular characteristics in our three cases.

Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?

PubMed

Villar, Jesús; Martínez, Domingo; Mosteiro, Fernando; Ambrós, Alfonso; Añón, José M; Ferrando, Carlos; Soler, Juan A; Montiel, Raquel; Vidal, Anxela; Conesa-Cayuela, Luís A; Blanco, Jesús; Arrojo, Regina; Solano, Rosario; Capilla, Lucía; Del Campo, Rafael; Civantos, Belén; Fernández, María Mar; Aldecoa, César; Parra, Laura; Gutiérrez, Andrea; Martínez-Jiménez, Chanel; González-Martín, Jesús M; Fernández, Rosa L; Kacmarek, Robert M

2018-06-01

Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. A secondary analysis from three prospective, multicenter, observational studies. A network of multidisciplinary ICUs. We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. None. We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p < 0.000001). Most deaths in acute respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.

Acute Kidney Injury in Pediatric Severe Sepsis, An Independent Risk Factor for Death and New Disability

PubMed Central

Fitzgerald, Julie C.; Basu, Rajit; Akcan-Arikan, Ayse; Izquierdo, Ledys M.; Piñeres Olave, Byron E.; Hassinger, Amanda B.; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A.; Nadkarni, Vinay M.; Thomas, Neal J.; Weiss, Scott L.; Furth, Susan

2017-01-01

Objective The prevalence of septic acute kidney injury (AKI) and impact on functional status of pediatric intensive care unit (PICU) survivors are unknown. We utilized data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic AKI. Design Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies (SPROUT) point prevalence study. AKI was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no AKI or stage 1 AKI (“No/mild AKI”) were compared to those with stage 2 or 3 AKI (“Severe AKI”). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher, and increased by 1 from baseline. Setting 128 PICUs in 26 countries. Patients Children with severe sepsis in the SPROUT study. Interventions None Measurements and Main Results One hundred two (21%) of 493 patients had Severe AKI. More than twice as many patients with Severe AKI died or developed new moderate disability compared to those with No/mild AKI (64% vs. 30%, p<0.001). Severe AKI was independently associated with death or new moderate disability (adjusted OR 2.5, 95% CI 1.5, 4.2; p=0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. Conclusions In a multi-national cohort of critically ill children with severe sepsis and high mortality rates, septic AKI is independently associated with further increased death or new disability. PMID:27513354

The PEARL score predicts 90-day readmission or death after hospitalisation for acute exacerbation of COPD

PubMed Central

Echevarria, C; Steer, J; Heslop-Marshall, K; Stenton, S C; Hughes, R; Wijesinghe, M; Harrison, R N; Steen, N; Simpson, A J; Gibson, G J; Bourke, S C

2017-01-01

Background One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. Methods In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. Results Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. Conclusions The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. Trial registration number UKCRN ID 14214. PMID:28235886

FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target

PubMed Central

Horton, Janet K.; Siamakpour-Reihani, Sharareh; Lee, Chen-Ting; Zhou, Ying; Chen, Wei; Geradts, Joseph; Fels, Diane R.; Hoang, Peter; Ashcraft, Kathleen A.; Groth, Jeff; Kung, Hsiu-Ni; Dewhirst, Mark W.; Chi, Jen-Tsan A.

2015-01-01

Although a standardized approach to radiotherapy has been used to treat breast cancer, regardless of subtype (e.g., luminal, basal), recent clinical data suggest that radiation response may vary significantly among subtypes. We hypothesized that this clinical variability may be due, in part, to differences in cellular radiation response. In this study, we utilized RNA samples for microarray analysis from two sources: 1. Paired pre- and postirradiation breast tumor tissue from 32 early-stage breast cancer patients treated in our unique preoperative radiation Phase I trial; and 2. Sixteen biologically diverse breast tumor cell lines exposed to 0 and 5 Gy irradiation. The transcriptome response to radiation exposure was derived by comparing gene expression in samples before and after irradiation. Genes with the highest coefficient of variation were selected for further evaluation and validated at the RNA and protein level. Gene editing and agonistic antibody treatment were performed to assess the impact of gene modulation on radiation response. Gene expression in our cohort of luminal breast cancer patients was distinctly different before and after irradiation. Further, two distinct patterns of gene expression were observed in our biologically diverse group of breast cancer cell lines pre- versus postirradiation. Cell lines that showed significant change after irradiation were largely luminal subtype, while gene expression in the basal and HER2+ cell lines was minimally impacted. The 100 genes with the most significant response to radiation in patients were identified and analyzed for differential patterns of expression in the radiation-responsive versus nonresponsive cell lines. Fourteen genes were identified as significant, including FAS, a member of the tumor necrosis factor receptor family known to play a critical role in programed cell death. Modulation of FAS in breast cancer cell lines altered radiation response phenotype and enhanced radiation sensitivity in

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation

PubMed Central

Rehal, Sunita; Arbane, Gill; Bourke, Stephen; Calverley, Peter M. A.; Crook, Angela M.; Dowson, Lee; Duffy, Nicholas; Gibson, G. John; Hughes, Philip D.; Hurst, John R.; Lewis, Keir E.; Mukherjee, Rahul; Nickol, Annabel; Oscroft, Nicholas; Patout, Maxime; Pepperell, Justin; Smith, Ian; Stradling, John R.; Wedzicha, Jadwiga A.; Polkey, Michael I.; Elliott, Mark W.; Hart, Nicholas

2017-01-01

Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0

Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

PubMed

Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

2014-09-01

We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

Painful acute radiation thyroiditis induced by 131I treatment of Graves’ disease

PubMed Central

Shah, Kinjal K; Tarasova, Valentina; Davidian, Michael; Anderson, Robert J

2015-01-01

A 44-year-old woman, chronic smoker with Graves’ disease was treated with radioactive iodine ablation (RAI). One week after the treatment, she presented with severe pain in the anterior neck with radiation to the angle of the jaw associated with fatigue, tremor and odynophagia. Physical examination demonstrated an asymmetric and exquisitely tender thyroid gland. There was no laboratory evidence of thyrotoxicosis. Acute radiation thyroiditis was diagnosed. Non-steroidal anti-inflammatory drugs and hydrocodone-acetaminophen started initially were ineffective for pain control. Prednisone provided relief and was continued for 1 month with a tapering dose. Symptoms completely resolved after 1 month at which time the thyroid remained diffusely enlarged and non-tender. Three months following RAI ablation she developed hypothyroid symptoms. Levothyroxine was initiated. The patient has remained asymptomatic on continued follow-up care. PMID:25576511

Painful acute radiation thyroiditis induced by 131I treatment of Graves' disease.

PubMed

Shah, Kinjal K; Tarasova, Valentina; Davidian, Michael; Anderson, Robert J

2015-01-09

A 44-year-old woman, chronic smoker with Graves' disease was treated with radioactive iodine ablation (RAI). One week after the treatment, she presented with severe pain in the anterior neck with radiation to the angle of the jaw associated with fatigue, tremor and odynophagia. Physical examination demonstrated an asymmetric and exquisitely tender thyroid gland. There was no laboratory evidence of thyrotoxicosis. Acute radiation thyroiditis was diagnosed. Non-steroidal anti-inflammatory drugs and hydrocodone-acetaminophen started initially were ineffective for pain control. Prednisone provided relief and was continued for 1 month with a tapering dose. Symptoms completely resolved after 1 month at which time the thyroid remained diffusely enlarged and non-tender. Three months following RAI ablation she developed hypothyroid symptoms. Levothyroxine was initiated. The patient has remained asymptomatic on continued follow-up care. 2015 BMJ Publishing Group Ltd.

The Association Between Urine Output, Creatinine Elevation, and Death.

PubMed

Engoren, Milo; Maile, Michael D; Heung, Michael; Jewell, Elizabeth S; Vahabzadeh, Christie; Haft, Jonathan W; Kheterpal, Sachin

2017-04-01

Acute kidney injury can be defined by a fall in urine output, and urine output criteria may be more sensitive in identifying acute kidney injury than traditional serum creatinine criteria. However, as pointed out in the Kidney Disease Improving Global Outcome guidelines, the association of urine output with subsequent creatinine elevations and death is poorly characterized. The purpose of this study was to determine what degrees of reduced urine output are associated with subsequent creatinine elevation and death. This was a retrospective cohort study of adult patients (age ≥18 years) cared for in a cardiovascular intensive care unit after undergoing cardiac operations in a tertiary care university medical center. All adult patients who underwent cardiac operations and were not receiving dialysis preoperatively were studied. The development of acute kidney injury was defined as an increase in creatinine of more than 0.3 mg/dL or by more than 50% above baseline by postoperative day 3. Acute kidney injury developed in 1,061 of 4,195 patients (25%). Urine output had moderate discrimination in predicting subsequent acute kidney injury (C statistic = .637 ± .054). Lower urine output and longer duration of low urine output were associated with greater odds of developing acute kidney injury and death. We found that there is similar accuracy in using urine output corrected for actual, ideal, or adjusted weight to discriminate future acute kidney injury by creatinine elevation and recommend using actual weight for its simplicity. We also found that low urine output is associated with subsequent acute kidney injury and that the association is greater for lower urine output and for low urine output of longer durations. Low urine output (<0.2 mL · kg -1 · h -1 ), even in the absence of acute kidney injury by creatinine elevation, is independently associated with mortality. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights

[Causes of the people death from drunkenness and alcoholism].

PubMed

Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

2012-01-01

We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

[A scale for early assessment of risk of death and myocardial infarction during initial hospitalization of patients with acute coronary syndromes (based on data from the RECORD registry)].

PubMed

Érlikh, A D

2010-01-01

Independent predictors of death and death or myocardial infarction (MI) during initial hospitalization of patients with acute coronary syndromes (ACS) were determined using database of Russian independent ACS registry RECORD. These predictors (admission Killip class II, ST-segment elevation 1 mm, systolic blood pressure 100 mm Hg, hemoglobin <110 g/L, age 65 years, history of diabetes) were attributed equal weight (1 point) and combined in a prognostic scale for assessment of risk of inhospital death and death or MI. The scale did not include markers of necrosis, and the most time consuming component was measurement of hemoglobin. Sensitivity and specificity of risk scores for prediction of death were 78.5%. The use of GRACE score in this group of patients gave similar results. These preliminary data require confirmation on larger populations of patients with ACS.

Radiation-Induced Central Nervous System Death - A study of the Pathologic Findings in Monkeys Irradiated with Massive Doses of Cobalt-60 (Gamma) Radiation

DTIC Science & Technology

1959-04-01

U.S. DEPARTMENT OF COMMERCE National Technical Information Service AD-AO36 168 RADIATION-INDUCED CENTRAL NERVOUS SYSTEM DEATH - A STUDY OF THE...ý." - ý " . :..’ýý.ý-. .. , . ý 4 ý .. -- ’ý.- -!:;:ý’,. 1,ý,-: WJiAUOK4KOUED CENTRAL NERVOUS SYSTEM NT A Study of the Pathologic Findings in...University SCHOOL OF AVIATION MEDICINE, USAF Randolph AFB, Texas April 1959 7757-. AdIAIONH-INDUCED CENTRAL NEVOUS $Y$194 DUTH A Study of the Pathologic

Psychometric Properties of the Persian Version of Death Depression Scale-Revised in Iranian Patients with Acute Myocardial Infarction.

PubMed

Sharif Nia, Hamid; Pahlevan Sharif, Saeed; Lehto, Rebecca H; Allen, Kelly A; Goudarzian, Amir Hossein; Yaghoobzadeh, Ameneh; Soleimani, Mohammad Ali

2017-07-01

Objective: Limited research has examined the psychometric properties of death depression scales in Persian populations with cardiac disease despite the need for valid assessment tools for evaluating depressive symptoms in patients with life-limiting chronic conditions. The present study aimed at evaluating the reliability and validity of the Persian Version of Death Depression Scale - Revised (DDS-R) in Iranian patients who had recent acute myocardial infarction (AMI). Method: This psychometric study was conducted with a convenience sample of 407 patients with AMI diagnosis who completed the Persian version of the DDS-R. The face, content, and construct validity of the scale were ascertained. Internal consistency, test-retest, and construct reliability (CR) were used to assess reliability of the Persian Version of DDS-R. Results: Based on maximum likelihood exploratory factor analysis and consideration of conceptual meaning, a 4-factor solution was identified, explaining 75.89% of the total variance. Goodness-of-fit indices (GFI), Comparative Fit Index (CFI), Normed Fit Index (NFI), Incremental Fit Index (IFI), and Root Mean Square Error of Approximation (RMSEA) in the final DDS-R structure demonstrated the adequacy of the 4-domain structure. The internal consistency, construct reliability, and Intra-class Correlation Coefficients (ICC) were greater than .70. Conclusion: The DDS-R was found to be a valid and reliable assessment tool for evaluating death depression symptoms in Iranian patients with AMI.

Acute death associated with Citrobacter freundii infection in an African elephant (Loxodonta africana).

PubMed

Ortega, Joaquín; Corpa, Juan M; Orden, José A; Blanco, Jorge; Carbonell, María D; Gerique, Amalia C; Latimer, Erin; Hayward, Gary S; Roemmelt, Andreas; Kraemer, Thomas; Romey, Aurore; Kassimi, Labib B; Casares, Miguel

2015-09-01

A 21-year-old male African elephant (Loxodonta africana) died suddenly with no previous medical history. Grossly, there were severe multifocal epicardial and endocardial hemorrhages of the atria and ventricles, hydropericardium, multifocal pleural hemorrhages, and severe pulmonary congestion and edema. Histologically, there was fibrinoid vasculitis and thrombosis in the heart and lung and myocardial necrosis. Citrobacter freundii was isolated in abundance in pure culture from liver and heart samples. Low levels of multiples types of elephant endotheliotropic herpesvirus (EEHV-6, EEHV-2B, and EEHV-3A) were detected in spleen samples, but not in heart samples. The levels of EEHV DNA found were much lower than those usually associated with acute EEHV hemorrhagic disease, and many other genomic loci that would normally be found in such cases were evidently below the level of detection. Therefore, these findings are unlikely to indicate lethal EEHV disease. Polymerase chain reaction for encephalomyocarditis virus (EMCV) and toxicology for oleander (Nerium oleander) were negative. Stress, resulting from recent transport, and antimicrobial therapy may have contributed to the death of this animal. © 2015 The Author(s).

Cell Death Biomarkers and Obstructive Sleep Apnea: Implications in the Acute Coronary Syndrome.

PubMed

Bauça, Josep Miquel; Yañez, Aina; Fueyo, Laura; de la Peña, Mónica; Pierola, Javier; Sánchez-de-la-Torre, Alicia; Mediano, Olga; Cabriada-Nuño, Valentín; Masdeu, María José; Teran-Santos, Joaquin; Duran-Cantolla, Joaquin; Masa, Juan Fernando; Abad, Jorge; Sanchez-de-la-Torre, Manuel; Barbé, Ferran; Barceló, Antònia

2017-05-01

Nucleosomes and cell-free double-stranded DNA (dsDNA) have been suggested as promising biomarkers in cell death-related diseases, such as acute coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA) in patients with ACS is unclear. Our aim was to evaluate the relationship between OSA, dsDNA, and nucleosomes and to assess their potential implication in the development of ACS. Up to 549 patients were included in the study and divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All patients underwent a sleep study, and serum concentrations of dsDNA and nucleosomes were measured. Nucleosome and dsDNA levels were higher in patients with OSA than in controls (nucleosomes: 1.47 ± 0.88 arbitary units [AU] vs. 1.00 ± 0.33 AU; p < .001, dsDNA: 315.6 ± 78.0 ng/mL vs. 282.6 ± 55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients with ACS than in non-ACS, independently of the presence of OSA. Both nucleosomes and dsDNA are increased in patients with OSA and might be related with the high cardiovascular risk seen in these patients. The extensive cell lysis during a myocardial infarction seems to be the major contributor to the high biomarker levels, and OSA does not seem to be implicated in such elevation when this acute event occurs. NCT01335087 (clinicaltrials.gov). © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency.

NASA Astrophysics Data System (ADS)

Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai

Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine

Reducing Human Radiation Risks on Deep Space Missions

DTIC Science & Technology

2017-09-01

Roadmap (2016). .........................................................108 Figure 53. Risk Assessment for Acute Radiation Syndrome Due to SPEs...Risk of Acute Radiation Syndromes Due to Solar Particle Events Figure 53 highlights the fact that acute radiation syndrome is a short-term risk...acceptable for long-term missions. Figure 53. Risk Assessment for Acute Radiation Syndrome Due to SPEs. Source: NASA Human Research Roadmap (2016

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

PubMed

Krige, Jake E J; Kotze, Urda K; Distiller, Greg; Shaw, John M; Bornman, Philippus C

2009-10-01

Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Sudden infant death syndrome caused by poliomyelitis.

PubMed

Dunne, J W; Harper, C G; Hilton, J M

1984-07-01

Most seemingly well infants who die suddenly and unexpectedly have no adequate cause of death found on thorough postmortem examination. Respiratory and enteric viruses are often present, especially in the upper respiratory tract, but the infective process seems, of itself, insufficient to cause death. In the remainder of the cases, a variety of lesions will be discovered, including viral myocarditis, bronchiolitis, and sepsis. We report a case of sudden and unexpected death in a 5-week-old male infant due to acute anterior poliomyelitis. This case illustrates the importance of a thorough postmortem examination, including histologic studies of the brain stem and spinal cord in cases of sudden infant death syndrome.

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

PubMed

Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

2012-01-01

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). Our results

[Use of lithium carbonate as a leukocyte stimulant in acute radiation sickness in humans].

PubMed

Konchalovskiĭ, M V; Shishkova, T V; Chotiĭ, V G; Baranov, A E

1989-03-01

A total of 50 patients, who had suffered from acute radiation sickness (I-III degree of severity) as a result of the accident at the Chernobyl Nuclear Power Plant, were followed up for hematological changes. The absorbed dose of relatively even gamma-irradiation assessed by karyometry fluctuated from 0.5 to 5.7 Gy. In 17 of the patients the influence of lithium carbonate on the course of radiation neutropenia was evaluated. No appreciable effect of the agent administration in a dose of 900 mg/patient/day was recorder from 9 to 42 day after irradiation. The authors have also considered the correlations of the values of irradiation doses calculated by varying methods of biological dosimetry.

