Hemorrhaging, fatal

Clinically, GM-CSF or G-CSF have been used to accelerate recovery after chemotherapy and total body or extended field irradiation, situations that cause neutropenia and decreased platelets, and possibly lead to fatal septic infection or diffuse hemorrhage, respectively. G-CSF and GM-CSF reproducibly decrease the period of granulocytopenia, the number of infectious episodes, and the length of hospitalization in such patients (152), although it is not clear that dose escalation of the cytotoxic agent and increased cure rate can be rehably achieved. One aspect of the effects of G-CSF and GM-CSF is that these agents can activate mature cells to function more efficiently. This may, however, also lead to the production of cytokines, such as TNF- a, that have some toxic side effects. In general, both cytokines are reasonably well tolerated. The side effect profile of G-CSF is more favorable than that of GM-CSF. Medullary bone pain is the only common toxicity. 

Renal Effects. Hemorrhage of the medullary layer of the kidneys was observed in an early report of three fatal cases of acute oral poisoning with endosulfan (Terziev et al. 1974). More recent studies have reported acute renal failure after ingestion of endosulfan as a major contributing cause of death in two individuals in both cases, postmortem examination showed extensive tubular necrosis (Blanco-Coronado et al. 1992 Lo et al. 1995). Neither case discussed the possible mechanism of endosulfan-induced acute renal failure, but in one case, the authors of the report indicate that the renal lesions may relate to sepsis and shock (Blanco-Coronado et al. 1992). Ingested doses were not determined in any of these cases, and it is not totally clear that the effects observed at autopsy were a direct result of endosulfan exposure, although based on results from acute animal studies, it seems likely. 

Cl 0.08-0.96) and symptomatic pulmonary embolism (PE) (OR 0.34, 95% Cl 0.17-0.69), but an increase in major extracranial hemorrhage when compared to placebo (OR 2.17, 95% Cl 1.10. 28). Nonsignificant reductions in combined death and disability, as well as increases in case fatality and sICH were also observed. The authors concluded that insufficient evidence existed to support the routine use of LMWH in the management of patients with ischemic stroke. 

Low-molecular-weight heparins and heparinoids are not recommended in the treatment of acute ischemic stroke.11 A meta-analysis was performed using data from 10 randomized controlled trials.19 A non-significant decrease in combined death and disability and a non-significant increase in case fatality and hemorrhage were seen. A reduction in venous thromboembolic events was observed in acute stroke patients however, there was also an increase in extracranial bleeding. 

Randomized trials have been completed assessing the role of antiplatelet therapy with aspirin for primary stroke prevention. The use of aspirin in patients with no history of stroke or ischemic heart disease reduced the incidence of non-fatal myocardial infarction (MI) but not of stroke. A meta-analysis of eight trials found that the risk of stroke was slightly increased with aspirin use, especially hemorrhagic stroke. Major bleeding risk was also increased with aspirin use.4 Aspirin is beneficial in the primary prevention of MI, but not for primary stroke prevention. 

Rats treated for 17.6-20.8 months with 0.1 mg/kg/day of endrin exhibited focal hemorrhage and congestion of the lungs (Deichmann et al. 1970). Shortness of breath was reported in rats, but not mice, exposed to endrin for 80 weeks (NCI 1978). Pulmonary hyperplasia and edema were reported in dogs fatally poisoned by diets containing 5 ppm or greater (0.20-0.27 mg/kg/day) of endrin (Treon et... 

Ebola—Ebola hemorrhagic fever (Ebola EF) is a severe, often-fatal disease in nonhuman primates such as monkeys, chimpanzees, and gorillas, and in humans. Ebola has appeared sporadically since 1976 when it was first recognized. 

Guess HA, West R, Strand LM, et al. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal antiinflammatory drugs in Saskatchewan, Canada... 

In humans concentrations of 159ppm and 48 ppm have been reported as fatal after 10 min and 30min, respectively. A concentration of 20 ppm was considered intolerable after 1 minute, and Ippm for 10 minutes was irritating. Symptoms of exposure include severe irritation of the eyes and respiratory tract, with hemorrhagic exudate of the bronchi and trachea and pulmonary edema. Repeated exposures may also cause dizziness, loss of appetite, mental deterioration, and weight loss. ... 

In guinea pigs, concentrations of 500-1000 ppm were fatal after 5-8 hours of exposure effects were immediate lacrimation and nasal irritation, followed by unsteadiness and coma autopsy findings were pulmonary edema, pulmonary hemorrhage, and occasional complete consolidation. Fatalities occurred when 300mg/kg was applied dermally to guinea pigs as a pure liquid for 24 hours. 

Cats exposed to 9000 ppm for 8 hours suffered irritation and labored breathing 20,000 ppm for 45 minutes caused deep narcosis, and 43,000ppm for 14—16 minutes was fatal at autopsy, findings were pulmonary edema with hemorrhage and hyperemia of the respiratory tract. Repeated exposure of rabbits to 4450 ppm resulted in secondary anemia with leukocytosis, hyperemia, and damage to the liver. ... 

Oral doses of 2.5 ml of a 1 1 v/v mixture in olive oil were fatal to rats. A historical study indicates that exposure of rats to 800-900 ppm for 7 hours/day for six exposures caused hemorrhagic liver necrosis in some of the rats as well as focal necrosis of the kidneys. No deaths occurred from these exposures. 

In monkeys and dogs, the LCso was 2 6 ppm for 1 hour signs of toxicity were lacrimation, dyspnea, muscular weakness, and vomiting at autopsy, massive pulmonary edema and hemorrhage were observed. In mice, exposure to a low concentration (1 ppm for 60 minutes) produced tolerance to subsequent exposures 8 days later at levels that would otherwise have been fatal (4.25ppm for 60 minutes). 

Postmortem examination in fatal cases has shown immediate onset of extreme rigor mortis in the muscles of the thighs and legs, edema and intraalveolar hemorrhage in the lungs, cerebral edema, and liver and kidney damage. The risk of serious intoxication is increased during hot weather. ... 

Of three chemical workers who were observed after accidental exposures to perchloromethyl mercaptan, two survived episodes of pulmonary edema, and the third died after 36 hours. The fatality resulted from a spill of the liquid on the clothing and floor with exposure to the vapor. At autopsy, there was necrotizing tracheitis, massive hemorrhagic pulmonary edema, marked toxic nephrosis, and vacuolization of centrilobular hepatic cells. 

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