Rapid Deaths Research Articles

Increased risk of coronary heart disease death in men with low total and low-density lipoprotein cholesterol in the Russian Lipid Research Clinics Prevalence Follow-up Study.

A continuously increasing risk of coronary heart disease with increasing levels of cholesterol has been reported by many observational and experimental studies. However, this type of association has not been observed in studies in the Russian Lipid Research Clinics. Twelve-year coronary heart disease mortality among 40- to 59-year-old men was analyzed in the Moscow and St Petersburg examines in the Russian Lipid Research Clinics Program. The baseline survey examined 6431 men fasting and free of prevalent coronary heart disease. Lipids and lipoproteins, blood pressure, body mass, education level, alcohol intake, and smoking history were obtained. Mortality follow-up was based on contacts with participants or their relatives or neighbors. Coronary heart disease mortality was analyzed based on risk factor levels and was further divided into rapid and nonrapid deaths. A J-shaped cholesterol-coronary heart disease risk function was present for both total and low-density lipoprotein cholesterol. Further examination showed hypocholesterolemic men to have lower low-density and higher high-density lipoprotein cholesterol, higher alcohol consumption, leaner body mass, and less education than men with normal or high cholesterol levels. When education level was considered, the J-shaped risk function was present only among men with less than a high school education. When deaths were classified into rapid (less than 24 hours after onset of symptoms) and nonrapid, the J-shaped risk function was restricted to rapid deaths. The results of disclose a sizeable subset of hypocholesterolemics in this population at increased risk of cardiac death associated with lifestyle characteristics.

Urinary catecholamines in hyperthermia-related deaths

A group of five hyperthermia-related deaths is presented in which urinary noradrenaline (NA) concentrations were elevated (172.1 ± 119.4 ng/ml) compared with a control group of rapid violent deaths (43.7 ± 26.1 ng/ml). Urinary adrenaline (A) concentrations were not elevated in the hyperthermia cases, nor were there any significant differences in urinary dopamine (DA) concentrations between the two groups. All except one of the hyperthermia victims were under the influence of ethanol. It is suggested that a combination of heat stress and ethanol consumption was responsible for the elevated urinary NA in the hyperthermia cases, reflecting increased sympathetic nervous system activity. A combination of high urinary NA with low A seems to be characteristic of hyperthermia fatalities, in contrast to hypothermia deaths, where both NA and A are usually elevated.

MORTALITY FROM DUCK PLAGUE VIRUS IN IMMUNOSUPPRESSED ADULT MALLARD DUCKS

Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

Computer-Assisted Interpretation in Forensic Toxicology: Morphine-Involved Deaths

Case data from 200 morphine-involved deaths (Spiehler, V. and Brown, R., Journal of Forensic Sciences, Vol. 32, No. 4, July 1987, pp. 906-916) were analyzed for patterns and relationships using artificial intelligence (AI) computer software. Case parameters were blood unconjugated morphine, blood, brain, and liver total morphine, sex, age, frequency of use, time of death after injection, cause of death, and presence of other drugs. The programs used were Expert 4 (Biosoft-Cambridge), BEAGLE (Warm Boot, Ltd.), and KnowledgeMaker (Knowledge Garden Inc.). Interpretation was defined as estimating the dose, response, and time after drug dosing. The AI programs were used to advise on time and response outcomes for cases, to calculate the probability of the estimate being true, to develop rules for interpretation of morphine-involved cases, and to diagram a decision tree. On known cases the AI programs were successful 70 to 90% of the time in classifying the cases as to response and time. No data on dose were available in this database. The success rate in individual cases was proportional to the program-estimated probability. All three programs found the case parameters of most value in predicting response to be blood unconjugated morphine, blood total morphine, and liver total morphine. The case data most useful in estimating time of death since drug injection were blood unconjugated morphine, percent unconjugated morphine in blood, and brain total morphine. The rule induction programs found that morphine overdoses were characterized by blood unconjugated morphine greater than 0.24 micrograms/mL, liver morphine greater than 0.50 to 0.75 micrograms/g, brain morphine greater than 0.08 micrograms/g or greater than blood unconjugated morphine, and percent blood unconjugated morphine greater than 37%. Rapid deaths were characterized by percent unconjugated morphine greater than 44 to 50%; blood unconjugated morphine, as a function of other drugs present, greater than 0.09 to 0.21 micrograms/mL; and brain total morphine greater than 0.16 to 0.22 micrograms/g. This work demonstrates that inexpensive AI programs commercially available for personal computers can be useful in interpretation in forensic toxicology.