Progressive liver failure post acute hepatitis A, over a three-month period, resulting in hepatorenal syndrome and death

PubMed Central

Al Saadi, Tareq; Sawaf, Bisher; Alkhatib, Mahmoud; Zakaria, Mhd Ismael; Daaboul, Bisher

2017-01-01

Abstract Hepatitis A is a common viral illness worldwide. It usually results in an acute, self-limiting disease and only rarely leads to fulminant hepatic failure or any other complications. During the period of conflict in Syria, and due to the damages to water infrastructure and poor sanitation, a dramatic increase in hepatitis A virus infection has been documented. Here we report a rare case of a 14-year-old male whose hepatitis A was complicated with hepatorenal syndrome and subacute liver failure. The war condition in Syria impeded transportation of the patient to a nearby country for liver transplantation, contributing to his unfortunate death. PMID:27247182

Multimorbid outpatients: A high frequency of FP appointments and/or family difficulties, should alert FPs to the possibility of death or acute hospitalization occurring within six months; A primary care feasibility study

PubMed Central

Nabbe, Patrice; Billot Grasset, Alice; Le Floch, Bernard; Grall, Pauline; Derriennic, Jeremy; odorico, Michele; Lalande, Sophie; le Goff, Delphine; Barais, Marie; Chiron, Benoit; Lingner, Heidrun; Guillou, Morgane; Barraine, Pierre

2017-01-01

Background The European General Practitioners Research Network (EGPRN) designed and validated a comprehensive definition of multimorbidity using a systematic literature review and qualitative research throughout Europe. This definition was tested as a model to assess death or acute hospitalization in multimorbid outpatients. Objective To assess which criteria in the EGPRN concept of multimorbidity could detect outpatients at risk of death or acute hospitalization in a primary care cohort at a 6-month follow-up and to assess whether a large scale cohort with FPs would be feasible. Method Family Physicians included a random sample of multimorbid patients who attended appointments in their offices from July to December 2014. Inclusion criteria were those of the EGPRN definition of Multimorbidity. Exclusion criteria were patients under legal protection and those unable to complete the 2-year follow-up. Statistical analysis was undertaken with uni- and multivariate analysis at a 6-month follow-up using a combination of approaches including both automatic classification and expert decision making. A Multiple Correspondence Analysis (MCA) completed the process with a projection of illustrative variables. A logistic regression was finally performed in order to identify and quantify risk factors for decompensation. Results 19 FPs participated in the study. 96 patients were analyzed. 3 different clusters were identified. MCA showed the central function of psychosocial factors and peaceful versus conflictual relationships with relatives in all clusters. While taking into account the limit of a small cohort, age, frequency of family physician visits and extent of family difficulties were the factors which predicted death or acute hospitalization. Conclusion A large scale cohort seems feasible in primary care. A sense of alarm should be triggered to prevent death or acute hospitalization in multimorbid older outpatients who have frequent family physician visits and who

Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hojka-Osinska, Anna, E-mail: hojka@immuno.iitd.pan.wroc.pl; Ziolo, Ewa, E-mail: ziolo@immuno.iitd.pan.wroc.pl; Rapak, Andrzej, E-mail: rapak@immuno.iitd.pan.wroc.pl

Highlights: Black-Right-Pointing-Pointer The combination of fenretinide and indomethacin induces a high level of cell death. Black-Right-Pointing-Pointer Apoptotic pathway is caspase-independent. Black-Right-Pointing-Pointer Jurkat cells undergo AIF-mediated cell death. -- Abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergisticmore » effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.« less

Acute cell death rate of vascular smooth muscle cells during or after short heating up to 20s ranging 50 to 60°C as a basic study of thermal angioplasty

NASA Astrophysics Data System (ADS)

Shinozuka, Machiko; Shimazaki, Natsumi; Ogawa, Emiyu; Machida, Naoki; Arai, Tsunenori

2014-02-01

We studied the relations between the time history of smooth muscle cells (SMCs) death rate and heating condition in vitro to clarify cell death mechanism in heating angioplasty, in particular under the condition in which intimal hyperplasia growth had been prevented in vivo swine experiment. A flow heating system on the microscope stage was used for the SMCs death rate measurement during or after the heating. The cells were loaded step-heating by heated flow using a heater equipped in a Photo-thermo dynamic balloon. The heating temperature was set to 37, 50-60°C. The SMCs death rate was calculated by a division of PI stained cell number by Hoechst33342 stained cell number. The SMCs death rate increased 5-10% linearly during 20 s with the heating. The SMCs death rate increased with duration up to 15 min after 5 s heating. Because fragmented nuclei were observed from approximately 5 min after the heating, we defined that acute necrosis and late necrosis were corresponded to within 5 min after the heating and over 5 min after the heating, respectively. This late necrosis is probably corresponding to apoptosis. The ratio of necrotic interaction divided the acute necrosis rate by the late necrosis was calculated based on this consideration as 1.3 under the particular condition in which intimal hyperplasia growth was prevented in vivo previous porcine experiment. We think that necrotic interaction rate is larger than expected rate to obtain intimal hyperplasia suppression.

Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gengozian, N.; Taylor, T.; Jameson, H.

1986-03-01

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, /sup 60/Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no differencemore » was observed between 6 MV and /sup 60/Co. Using /sup 60/Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = /sup 60/Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.« less

Acute kidney injury subphenotypes based on creatinine trajectory identifies patients at increased risk of death.

PubMed

Bhatraju, Pavan K; Mukherjee, Paramita; Robinson-Cohen, Cassianne; O'Keefe, Grant E; Frank, Angela J; Christie, Jason D; Meyer, Nuala J; Liu, Kathleen D; Matthay, Michael A; Calfee, Carolyn S; Christiani, David C; Himmelfarb, Jonathan; Wurfel, Mark M

2016-11-17

Acute kidney injury (AKI) is common among intensive care unit (ICU) patients. AKI is highly heterogeneous, with variable links to poor outcomes. Current approaches to classify AKI severity and identify patients at highest risk for poor outcomes focus on the maximum change in serum creatinine (SCr) values. However, these scores are hampered by the need for a reliable baseline SCr value and the absence of a component differentiating transient from persistent rises in SCr. We hypothesized that identification of resolving or nonresolving AKI subphenotypes based on the early trajectory of SCr values in the ICU would better differentiate patients at risk of hospital mortality. We performed a secondary analysis of two prospective studies of ICU patients admitted to a trauma ICU (group 1; n = 1914) or general medical-surgical ICUs (group 2; n = 1867). In group 1, we tested definitions for resolving and nonresolving AKI subphenotypes and selected the definitions resulting in subphenotypes with the greatest separation in risk of death relative to non-AKI controls. We applied this definition to group 2 and tested whether the subphenotypes were independently associated with hospital mortality after adjustment for AKI severity. AKI occurred in 46% and 69% of patients in groups 1 and 2, respectively. In group 1, a resolving AKI subphenotype (defined as a decrease in SCr of 0.3 mg/dl or 25% from maximum in the first 72 h of study enrollment) was associated with a low risk of death. A nonresolving AKI subphenotype (defined as all AKI cases not meeting the "resolving" definition) was associated with a high risk of death. In group 2, the resolving AKI subphenotype was not associated with increased mortality (relative risk [RR] 0.86, 95% CI 0.63-1.17), whereas the nonresolving AKI subphenotype was associated with higher mortality (RR 1.68, 95% CI 1.15-2.44) even after adjustment for AKI severity stage. The trajectory of SCr levels identifies AKI subphenotypes with different

Leukapheresis do not improve early death rates in acute myeloid leukemia patients with hyperleukocytosis.

PubMed

Malkan, Umit Yavuz; Ozcebe, Osman Ilhami

2017-12-01

Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm 3 in peripheral blood. It has been already shown in the literature that leukapheresis, a conventional technique to decrease the serum WBC level, is ineffective for long-term survival in cases of hyperleukocytotic acute myeloid leukemia (AML) with leukostasis. However, the effect of leukapheresis on early mortality is still unclear. In this study, we aimed to evaluate the effect of leukapheresis on early mortality of patients with AML who have HL. Twenty-eight de novo patients with AML, diagnosed with HL between 2002 and 2015 at the Hacettepe Hematology Department, were analyzed retrospectively. Leukapheresis was performed in 10 patients, and the mean WBC decrease with leukapheresis was 57.4×10 3 /μl which accounts for 31% of the initial WBC count. The indications for leukapheresis were hyperviscosity and prophylaxis in four and six patients, respectively. In the group of patients who received leukapheresis, three of four patients who had hyperviscosity symptoms died, and three of six patients died who did not have symptoms. In our study, we observed that the leukapheresis procedure is highly effective in reducing plasma WBC levels. However, although it is statistically insignificant, our findings also revealed that there is a much higher rate of death in patients who were treated with leukapheresis. Therefore we conclude that leukapheresis does not lower rates of early death; nevertheless, this finding should be confirmed by prospective studies with larger cohorts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frequently Asked Questions about Radiation Emergencies

MedlinePlus

... Health Effects Contamination and Exposure Acute Radiation Syndrome (ARS) Cutaneous Radiation Injury (CRI) Cancer and Long-Term ... period of time can cause Acute Radiation Syndrome (ARS). If you have symptoms of ARS (skin burns, ...

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

2014-07-01

Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival

PubMed Central

Quintens, Roel; Samari, Nada; de Saint-Georges, Louis; van Oostveldt, Patrick; Baatout, Sarah; Benotmane, Mohammed Abderrafi

2016-01-01

During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight. PMID:27203085

Acute myocardial infarction mortality in Cuba, 1999-2008.

PubMed

Armas, Nurys B; Ortega, Yanela Y; de la Noval, Reinaldo; Suárez, Ramón; Llerena, Lorenzo; Dueñas, Alfredo F

2012-10-01

Acute myocardial infarction is one of the leading causes of death in the world. This is also true in Cuba, where no national-level epidemiologic studies of related mortality have been published in recent years. Describe acute myocardial infarction mortality in Cuba from 1999 through 2008. A descriptive study was conducted of persons aged ≥25 years with a diagnosis of acute myocardial infarction from 1999 through 2008. Data were obtained from the Ministry of Public Health's National Statistics Division database for variables: age; sex; site (out of hospital, in hospital or in hospital emergency room) and location (jurisdiction) of death. Proportions, age- and sex-specific rates and age-standardized overall rates per 100,000 population were calculated and compared over time, using the two five-year time frames within the study period. A total of 145,808 persons who had suffered acute myocardial infarction were recorded, 75,512 of whom died, for a case-fatality rate of 51.8% (55.1% in 1999-2003 and 49.7% in 2004-2008). In the first five-year period, mortality was 98.9 per 100,000 population, falling to 81.8 per 100,000 in the second; most affected were people aged ≥75 years and men. Of Cuba's 14 provinces and special municipality, Havana, Havana City and Camagüey provinces, and the Isle of Youth Special Municipality showed the highest mortality; Holguín, Ciego de Ávila and Granma provinces the lowest. Out-of-hospital deaths accounted for the greatest proportion of deaths in both five-year periods (54.8% and 59.2% in 1999-2003 and 2004-2008, respectively). Although risk of death from acute myocardial infarction decreased through the study period, it remains a major health problem in Cuba. A national acute myocardial infarction case registry is needed. Also required is further research to help elucidate possible causes of Cuba's high acute myocardial infarction mortality: cardiovascular risk studies, studies of out-of-hospital mortality and quality of care

Occupational Deaths among Healthcare Workers

PubMed Central

Eisenberg, Leon

2005-01-01

Recent experiences with severe acute respiratory syndrome and the US smallpox vaccination program have demonstrated the vulnerability of healthcare workers to occupationally acquired infectious diseases. However, despite acknowledgment of risk, the occupational death rate for healthcare workers is unknown. In contrast, the death rate for other professions with occupational risk, such as police officer or firefighter, has been well defined. With available information from federal sources and calculating the additional number of deaths from infection by using data on prevalence and natural history, we estimate the annual death rate for healthcare workers from occupational events, including infection, is 17–57 per 1 million workers. However, a much more accurate estimate of risk is needed. Such information could inform future interventions, as was seen with the introduction of safer needle products. This information would also heighten public awareness of this often minimized but essential aspect of patient care. PMID:16022771

Local exposure of 849 MHz and 1763 MHz radiofrequency radiation to mouse heads does not induce cell death or cell proliferation in brain

PubMed Central

Kim, Tae-Hyoung; Huang, Tai-Qin; Jang, Ja-June; Kim, Man Ho; Kim, Hyun-Jeong; Lee, Jae-Seon; Pack, Jeong Ki; Seo, Jeong-Sun

2008-01-01

Even though there is no direct evidence to prove the cellular and molecular changes induced by radiofrequency (RF) radiation itself, we cannot completely exclude the possibility of any biological effect of mobile phone frequency radiation. We established a carousel-type exposure chamber for 849 MHz or 1763 MHz of mobile phone RF radiation to expose RF to the heads of C57BL mice. In this chamber, animals were irradiated intermittently at 7.8 W/kg for a maximum of 12 months. During this period, the body weights of 3 groups-sham, 849 MHz RF, and 1763 MHz RF-did not show any differences between groups. The brain tissues were obtained from 3 groups at 6 months and 12 months to examine the differences in histology and cell proliferation between control and RF exposure groups, but we could not find any change upon RF radiation. Likewise, we could not find changes in the expression and distribution of NeuN and GFAP in hippocampus and cerebellum, or in cell death by TUNEL assay in RF exposure groups. From these data, we conclude that the chronic exposure to 849 MHz and 1763 MHz RF radiation at a 7.8 W/kg specific absorption rate (SAR) could not induce cellular alterations such as proliferation, death, and reactive gliosis. PMID:18587267

Main Sources and Doses of Space Radiation during Mars Missions and Total Radiation Risk for Cosmonauts

NASA Astrophysics Data System (ADS)

Mitrikas, Victor; Aleksandr, Shafirkin; Shurshakov, Vyacheslav

This work contains calculation data of generalized doses and dose equivalents in critical organs and tissues of cosmonauts produces by galactic cosmic rays (GCR), solar cosmic rays (SCR) and the Earth’s radiation belts (ERB) that will impact crewmembers during a flight to Mars, while staying in the landing module and on the Martian surface, and during the return to Earth. Also calculated total radiation risk values during whole life of cosmonauts after the flight are presented. Radiation risk (RR) calculations are performed on the basis of a radiobiological model of radiation damage to living organisms, while taking into account reparation processes acting during continuous long-term exposure at various dose rates and under acute recurrent radiation impact. The calculations of RR are performed for crewmembers of various ages implementing a flight to Mars over 2 - 3 years in maximum and minimum of the solar cycle. The total carcinogenic and non-carcinogenic RR and possible life-span shortening are estimated on the basis of a model of the radiation death probability for mammals. This model takes into account the decrease in compensatory reserve of an organism as well as the increase in mortality rate and descent of the subsequent lifetime of the cosmonaut. The analyzed dose distributions in the shielding and body areas are applied to making model calculations of tissue equivalent spherical and anthropomorphic phantoms.

Distinctions in manifestation of the hemorrhagic syndrome related to chronic, long-term and acute irradiation. [Rats;. gamma. rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arlashchenko, N.I.; Gorlov, V.G.; Maksimova, E.N.

Two phenomena, decrease in strength of the vascular wall and decreased amount of thrombocytes in blood, must coincide for manifestation of the hemorrhagic syndrome. Either almost simultaneous injury to the vascular wall and thrombocyte function (with acute irradiation) or dissociation of these two processes (with long-term irradiation) may be observed, depending on the radiation dose. Chronic exposure at low (subliminal) dose rates does not elicit hemorrhagic manifestations or death of rats due to pathological bleeding.

Place of Death in Patients with Lung Cancer: A Retrospective Cohort Study from 2004-2013.

PubMed

O'Dowd, Emma L; McKeever, Tricia M; Baldwin, David R; Hubbard, Richard B

2016-01-01

Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access.

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

PubMed

Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

2015-11-01

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy

PubMed Central

Johnson, Adam G.; Ruiz, Jimmy; Isom, Scott; Lucas, John T.; Hinson, William H.; Watabe, Kounosuke; Laxton, Adrian W.; Tatter, Stephen B.; Chan, Michael D.

2017-01-01

Abstract Background. In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. Methods. We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Results. Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Conclusions. Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death. PMID:27571883

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990–2009

PubMed Central

Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

2016-01-01

Background: Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. Methods: AL cases diagnosed over 1990–2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002–2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. Results: AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Conclusions: Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland. Citation: Demoury C, Marquant F, Ielsch G, Goujon S, Debayle C, Faure L, Coste A, Laurent O, Guillevic J, Laurier D, Hémon D, Clavel J

Successful Teaching of Radiobiology Students in the Medical Management of Acute Radiation Effects From Real Case Histories Using Clinical Signs and Symptoms and Taking Advantage of Recently Developed Software Tools.

PubMed

Majewski, Matthäus; Combs, Stephanie E; Trott, Klaus-Rüdiger; Abend, Michael; Port, Matthias

2018-07-01

In 2015, the Bundeswehr Institute of Radiobiology organized a North Atlantic Treaty Organization exercise to examine the significance of clinical signs and symptoms for the prediction of late-occurring acute radiation syndrome. Cases were generated using either the Medical Treatment Protocols for Radiation Accident Victims (METREPOL, n = 167) system or using real-case descriptions extracted from a database system for evaluation and archiving of radiation accidents based on case histories (SEARCH, n = 24). The cases ranged from unexposed [response category 0 (RC 0, n = 89)] to mild (RC 1, n = 45), moderate (RC 2, n = 19), severe (RC 3, n = 20), and lethal (RC 4, n = 18) acute radiation syndrome. During the previous exercise, expert teams successfully predicted hematological acute radiation syndrome severity, determined whether hospitalization was required, and gave treatment recommendations, taking advantage of different software tools developed by the North Atlantic Treaty Organization teams. The authors provided the same data set to radiobiology students who were introduced to the medical management of acute effects after radiation exposure and the software tools during a class lasting 15 h. Corresponding to the previous results, difficulties in the discrimination between RC 0/RC 1 and RC 3/RC 4, as well as a systematic underestimation of RC 1 and RC 2, were observed. Nevertheless, after merging reported response categories into clinically relevant groups (RC 0-1, RC 2-3, and RC 3-4), it was found that the majority of cases (95.2% ± 2.2 standard deviations) were correctly identified and that 94.7% (±2.6 standard deviations) developing acute radiation syndrome and z96.4% (±1.6 standard deviations) requiring hospitalization were identified correctly. Two out of three student teams also provided a dose estimate. These results are comparable to the best-performing team of the 2015 North Atlantic Treaty Organization exercise (response category: 92.5%; acute

Citrulline as a Biomarker for Gastrointestinal-Acute Radiation Syndrome: Species Differences and Experimental Condition Effects.

PubMed

Bujold, K; Hauer-Jensen, M; Donini, O; Rumage, A; Hartman, D; Hendrickson, H P; Stamatopoulos, J; Naraghi, H; Pouliot, M; Ascah, A; Sebastian, M; Pugsley, M K; Wong, K; Authier, S

2016-07-01

Animal models of hematopoietic and gastrointestinal acute radiation syndromes (ARS) have been characterized to develop medical countermeasures. Acute radiation-induced decrease of intestinal absorptive function has been correlated to a decrease in the number of intestinal crypt cells resulting from apoptosis and enterocyte mass reduction. Citrulline, a noncoded amino acid, is produced almost exclusively by the enterocytes of the small intestine. Citrullinemia has been identified as a simple, sensitive and suitable biomarker for radiation-induced injury associated with gastrointestinal ARS (GI-ARS). Here we discuss the effect of radiation on plasma citrulline levels in three different species, C57BL/6 mice, Göttingen minipigs and rhesus nonhuman primates (NHPs), measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). The effects of experimental study conditions such as feeding and anesthesia were also examined on plasma citrulline levels in the NHPs. Both the mice and Göttingen minipigs were partial-body irradiated (PBI) with doses from 13-17 Gy and 8-16 Gy, respectively, whereas NHPs were total-body irradiated (TBI) with doses from 6.72-13 Gy. Blood samples were taken at different time points and plasma citrulline levels were measured in the three species at baseline and after irradiation. Basal plasma citrulline concentrations (mean ± SEM) in mice and minipigs were 57.8 ± 2.8 μM and 63.1 ± 2.1 μM, respectively. NHPs showed a basal plasma citrulline concentration of 32.6 ± 0.7 μM, very similar to that of humans (∼40 μM). Plasma citrulline progressively decreased after irradiation, reaching nadir values between day 3.5 and 7. The onset of citrulline recovery was observed earlier at lower radiation doses, while only partial citrulline recovery was noted at higher radiation doses in minipigs and NHPs, complete recovery was noted in mice at all doses. Plasma citrulline levels in NHPs anesthetized with ketamine and acepromazine significantly

Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model.

PubMed

Hussein, Mahmoud R; Abu-Dief, Eman E; Kamel, Esam; Abou El-Ghait, Amal T; Abdulwahed, Saad Rezk; Ahmad, Mohamed H

2008-11-01

Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking. This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis". We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy). We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural

Influence of radiation quality on mouse chromosome 2 deletions in radiation-induced acute myeloid leukaemia.

PubMed

Brown, Natalie; Finnon, Rosemary; Manning, Grainne; Bouffler, Simon; Badie, Christophe

2015-11-01

Leukaemia is the prevailing neoplastic disorder of the hematopoietic system. Epidemiological analyses of the survivors of the Japanese atomic bombings show that exposure to ionising radiation (IR) can cause leukaemia. Although a clear association between radiation exposure and leukaemia development is acknowledged, the underlying mechanisms remain incompletely understood. A hemizygous deletion on mouse chromosome 2 (del2) is a common feature in several mouse strains susceptible to radiation-induced acute myeloid leukaemia (rAML). The deletion is an early event detectable 24h after exposure in bone marrow cells. Ultimately, 15-25% of exposed animals develop AML with 80-90% of cases carrying del2. Molecular mapping of leukaemic cell genomes identified a minimal deleted region (MDR) on chromosome 2 (chr2) in which a tumour suppressor gene, Sfpi1 is located, encoding the transcription factor PU.1, essential in haematopoiesis. The remaining copy of Sfpi1 has a point mutation in the coding sequence for the DNA-binding domain of the protein in 70% of rAML, which alters a single CpG sequence in the codon for arginine residue R235. In order to identify chr2 deletions and Sfpi.1/PU.1 loss, we performed array comparative genomic hybridization (aCGH) on a unique panel of 79rAMLs. Using a custom made CGH array specifically designed for mouse chr2, we analysed at unprecedentedly high resolution (1.4M array- 148bp resolution) the size of the MDR in low LET and high-LET induced rAMLs (32 X-ray- and 47 neutron-induced). Sequencing of Sfpi1/PU.1DNA binding domain identified the presence of R235 point mutations, showing no influence of radiation quality on R235 type or frequency. We identified for the first time rAML cases with complex del2 in a subset of neutron-induced AMLs. This study allowed us to re-define the MDR to a much smaller 5.5Mb region (still including Sfpi1/PU.1), identical regardless of radiation quality. Crown Copyright © 2015. Published by Elsevier B.V. All rights

Influence of pesticide regulation on acute poisoning deaths in Sri Lanka.

PubMed Central

Roberts, Darren M.; Karunarathna, Ayanthi; Buckley, Nick A.; Manuweera, Gamini; Sheriff, M. H. Rezvi; Eddleston, Michael

2003-01-01

OBJECTIVES: To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka from the 1970s, aimed to reduce the number of deaths - the majority from self-poisoning - by limiting the availability and use of highly toxic pesticides. METHODS: Information on legislative changes was obtained from the Ministry of Agriculture, national and district hospital admission data were obtained from the Sri Lanka Health Statistics Unit, and individual details of deaths by pesticide poisoning were obtained from a manual review of patients' notes and intensive care unit records in Anuradhapura. FINDINGS: Between 1986 and 2000, the total national number of admissions due to poisoning doubled, and admissions due to pesticide poisoning increased by more than 50%. At the same time, the case fatality proportion (CFP) fell for total poisonings and for poisonings due to pesticides. In 1991_92, 72% of pesticide-induced deaths in Anuradhapura were caused by organophosphorus (OP) and carbamate pesticides - in particular, the WHO class I OPs monocrotophos and methamidophos. From 1991, the import of these pesticides was reduced gradually until they were banned for routine use in January 1995, with a corresponding fall in deaths. Unfortunately, their place in agricultural practice was taken by the WHO class II organochlorine endosulfan, which led to a rise in deaths from status epilepticus - from one in 1994 to 50 in 1998. Endosulfan was banned in 1998, and over the following three years the number of endosulfan deaths fell to three. However, at the end of the decade, the number of deaths from pesticides was at a similar level to that of 1991, with WHO class II OPs causing the most deaths. Although these drugs are less toxic than class I OPs, the management of class II OPs remains difficult because they are, nevertheless, still highly toxic, and their toxicity is exacerbated by the paucity

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase-expressing umbilical cord mesenchymal stromal cells.

PubMed

Gan, Jingyi; Meng, Fanwei; Zhou, Xin; Li, Chan; He, Yixin; Zeng, Xiaoping; Jiang, Xingen; Liu, Jia; Zeng, Guifang; Tang, Yunxia; Liu, Muyun; Mrsny, Randall J; Hu, Xiang; Hu, Jifan; Li, Tao

2015-04-01

Acute radiation syndrome (ARS) leads to pancytopenia and multi-organ failure. Transplantation of hematopoietic stem cells provides a curative option for radiation-induced aplasia, but this therapy is limited by donor availability. We examined an alternative therapeutic approach to ARS with the use of human extracellular superoxide dismutase (ECSOD)-modified umbilical cord mesenchymal stromal cells (UCMSCs). This treatment combines the unique regenerative role of UCMSCs with the anti-oxidative activity of ECSOD. We demonstrated that systemically administered ECSOD-UCMSCs are able to protect mice from sub-lethal doses of radiation and improve survival by promoting multilineage hematopoietic recovery. The therapeutic effect of this treatment is related to the decrease in radiation-induced O(2)(-) and apoptosis. Our data highlight the clinical potential of this two-pronged approach to the treatment of ARS, thereby serving as a rapid and effective first-line strategy to combat the hematopoietic failure resulting from a radiation accident, nuclear terrorism and other radiologic emergencies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field.

PubMed

Kaszuba-Zwoińska, Jolanta; Ćwiklińska, Magdalena; Balwierz, Walentyna; Chorobik, Paulina; Nowak, Bernadeta; Wójcik-Piotrowicz, Karolina; Ziomber, Agata; Malina-Novak, Kinga; Zaraska, Wiesław; Thor, Piotr J

2015-03-01

Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells

PubMed Central

Weeks, Robert J.; Ludgate, Jackie L.; LeMée, Gwenn; Morison, Ian M.

2016-01-01

Background Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity. Methods Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5’-aza-2’-deoxycytidine (decitabine) exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays. Results In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity. Conclusions These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL. PMID:26985820

Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury.

PubMed

Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

2017-01-01

Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2016-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2015-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Singlet Oxygen-Induced Membrane Disruption and Serpin-Protease Balance in Vacuolar-Driven Cell Death.

PubMed

Koh, Eugene; Carmieli, Raanan; Mor, Avishai; Fluhr, Robert

2016-07-01

Singlet oxygen plays a role in cellular stress either by providing direct toxicity or through signaling to initiate death programs. It was therefore of interest to examine cell death, as occurs in Arabidopsis, due to differentially localized singlet oxygen photosensitizers. The photosensitizers rose bengal (RB) and acridine orange (AO) were localized to the plasmalemma and vacuole, respectively. Their photoactivation led to cell death as measured by ion leakage. Cell death could be inhibited by the singlet oxygen scavenger histidine in treatments with AO but not with RB In the case of AO treatment, the vacuolar membrane was observed to disintegrate. Concomitantly, a complex was formed between a vacuolar cell-death protease, RESPONSIVE TO DESSICATION-21 and its cognate cytoplasmic protease inhibitor ATSERPIN1. In the case of RB treatment, the tonoplast remained intact and no complex was formed. Over-expression of AtSerpin1 repressed cell death, only under AO photodynamic treatment. Interestingly, acute water stress showed accumulation of singlet oxygen as determined by fluorescence of Singlet Oxygen Sensor Green, by electron paramagnetic resonance spectroscopy and the induction of singlet oxygen marker genes. Cell death by acute water stress was inhibited by the singlet oxygen scavenger histidine and was accompanied by vacuolar collapse and the appearance of serpin-protease complex. Over-expression of AtSerpin1 also attenuated cell death under this mode of cell stress. Thus, acute water stress damage shows parallels to vacuole-mediated cell death where the generation of singlet oxygen may play a role. © 2016 American Society of Plant Biologists. All Rights Reserved.

Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daila S. Gridley, PhD

2012-03-30

FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findingsmore » remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide

Determinants of Hospital Death for Taiwanese Pediatric Cancer Decedents, 2001-2010.

PubMed

Hung, Yen-Ni; Liu, Tsang-Wu; Tang, Siew Tzuh

2015-11-01

Factors influencing pediatric cancer patients' place of death may have evolved with advances in medical and hospice care since earlier studies were done. To comprehensively analyze factors associated with hospital death in an unbiased population of pediatric cancer patients in Taiwan. This was a retrospective cohort study using administrative data for 1603 Taiwanese pediatric cancer patients who died in 2001-2010. Place of death was hypothesized to be associated with 1) patient sociodemographics and disease characteristics, 2) primary physician's specialty, 3) characteristics and health care resources at both the hospital and regional levels, and 4) historical trends. Most Taiwanese pediatric cancer patients (87.4%) died in an acute care hospital. The probability of dying in hospital increased slightly over time, reaching significance only in 2009 (adjusted odds ratio [AOR], 95% CI: 2.84 [1.32-6.11]). Children were more likely to die in an acute care hospital if they resided in the most urbanized area, were diagnosed with leukemia or lymphoma (2.32 [1.39-3.87]), and received care from a pediatrician (1.58 [1.01-2.47]) in a nonprofit proprietary hospital (1.50 [1.01-2.24]) or large hospital, reaching significance for the third quartile (2.57 [1.28-5.18]) of acute care hospital beds. Taiwanese pediatric cancer patients predominantly died in an acute care hospital with a slightly increasing trend of shifting place of death from home to hospital. Propensity for hospital death was determined by residential urbanization level, diagnosis, primary physician's specialty, and the primary hospital's characteristics and health care resources. Clinical interventions and health policies should ensure that resources are allocated to allow pediatric cancer patients to die in the place they and their parents prefer to achieve a good death and promote their parents' bereavement adjustment. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier

Methods for Ensuring High Quality of Coding of Cause of Death. The Mortality Register to Follow Southern Urals Populations Exposed to Radiation.

PubMed

Startsev, N; Dimov, P; Grosche, B; Tretyakov, F; Schüz, J; Akleyev, A

2015-01-01

To follow up populations exposed to several radiation accidents in the Southern Urals, a cause-of-death registry was established at the Urals Center capturing deaths in the Chelyabinsk, Kurgan and Sverdlovsk region since 1950. When registering deaths over such a long time period, quality measures need to be in place to maintain quality and reduce the impact of individual coders as well as quality changes in death certificates. To ensure the uniformity of coding, a method for semi-automatic coding was developed, which is described here. Briefly, the method is based on a dynamic thesaurus, database-supported coding and parallel coding by two different individuals. A comparison of the proposed method for organizing the coding process with the common procedure of coding showed good agreement, with, at the end of the coding process, 70  - 90% agreement for the three-digit ICD -9 rubrics. The semi-automatic method ensures a sufficiently high quality of coding by at the same time providing an opportunity to reduce the labor intensity inherent in the creation of large-volume cause-of-death registries.

Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate.

PubMed

Sutherland, George R

2017-10-21

Sudden cardiac death (SCD) is a complex phenomenon, occurring either in apparently normal individuals or in those where there is a recognized underlying cardiac abnormality. In both groups, the lethal arrhythmia has frequently been related to the physiologic trigger of either exercise or stress. Prior research into SCD has focused mainly on a combination of identifying either vulnerable myocardial substrates; pharmacological approaches to altering electrical activation/repolarisation in substrates; or the suppression of induced lethal arrhythmias with implantable defibrillators. However, it has been suggested that in a significant number of cases, the interaction of a transient induced trigger with a pre-existing electrical or mechanical substrate is the basis for the induction of the sustained lethal arrhythmia. In this manuscript we will discuss the precise mechanisms whereby one of such potential physiologic trigger: an acute change in systolic blood pressure, can induce a sequence of alterations in global and local cardiac mechanics which in turn result in regional left ventricular post-systolic deformation which, mediated (through stretch-induced changes in local mechano-electrical coupling) provokes local electrical after-depolarisations which can spill over into complex runs of premature ventricular beats. These local acute pressure/stretch induced runs of ventricular ectopy originate in either basal or apical normal myocardium and, in combination with a co-existing distal pro-arrhymic substrate, can interact to induce a lethal arrhythmia. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

The NRF2 Activation and Antioxidative Response Are Not Impaired Overall during Hyperoxia-Induced Lung Epithelial Cell Death

PubMed Central

Potteti, Haranatha R.; Reddy, Narsa M.; Hei, Tom K.; Kalvakolanu, Dhananjaya V.; Reddy, Sekhar P.

2013-01-01

Lung epithelial and endothelial cell death caused by pro-oxidant insults is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients. The NF-E2-related factor 2 (NRF2) activation in response to oxidant exposure is crucial to the induction of several antioxidative and cytoprotective enzymes that mitigate cellular stress. Since prolonged exposure to hyperoxia causes cell death, we hypothesized that chronic hyperoxia impairs NRF2 activation, resulting in cell death. To test this hypothesis, we exposed nonmalignant small airway epithelial cells (AECs) to acute (1–12 h) and chronic (36–48 h) hyperoxia and evaluated cell death, NRF2 nuclear accumulation and target gene expression, and NRF2 recruitment to the endogenous HMOX1 and NQO1 promoters. As expected, hyperoxia gradually induced death in AECs, noticeably and significantly by 36 h; ~60% of cells were dead by 48 h. However, we unexpectedly found increased expression levels of NRF2-regulated antioxidative genes and nuclear NRF2 in AECs exposed to chronic hyperoxia as compared to acute hyperoxia. Chromatin Immunoprecipitation (ChIP) assays revealed an increased recruitment of NRF2 to the endogenous HMOX1 and NQO1 promoters in AECs exposed to acute or chronic hyperoxia. Thus, our findings demonstrate that NRF2 activation and antioxidant gene expression are functional during hyperoxia-induced lung epithelial cell death and that chronic hyperoxia does not impair NRF2 signaling overall. PMID:23738042

Evaluation of prophylactic and therapeutic effects of ruscogenin on acute radiation proctitis: an experimental rat model.

PubMed

Yavuz, Erkan; Karagulle, Onur Olgac; Ercan, Gulcin; Celik, Atilla; Yigitbas, Hakan; Bayrak, Busra Yaprak; Tartar, Rumeysa; Kusaslan, Ramazan; Altinel, Yuksel; Gulcicek, Osman Bilgin

2018-04-01

Radiation proctitis (RP) is inflammation and damage to the rectum, manifested secondary to ionizing radiation utilized for treatment. In this study, we evaluated the anti-inflammatory therapeutical and protective effects of ruscogenin in a model of acute RP. Thirty-two Sprague-Dawley rats were divided into 4 groups (n = 8) as sham, control, treatment, and prophylaxis groups. Prophylaxis group and treatment group were dosed ruscogenin by oral gavage for 14 days pre- and postradiation. At the end of the 28th day, all subjects were sacrificed. Histopathological analysis showed a significant increase in cryptitis abscess, cryptitis and reactive atypia, and depth of lymphocytic infiltration of the control group, compared to the other groups (P < 0.05), while treatment and prophylaxis groups showed significant decreases (P < 0.05). Immunohistochemical analysis indicated that immunoreactivity were significantly higher in control group (P < 0.05, P < 0.001, and P < 0.01, respectively), but vice versa for treatment and prophylaxis groups. There was not any significant difference for fibroblast growth factor 2 immunoreactivity. The epithelium of control rectums indicated an increase in TNF-α immunoreactivity while other groups had significant decrease (P < 0.01). Electron microscopical findings were parallel to light microscopy. In this study, ruscogenin was observed to be effective on prophylaxis or treatment of acute RP. Although there are various reports on the treatment of the rectum damaged by acute RP in the literature, this could be the first study since there is no research indicating the ultrastructural effect of ruscogenin.

The effect of Mepitel Film on acute radiation-induced skin reactions in head and neck cancer patients: a feasibility study.

PubMed

Wooding, Hayley; Yan, Jing; Yuan, Ling; Chyou, Te-Yu; Gao, Shanbao; Ward, Iain; Herst, Patries M

2018-01-01

Mepitel Film significantly decreases acute radiation-induced skin reactions in breast cancer patients. Here we investigated the feasibility of using Mepitel Film in head and neck cancer patients (ACTRN12614000932662). Out of a total of 36 head and neck cancer patients from New Zealand (NZ) (n = 24) and China (n = 12) recruited between June 2015 and December 2016, 33 patients complied with protocol. Of these, 11 NZ patients followed a management protocol; 11 NZ patients and 11 Chinese patients followed a prophylactic protocol. An area of the neck receiving a homogenous radiation dose of > 35 Gy was divided into two equal halves; one half was randomized to Film and the other to either Sorbolene cream (NZ) or Biafine cream (China). Skin reaction severity was measured by Radiation Induced Skin Reaction Assessment Scale and expanded Radiation Therapy Oncology Group toxicity criteria. Skin dose was measured by thermoluminescent dosimeters or gafchromic film. Film decreased overall skin reaction severity (combined Radiation Induced Skin Reaction Assessment Scale score) by 29% and moist desquamation rates by 37% in the Chinese cohort and by 27 and 28%, respectively in the NZ cohort. Mepitel Film did not affect head movements but did not adhere well to the skin, particularly in males with heavy beard stubble, and caused itchiness, particularly in Chinese patients. Mepitel Film reduced acute radiation-induced skin reactions in our head and neck cancer patients, particularly in patients without heavy stubble. Advances in knowledge: This is the first study to confirm the feasibility of using Mepitel Film in head and neck cancer patients.

European consensus on the medical management of acute radiation syndrome and analysis of the radiation accidents in Belgium and Senegal.

PubMed

Gourmelon, Patrick; Benderitter, Marc; Bertho, Jean Marc; Huet, Christelle; Gorin, Norbert Claude; De Revel, Patrick

2010-06-01

A European consensus concerning the medical management of mass radiation exposure was obtained in 2005 during a conference held by the European Group for Blood and Bone Marrow Transplantation, the Institute of Radioprotection and Nuclear Safety, and the University of Ulm. At the conference, a two-step triage strategy to deal with large masses of radiation-exposed patients was designed. The first step of this strategy concerns the first 48 h and involves scoring the patients exclusively on the basis of their clinical symptoms and biological data. This allows the non-irradiated bystanders and outpatient candidates to be identified. The remaining patients are hospitalized and diagnosis is confirmed after the first 48-h period according to the METREPOL (Medical Treatment Protocols for radiation accident victims) scale. This grades the patients according to the severity of their symptoms. It was also agreed that in the case of acute radiation syndrome (ARS), emergency hematopoietic stem cell (HSC) transplantation is not necessary. Instead, cytokines that promote hematological reconstruction should be administered as early as possible for 14-21 d. Crucial tests for determining whether the patient has residual hematopoiesis are physical dose reconstructions combined with daily blood count analyses. It was agreed that HSC transplantation should only be considered if severe aplasia persists after cytokine treatment. Two recent cases of accidental radiation exposure that were managed successfully by following the European consensus with modification are reviewed here. Thus, a European standard for the evaluation and treatment of ARS victims is now available. This standard may be suitable for application around the world.

Hepatic ischemia reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation.

PubMed

Leithead, Joanna A; Armstrong, Matthew J; Corbett, Christopher; Andrew, Mark; Kothari, Chirag; Gunson, Bridget K; Muiesan, Paolo; Ferguson, James W

2013-11-01

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia-reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single-center study was to determine if hepatic ischemia-reperfusion injury, estimated by peak peri-operative serum amino-transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500-2999 and ≥ 3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia-reperfusion injury demonstrates a strong relationship with peri-operative AKI in DBD liver transplant recipients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Predictors of neurologic and nonneurologic death in patients with brain metastasis initially treated with upfront stereotactic radiosurgery without whole-brain radiation therapy.

PubMed

McTyre, Emory R; Johnson, Adam G; Ruiz, Jimmy; Isom, Scott; Lucas, John T; Hinson, William H; Watabe, Kounosuke; Laxton, Adrian W; Tatter, Stephen B; Chan, Michael D

2017-04-01

In this study we attempted to discern the factors predictive of neurologic death in patients with brain metastasis treated with upfront stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) while accounting for the competing risk of nonneurologic death. We performed a retrospective single-institution analysis of patients with brain metastasis treated with upfront SRS without WBRT. Competing risks analysis was performed to estimate the subdistribution hazard ratios (HRs) for neurologic and nonneurologic death for predictor variables of interest. Of 738 patients treated with upfront SRS alone, neurologic death occurred in 226 (30.6%), while nonneurologic death occurred in 309 (41.9%). Multivariate competing risks analysis identified an increased hazard of neurologic death associated with diagnosis-specific graded prognostic assessment (DS-GPA) ≤ 2 (P = .005), melanoma histology (P = .009), and increased number of brain metastases (P<.001), while there was a decreased hazard associated with higher SRS dose (P = .004). Targeted agents were associated with a decreased HR of neurologic death in the first 1.5 years (P = .04) but not afterwards. An increased hazard of nonneurologic death was seen with increasing age (P =.03), nonmelanoma histology (P<.001), presence of extracranial disease (P<.001), and progressive systemic disease (P =.004). Melanoma, DS-GPA, number of brain metastases, and SRS dose are predictive of neurologic death, while age, nonmelanoma histology, and more advanced systemic disease are predictive of nonneurologic death. Targeted agents appear to delay neurologic death. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Efficacy of Polaprezinc for Acute Radiation Proctitis in a Rat Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doi, Hiroshi, E-mail: h-doi@hyo-med.ac.jp; Kamikonya, Norihiko; Takada, Yasuhiro

Purpose: The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. Methods and Materials: A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ-), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10thmore » day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. Results: According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ-, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ-, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. Conclusions: This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.« less

THE PROTECTIVE EFFECT OF LOCAL BONE MARROW ASPHYXIA IN ACUTE RADIATION SICKNESS IN ANIMALS (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zherebchenko, P.G.; Krasnykh, I.G.; Lebkova, N.P.