Unconjugated Morphine in Blood by Radioimmunoassay and Gas Chromatography/Mass Spectrometry

Morphine, the active metabolite of heroin, is rapidly inactivated by glucuronidation at the 3 carbon. Unconjugated (pharmacologically active) morphine was measured in postmortem blood by radioimmunoassay using an antibody-coated tube kit. The kit shows less than 0.2% cross-reactivity with codeine and morphine-glucuronide. Unconjugated morphine concentrations were confirmed by gas chromatography/mass spectrometry (GC/MS) using deuterated morphine as the internal standard. The blood was precipitated with 10% trichloroacetic acid (TCA) and concentrated hydrochloric acid (HCl), centrifuged, and decanted. The supernatant was then either diluted (unhydrolyzed) or heated to 100 degrees C, 30 min (hydrolyzed), followed by a wash with 4:1 chloroform:isopropranol. The upper aqueous layer was then saturated with sodium bicarbonate (NaHCO3) and extracted with 4:1 chloroform:isopropranol. The organic layer was evaporated, derivatized with trifluoroacetic anhydride (TFA), and analyzed by selected ion monitoring (SIM) GC/MS. Comparison of the results for unconjugated morphine by radioimmunoassay and unhydrolyzed morphine by GC/MS gave a correlation coefficient of r = 0.98, n = 100. Unconjugated morphine ranged from 0 to 100% of total morphine with a mean of 42%, n = 200, for heroin or morphine involved deaths. Review of 56 putative rapid deaths gave a mean of 68% unconjugated morphine with a range of 26 to 100%. The ratio of unconjugated to total morphine was found to be stable in postmortem blood after more than a year of storage at room temperature, within the precision of the method.

The toxicity of methyl isocyanate: Where do we stand?

papers in this issue of Environmental Health Perspectives were presented at a conference titled The Toxicity of Methyl Isocyanate held at the National In? stitute of Environmental Health Sciences, March 12 and 13, 1986. works presented are varied in their ap? proach and scope, but all of the studies shared the goal of providing basic toxicological information on MIC to augment the meager data available at the time of the accident in Bhopal. Taken together, the animal inhalation exposure stud? ies mimicked in effect, the gradation of exposures that occurred at different distances from the chemical plant. studies of Union Carbide scientists attempted to recreate in several animal species the spectrum of re? sponses, including rapid unconsciousness and death, seen close to the facility and examined a number of possible biochemical and physiological mechanisms for these phenomena. NIEHS studies, and many of the other studies reported at this conference, used lower doses and longer exposures in an attempt to examine both the resulting toxicities and the potential for re? versal or progression of these effects in survivors. Clearly, MIC inhalation is profoundly damaging to the respiratory system. Rapid deaths following expo? sure to high concentrations and delayed deaths resulting from exposures to lower concentrations of MIC have both been attributed to respiratory injury. As indicated, certain Union Carbide studies were designed to deter? mine the pathogenesis of the immediate deaths of in? dividuals in Bhopal who were exposed to high concen? trations of MIC. These studies have evaluated several

The Cigarette Safety Bill: A Case Study in Injury Control Advocacy

ra 6 IGARETTE S kill people in two distinct ways: one > way is slow; the other, rapid. Slow deaths occur by cancer, heart disease and lung disease. The less frequently g t 3 discussed rapid deaths occur to about 2300 Americans each year in housefires. These lives are lost and others are physically and emotionally scarred by cigarettes and little cigars that do not have reduced heating capacity or do not burn out when left unattended. The unattended lit cigarette or little cigar frequently comes in contact with upholstered ftrniture, mattresses or bedding and creates a smoldering fire that becomes a deadly inferno. This tragic scenario repeats itself year after year in every state throughout the country, with the result that smoking is the leading cause of residential fire deaths and injuries. Aimed at ending this preventable human suffering, cigarette safety legislation has been introduced in the United States Congress and in ten state legislatures. Generally, the bills seek to have established a standard for cigarettes and little cigars which would lower their propensity to ignite housefires. Although these several bills are generally similar, their content varies in some important areas. For example, the standards themselves are differently defined, and there are variations in terms of who is authorized to promulgate the standard. The Injury Control Council of the National Association for Public Health Policy (NAPHP) undertook an analysis of the cigarette safety issue and the bills designed to address that issue. A prototype bill was prepared which was subsequently introduced in the Maryland State Legislature. What follows is the text of that bill with a section by section analysis. It is offered both for use (with modification where necessary) in other states, and as an example of the ability of a public health advocacy group to address the risk of death of thousands by a relatively simple piece of legislation.

Increased Urinary Concentration of Catecholamines in Hypothermia Deaths

Observations are presented on 24 hypothermia deaths, either accidental or suicidal. Most cases occurred in dry, cold circumstances, the air temperature being below 0 degree C. More cases were seen in early winter, suggesting a lack of acclimatization to the cold. Purple skin and swelling of the ears and nose (mild frostbite) were the most frequent external signs of exposure. Frequent internal signs were stomach ulcerations or hemorrhagic gastritis and small degenerative foci in the myocardium. High blood alcohol (about 200 mg/dL) was the most common contributory factor, but psychotropic drugs were detected in a few cases. The total urinary catecholamine content was increased in the hypothermia deaths, with levels of 0.20 +/- 0.16 microgram/mL (mean +/- standard deviation) versus 0.07 +/- 0.07 microgram/mL in sudden natural deaths and 0.02 +/- 0.02 microgram/mL in rapid violent deaths. Adrenaline was more abundant than noradrenaline. It is suggested that urine catecholamine measurements can give useful information for the diagnosis of acute hypothermia.