1960-10-01

In experiments on mice, rats, and dogs, a study was made of the effect of local bone marrow asphyxia on the course and outcome of radiation sickness. Asphyxia was induced by applying a hemostatic tourniquet on the extremity of animals during irradiation. It was established that local asphyxia of the bone marrow alleviates the severity of acute radiation sickness and increases the survival of animals. It is shown that at the basis of the radioprotective action lies the reduced degeneration of the bone marrow, subsequently facilitating the regeneration of hematopeiesis. Data are obtained relative to the intensification of the effectmore » of local asphyxia with the aid of prophylactic (mercamine) and curative (streptomycin) agents. (auth)« less

Acute Cardiopulmonary Failure From Sleep-Disordered Breathing

PubMed Central

Carr, Gordon E.; Mokhlesi, Babak

2012-01-01

Sleep-disordered breathing (SDB) comprises a diverse set of disorders marked by abnormal respiration during sleep. Clinicians should realize that SDB may present as acute cardiopulmonary failure in susceptible patients. In this review, we discuss three clinical phenotypes of acute cardiopulmonary failure from SDB: acute ventilatory failure, acute congestive heart failure, and sudden death. We review the pathophysiologic mechanisms and recommend general principles for management. Timely recognition of, and therapy for, SDB in the setting of acute cardiopulmonary failure may improve short- and long-term outcomes. PMID:22396567

The changing nature of death on the trauma service.

PubMed

Kahl, Jessica E; Calvo, Richard Y; Sise, Michael J; Sise, C Beth; Thorndike, Jonathan F; Shackford, Steven R

2013-08-01

Recent innovations in care have improved survival following injury. Coincidentally, the population of elderly injured patients with preexisting comorbidities has increased. We hypothesized that this increase in elderly injured patients may have combined with recent care innovations to alter the causes of death after trauma. We reviewed demographics, injury characteristics, and cause of death of in-hospital deaths of patients admitted to our Level I trauma service from 2000 through 2011. Cause of death was classified as acute hemorrhagic shock; severe traumatic brain injury or high spinal cord injury; complications of preexisting medical condition only (PM); survivable trauma combined with complications of preexisting medical condition (TCoM); multiple-organ failure, sepsis, or adult respiratory distress syndrome (MOF/S/ARDS), or trauma not otherwise categorized (e.g., asphyxiation). Major trauma care advances implemented on our service during the period were identified, and trends in the causes of death were analyzed. Of the 27,276 admissions, 819 (3%) eligible nonsurvivors were identified for the cause-of-death analyses. Causes of death were severe traumatic brain injury or high spinal cord injury at 44%, acute hemorrhagic shock at 28%, PM at 11%, TCoM at 10%, MOF/S/ARDS at 2%, and trauma not otherwise categorized at 5%. Mean age at death increased across the study interval (range, 47-57 years), while mean Injury Severity Score (ISS) decreased (range, 28-35). There was a significant increase in deaths because of TCoM (3.3-20.9%) and PM (6.7-16.4%), while deaths caused by MOF/S/ARDS decreased from 5% to 0% by 2007. Compared with year 2000, the annual adjusted mortality rate decreased consistently starting in 2009, after the 2002 to 2007 adoption of four major trauma practice guidelines. Mortality caused by preexisting medical conditions has increased, while markedly fewer deaths resulted from the complications of injury. Future improvements in outcomes will require

Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

NASA Astrophysics Data System (ADS)

Zhang, Hong

2016-07-01

We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

Medical management of acute radiation syndrome and associated infections in a high-casualty incident.

PubMed

Dainiak, Nicholas

2018-04-01

A high-casualty incident may result in a significant human toll due to the inability of a community to meet the health care demands of the population. A successful medical response requires health care facilities to not only communicate and integrate medical services, meet surge capacity, protect health care workers and implement triage and treatment protocols, but also to provide the venue for clinical management of acute radiation injuries and their associated infections. Today, clinical management is primarily guided by the recommendations of a Consultancy that were made at the World Health Organization (WHO). This international consensus was reached on evidence-based, clinical management of each of the four sub-syndromes that compose acute radiation syndrome (ARS), including the hematopoietic subsyndrome (HS), gastrointestinal subsyndrome (GIS), neurovascular subsyndrome (NVS) and cutaneous subsyndrome (CS). Major findings in studies meeting inclusion criteria for management strategies for HS were that (i) no randomized controlled studies of medical countermeasures have been (or will likely ever be) performed for ARS cases, (ii) the data for management of HS are restricted by the lack of comparator groups, and (iii) reports of countermeasures for management of injury to non-hematopoietic organs are often incompletely described. Here, (i) recommendations made in Geneva are summarized; (ii) the analysis of countermeasures for HS is updated by review of two additional cases and extended to published reports not meeting inclusion criteria; and (iii) guidelines are provided for management of microbial infections based upon patient risk for prolonged immunosuppression.

Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial.

PubMed

Sahebnasagh, Adeleh; Ghasemi, Arash; Akbari, Jafar; Alipour, Abbas; Lashkardoost, Hossein; Ala, Shahram; Salehifar, Ebrahim

2017-11-01

Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area. In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). There was a significant (p < 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively. A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.

Maternal organ donation and acute injuries in surviving children.

PubMed

Redelmeier, Donald A; Woodfine, Jason D; Thiruchelvam, Deva; Scales, Damon C

2014-12-01

The purpose of this study is to test whether maternal deceased organ donation is associated with rates of subsequent acute injuries among surviving children after their mother's death. This is a longitudinal cohort analysis of children linked to mothers who died of a catastrophic brain event in Ontario, Canada, between April 1988 and March 2012. Surviving children were distinguished by whether their mother was an organ donor after death. The primary outcome was an acute injury event in surviving children during the year after their mother's death. Surviving children (n=454) had a total of 293 injury events during the year after their mother's death, equivalent to an average of 65 events per 100 children per year and a significant difference comparing children of mothers who were organ donors to children of mothers who were not organ donors (21 vs 82, P<.001). This difference in subsequent injury rates between groups was equal to a 76% relative reduction in risk (95% confidence interval, 62%-85%). Deceased organ donation was associated with a reduction in excess acute injuries among surviving children after their mother's death. An awareness of this positive association provides some reassurance about deceased organ donation programs. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary.

PubMed

Yildirim, G; Ozsaran, Z; Yalman, D; Kamer, S; Aras, A

2008-01-01

The purpose of this study was to evaluate acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary, and to compare the usefulness and disadvantages of each system. Between February 2001 and February 2003, 107 patients with gynaecologic malignancy who received either radical or djuvant external radiotherapy +/- intracavitary brachytherapy or radiochemotherapy were enrolled in this study. The patients were evaluated before radiotherapy and weekly during radiotherapy for acute morbidity using the RTOG grading system and Franco-Italian glossary. Postradiotherapy evaluation was done one month after radiotherapy and at 3-month intervals thereafter. Median follow-up duration was 17 months. Morbidity was graded and recorded according to each scoring system. Median age was 46 years (range 37-82). Sixty-four patients (59.8%) had endometrial cancer. Radical radiotherapy was applied to 26 patients because of inoperability and 81 patients received postoperative radiotherapy. Biologically effective doses for the bladder, rectum and vagina were 98.39, 103.54 and 121.81, respectively, for late morbidity (BED3); 70.88, 72.84 and 80.92, respectively, for acute morbidity (BED10). According to the RTOG grading system acute morbidity rate for the genitourinary and gastrointestinal systems, and skin were 52.3%, 83.2% and 63.5%, respectively. Late morbidity rate for the bladder, colon-rectum, skin and vagina were 16.8%, 20.6%, 47.7% and 51.4%, respectively. The morbidity rate for the bladder, nonspecific abdominal, hematopoietic system, uterus-vulva-vagina, skin and rectum were 35.4%, 29.9%, 5.6%, 60.8%, 40.1% and 32.7%, respectively using the Franco-Italian glossary. In patients with carcinoma of the vulva--whose treatment fields were wider--acute morbidity rate according to RTOG criteria was higher (p = 0.057); photon energy (6 Mv rather than 1.25 MV) (p = 0.01) and treatment interruption of more than eight days (p

Glutathione in Cancer Cell Death

PubMed Central

Ortega, Angel L.; Mena, Salvador; Estrela, Jose M.

2011-01-01

Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy. PMID:24212662

Biomarkers Investigation for In-Hospital Death in Patients With Stanford Type A Acute Aortic Dissection.

PubMed

Zhang, Ruoxi; Chen, Shuyuan; Zhang, Hui; Wang, Wei; Xing, Jianpang; Wang, Yu; Yu, Bo; Hou, Jingbo

2016-09-28

This retrospective study aimed to investigate the predictive value of biomarkers for in-hospital mortality of patients with Stanford type A acute aortic dissection (AAD).AAD is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year.A total of 67 consecutive Stanford type A AAD patients admitted to hospital were divided into a deceased group and survival group. The baseline information of the patients between two groups was systematically compared, followed by examination of the electrocardiograms (ECG). Based on the follow-up during hospitalization, we investigated the simultaneous assessment of indexes like fragmented QRS complex (fQRS), admission systolic blood pressure (SBP), aortic diameter, surgical management, troponin I (TnI), white blood cell (WBC) count, N-terminal pro-brain natriuretic peptide (NT-proBNP), and D-dimer.The levels of TnI and NT-proBNP, WBC counts, and rate of fQRS (+) in patients of the deceased group were significantly higher than those in the survival group. The male sex (hazard ratio, 10.88; P = 0.001), admission SBP (hazard ratio, 0.98; P = 0.012), NT-proBNP (hazard ratio, 1.00; P = 0.001), and WBC count (hazard ratio, 1.10; P = 0.033) were independently related with in-hospital death. As a single marker, WBC count had the highest sensitivity at 84.6% (specificity 65.9%).Admission SBP, NT-proBNP, and WBC count were potential independent risk factors of in-hospital death in Stanford type A AAD patients. WBC count may be a more accurate predictor of type A AAD than either alone.

Regulation of human glioblastoma cell death by combined treatment of cannabidiol, γ-radiation and small molecule inhibitors of cell signaling pathways

PubMed Central

Ivanov, Vladimir N.; Wu, Jinhua; Hei, Tom K.

2017-01-01

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The challenging problem in cancer treatment is to find a way to upregulate radiosensitivity of GBM while protecting neurons and neural stem/progenitor cells in the brain. The goal of the present study was upregulation of the cytotoxic effect of γ-irradiation in GBM by non-psychotropic and non-toxic cannabinoid, cannabidiol (CBD). We emphasized three main aspects of signaling mechanisms induced by CBD treatment (alone or in combination with γ-irradiation) in human GBM that govern cell death: 1) CBD significantly upregulated the active (phosphorylated) JNK1/2 and MAPK p38 levels with the subsequent downregulation of the active phospho-ERK1/2 and phospho-AKT1 levels. MAPK p38 was one of the main drivers of CBD-induced cell death, while death levels after combined treatment of CBD and radiation were dependent on both MAPK p38 and JNK. Both MAPK p38 and JNK regulate the endogenous TRAIL expression. 2) NF-κB p65-P(Ser536) was not the main target of CBD treatment and this transcription factor was found at high levels in CBD-treated GBM cells. Additional suppression of p65-P(Ser536) levels using specific small molecule inhibitors significantly increased CBD-induced apoptosis. 3) CBD treatment substantially upregulated TNF/TNFR1 and TRAIL/TRAIL-R2 signaling by modulation of both ligand and receptor levels followed by apoptosis. Our results demonstrate that radiation-induced death in GBM could be enhanced by CBD-mediated signaling in concert with its marginal effects for neural stem/progenitor cells and astrocytes. It will allow selecting efficient targets for sensitization of GBM and overcoming cancer therapy-induced severe adverse sequelae. PMID:29088769

[Acute necrotic hemorrhagic pancreatitis. Major complications (author's transl)].

PubMed

Reynaert, M; Bauer, G; Haot, J; Bellassai, J; Trémouroux, J

1981-01-01

Forty-four cases of acute necrotic haemorrhagic pancreatitis are studied. Fourteen cases were treated medically by peritoneal dialysis, 20 were treated surgically of which 16 had been medically treated by peritoneal dialysis. Fifteen died or 34%. Forty-one patients, 93.1% presented 8 major complications on admission and 2 complications were observed during the course of medical treatment (pulmonary shock and high digestive haemorrhage). The post surgical complications are excluded from this study. We report in order of frequency; effusion of the large peritoneal cavity (37 cases : 84%), hypocalcaemia less than or equal to 8 mg% (21 cases : 47.7%), renal insufficiency defined by a creatinaemia greater than or equal 2 mg% (17 cases : 38.6%), state of shock (13 cases : 29.5%), severe neurological disorders (11 cases : 25%), peritoneal haemorrhage (3 cases : 4.5%), disseminated intravascular coagulation (1 case : 2.2%), acute rabdomyolysis (1 case : 2.2%). Certain cases are particularly derogatory : pulmonary shock : 2 cases -- 2 deaths (100%); hypocalcaemia less than or equal to 7 mg/ : 6 cases -- 5 deaths (83.3%); acute tubular necrosis : 8 cases -- 6 deaths (75%); hypocalcaemia less than or equal 8 mg% : 21 cases -- 12 deaths (57.1%); high digestive haemorrhage : 3 cases -- 1 death (33.3%); amber known brown peritoneal effusion : 27 cases -- 12 deaths (44.4%); shock : 13 cases -- 5 deaths (38.5%). When in the same patients, less than 3 complications were present, the mortality rate was 20.8%. If more than 3 signs were observed the mortality rate rose to 53.3%. Except for pulmonary shock, six major complications were needed to give 100% mortality rate.

Survival after acute hemodialysis in Pennsylvania, 2005-2007: a retrospective cohort study.

PubMed

Ramer, Sarah J; Cohen, Elan D; Chang, Chung-Chou H; Unruh, Mark L; Barnato, Amber E

2014-01-01

Little is known about acute hemodialysis in the US. Here we describe predictors of receipt of acute hemodialysis in one state and estimate the marginal impact of acute hemodialysis on survival after accounting for confounding due to illness severity. This is a retrospective cohort study of acute-care hospitalizations in Pennsylvania from October 2005 to December 2007 using data from the Pennsylvania Health Care Cost Containment Council. Exposure variable is acute hemodialysis; dependent variable is survival following acute hemodialysis. We used multivariable logistic regression to determine propensity to receive acute hemodialysis and then, for a Cox proportional hazards model, matched acute hemodialysis and non-acute hemodialysis patients 1∶5 on this propensity. In 2,131,248 admissions of adults without end-stage renal disease, there were 6,657 instances of acute hemodialysis. In analyses adjusted for predicted probability of death upon admission plus other covariates and stratified on age, being male, black, and insured were independent predictors of receipt of acute hemodialysis. One-year post-admission mortality was 43% for those receiving acute hemodialysis, compared to 13% among those not receiving acute hemodialysis. After matching on propensity to receive acute hemodialysis and adjusting for predicted probability of death upon admission, patients who received acute hemodialysis had a higher risk of death than patients who did not over at least 1 year of follow-up (hazard ratio 1·82, 95% confidence interval 1·68-1·97). In a populous US state, receipt of acute hemodialysis varied by age, sex, race, and insurance status even after adjustment for illness severity. In a comparison of patients with similar propensity to receive acute hemodialysis, those who did receive it were less likely to survive than those who did not. These findings raise questions about reasons for lack of benefit.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

PubMed

Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

2017-02-01

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

PubMed

Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

2014-06-01

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

Clinical Risk Factors of Death From Pneumonia in Children with Severe Acute Malnutrition in an Urban Critical Care Ward of Bangladesh

PubMed Central

Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Ashraf, Hasan; Faruque, Abu S. G.; Bardhan, Pradip Kumar; Hossain, Md Iqbal; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Imran, Gazi; Ahmed, Tahmeed

2013-01-01

Background Risks of death are high when children with pneumonia also have severe acute malnutrition (SAM) as a co-morbidity. However, there is limited published information on risk factors of death from pneumonia in SAM children. We evaluated clinically identifiable factors associated with death in under-five children who were hospitalized for the management of pneumonia and SAM. Methods For this unmatched case-control design, SAM children of either sex, aged 0–59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) during April 2011 to July 2012 with radiological pneumonia were studied. The SAM children with pneumonia who had fatal outcome constituted the cases (n = 35), and randomly selected SAM children with pneumonia who survived constituted controls (n = 105). Results The median (inter-quartile range) age (months) was comparable among the cases and the controls [8.0 (4.9, 11.0) vs. 9.7 (5.0, 18.0); p = 0.210)]. In logistic regression analysis, after adjusting for potential confounders, such as vomiting, abnormal mental status, and systolic hypotension (<70 mm of Hg) in absence of dehydration, fatal cases of severely malnourished under-five children with pneumonia were more often hypoxemic (OR = 23.15, 95% CI = 4.38–122.42), had clinical dehydration (some/severe) (OR = 9.48, 95% CI = 2.42–37.19), abdominal distension at admission (OR = 4.41, 95% CI = 1.12–16.52), and received blood transfusion (OR = 5.50, 95% CI = 1.21–24.99) for the management of crystalloid resistant systolic hypotension. Conclusion and Significance We identified hypoxemia, clinical dehydration, and abdominal distension as the independent predictors of death in SAM children with pneumonia. SAM children with pneumonia who required blood transfusion for the management of crystalloid resistant systolic hypotension were also at risk for death. Thus, early identification and

Exploring the Relationship Between Spiritual Well-Being and Death Anxiety in Survivors of Acute Myocardial Infarction: Moderating Role of Sex, Marital Status and Social Support.

PubMed

Soleimani, Mohammad Ali; Sharif, Saeed Pahlevan; Yaghoobzadeh, Ameneh; Yeoh, Ken Kyid; Panarello, Bianca

2018-04-01

Previous empirical studies have shown that both spiritual well-being (SWB) and death anxiety (DA) significantly affect the mental health of patients with acute diseases. In this regard, our paper contributes to the extant literature by scrutinizing the conditional relationship between SWB and DA as well as the various mechanisms underpinning such a relationship in patients with acute myocardial infraction (AMI). A descriptive, correlational methodology was utilized. Our main sample consisted of 300 patients with acute myocardial infraction who were hospitalized in a specialized medical institution in Iran throughout a two-month period (i.e. August-October 2015). Patients completed Spiritual Well-Being Scale (SWBS) and Templer's Death Anxiety Scale (TDAS). Even though our study showed that the relationship between SWB and DA in patients with AMI is non-significant, we found that (1) single patients with higher SWB have lower DA, (2) single patients with higher SWB as well as social support have significantly lower DA, and (3) for single men/men without social support, there is a negative relationship between SWB and DA. The relationship between SWB and DA is influenced by factors such as sex, marital status and social support. In addition, the specific nature of this relationship (i.e. strength and sign) is dependent upon the sociodemographic characteristics of patients as well as other contextual influences. Result revealed that although relationship between SWB and DA is non-significant, this is influenced by factors such as sex and social support. In addition, the specific nature of this relationship (i.e. strength and sign) is dependent upon the sociodemographic characteristics of patients as well as other contextual influences.

Sudden death in eating disorders

PubMed Central

Jáuregui-Garrido, Beatriz; Jáuregui-Lobera, Ignacio

2012-01-01

Eating disorders are usually associated with an increased risk of premature death with a wide range of rates and causes of mortality. “Sudden death” has been defined as the abrupt and unexpected occurrence of fatality for which no satisfactory explanation of the cause can be ascertained. In many cases of sudden death, autopsies do not clarify the main cause. Cardiovascular complications are usually involved in these deaths. The purpose of this review was to report an update of the existing literature data on the main findings with respect to sudden death in eating disorders by means of a search conducted in PubMed. The most relevant conclusion of this review seems to be that the main causes of sudden death in eating disorders are those related to cardiovascular complications. The predictive value of the increased QT interval dispersion as a marker of sudden acute ventricular arrhythmia and death has been demonstrated. Eating disorder patients with severe cardiovascular symptoms should be hospitalized. In general, with respect to sudden death in eating disorders, some findings (eg, long-term eating disorders, chronic hypokalemia, chronically low plasma albumin, and QT intervals >600 milliseconds) must be taken into account, and it must be highlighted that during refeeding, the adverse effects of hypophosphatemia include cardiac failure. Monitoring vital signs and performing electrocardiograms and serial measurements of plasma potassium are relevant during the treatment of eating disorder patients. PMID:22393299

Singlet Oxygen-Induced Membrane Disruption and Serpin-Protease Balance in Vacuolar-Driven Cell Death1[OPEN

PubMed Central

Carmieli, Raanan; Mor, Avishai; Fluhr, Robert

2016-01-01

Singlet oxygen plays a role in cellular stress either by providing direct toxicity or through signaling to initiate death programs. It was therefore of interest to examine cell death, as occurs in Arabidopsis, due to differentially localized singlet oxygen photosensitizers. The photosensitizers rose bengal (RB) and acridine orange (AO) were localized to the plasmalemma and vacuole, respectively. Their photoactivation led to cell death as measured by ion leakage. Cell death could be inhibited by the singlet oxygen scavenger histidine in treatments with AO but not with RB. In the case of AO treatment, the vacuolar membrane was observed to disintegrate. Concomitantly, a complex was formed between a vacuolar cell-death protease, RESPONSIVE TO DESSICATION-21 and its cognate cytoplasmic protease inhibitor ATSERPIN1. In the case of RB treatment, the tonoplast remained intact and no complex was formed. Over-expression of AtSerpin1 repressed cell death, only under AO photodynamic treatment. Interestingly, acute water stress showed accumulation of singlet oxygen as determined by fluorescence of Singlet Oxygen Sensor Green, by electron paramagnetic resonance spectroscopy and the induction of singlet oxygen marker genes. Cell death by acute water stress was inhibited by the singlet oxygen scavenger histidine and was accompanied by vacuolar collapse and the appearance of serpin-protease complex. Over-expression of AtSerpin1 also attenuated cell death under this mode of cell stress. Thus, acute water stress damage shows parallels to vacuole-mediated cell death where the generation of singlet oxygen may play a role. PMID:26884487

Impact of Experiencing Acute Coronary Syndrome Prior to Open Heart Surgery on Psychiatric Status.

PubMed

Yüksel, Volkan; Gorgulu, Yasemin; Cinar, Rugul Kose; Huseyin, Serhat; Sonmez, Mehmet Bulent; Canbaz, Suat

2016-01-01

The incidence of depression and anxiety is higher in patients with acute coronary syndrome. The aim of this study is to determine whether experiencing acute coronary syndrome prior to open heart surgery affects patients in terms of depression, hopelessness, anxiety, fear of death and quality of life. The study included 63 patients who underwent coronary bypass surgery between January 2015 and January 2016. The patients were divided into two groups: those diagnosed after acute coronary syndrome (Group 1) and those diagnosed without acute coronary syndrome (Group 2). Beck depression scale, Beck hopelessness scale, Templer death anxiety scale and death depression scale, State-Trait anxiety inventory and WHOQOL-Bref quality of life scale were applied. There was no significant difference between the two groups in terms of the total score obtained from Beck depression scale, Beck hopelessness scale - future-related emotions, loss of motivation, future-related expectations subgroups, death anxiety scale, the death depression scale, State-Trait Anxiety Inventory - social and environmental subgroups. The mental quality of life sub-scores of group 2 were significantly higher. The patients in both groups were found to be depressed and hopeless about the future. Anxiety levels were found to be significantly higher in all of the patients in both groups. Acute coronary syndrome before coronary artery bypass surgery impairs more the quality of life in mental terms. But unexpectedly there are no differences in terms of depression, hopelessness, anxiety and fear of death.

Cannabis, possible cardiac deaths and the coroner in Ireland.

PubMed

Tormey, W P

2012-12-01

The elevated risk of triggering a myocardial infarction by smoking cannabis is limited to the first 2 h after smoking. To examine the possible role of cannabis in cardiac deaths. CASES AND RESULTS: From 3,193 coroners' cases over 2 years, there were 13 cases where the clinical information was compatible with a primary cardiac cause of death. An inquest was held in three cases. Myocardial infarction was the primary cause of death in 54%. Other causes were sudden adult death syndrome, sudden death in epilepsy, and poisoning by alcohol and diazepam. Cannabis was mentioned once only on a death certificate, but not as a cause of death. Blood delta9-tetrahydrocannabinol-carboxylic acid was recorded in one case and in no case was plasma tetrahydrocannabinol (THC) measured. To attribute sudden cardiac death to cannabis, plasma THC should be measured in the toxicology screen in coroners' cases where urine cannabinoids are positive. A positive urine cannabinoids immunoassay alone is insufficient evidence in the linkage of acute cardiac death and cannabis.

Deaths from occlusive arterial disease in renal allograft recipients.

PubMed

Ibels, L S; Stewart, J H; Mahony, J F; Sheil, A G

1974-08-31

In a series of 325 recipients of cadaveric renal transplants sudden occlusive arterial disease was found to be responsible for 12% of deaths. Acute myocardial infarction (9%) occurred 25 times more than expected in the normal population and cerebral thrombosis (3%) 300 times more. The greatest loss was in the initial three-month period after transplantation. Patients with renal failure due to essential hypertension were especially at risk, accounting for six of the 12 deaths.

Principals Of Radiation Toxicology: Important Aspects.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

“All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” Paracelsus Key Words: Radiation Toxins (RT), Radiation Toxicants (RTc), Radiation Poisons (RP), Radiation Exposure (RE), Radiation Toxicology is the science about radiation poisons. [D.Popov et al. 2012,J.Zhou et al. 2007,] Radiation Toxins is a specific proteins with high enzymatic activity produced by living irradiated mammals. [D.Popov et al. 2012,] Radiation Toxicants is a substances that produce radiomimetics effects, adverse biological effects which specific for radiation. [D.Popov et al. 2012,] Radiation Toxic agent is specific proteins that can produce pathological biological effects specific for physical form of radiation.[D.Popov et al. 1990,2012,V. Maliev 2007] Different Toxic Substances isolated from cells or from blood or lymph circulation. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007,] Radiation Toxins may affects many organs or specific organ, tissue, specific group of cells. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007] For example: Radiation Toxins could induce collective toxic clinical states to include: systemic inflammatory response syndrome (SIRS),toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [T. Azizova et al. 2005, Konchalovsky et al., 2005, D. Popov et al 2012] However, Radiation Toxins could induce specific injury of organs or tissue and induce Acute Radiation Syndromes such as Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Hematopoietic Syndrome, Acute Radiation GastroIntestinal Syndrome. [ D.Popov et al. 1990, 2012, V. Maliev et al. 2007] Radiation Toxins correlates with Radiation Exposure and the dose-response relationship is a fundamental and essential concept in classic Toxicology and Radiation Toxicology.[ D.Popov et al

Models of CNS radiation damage during space flight

NASA Astrophysics Data System (ADS)

Hopewell, J. W.

1994-10-01

The primary structural and functional arrangement of the different cell types within the CNS are reviewed. This was undertaken with a view to providing a better understanding of the complex interrelationships that may contribute to the pathogenesis of lesions in this tissue after exposure to ionizing radiation. The spectrum of possible CNS radiation-induced syndromes are discussed although not all have an immediate relevance to exposure during space flight. The specific characteristics of the lesions observed would appear to be dose related. Very high doses may produce an acute CNS syndrome that can cause death. Of the delayed lesions, selective coagulation necrosis of white matter and a later appearing vascular microangiopathy, have been reported in patients after cancer therapy doses. Lower doses, perhaps very low doses, may produce a delayed generalised CNS atrophy; this effect and the probability of the induction of CNS tumors could potentially have the greatest significance for space flight.

Acute brain herniation from lead toxicity.

PubMed

Berkowitz, Sheldon; Tarrago, Rod

2006-12-01

A 4-year-old black boy was admitted to the hospital with vomiting, low-grade fever, and dehydration that were thought to be caused by viral gastroenteritis. He proceeded over the next 12 hours to rapidly deteriorate with brain herniation leading to brain death. The ultimate cause of death was found to be acute lead intoxication from a swallowed foreign body.

No detectable bioeffects following acute exposure to high peak power ultra-wide band electromagnetic radiation in rats.

PubMed

Walters, T J; Mason, P A; Sherry, C J; Steffen, C; Merritt, J H

1995-06-01

A wide range assessment of the possible bioeffects of an acute exposure to high peak power ultra-wide band (UWB) electromagnetic radiation was performed in rats. The UWB-exposure consisted of 2 min of pulsed (frequency: 60 Hz, pulse width: 5-10 ns) UWB (bandwidth: 0.25-2.50 GHz) electromagnetic radiation. Rats were examined using one of the following: 1) a functional observational battery (FOB); 2) a swimming performance test; 3) a complete panel of blood chemistries; or 4) determination of the expression of the c-fos protein in immunohistologically-stained sections of the brain. No significant differences were found between UWB- or sham-exposed rats on any of the measured parameters.

Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome-A Concise Review.

PubMed

Hofer, Michal; Hoferová, Zuzana; Depeš, Daniel; Falk, Martin

2017-05-19

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

Acute radiation sickness amelioration analysis. Technical report, 20 July 1990-19 July 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, S.I.; Feister, A.J.; Bareis, D.L.

1994-05-01

Three tasks were conducted under the Acute Radiation Sickness Amelioration Analysis in support of the Defense Nuclear Agency (DNA) and NATO Army Armaments Group (NAAG) Project Group 29 (PG-29) on drugs for the prevention of radiation-induced nausea and vomiting: (1) documents were collected and entered into a data base, (2) data reviews and analyses were performed, and (3) PG-29 and Triservice meetings involving anti-emetic drug development were supported and documented. Approximately 2000 documents were collected, with 1424 complete bibliographic citations entered into a WordPerfect 5.1 data base. Eight reviews and analyses addressing different aspects of the safety and efficacy ofmore » the candidate anti-emetic drugs ondansetron and granistron were prepared. Support was provided for seven international PG-29 meetings and two U.S. Triservice meetings in which the efforts of PG-29 were discussed. These tasks have enabled the DNA and PG-29 to make good progress toward the goal of recommending a serotonin type-3 (5-HT3) receptor antagonist anti-emetic drug for use in military personnel.« less

Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death.

PubMed

Nagaraja, Pramod; Roberts, Gareth W; Stephens, Michael; Horvath, Szabolcs; Fialova, Jana; Chavez, Rafael; Asderakis, Argiris; Kaposztas, Zsolt

2012-12-27

Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.

Survival after Acute Hemodialysis in Pennsylvania, 2005–2007: A Retrospective Cohort Study

PubMed Central

Ramer, Sarah J.; Cohen, Elan D.; Chang, Chung-Chou H.; Unruh, Mark L.; Barnato, Amber E.

2014-01-01

Background Little is known about acute hemodialysis in the US. Here we describe predictors of receipt of acute hemodialysis in one state and estimate the marginal impact of acute hemodialysis on survival after accounting for confounding due to illness severity. Materials and Methods This is a retrospective cohort study of acute-care hospitalizations in Pennsylvania from October 2005 to December 2007 using data from the Pennsylvania Health Care Cost Containment Council. Exposure variable is acute hemodialysis; dependent variable is survival following acute hemodialysis. We used multivariable logistic regression to determine propensity to receive acute hemodialysis and then, for a Cox proportional hazards model, matched acute hemodialysis and non-acute hemodialysis patients 1∶5 on this propensity. Results In 2,131,248 admissions of adults without end-stage renal disease, there were 6,657 instances of acute hemodialysis. In analyses adjusted for predicted probability of death upon admission plus other covariates and stratified on age, being male, black, and insured were independent predictors of receipt of acute hemodialysis. One-year post-admission mortality was 43% for those receiving acute hemodialysis, compared to 13% among those not receiving acute hemodialysis. After matching on propensity to receive acute hemodialysis and adjusting for predicted probability of death upon admission, patients who received acute hemodialysis had a higher risk of death than patients who did not over at least 1 year of follow-up (hazard ratio 1·82, 95% confidence interval 1·68–1·97). Conclusions In a populous US state, receipt of acute hemodialysis varied by age, sex, race, and insurance status even after adjustment for illness severity. In a comparison of patients with similar propensity to receive acute hemodialysis, those who did receive it were less likely to survive than those who did not. These findings raise questions about reasons for lack of benefit. PMID:25141028

[The analysis of the low and medium molecular weight substances for differential diagnostics of deaths from acute small-focal myocardial infarction and other forms of cardiac pathology].

PubMed

Edelev, N S; Obuhova, L M; Edelev, I S; Katirkina, A A

The objective of the present study was to analyze the possibilities for the use of the low and medium molecular weight substances for differential diagnostics of deaths from acute small-focal myocardial infarction and other forms of cardiac pathology. We determined the amount of the low and medium molecular weight substances in the urine obtained from the subjects who had died as a result of chronic coronary heart disease, acute myocardial infarction, and alcoholic cardiomyopathy. The levels of the low and medium molecular weight substances in the urine were measured by the method of N.Ya. Malakhov in the modification of T.V. Kopytova [5]. The study has demonstrated the appearance of the products of cardiomyocyte degradation (giving rise to a peak at a wavelength of 278 nm) in the fraction of the low and medium molecular weight substances of the urine from the patients suffering from acute small-focal myocardial infarction and some other forms of cardiac pathology.

Death from Barotrauma Due to Compressed Air: A Medico-legal Analysis.

PubMed

Giugliano, Pasquale; Massoni, Francesco; Crisci, Antonello; Ricci, Serafino

2016-11-01

Lesions of the digestive tract due to barotrauma resulting from compressed air application are not common, are rarely lethal, and largely affect the sigmoid and descending colon. Moreover, their pathogenic mechanism is a topic of discussion because these lesions have multiple characteristics. Here, the authors describe an autoptic case of death from lesions of the ascending and transverse segments, with perforations and bleeding suffusions as well as ischemic areas covered the colonic wall that was extremely thinned, congested, and hemorrhagic, with considerable flattening leading to disappearance of the mucosal folds and with numerous petechial hemorrhages. The pathological framework of lung congestion made it possible to identify the mechanism responsible for this death as depletion of the heart's pumping function, which contributed significantly to the acute respiratory failure due to respiratory distress as well as to reduced mobility of the diaphragm due to intestinal distension. Acute heart failure played an important role in this death. © 2016 American Academy of Forensic Sciences.

Does smoking affect hospital use before death? A comparison of ever- and never-smokers in the last years of life.

PubMed

McGhee, Sarah M; Schooling, C Mary; Wong, Lai Chin; Leung, Gabriel M; Ho, Lai Ming; Thomas, G Neil; Ho, Daniel S Y; Lam, Tai Hing; Hedley, Anthony J

2008-06-01

Given the apparent greater use of health care services by smokers and predictions of higher costs for a never-smoking population, we aimed in this study to determine whether the acute hospital costs in the last years of life of never- and ever-smokers differed before death using a database of the decedents in 1 year in Hong Kong. To compare the acute hospital use of ever- and never-smoker decedents. The data on cause of death, personal characteristics, and public hospital discharges were linked for all decedents in 1998 in Hong Kong. The incidence rate ratio was used to compare, for ever- and never-smokers, the number of days spent in an acute hospital over the prior 7 years. Analyses were done using specific and all cause mortality, adjusted for sex, lifestyle factors, and life expectancy. Compared with never-smokers who died of the same condition, ever-smokers who died of chronic obstructive pulmonary disease used 28% more acute hospital bed days and those dying of smoking-related cancer 9% fewer. These differences cancelled out over the case-mix of deaths with no net difference in acute bed day use by smoking status for all-cause mortality. There was no difference in acute hospital bed days in the last years of life of ever- and never-smokers but some differences by cause of death. Reducing smoking in this population will not increase acute hospital use.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

Radiation-induced radioresistance of mammals and risk assessment

NASA Astrophysics Data System (ADS)

Smirnova, O.; Yonezawa, M.

It is shown experimentally that a preliminary low dose exposure can induce radioresistance in mice in two (early and late) periods after preirradiation. The manifestation of such effects is reduced mortality of pre-exposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic subsyndrome of the acute radiation syndrome. Therefore, proceeding from the radiobiological concept of the critical system, the theoretical investigation of the influence of preirradiation on mammalian radiosensitivity is conducted by making use of mathematical models of the vital body system, hematopoiesis. Modeling results make it possible to elucidate the mechanisms of the radioprotection effect of low level priming irradiation on mammals. Specifically, the state of acquired radioresistance in mice is caused by reduced radiosensitivity of lymphopoietic and thrombocytopoietic systems in the early period and by reduced radiosensitivity of granulocytopoietic system in the late period after preirradiation. It is important to emphasize that the evaluations of the duration of the early and late periods of postirradiation radioresistance in mice, carried out on the basis of the modeling and experimental investigations, practically coincide. All this demonstrates the effectiveness of joint modeling and experimental methods in studies and predictions of modification effects of preirradiation on mammalian radiosensitivity. The results obtained show the importance of accounting such effects in radiation risk assessments for cosmonauts and astronauts on long-term missions.

γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status.

PubMed

Singh, Vijay K; Hauer-Jensen, Martin

2016-05-03

The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication.

γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status

PubMed Central

Singh, Vijay K.; Hauer-Jensen, Martin

2016-01-01

The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication. PMID:27153057

Beatquency domain and machine learning improve prediction of cardiovascular death after acute coronary syndrome.

PubMed

Liu, Yun; Scirica, Benjamin M; Stultz, Collin M; Guttag, John V

2016-10-06

Frequency domain measures of heart rate variability (HRV) are associated with adverse events after a myocardial infarction. However, patterns in the traditional frequency domain (measured in Hz, or cycles per second) may capture different cardiac phenomena at different heart rates. An alternative is to consider frequency with respect to heartbeats, or beatquency. We compared the use of frequency and beatquency domains to predict patient risk after an acute coronary syndrome. We then determined whether machine learning could further improve the predictive performance. We first evaluated the use of pre-defined frequency and beatquency bands in a clinical trial dataset (N = 2302) for the HRV risk measure LF/HF (the ratio of low frequency to high frequency power). Relative to frequency, beatquency improved the ability of LF/HF to predict cardiovascular death within one year (Area Under the Curve, or AUC, of 0.730 vs. 0.704, p < 0.001). Next, we used machine learning to learn frequency and beatquency bands with optimal predictive power, which further improved the AUC for beatquency to 0.753 (p < 0.001), but not for frequency. Results in additional validation datasets (N = 2255 and N = 765) were similar. Our results suggest that beatquency and machine learning provide valuable tools in physiological studies of HRV.

Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia.

PubMed

Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

2015-06-01

Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m(2) in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3-4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). Copyright© Ferrata Storti Foundation.

Acute lower gastrointestinal bleeding.