Temperature and oxygen-nitrogen gas ratios affect fish survival in air-supersaturated water

Juvenile steelhead trout and juvenile chinook, coho and sockeye salmon were tested at different temperatures (8°, 9°, 10°, 12°, 15°, 18° and 20°C) at the same concentration of air-supersaturated water. Supersaturated water concentrations in different tests were 115, 116, 117, 118 and 120% saturation. Increased temperatures caused a significant ( P< 0.005) increase in steelhead mortality, a significant increase ( P < 0.025) in chinook deaths, but no significant effect on coho or sockeye mortality. Regression model data for steelhead indicate that a 10°C increase in temperature will decrease the time to 50% death by a factor of 2.7, e.g. from 190h at 8°C to 70h at 18°C, when tested at the same total dissolved gas pressure. Effects of different oxygen-nitrogen gas ratios on fish mortality at the same total dissolved gas pressure in supersaturated water were demonstrated with juvenile steelhead trout. Mortality was rapid (time to 50% death in 1–6 h) at 140, 135 and 130% saturation, with fish dying more rapidly as the ratio of oxygen-nitrogen decreased (decrease in O 2, increase in N 2) Mortality patterns were similar at 125%; time to 50% death occurred in 5–20 h, with more rapid deaths occurring as oxygen (O 2/N 2 ratio) was decreased.

Toxicity of Prudhoe Bay Crude Oil to Alaskan Arctic Zooplankton

Bioassay experiments were conducted to determine the relative susceptibilities of three arctic zooplankton species to oil pollution, and the results were compared with the effects of an actual oil spill on a pond near Barrow. In both the bioassays and the pond, the addition of Prudhoe Bay crude oil was toxic to fairy shrimp (Branchionecta paladosa O. F. M&uuml;ller), which seemed most sensitive, Daphnia middendorffiana Fischer, which was next most susceptible and Heterocope septentrionalis Juday and Muttkowski, which appeared somewhat resistant to the effects of oil. Cyclopoid copepods were the only common zooplankters able to survive the pond oil spill, and these were still present two and one half weeks after the spill. The rapid deaths of the other species, especially the branchiopods, suggest that zooplankton may be the most susceptible of all arctic freshwater organisms to oil pollution.

Fatal road accidents in Birmingham: Times to death and their causes

The intervals between injury and death in the 254 fatalities after road traffic accidents in Birmingham during 1969 and 1970 were analysed and correlated with other data. Sixty-three per cent were pedestrians and 23 per cent were passengers and drivers of vehicles. In round figures, about a third of the series died within half an hour, a half by 2 hours, two-thirds by 24 hours, and three-quarters by 2–4 days. The patterns of survival-time could be divided into three phases. There was an early steep decline, with 36 per cent dying during the first half-hour and 44 per cent within 1 hour of the accidents. This was followed by a longer stage during which the rate of dying decreased progressively in logarithmic fashion. The cumulative tolls were 51 per cent by 2 hours, 58 per cent by 4 hours, 68 per cent by 24 hours, and 83 per cent by 7 days. The curve then flattened into a prolonged tail. Between 7 and 28 days another 10 per cent died, making 93 per cent by 28 days. The remaining 7 per cent succumbed during the subsequent weeks and months, 3 patients surviving longer than a year. Fifty-six per cent of vehicle occupants and 40 per cent of pedestrians died within an hour of injury, and the excess of rapid deaths among vehicle occupants was mainly due to a higher proportion of rupture of the aorta. All the ruptured aortae in vehicle occupants occurred after accidents at night or the early hours of the morning. Many of the affected drivers and passengers had consumed alcohol and their injuries were more rapidly lethal than after accidents at other times. Serious cerebral trauma dominated all groups of road users and multiple injuries were common. Included among the fatality tail was a group of subjects, mainly pedestrians, with relatively modest injuries who might have survived had they not developed pulmonary embolism, respiratory infection, or other complications.

The effect of endotoxins on frog blood and survival time at several ambient temperatures.

SummaryTreatment of frogs with any of three endotoxins resulted in more rapid deaths at 30 and at 37° and a decrease in blood thrombocytes. The frogs were unaffected by bacterial endotoxin at 5 and at 20° at doses of 1 through 30 mg, and repeated injections at a 2-week interval were equally without effect. Other than thrombocytes, the formed elements of the blood were unchanged after endotoxin treatment.

ESOPHAGEAL OBSTRUCTION

The effect of complete stricture of the esophagus on life and nutrition has been the subject of but few investigations. Pavlov,1in 1895, first mentioned the use of an esophageal fistula in the study of psychic secretion in dogs. Our impression is that few of the earlier clinicians or physiologists believed that closure of the esophagus had any serious effect on health, though this belief, as far as we can find, was not the result of experimental investigation or of clinical experience. A few years ago Wangensteen and Chunn2and Haden and Orr3recorded rapid deaths in dogs following acute experimental closure of the esophagus. Andrus and Donnelly4more recently have again studied the question and have concluded that the loss of saliva may have played an important role in the lethal outcome of all their animal experiments. Chevalier Jackson,5who has had probably the