PubMed

Jocić, Tatiana; Latinović Bošnjak, Olgica; Hadnađev, Ljiljana; Damjanov, Dragomir; Savić, Željka; Orlić, Tihomir

2014-01-01

Acute lower gastrointestinal bleeding accounts for approximately 20% of all acute gastrointestinal hemorrhages, and they are the most common urgent cases in gastroenterology. The aim of this study was to determine the most common etiology, efficacy in diagnostics and therapy, and the outcome in patients with acute lower gastrointestinal bleeding. Data were collected from the medical records of 86 patients who had been hospitalized for acute lower gastrointestinal bleeding in 2009 at the Ward of Gastroenterology and Hepatology, Clinical Centre of Vojvodina. The average age of the patients was 70.4 years (ranging from 37 to 88), and the largest number of patients 41/86 (47.7%) were between the ages 71 and 80. Colon diverticulosis was the most common cause of bleeding, and it occurred in 21 patients from the study sample (24.4%), and the other causes were malignant tumors (12/86, i.e. 13.9%), polyps (10/86, i.e. 11.6%), anorectal diseases (7/86, i.e. 8.3%/0) and colitis (8/86, i.e. 9.3%). No diagnostic procedures were performed in 15 patients (17.4%) due to their poor medical condition and comorbidities. The total mortality rate was 6/86 (6.9%), and the largest number of deaths occurred (5/86 i.e. 5.8%) due to a multisystem organ failure and underlying diseases which were not associated with acute lower gastrointestinal bleeding. Uncontrolled bleeding was the cause of death in only 1 patient (1.2%). Acute lower gastrointestinal bleeding is most commonly found in the older population, whose age, comorbidities, and ongoing therapy have impact on bleeding lesions, diagnostic and therapeutic modalities and the outcomes of bleeding. Endoscopic procedures are still the gold standard in diagnostics.

Survival of Mice with Gastrointestinal Acute Radiation Syndrome through Control of Bacterial Translocation.

PubMed

Suzuki, Fujio; Loucas, Bradford D; Ito, Ichiaki; Asai, Akira; Suzuki, Sumihiro; Kobayashi, Makiko

2018-07-01

Macrophages (Mϕ) with the M2b phenotype (Pheno2b-Mϕ) in bacterial translocation sites have been described as cells responsible for the increased susceptibility of mice with gastrointestinal acute radiation syndrome to sepsis caused by gut bacteria. In this study, we tried to reduce the mortality of mice exposed to 7-10 Gy of gamma rays by controlling Pheno2b-Mϕ polarization in bacterial translocation sites. MicroRNA-222 was induced in association with gamma irradiation. Pheno2b-Mϕ polarization was promoted and maintained in gamma-irradiated mice through the reduction of a long noncoding RNA growth arrest-specific transcript 5 (a CCL1 gene silencer) influenced by this microRNA. Therefore, the host resistance of 7-9-Gy gamma-irradiated mice to sepsis caused by bacterial translocation was improved after treatment with CCL1 antisense oligodeoxynucleotide. However, the mortality of 10-Gy gamma-irradiated mice was not alleviated by this treatment. The crypts and villi in the ileum of 10-Gy gamma-irradiated mice were severely damaged, but these were markedly improved after transplantation of intestinal lineage cells differentiated from murine embryonic stem cells. All 10-Gy gamma-irradiated mice given both of the oligodeoxynucleotide and intestinal lineage cells survived, whereas all of the same mice given either of them died. These results indicate that high mortality rates of mice irradiated with 7-10 Gy of gamma rays are reducible by depleting CCL1 in combination with the intestinal lineage cell transplantation. These findings support the novel therapeutic possibility of victims who have gastrointestinal acute radiation syndrome for the reduction of their high mortality rates. Copyright © 2018 by The American Association of Immunologists, Inc.

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

CRM1 protein-mediated regulation of nuclear clusterin (nCLU), an ionizing radiation-stimulated, Bax-dependent pro-death factor.

PubMed

Leskov, Konstantin S; Araki, Shinako; Lavik, John-Paul; Gomez, Jose A; Gama, Vivian; Gonos, Efstathios S; Trougakos, Ioannis P; Matsuyama, Shigemi; Boothman, David A

2011-11-18

Expression of the clusterin (CLU) gene results in the synthesis of a conventional secretory isoform set (pre- and mature secretory clusterin proteins, psCLU/sCLU), as well as another set of intracellular isoforms, appearing in the cytoplasm (pre-nuclear CLU, pnCLU) and in the nucleus as an ∼55-kDa mature nuclear clusterin (nCLU) form. These two isoform sets have opposing cell functions: pro-survival and pro-death, respectively. Although much is known about the regulation and function of sCLU as a pro-survival factor, the regulation and function of endogenous nCLU in cell death are relatively unexplored. Here, we show that depletion of endogenous nCLU protein using siRNA specific to its truncated mRNA increased clonogenic survival of ionizing radiation (IR)-exposed cells. nCLU-mediated apoptosis was Bax-dependent, and lethality correlated with accumulation of mature nCLU protein. nCLU accumulation was regulated by CRM1 because binding between CRM1 and nCLU proteins was significantly diminished by leptomycin B (LMB), and nuclear levels of nCLU protein were significantly enhanced by LMB and IR co-treatment. Moreover, LMB treatment significantly enhanced IR-induced nCLU-mediated cell death responses. Importantly, bax(-/-) and bax(-/-)/bak(-/-) double knock-out cells were resistant to nCLU-mediated cell death, whereas bak(-/-) or wild-type bax(+/+)/bak(+/+) cells were hypersensitive. The regulation of nCLU by CRM1 nuclear export/import may explain recent clinical results showing that highly malignant tumors have lost the ability to accumulate nCLU levels, thereby avoiding growth inhibition and cell death.

Enhanced UV-B radiation during pupal stage reduce body mass and fat content, while increasing deformities, mortality and cell death in female adults of solitary bee Osmia bicornis.

PubMed

Wasielewski, Oskar; Wojciechowicz, Tatiana; Giejdasz, Karol; Krishnan, Natraj

2015-08-01

The effects of enhanced UV-B radiation on the oogenesis and morpho-anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m(2) /d) of artificial UV-B. Our experiments revealed that enhanced UV-B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV-B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV-B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV-B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV-B poorly induced the cell death during early development. However, exposure to moderate UV-B dose increased programmed cell death. In females treated with the highest dose of UV-B the vast majority of germarium cells were TUNEL-positive. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Acoustic radiation force impulse shear wave elastography (ARFI) of acute and chronic pancreatitis and pancreatic tumor.

PubMed

Goertz, Ruediger S; Schuderer, Johanna; Strobel, Deike; Pfeifer, Lukas; Neurath, Markus F; Wildner, Dane

2016-12-01

Acoustic Radiation Force Impulse (ARFI) elastography evaluates tissue stiffness non-invasively and has rarely been applied to pancreas examinations so far. In a prospective and retrospective analysis, ARFI shear wave velocities of healthy parenchyma, pancreatic lipomatosis, acute and chronic pancreatitis, adenocarcinoma and neuroendocrine tumor (NET) of the pancreas were evaluated and compared. In 95 patients ARFI elastography of the pancreatic head, and also of the tail for a specific group, was analysed retrospectively. Additionally, prospectively in 100 patients ARFI was performed in the head and tail of the pancreas. A total of 195 patients were included in the study. Healthy parenchyma (n=21) and lipomatosis (n=30) showed similar shear wave velocities of about 1.3m/s. Acute pancreatitis (n=35), chronic pancreatitis (n=53) and adenocarcinoma (n=52) showed consecutively increasing ARFI values, respectively. NET (n=4) revealed the highest shear wave velocities amounting to 3.62m/s. ARFI elastography showed relevant differences between acute pancreatitis and chronic pancreatitis or adenocarcinoma. With a cut-off value of 1.74m/s for the diagnosis of a malignant disease the sensitivity was 91.1% whereas the specificity amounted to 60.4%. ARFI shear wave velocities present differences in various pathologies of the pancreas. Acute and chronic pancreatitis as well as neoplastic lesions show high ARFI values. Very high elasticity values may indicate malignant disease of the pancreas. However, there is a considerable overlap between the entities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute and Fractionated Exposure to High-LET 56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis

PubMed Central

Rivera, Phillip D.; Shih, Hung-Ying; LeBlanc, Junie A.; Cole, Mara G.; Amaral, Wellington Z.; Mukherjee, Shibani; Zhang, Shichuan; Lucero, Melanie J.; DeCarolis, Nathan A.; Chen, Benjamin P. C.; Eisch, Amelia J.

2014-01-01

Astronauts on multi-year interplanetary missions will be exposed to a low, chronic dose of high-energy, high-charge particles. Studies in rodents show acute, nonfractionated exposure to these particles causes brain changes such as fewer adult-generated hippocampal neurons and stem cells that may be detrimental to cognition and mood regulation and thus compromise mission success. However, the influence of a low, chronic dose of these particles on neurogenesis and stem cells is unknown. To examine the influence of galactic cosmic radiation on neurogenesis, adult-generated stem and progenitor cells in Nestin-CreERT2/R26R-YFP transgenic mice were inducibly labeled to allow fate tracking. Mice were then sham exposed or given one acute 100 cGy 56Fe-particle exposure or five fractionated 20 cGy 56Fe-particle exposures. Adult-generated hippocampal neurons and stem cells were quantified 24 h or 3 months later. Both acute and fractionated exposure decreased the amount of proliferating cells and immature neurons relative to sham exposure. Unexpectedly, neither acute nor fractionated exposure decreased the number of adult neural stem cells relative to sham expsoure. Our findings show that single and fractionated exposures of 56Fe-particle irradiation are similarly detrimental to adult-generated neurons. Implications for future missions and ground-based studies in space radiation are discussed. PMID:24320054

[Modern condition and prospects of improvement of the specialized medical care for acute bone marrow syndrome of radiation etiology].

PubMed

Khalimov, Iu Sh; Grebeniuk, A N; Legeza, V I; Karamullin, M A; Salukhov, V V

2013-01-01

It is shown, that tactics of treatment of acute marrow failure of radiant etiology is based, first of all, on measures of supporting, replaceable and stimulating therapy. The modern means, used for prophylactic and treatment of infectious complications, are resulted. Opportunities and restrictions of transfusion of donor thrombocytes and granulocytes, erythrocytes and chilled plasma are described. Therapeutic efficiency of transplantation of a bone marrow, cells of embryonic liver and stem cells of peripheral or umbilical cord blood is analyzed. It is shown, that the greatest prospects in perfection of the specialized medical aid at acute radiation syndrome are connected to complex application of interleukin-1beta, interleukin-3, granulocyte or granulocyte/macrophage colony stimulated factor, thrombopoietin and others cytokines.

Combined exposure to simulated microgravity and acute or chronic radiation reduces neuronal network integrity and cell survival

NASA Astrophysics Data System (ADS)

Benotmane, Rafi

During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. This study aimed at assessing the effect of these combined conditions on neuronal network density, cell morphology and survival, using well-connected mouse cortical neuron cultures. To this end, neurons were exposed to acute low and high doses of low LET (X-rays) radiation or to chronic low dose-rate of high LET neutron irradiation (Californium-252), under the simulated microgravity generated by the Random Positioning Machine (RPM, Dutch space). High content image analysis of cortical neurons positive for the neuronal marker βIII-tubulin unveiled a reduced neuronal network integrity and connectivity, and an altered cell morphology after exposure to acute/chronic radiation or to simulated microgravity. Additionally, in both conditions, a defect in DNA-repair efficiency was revealed by an increased number of γH2AX-positive foci, as well as an increased number of Annexin V-positive apoptotic neurons. Of interest, when combining both simulated space conditions, we noted a synergistic effect on neuronal network density, neuronal morphology, cell survival and DNA repair. Furthermore, these observations are in agreement with preliminary gene expression data, revealing modulations in cytoskeletal and apoptosis-related genes after exposure to simulated microgravity. In conclusion, the observed in vitro changes in neuronal network integrity and cell survival induced by space simulated conditions provide us with mechanistic understanding to evaluate health risks and the development of countermeasures to prevent neurological disorders in astronauts over long-term space travels. Acknowledgements: This work is supported partly by the EU-FP7 projects CEREBRAD (n° 295552)

Rapid Prediction of Hematologic Acute Radiation Syndrome in Radiation Injury Patients Using Peripheral Blood Cell Counts.

PubMed

Port, M; Pieper, B; Knie, T; Dörr, H; Ganser, A; Graessle, D; Meineke, V; Abend, M

2017-08-01

Rapid clinical triage of radiation injury patients is essential for determining appropriate diagnostic and therapeutic interventions. We examined the utility of blood cell counts (BCCs) in the first three days postirradiation to predict clinical outcome, specifically for hematologic acute radiation syndrome (HARS). We analyzed BCC test samples from radiation accident victims (n = 135) along with their clinical outcome HARS severity scores (H1-4) using the System for Evaluation and Archiving of Radiation Accidents based on Case Histories (SEARCH) database. Data from nonirradiated individuals (H0, n = 132) were collected from an outpatient facility. We created binary categories for severity scores, i.e., 1 (H0 vs. H1-4), 2 (H0-1 vs. H2-4) and 3 (H0-2 vs. H3-4), to assess the discrimination ability of BCCs using unconditional logistic regression analysis. The test sample contained 454 BCCs from 267 individuals. We validated the discrimination ability on a second independent group comprised of 275 BCCs from 252 individuals originating from SEARCH (HARS 1-4), an outpatient facility (H0) and hospitals (e.g., leukemia patients, H4). Individuals with a score of H0 were easily separated from exposed individuals based on developing lymphopenia and granulocytosis. The separation of H0 and H1-4 became more prominent with increasing hematologic severity scores and time. On day 1, lymphocyte counts were most predictive for discriminating binary categories, followed by granulocytes and thrombocytes. For days 2 and 3, an almost complete separation was achieved when BCCs from different days were combined, supporting the measurement of sequential BCC. We found an almost complete discrimination of H0 vs. irradiated individuals during model validation (negative predictive value, NPV > 94%) for all three days, while the correct prediction of exposed individuals increased from day 1 (positive predictive value, PPV 78-89%) to day 3 (PPV > 90%). The models were unable to provide

THE EFFECT OF IONIZING RADIATION OF THE PROGENY IN IRRADIATION OF ANIMALS DURING THE LAST DAYS OF PREGNANCY (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuikova, E.A.; Chaikovskaya, M.Ya.; Petrosian, S.L.

1959-09-01

The result of investigations demonstrated that a total single irradiation of dogs in a dose of 500 r during the last days of pregnancy leads to the development of acute radiation sickness in newborn puppies and causes their death soon after birth. Radiation sickness in newborn puppies as distinct from adult animals in a number of cases was associated with necrotic lesions of the urinary bladder, atelectasis of the lungs, and cerebral edema. Hemodynamic disturbances of the central nervous system play an important role in the appearance of atelectasis and of the cerebral edema. The course of radiation sickness inmore » dogs irradiated during the last days of pregnancy was comparatively mild. Reaction of peripheral blood to irradiation was short and of peculiar nature. (auth)« less

Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.

PubMed

Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

2017-04-01

Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.

Apoptotic cell death during Drosophila oogenesis is differentially increased by electromagnetic radiation depending on modulation, intensity and duration of exposure.

PubMed

Sagioglou, Niki E; Manta, Areti K; Giannarakis, Ioannis K; Skouroliakou, Aikaterini S; Margaritis, Lukas H

2016-01-01

Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary.

Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease.

PubMed

Pello Lázaro, Ana María; Cristóbal, Carmen; Franco-Peláez, Juan Antonio; Tarín, Nieves; Aceña, Álvaro; Carda, Rocío; Huelmos, Ana; Martín-Mariscal, María Luisa; Fuentes-Antras, Jesús; Martínez-Millá, Juan; Alonso, Joaquín; Lorenzo, Óscar; Egido, Jesús; López-Bescós, Lorenzo; Tuñón, José

2017-01-01

Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD. We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death. Patients on PPIs were older [62.0 (53.0-73.0) vs. 58.0 (50.0-70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244-4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628-20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results. In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings.

Functional genomics of chlorine-induced acute lung injury in mice.

PubMed

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

2010-07-01

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.

Scenario of a dirty bomb in an urban environment and acute management of radiation poisoning and injuries.

PubMed

Chin, F K C

2007-10-01

In the new security environment, there is a clear and present danger of terrorists using non-conventional weapons to inflict maximum psychological and economic damage on their targets. This article examines two scenarios of radiation contamination and injury, one accidental in nature leading to environmental contamination, and another of deliberate intent resulting in injury and death. This article also discusses the management of injury from radiological dispersion devices or dirty bombs, with emphasis on the immediate aftermath as well as strategy recommendations.

Dementia in the acute hospital: the prevalence and clinical outcomes of acutely unwell patients with dementia.

PubMed

Briggs, R; Dyer, A; Nabeel, S; Collins, R; Doherty, J; Coughlan, T; O'Neill, D; Kennelly, S P

2017-01-01

Studies have demonstrated that a significant minority of older persons presenting to acute hospital services are cognitively impaired; however, the impact of dementia on long-term outcomes is less clear. To evaluate the prevalence of dementia, both formally diagnosed and hitherto unrecognised in a cohort of acutely unwell older adults, as well as its impact on both immediate outcomes (length of stay and in-hospital mortality) and 12-month outcomes including readmission, institutionalisation and death. Prospective observational study. 190 patients aged 70 years and over, presenting to acute hospital services underwent a detailed health assessment including cognitive assessment (standardised Mini Mental State Examination, AD8 and Confusion Assessment Method for the Intensive Care Unit). Patients or informants were contacted directly 12 months later to compile 1-year outcome data. Dementia was defined as a score of 2 or more on the AD8 screening test. Dementia was present in over one-third of patients (73/190). Of these patients, 36% (26/73) had a prior documented diagnosis of dementia with the remaining undiagnosed before presentation. The composite outcome of death or readmission to hospital within the following 12 months was more likely to occur in patients with dementia (73% (53/73) vs. 58% (68/117), P = 0.043). This finding persisted after controlling for age, gender, frailty status and medical comorbidities, including stroke and heart disease. A diagnosis of dementia confers an increased risk of either death or further admission within the following 12 months, highlighting the need for better cognitive screening in the acute setting, as well as targeted intervention such as comprehensive geriatric assessment. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sensitive Detection of Radiation-Induced Medulloblastomas after Acute or Protracted Gamma-Ray Exposures in Ptch1 Heterozygous Mice Using a Radiation-Specific Molecular Signature.

PubMed

Tsuruoka, Chizuru; Blyth, Benjamin J; Morioka, Takamitsu; Kaminishi, Mutsumi; Shinagawa, Mayumi; Shimada, Yoshiya; Kakinuma, Shizuko

2016-10-01

Recently reported studies have led to a heightened awareness of the risks of cancer induced by diagnostic radiological imaging, and in particular, the risk of brain cancer after childhood CT scans. One feature of Ptch1 +/- mice is their sensitivity to radiation-induced medulloblastomas (an embryonic cerebellar tumor) during a narrow window of time centered on the days around birth. Little is known about the dynamics of how dose protraction interacts with such narrow windows of sensitivity in individual tissues. Using medulloblastomas from irradiated Ptch1 +/- mice with a hybrid C3H × C57BL/6 F1 genetic background, we previously showed that the alleles retained on chromosome 13 (which harbors the Ptch1 gene) reveal two major mechanisms of loss of the wild-type allele. The loss of parental alleles from the telomere extending up to or past the Ptch1 locus by recombination (spontaneous type) accounts for almost all medulloblastomas in nonirradiated mice, while tumors in irradiated mice often exhibited interstitial deletions, which start downstream of the wild-type Ptch1 and extend up varying lengths towards the centromere (radiation type). In this study, Ptch1 +/- mice were exposed to an acute dose of either 100 or 500 mGy gamma rays in utero or postnatally, or the same radiation doses protracted over a four-day period, and were monitored for medulloblastoma development. The results showed dose- and age-dependent radiation-induced type tumors. Furthermore, the size of the radiation-induced deletion differed with the dose rate. The results of this work suggest that tumor latency may be related to the size of the deletion. In this study, 500 mGy exposure produced radiation-induced type tumors at all ages and dose rates, while 100 mGy exposure did not significantly produce radiation-induced type tumors. The radiation signature allows for unique mechanistic insight into the action of radiation to induce DNA lesions with known causal relationship to a specific tumor type

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less

Risk model for deaths and renal replacement therapy dependence in patients with acute kidney injury after cardiac surgery.

PubMed

Sun, Shiren; Ma, Feng; Li, Qiaoneng; Bai, Ming; Li, Yangping; Yu, Yan; Huang, Chen; Wang, Hanmin; Ning, Xiaoxuan

2017-10-01

Acute kidney injury (AKI) is a serious complication after cardiac surgery and is associated with increased in-hospital deaths. Renal replacement therapy (RRT) is becoming a routine strategy for severe AKI. Our goal was to evaluate the risk factors for death and RRT dependence in patients with AKI after cardiac surgery. We included 190 eligible adult patients who had AKI following cardiac surgery and who required RRT at our centre from November 2010 to March 2015. We collected preoperative, intraoperative, postoperative and RRT data for all patients. In this cohort, 87 patients had successful RRT in the hospital, whereas 103 patients had RRT that failed (70 deaths and 33 cases of RRT dependence). The multivariable logistic analysis identified old age [odds ratio (OR): 1.042, 95% confidence interval (CI): 1.012-1.074; P = 0.011], serum uric acid (OR: 1.015, 95% CI: 1.003-1.031; P = 0.024), intraoperative concentrated red blood cell transfusions (OR: 1.144, 95% CI: 1.006-1.312; P = 0.041), postoperative low cardiac output syndrome (OR: 3.107, 95% CI: 1.179-8.190; P = 0.022) and multiple organ failure (OR: 5.786, 95% CI: 2.115-15.832; P = 0.001) as factors associated with a higher risk for RRT failure. The prediction model (-4.3 + 0.002 × preuric acid + 0.10 × concentrated red blood cells + 0.04 × age + 1.12 × [low cardiac output syndrome = 1] + 1.67 × [multiple organ failure = 1]) based on the multivariate analysis had statistically significant different incriminatory power with an area under the curve of 0.786. The prediction model may serve as a simple, accurate tool for predicting in-hospital RRT failure for patients with AKI following cardiac surgery. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome].

PubMed

Yoshimura, Junichi; Natsumeda, Manabu; Nishihira, Yasushi; Nishiyama, Kenichi; Saito, Akihiko; Okamoto, Kouichirou; Takahashi, Hitoshi; Fujii, Yukihiko

2013-06-01

A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome.

Hematopoietic stem cell injury induced by ionizing radiation.

PubMed

Shao, Lijian; Luo, Yi; Zhou, Daohong

2014-03-20

Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid.

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome.

PubMed

Galal, Shereen Mohamed; Abdel-Rafei, Mohamed Khairy; Hasan, Hesham Farouk

2018-05-01

The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ-radiation (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed for 30 days of survival analysis. Administration of EPO improved 30-day survival, alleviated TBI-induced myelosuppression and pancytopenia, by augmenting lymphocytes and other white blood cells in the peripheral blood of rats, while bone marrow and spleen cellularity were restored. EPO post-exposure treatment alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated radiation-induced oxidative stress through the upregulation of the cholinergic anti-inflammatory nicotinic acetylcholine receptor (α-7-nAChR) and the pro-survival Janus kinase-2 and signal transducers and activators of transcription JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats. Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present study establishes the implication of α-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling cascade in the radiomitigative potential of EPO against ARS.

Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya

PubMed Central

Cavalcanti, Luciano Pamplona de Góes; Freitas, André Ricardo Ribas; Brasil, Patrícia; da Cunha, Rivaldo Venâncio

2017-01-01

Did death occur DUE TO dengue, or in a patient WITH dengue virus infection? It seems a matter of semantics, but in fact, it underscores how challenging it is to distinguish whether the disease contributed to death, or was itself the underlying cause of death. Can a death be attributed to chikungunya virus, when some deaths occur after the acute phase? Did the virus decompensate the underlying diseases, leading to death? Did prolonged hospitalisation lead to infection, resulting in the patient’s progression to death? Were there iatrogenic complications during patient care? The dengue question, for which there has not yet been a definitive response, resurfaces prominently under the chikungunya surveillance scenario. We are facing an epidemic of a disease that seems to be more lethal than previously thought. The major challenge ahead is to investigate deaths suspected of occurring due to arbovirus infections and to understand the role of each infection in the unfavourable outcome. PMID:28767985

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke: The Stroke Oxygen Study Randomized Clinical Trial.

PubMed

Roffe, Christine; Nevatte, Tracy; Sim, Julius; Bishop, Jon; Ives, Natalie; Ferdinand, Phillip; Gray, Richard

2017-09-26

Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement. A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicitymore » questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.« less

Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease

PubMed Central

Pello Lázaro, Ana María; Cristóbal, Carmen; Franco-Peláez, Juan Antonio; Tarín, Nieves; Aceña, Álvaro; Carda, Rocío; Huelmos, Ana; Martín-Mariscal, María Luisa; Fuentes-Antras, Jesús; Martínez-Millá, Juan; Alonso, Joaquín; Lorenzo, Óscar; Egido, Jesús; López-Bescós, Lorenzo; Tuñón, José

2017-01-01

Objectives Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD. Methods We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death. Results Patients on PPIs were older [62.0 (53.0–73.0) vs. 58.0 (50.0–70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244–4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628–20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results. Conclusions In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings. PMID:28103324

Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

PubMed

Won, Seok Joon; Jang, Bong Geom; Yoo, Byung Hoon; Sohn, Min; Lee, Min Woo; Choi, Bo Young; Kim, Jin Hee; Song, Hong Ki; Suh, Sang Won

2012-06-01

Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.

Efficacy of Synbiotics to Reduce Acute Radiation Proctitis Symptoms and Improve Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nascimento, Mariana, E-mail: mari1980hemato@yahoo.com.br; Aguilar-Nascimento, José Eduardo; Caporossi, Cervantes

Purpose: To evaluate whether the daily intake of synbiotics interferes in radiation-induced acute proctitis symptoms and in quality of life in patients with prostate cancer. Methods and Materials: Twenty patients who underwent 3-dimensional conformal radiation therapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri 10{sup 8} colony-forming units and 4.3 g of soluble fiber (Nestlé) or placebo. The questionnaire EORTC QLQ-PRT23 was applied before the beginning of radiation therapy and in every week for the first 4 weeks of treatment. The sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scoresmore » of the EORTC QLQ-PRT23 (European Organization for Research and Treatment of Cancer Quality of Life Module for Proctitis–23 items) questionnaire were the main endpoints. Results: This pilot study showed that the complete questionnaire score (median [range]) was higher in the second (23 [21-30] vs 26.5 [22-34], P<.05) and third (23 [21-32] vs 27.5 [24-33], P<.01) weeks in the placebo group. Proctitis symptoms were highest scored in the placebo group in both the second (19.5 [16-25]) and third (19 [17-24]) weeks than in the synbiotic group (week 2: 16.5 [15-20], P<.05; week 3: 17 [15-23], P<.01). In both scores the placebo group had a significantly higher result (P<.01) than the synbiotic group (repeated-measures analysis of variance). Conclusions: Synbiotics reduce proctitis symptoms and improve quality of life in radiation-induced acute proctitis during radiation therapy for prostate cancer.« less

[Radiation-induced cytogenetic markers detected 8 years after the accident at the Chernobyl Atomic Electric Power Station by different methods of analyzing metaphase chromosome preparations in persons who have had acute radiation sickness].

PubMed

Pilinskaia, M A; Shemetun, E V; Shemetun, A M

1995-01-01

A comparative cytogenetic observation of 10 patients suffered from acute radiation sickness of second and third degree as a result of Chernobyl accident has been carried out. The new data about the level of unstable and stable biomarkers of irradiation delayed exposure were established using conventional G-banding and FISH-staining.

Ischaemic heart disease following conventional and hypofractionated radiation treatment in a contemporary breast cancer series.

PubMed

James, Melissa; Swadi, Sami; Yi, Ma; Johansson, Lisa; Robinson, Bridget; Dixit, Ashutosh

2018-06-01

We report the incidence of ischaemic cardiac toxicity in a contemporary cohort of patients receiving conventional (CFRT) or hypofractionated (HFRT) radiation after surgery for early breast cancer and investigate the interplay of cardiac risk factors and fractionation. Included were patients receiving external beam radiation treatment from 2002 to 2006 at the Christchurch public hospital. Hospital coding databases, oncology databases and medical records were reviewed for baseline characteristics, treatment details and outcomes. The primary outcome was cardiac toxicity (including myocardial infarction, admission for cardiac chest pain, coronary angiogram positivity and ischaemic cardiac death). Kaplan-Meier methods were used to derive ischaemic cardiac event free and overall survival. Predefined univariate and multivariate analysis was performed to investigate interaction with radiation fraction size, cardiac risk factors, age and side of cancer. Standardised mortality ratios were constructed. Five hundred and one patients were identified, 220 treated with CFRT and 281 with HFRT. The median age was 56 and median follow-up 10.33 years. The 10-year breast cancer specific survival was 81.8% (95% CI %.78.1-85.0). The 10-year freedom from cardiac death was 98.6% (95% CI 96.9-99.4). There were 27 post radiation cardiac events including 5 cardiac deaths and 19 cases of acute myocardial infarction. 265 (53%) had at least one cardiac risk factor. Twenty five of the 27 patients with a cardiac event had cardiac risk factors. On univariate and multivariate analysis, fractionation schedule was not significantly associated with a post radiation ischaemic event, however, there was a significant relationship with age and the presence of a cardiac risk factor. The standardised mortality ratio was 0.89 (95% CI: 0-3.13). Our study has shown a low rate of ischaemic cardiac disease for both CFRT and HFRT in women treated for breast cancer with no evidence of an effect with fractionation

Thanatophobia (Death Anxiety) in the Elderly: The Problem of the Child's Inability to Assess Their Own Parent's Death Anxiety State.

PubMed

Sinoff, Gary

2017-01-01

Thanatophobia is omnipresent in our lives. Research has shown separate but connected constructs: fear of death or fear of the dying process. The influences on death anxiety are varied including religiosity, gender, psychological state, and age. It is often assumed by the children of the elderly that the fear of death is prevalent in their parents. Daily the medical staff encounters the presence of death anxiety: from family members or the staff itself. In order to understand this phenomenon, a three-tier study was conducted on non-terminal elderly inpatients in an acute geriatric care ward. The study showed that the elderly had low levels of anxiety (scoring 4/15 on Templer's Death Anxiety Scale) but their children scored higher for themselves (6.9/15) and for their parents (8.9/15). A regression model showed that only the presence of generalized anxiety and religiosity of parent had an effect explaining 33.6% of the variance. Death anxiety of death is usually absent in the elderly but rather they fear the dying process. On the other hand, their children do fear death, which they extrapolate onto their parents. This causes conflicts since the children prevent disclosure of relevant medical information to their parents. This has to be addressed by the staff when dealing with family members, to allow open and honest communication with their patients. The staff need to explain to the family that the elderly are not afraid of death but of the suffering from the dying process.

Death of a child in the emergency department.

PubMed

O'Malley, Patricia J; Barata, Isabel A; Snow, Sally K

2014-07-01

The death of a child in the emergency department (ED) is one of the most challenging problems facing ED clinicians. This revised technical report and accompanying policy statement reaffirm principles of patient- and family-centered care. Recent literature is examined regarding family presence, termination of resuscitation, bereavement responsibilities of ED clinicians, support of child fatality review efforts, and other issues inherent in caring for the patient, family, and staff when a child dies in the ED. Appendices are provided that offer an approach to bereavement activities in the ED, carrying out forensic responsibilities while providing compassionate care, communicating the news of the death of a child in the acute setting, providing a closing ritual at the time of terminating resuscitation efforts, and managing the child with a terminal condition who presents near death in the ED.

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

PubMed

Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

2015-10-13

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na

Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cellmore » lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.« less

Radiation Injury to the Brain

MedlinePlus

... healthy cells. The Merck Manual states the following: Radiation Injury to the Nervous System: The nervous system can be damaged by radiation therapy. Acute and subacute transient symptoms may develop early, but ...

Immunological consequences of kidney cell death.

PubMed

Sarhan, Maysa; von Mässenhausen, Anne; Hugo, Christian; Oberbauer, Rainer; Linkermann, Andreas

2018-01-25

Death of renal cells is central to the pathophysiology of acute tubular necrosis, autoimmunity, necrotizing glomerulonephritis, cystic kidney disease, urosepsis, delayed graft function and transplant rejection. By means of regulated necrosis, immunogenic damage-associated molecular patterns (DAMPs) and highly reactive organelles such as lysosomes, peroxisomes and mitochondria are released from the dying cells, thereby causing an overwhelming immunologic response. The rupture of the plasma membrane exhibits the "point of no return" for the immunogenicity of regulated cell death, explaining why apoptosis, a highly organized cell death subroutine with long-lasting plasma membrane integrity, elicits hardly any immune response. Ferroptosis, an iron-dependent necrotic type cell death, results in the release of DAMPs and large amounts of lipid peroxides. In contrast, anti-inflammatory cytokines are actively released from cells that die by necroptosis, limiting the DAMP-induced immune response to a surrounding microenvironment, whereas at the same time, inflammasome-associated caspases drive maturation of intracellularly expressed interleukin-1β (IL-1β). In a distinct setting, additionally interleukin-18 (IL-18) is expressed during pyroptosis, initiated by gasdermin-mediated plasma membrane rupture. As all of these pathways are druggable, we provide an overview of regulated necrosis in kidney diseases with a focus on immunogenicity and potential therapeutic interventions.

Synergistic Tumor-Killing Effect of Radiation and Berberine Combined Treatment in Lung Cancer: The Contribution of Autophagic Cell Death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng Peiling; Division of Gastroenterology, Armed Forces Taichung Hospital, Taichung, Taiwan; Kuo, W.-H.

2008-02-01

Purpose: Radiotherapy is the most efficacious strategies for lung cancer. The radiation-enhancing effects and the underlying mechanisms of berberine were investigated both in vitro and in vivo. Methods and Materials: Clonogenic survival assays were used to evaluate the radio-sensitivity of berberine on non-small-cell lung cancer. Electron microscopic observation of the features of cell death, flow cytometry of acidic vascular organelles formation, mitochondria membrane potential and cell-cycle progression, and Western blotting of caspase 3, PARP, and LC3 were performed to identify the mechanisms underlying the enhancing effects. Lewis lung carcinoma model in mice was conducted to evaluate the possible application ofmore » berberine in synergistic treatment with irradiation. Results: Compared with radiation alone (SF2 = 0.423; D{sub 0} = 5.29 Gy), berberine at 5 and 10 {mu}M concentrations in combination with radiation showed significant enhancement on radiation-induced clonogenic inhibition (SF2 = 0.215: D{sub 0} = 2.70 Gy and SF2 = 0.099: D{sub 0} = 1.24 Gy) on A549 cells. The cellular ultrastructure showed the presence of autophagosome and an increased proportion of acridine orange stain-positive cells, demonstrating that berberine enhanced radiosensitivity via autophagy. The process involved LC3 modification and mitochondrial disruption. The animal model verified the synergistic cytotoxic effect of berberine and irradiation resulting in a substantial shrinkage of tumor volume. Conclusion: Supplement of berberine enhanced the cytotoxicity of radiation in both in vivo and in vitro models of lung cancer. The mechanisms underlying this synergistic effect involved the induction of autophagy. It suggests that berberine could be used as adjuvant therapy to treat lung cancer.« less

Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

NASA Astrophysics Data System (ADS)

Makale, Milan Theodore

This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

PubMed

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2013-10-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

PubMed Central

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2014-01-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

Ischemic Strokes Due to Large-Vessel Occlusions Contribute Disproportionately to Stroke-Related Dependence and Death: A Review.

PubMed

Malhotra, Konark; Gornbein, Jeffrey; Saver, Jeffrey L

2017-01-01

Since large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death. To delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3-6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset. Among 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3-6) within 3-6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53-5.63, p  < 0.0001). Mortality within 3-6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5-6.68), p  < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8-55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8-81.3%) of poststroke dependence or death and 95.6% (CI: 89.0-98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality. LVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes.

Clinical signs of impending death in cancer patients.

PubMed

Hui, David; dos Santos, Renata; Chisholm, Gary; Bansal, Swati; Silva, Thiago Buosi; Kilgore, Kelly; Crovador, Camila Souza; Yu, Xiaoying; Swartz, Michael D; Perez-Cruz, Pedro Emilio; Leite, Raphael de Almeida; Nascimento, Maria Salete de Angelis; Reddy, Suresh; Seriaco, Fabiola; Yennu, Sriram; Paiva, Carlos Eduardo; Dev, Rony; Hall, Stacy; Fajardo, Julieta; Bruera, Eduardo

2014-06-01

The physical signs of impending death have not been well characterized in cancer patients. A better understanding of these signs may improve the ability of clinicians to diagnose impending death. We examined the frequency and onset of 10 bedside physical signs and their diagnostic performance for impending death. We systematically documented 10 physical signs every 12 hours from admission to death or discharge in 357 consecutive patients with advanced cancer admitted to two acute palliative care units. We examined the frequency and median onset of each sign from death backward and calculated their likelihood ratios (LRs) associated with death within 3 days. In total, 203 of 357 patients (52 of 151 in the U.S., 151 of 206 in Brazil) died. Decreased level of consciousness, Palliative Performance Scale ≤20%, and dysphagia of liquids appeared at high frequency and >3 days before death and had low specificity (<90%) and positive LR (<5) for impending death. In contrast, apnea periods, Cheyne-Stokes breathing, death rattle, peripheral cyanosis, pulselessness of radial artery, respiration with mandibular movement, and decreased urine output occurred mostly in the last 3 days of life and at lower frequency. Five of these signs had high specificity (>95%) and positive LRs for death within 3 days, including pulselessness of radial artery (positive LR: 15.6; 95% confidence interval [CI]: 13.7-17.4), respiration with mandibular movement (positive LR: 10; 95% CI: 9.1-10.9), decreased urine output (positive LR: 15.2; 95% CI: 13.4-17.1), Cheyne-Stokes breathing (positive LR: 12.4; 95% CI: 10.8-13.9), and death rattle (positive LR: 9; 95% CI: 8.1-9.8). We identified highly specific physical signs associated with death within 3 days among cancer patients. ©AlphaMed Press.

Direct Peritoneal Resuscitation Reduces Leukocyte Infiltration in the Kidney after Acute Brain Death.

PubMed

Weaver, Jessica Lee; Matheson, Paul J; Matheson, Amy; Graham, Victoria S; Downard, Cynthia; Garrison, Richard Neal; Smith, Jason W

2018-04-18

Brain death is associated with significant inflammation within the kidneys, which may contribute to reduced graft survival. Direct peritoneal resuscitation (DPR) has been shown to reduce systemic inflammation after brain death. To determine its effects, brain dead rats were resuscitated with normal saline (targeted intravenous fluid, TIVF) to maintain a mean arterial pressure of 80 mmHg and DPR animals also received 30cc of intraperitoneal peritoneal dialysis solution. Rats were euthanized at zero, two, four, and six hours after brain death. Pro-inflammatory cytokines were measured using ELISA. Levels of IL-1β, TNF-α, and IL-6 in the kidney were significantly increased as early as two hours after brain death and significantly decreased with DPR. Levels of leukocyte adhesion molecules ICAM and VCAM increased after brain death and were decreased with DPR (ICAM 2.33{plus minus}0.14 v 0.42{plus minus}0.04 p=0.002, VCAM 82.6{plus minus}5.8 v 37.3{plus minus}1.9 p=0.002 at four hours) as were E-selectin and P-selectin (E-selectin 25605 v 16144 p=0.005, P-selectin 82.5{plus minus}3.3 v 71.0{plus minus}2.3 p=0.009 at four hours). Use of DPR reduces inflammation and adhesion molecule expression in the kidneys, and is associated with reduced macrophages and neutrophils on immunohistochemistry. Using DPR in brain dead donors has the potential to reduce the immunologic activity of transplanted kidneys and could improve graft survival.

Urinary NGAL in patients with and without acute kidney injury in a cardiology intensive care unit

PubMed Central

Watanabe, Mirian; Silva, Gabriela Fulan e; da Fonseca, Cassiane Dezoti; Vattimo, Maria de Fatima Fernandes

2014-01-01

Objective To assess the diagnostic and prognostic efficacy of urine neutrophil gelatinase-associated lipocalin in patients admitted to an intensive care unit. Methods Longitudinal, prospective cohort study conducted in a cardiology intensive care unit. The participants were divided into groups with and without acute kidney injury and were followed from admission to the intensive care unit until hospital discharge or death. Serum creatinine, urine output and urine neutrophil gelatinase-associated lipocalin were measured 24 and 48 hours after admission. Results A total of 83 patients admitted to the intensive care unit for clinical reasons were assessed, most being male (57.8%). The participants were divided into groups without acute kidney injury (N=18), with acute kidney injury (N=28) and with severe acute kidney injury (N=37). Chronic diseases, mechanical ventilation and renal replacement therapy were more common in the groups with acute kidney injury and severe acute kidney injury, and those groups exhibited longer intensive care unit stay and hospital stay and higher mortality. Serum creatinine did not change significantly in the group with acute kidney injury within the first 24 hours of admission to the intensive care unit, although, urine neutrophil gelatinase-associated lipocalin was high in the groups with acute kidney injury and severe acute kidney injury (p<0.001). Increased urine neutrophil gelatinase-associated lipocalin was associated with death. Conclusion An increase in urine neutrophil gelatinase-associated lipocalin precedes variations in serum creatinine in patients with acute kidney injury and may be associated with death. PMID:25607262

Therapeutic effect of long-term melatonin treatment on the course and fatal outcome of modeled acute radiation sickness.

PubMed

Vasin, M V; Ushakov, I B; Kovtun, V Yu; Semenova, L A; Koroleva, L V; Galkin, A A; Afanas'ev, R V

2014-04-01

We studied the effect of long-term administration of melatonin to male C57Bl/6 mice starting from day 3 after whole-body γ-irradiation (9.5-10.0 Gy, 7.7-17.1 cGy/min). It was found that replacement of drinking water with melatonin solution (5 mg/liter) did not reduce the amount of fluid intake throughout the period of acute radiation injury. The daily dose of melatonin was 0.9-1.2 mg/kg body weight (this parameter was lower at the peak of the disease and increased during the recovery stage). Melatonin by more than 20% (p<0.05) improved survival of mice exposed to γ-irradiation in a dose of LD97/30, reduced leukopenia during the stage of acute manifestations of the disease and maximum mortality, and increased blood leukocyte count by 40% (p<0.05) by day 12 after irradiation.

Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

irradiation was generated in heavy ion (Fe56) accelerator - UTI. Heavy Ion linear transfer energy - 2000- 2600 KeV -mkm, 600 MeV -92U. Absorbed Dose - 3820 Rad. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A: control-10 rabbits; Group B: placebo-5 rabbits; Group C: Radioprotectant Cystamine (50 mg-kg)-5 rabbits, 15 minutes before irradiation - 5 rabbits; Group D: Radioprotectant Gammafos (Amifostine 400mg -kg ) - 5 rabbits; Group E: Antiradiation Vaccine: subcutaneus administration or IM - 2 ml of active substance, 14 days before irradiation Results: Group A 100% mortality within two hours after heavy ion irradiation with clinical symptoms of Acute Cerebro- and Cardio-Vascular Radiation syndromes. Group B 100% mortality within 15 hours following irradiation. Group C 100% mortality within 14-15 hours after irradiation. Group D 100% mortality within 15-16 hours after irradiation. In groups A- D registered the development of acute radiation cerebrovascular and cardiovascular syndromes and also extensive burns. of skin produced rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation with animals exhibiting a combination or individual forms of Acute Cerebrovascular, Cardiovascular, and Gastrointestinal forms and focal skin burns. Discussion Antiradiation vaccine and immune-prophylaxis is an effective method of neutralization of Radiation Toxins. Vaccination before irradiation extended survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of Acute Radiation Syndromes were diminished in their clinical manifestation and severity. Groups A-D demonstrated extremely severe level of Cerebrovascular and Cardiovascular forms of Acute Radiation Syndromes and lethality 100% was registered in short time after irradiation. Radiation induced burns in this groups (with Cutaneous sub

Potentially preventable infant and child deaths identified at autopsy; findings and implications.

PubMed

Bamber, Andrew R; Mifsud, William; Wolfe, Ingrid; Cass, Hilary; Pryce, Jeremy; Malone, Marian; Sebire, Neil J

2015-09-01

The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%). Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Acute myeloid leukemia (AML; also called acute myelogenous leukemia, acute nonlymphocytic leukemia) treatment advances have resulted in substantially improved CR rates. Cytogenetic analysis helps predict outcomes of treatment which includes chemotherapy, radiation, and stem cell transplant. Get detailed information about AML in this clinician summary.

Death of a child in the emergency department.

PubMed

O'Malley, Patricia; Barata, Isabel; Snow, Sally

2014-07-01

The death of a child in the emergency department (ED) is one of the most challenging problems facing ED clinicians. This revised technical report and accompanying policy statement reaffirm principles of patient- and family-centered care. Recent literature is examined regarding family presence, termination of resuscitation, bereavement responsibilities of ED clinicians, support of child fatality review efforts, and other issues inherent in caring for the patient, family, and staff when a child dies in the ED. Appendices are provided that offer an approach to bereavement activities in the ED, carrying out forensic responsibilities while providing compassionate care, communicating the news of the death of a child in the acute setting, providing a closing ritual at the time of terminating resuscitation efforts, and managing the child with a terminal condition who presents near death in the ED. Copyright © 2014 by the American Academy of Pediatrics.

Heliogeophysical factors at time of death determine lifespan for people who die of cardiovascular diseases

NASA Astrophysics Data System (ADS)

Melnikov, Vladimir N.

2010-09-01

The aim of the study is to explore whether age at death from cardiovascular diseases depends on solar and geomagnetic activities. The data were collected for 1970-1978 in Novosibirsk, West Siberia, for industrial workers of Siberian origin. The Spearman correlations are computed between linearly detrended lifespan and daily or monthly physical variables to establish immediate (lag, L = 0), delayed ( L = 1-3 days) and cumulative ( L = ±30 days) influences. Significant correlations ranging from r = -0.26 to r = -0.30 for L from 0 to 3, respectively, are found for men between solar radio flux at wavelength 10.7 cm and age at death from acute myocardial infarction (AMI) but not from acute heart failure, ischemic heart disease and stroke. For AMI, women's longevity displays an opposite (direct) association with the average solar character occurred at the calendar month of death. The index of geomagnetic activity, Ap, exhibits inverse association with longevity for the AMI stratum for both sexes. GLM univariate procedure revealed higher contribution of Ap to the variance of lifespan compared to season of death. The individual age at death susceptibility to cosmic influences is found to depend upon solar activity at year of birth. It is concluded that associations between the lifespan for cardiovascular decedents and the indices of solar and geomagnetic activities at time of death and of birth are cause-of-death- and sex-specific.

Malnutrition as an underlying cause of childhood deaths associated with infectious diseases in developing countries.

PubMed Central

Rice, A. L.; Sacco, L.; Hyder, A.; Black, R. E.

2000-01-01

INTRODUCTION: Recent estimates suggest that malnutrition (measured as poor anthropometric status) is associated with about 50% of all deaths among children. Although the association between malnutrition and all-cause mortality is well documented, the malnutrition-related risk of death associated with specific diseases is less well described. We reviewed published literature to examine the evidence for a relation between malnutrition and child mortality from diarrhoea, acute respiratory illness, malaria and measles, conditions that account for over 50% of deaths in children worldwide. METHODS: MEDLINE was searched for suitable review articles and original reports of community-based and hospital-based studies. Findings from cohort studies and case-control studies were reviewed and summarized. RESULTS: The strongest and most consistent relation between malnutrition and an increased risk of death was observed for diarrhoea and acute respiratory infection. The evidence, although limited, also suggests a potentially increased risk for death from malaria. A less consistent association was observed between nutritional status and death from measles. Although some hospital-based studies and case-control studies reported an increased risk of mortality from measles, few community-based studies reported any association. DISCUSSION: The risk of malnutrition-related mortality seems to vary for different diseases. These findings have important implications for the evaluation of nutritional intervention programmes and child survival programmes being implemented in settings with different disease profiles. PMID:11100616

Threats to security and ischaemic heart disease deaths: the case of homicides in Mexico.

PubMed

Lee, Eileen H; Bruckner, Tim A

2017-02-01

Ischaemic heart disease (IHD) ranks as the leading cause of death worldwide. Whereas much attention focuses on behavioural and lifestyle factors, less research examines the role of acute, ambient stressors. An unprecedented rise in homicides in Mexico over the past decade and the attendant media coverage and publicity have raised international concern regarding its potential health sequelae. We hypothesize that the rise in homicides in Mexico acts as an ecological threat to security and elevates the risk of both transient ischaemic events and myocardial infarctions, thereby increasing IHD deaths. We applied time-series methods to monthly counts of IHD deaths and homicides in Mexico for 156 months spanning January 2000 to December 2012. Methods controlled for strong temporal patterns in IHD deaths, the unemployment rate and changes in the population size at risk. After controlling for trend and seasonality in IHD deaths, a 1-unit increase in the logged count of homicides coincides with a 7% increase in the odds of IHD death in that same month (95% confidence interval: 0.04 - 0.10). Inference remains robust to additional sensitivity checks, including a state-level fixed effects analysis. Our findings indicate that the elevated level of homicides in Mexico serves as a population-level stressor that acutely increases the risk of IHD death. This research adds to the growing literature documenting the role of ambient threats, or perceived threats, to security on cardiovascular health. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Accuracy and Radiation Dose Reduction of Limited-Range CT in the Evaluation of Acute Appendicitis in Pediatric Patients.

PubMed

Jin, Michael; Sanchez, Thomas R; Lamba, Ramit; Fananapazir, Ghaneh; Corwin, Michael T

2017-09-01

The purpose of this article is to determine the accuracy and radiation dose reduction of limited-range CT prescribed from the top of L2 to the top of the pubic symphysis in children with suspected acute appendicitis. We performed a retrospective study of 210 consecutive pediatric patients from December 11, 2012, through December 11, 2014, who underwent abdominopelvic CT for suspected acute appendicitis. Two radiologists independently reviewed the theoretic limited scans from the superior L2 vertebral body to the top of the pubic symphysis, to assess for visualization of the appendix, acute appendicitis, alternative diagnoses, and incidental findings. Separately, the same parameters were assessed on the full scan by the same two reviewers. Whole-body effective doses were determined for the full- and limited-range scans and were compared using the paired t test. The appendix or entire cecum was visualized on the limited scan in all cases, and no cases of acute appendicitis were missed on the simulated limited scan compared with the full scan. Two alternative diagnoses were missed with the limited scan: one case of hydronephrosis and one of acute acalculous cholecystitis. The mean effective dose for the original scan was 5.6 mSv and that for the simulated limited scan was 3.0 mSv, resulting in a dose reduction of 46.4% (p < 0.001). A limited-range CT examination performed from the top of L2 to the top of the pubic symphysis is as accurate as a full-range abdominopelvic CT in evaluating pediatric patients with suspected appendicitis and reduces the dose by approximately 46%.

The causes and frequency of acute hospitalization of patients with dementia in a long-term care facility.

PubMed Central

Zarian, D. A.; Peter, S. A.; Lee, S.; Kleinfeld, M.

1989-01-01

A retrospective study of 81 patients with dementia in a long-term care facility was conducted to determine the causes and frequency of acute hospitalization and the cause of death in the patients who succumbed during the acute hospital admission. Pneumonia and urinary tract infections were the most frequent causes of acute hospitalization; septicemia and respiratory failure were the most frequent causes of death. These results suggest that patients with dementia are prone to acquire life-threatening infections. Preventive measures to decrease the incidence of these complications are discussed. PMID:2500533

Radiation Exposure and Vascular Access in Acute Coronary Syndromes: The RAD-Matrix Trial.

PubMed

Sciahbasi, Alessandro; Frigoli, Enrico; Sarandrea, Alessandro; Rothenbühler, Martina; Calabrò, Paolo; Lupi, Alessandro; Tomassini, Francesco; Cortese, Bernardo; Rigattieri, Stefano; Cerrato, Enrico; Zavalloni, Dennis; Zingarelli, Antonio; Calabria, Paolo; Rubartelli, Paolo; Sardella, Gennaro; Tebaldi, Matteo; Windecker, Stephan; Jüni, Peter; Heg, Dik; Valgimigli, Marco

2017-05-23

It remains unclear whether radial access increases the risk of operator or patient radiation exposure compared to transfemoral access when performed by expert operators. This study sought to determine whether radial access increases radiation exposure. A total of 8,404 patients, with or without ST-segment elevation acute coronary syndrome, were randomly assigned to radial or femoral access for coronary angiography and percutaneous intervention, and collected fluoroscopy time and dose-area product (DAP). RAD-MATRIX is a radiation sub-study of the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) trial. We anticipated that 13 or more operators, each wearing a thorax (primary endpoint), wrist, and head (secondary endpoints) lithium fluoride thermoluminescent dosimeter, and randomizing at least 13 patients per access site, were needed to establish noninferiority of radial versus femoral access. Among 18 operators, performing 777 procedures in 767 patients, the noninferiority primary endpoint was not achieved (p value for noninferiority = 0.843). Operator equivalent dose at the thorax (77 μSv) was significantly higher with radial than femoral access (41 μSv; p = 0.02). After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ for right radial (84 μSv) compared to left radial access (52 μSv; p = 0.15). In the overall MATRIX population, fluoroscopy time and DAP were higher with radial compared to femoral access: 10 min versus 9 min (p < 0.0001) and 65 Gy·cm 2 versus 59 Gy·cm 2 (p = 0.0001), respectively. Compared to femoral access, radial access is associated with greater operator and patient radiation exposure when performed by expert operators in current practice. Radial operators and institutions should be sensitized towards

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

PubMed Central

Shao, Lijian; Luo, Yi

2014-01-01

Abstract Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid. Redox Signal. 20, 1447–1462. PMID:24124731

Endoscopic treatment of chronic radiation proctopathy.

PubMed

Wilson, Sydney A; Rex, Douglas K

2006-09-01

Chronic radiation proctopathy is a complication of pelvic radiation therapy. The acute phase of radiation injury to the rectum occurs during or up to 3 months following radiation. Acute radiation injury can continue into a chronic phase or chronic radiation proctopathy may develop after a latent period of several months or years. Symptoms associated with the condition include diarrhea, rectal pain, bleeding, tenesmus, and stricture formation. Of the various symptoms, only bleeding from radiation-induced telangiectasias is amenable to endoscopic therapy. This paper summarizes the findings of experts in the field on endoscopic treatment of bleeding from chronic radiation proctopathy. Medical management is generally ineffective in controlling bleeding from chronic radiation proctopathy. Surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including formalin, neodymium/yttrium aluminum garnet, argon and potassium titanyl phosphate laser treatments, as well as argon plasma coagulation. Argon plasma coagulation presents an effective, efficient, inexpensive and reasonably safe noncontact method for destruction of radiation telangiectasias. Based on currently available data and trends, argon plasma coagulation is the favored treatment for bleeding from chronic radiation proctopathy.

Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.

PubMed

Cornel, Jan H; Lopes, Renato D; James, Stefan; Stevens, Susanna R; Neely, Megan L; Liaw, Danny; Miller, Julie; Mohan, Puneet; Amerena, John; Raev, Dimitar; Huo, Yong; Urina-Triana, Miguel; Gallegos Cazorla, Alex; Vinereanu, Dragos; Fridrich, Viliam; Harrington, Robert A; Wallentin, Lars; Alexander, John H

2015-04-01

Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in

Risk of death among children of atomic bomb survivors after 62 years of follow-up: a cohort study.

PubMed

Grant, Eric J; Furukawa, Kyoji; Sakata, Ritsu; Sugiyama, Hiromi; Sadakane, Atsuko; Takahashi, Ikuno; Utada, Mai; Shimizu, Yukiko; Ozasa, Kotaro

2015-10-01

No clear epidemiological hereditary effects of radiation exposure in human beings have been reported. However, no previous studies have investigated mortality into middle age in a population whose parents were exposed to substantial amounts of radiation before conception. We assessed mortality in children of the atomic bomb survivors after 62 years of follow-up. In this prospective cohort study, we assessed 75 327 singleton children of atomic bomb survivors in Hiroshima and Nagasaki and unexposed controls, born between 1946 and 1984, and followed up to Dec 31, 2009. Parental gonadal doses of radiation from the atomic bombings were the primary exposures. The primary endpoint was death due to cancer or non-cancer disease, based on death certificates. Median follow-up was 54·3 years (IQR 45·4-59·3). 5183 participants died from disease. The mean age of the 68 689 surviving children at the end of follow-up was 53·1 years (SD 7·9) with 15 623 (23%) older than age 60 years. For parents who were exposed to a non-zero gonadal dose of radiation, the mean dose was 264 mGy (SD 463). We detected no association between maternal gonadal radiation exposure and risk of death caused by cancer (hazard ratio [HR] for 1 Gy change in exposure 0·891 [95% CI 0·693-1·145]; p=0·36) or risk of death caused by non-cancer diseases (0·973 [0·849-1·115]; p=0·69). Likewise, paternal exposure had no effect on deaths caused by cancer (0·815 [0·614-1·083]; p=0·14) or deaths caused by non-cancer disease (1·103 [0·979-1·241]; p=0·12). Age or time between parental exposure and delivery had no effect on risk of death. Late effects of ionising radiation exposure include increased mortality risks, and models of the transgenerational effects of radiation exposure predict more genetic disease in the children of people exposed to radiation. However, children of people exposed to the atomic bombs in Hiroshima and Nagasaki had no indications of deleterious health effects after 62

Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

PubMed

Szczech, Lynda A; Granger, Christopher B; Dasta, Joseph F; Amin, Alpesh; Peacock, W Frank; McCullough, Peter A; Devlin, John W; Weir, Matthew R; Katz, Jason N; Anderson, Frederick A; Wyman, Allison; Varon, Joseph

2010-05-25

Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

The death of Wolfgang Amadeus Mozart: an epidemiologic perspective.

PubMed

Zegers, Richard H C; Weigl, Andreas; Steptoe, Andrew

2009-08-18

The early death of the composer Wolfgang Amadeus Mozart on 5 December 1791 has fascinated the world for more than 2 centuries. It has been suggested that his final illness was caused by poisoning, renal failure, Henoch-Schönlein purpura, trichinosis, and many other conditions. The official daily register of deaths in Mozart's Vienna was evaluated to provide an epidemiologic framework into which the observations of contemporary witnesses of his death can be integrated. All recorded deaths in Vienna during November and December 1791 and January 1792 were analyzed, together with the corresponding periods in 1790 to 1791 and 1792 to 1793. The deaths of 5011 adults (3442 men, 1569 women) were recorded over these periods. The mean ages of death were 45.5 years (SD, 18.5) for men and 54.5 years (SD, 19.9) for women. Tuberculosis and related conditions accounted for the highest number of deaths; cachexia and malnutrition ranked second, and edema was the third most common cause. According to eyewitness accounts, the hallmark of Mozart's final disease was severe edema. Deaths from edema were markedly increased among younger men in the weeks surrounding Mozart's death compared with the previous and following years. This minor epidemic may have originated in the military hospital. Our analysis is consistent with Mozart's last illness and death being due to a streptococcal infection leading to an acute nephritic syndrome caused by poststreptococcal glomerulonephritis. Scarlet fever, which represents the same underlying disease from an etiologic perspective, is a less likely possibility.

Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway.

PubMed

Wan, Peixing; Su, Wenru; Zhang, Yingying; Li, Zhidong; Deng, Caibin; Zhuo, Yehong

2017-09-15

Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro TMZ treatment also reduced the production of inflammatory cytokines in vitro Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma. © 2017 The Author(s).

Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species

PubMed Central

Webster, Keith A

2013-01-01

Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia–reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia–reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed. PMID:23176689

Effect of ionizing radiation on human skeletal muscle precursor cells

PubMed Central

Jurdana, Mihaela; Cemazar, Maja; Pegan, Katarina; Mars, Tomaz

2013-01-01

Background Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures. Materials and methods Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin – 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death. Results Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70). Conclusions Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions. PMID:24294183

Influence of climate variability on acute myocardial infarction mortality in Havana, 2001-2012.

PubMed

Rivero, Alina; Bolufé, Javier; Ortiz, Paulo L; Rodríguez, Yunisleydi; Reyes, María C