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[Risk factors of sudden infant death and of death by accidents. According to a national survey in the total postneonatal death].

BACKGROUND: The incidence of sudden infant death syndrome (SIDS) peaks at 2-4 month of age and during the colder months of the year. Other risk factors such as sex, birth weight, maternal age and multiple pregnancy also seem to be shared by the other causes of death after the neonatal period. POPULATION AND METHODS: A retrospective, exhaustive survey of all deaths of infants aged 28 days-one year was carried out between September 1986 to December 1987. The control group was a representative sample of the live births in France during 1989. The deaths were classified into 3 groups: group I, 1184 SIDS, group II 228 SIDS remaining unexplained after autopsy (out of 315 autopsied SIDS), and group III 83 accidental deaths. The factors studied were: sex, birth weight, maternal age, number of infants born from the pregnancy. The risk factors were measured by Odds Ratios and the variables related to mortality were introduced into a logistic model. RESULTS: Incidence of deaths peaked between the 2nd and the 4th month of age in groups I and II while deaths were evenly distributed throughout the first year in group III. Colder months, male gender, low birthweight, multiple birth and the young age of the mother all increased the risk of death in SIDS (groups I and II) but the same factors were also linked to accidental deaths. CONCLUSION: The results confirm those of earlier reports and raise the question why the risk factors for accidental deaths are similar to those for explained or unexplained SIDS, except for infant age.

Accidents

Newcastle survey of deaths in early childhood 1974/76, with special reference to sudden unexpected deaths. Working party for early childhood deaths in Newcastle.

All early childhood deaths within a total population of 297 000 were studied by prospective methods. 70 deaths of children aged 1 week to 5 years occurred during a 27-month period; 36 died at home, 29 suddenly and unexpectedly. An extensive standardized necropsy showed a disease process clearly or probably related to death in half the sudden unexpected deaths; in the remainder no recognized disease process was identified. The events preceding sudden unexpected death, and the child's environment, were investigated by a controlled parental interview. Symptoms of serious illness within 24 hours of death were identified in 9 of the 29 children, but in the majority symptoms were thought to have been absent or no more severe than those of the control children. Most children with major symptoms had been seen by a doctor within a few days of death. The two most striking social findings were that 16 of the 29 sudden unexpected deaths occurred at a weekend or bank holiday, and that 45% occurred in three adjacent city wards which contain only 13% of the under-five study population. The additional support and explanation provided during the home visits was greatly appreciated by the bereaved families.

Age Factors

Coronary atherosclerosis in cases of coronary death as compared with that occurring in the populatiom. A study of a medico-legal autopsy series of coronary deaths and violent deaths.

The severity of coronary atherosclerosis at autopsy was studied in two series comprising 169 cases of coronary death and 231 people who died of violent causes. In the former the fatal attack lasted less than 24 hours from the onset of symptoms in 70% of cases. In only three men did the terminal attack last more than 24 hours, while in the remaining 28% of cases, although death was not witnessed these were also likely to have been sudden deaths. A recent infarct with or without an old myocardial infarct was found at autopsy in 47% of cases and an old infarct alone in 34%. In 19% of coronary deaths no recent or old infarct was detected. The surface areas of the atherosclerotic lesions were assessed in arterial specimens by pointcounting. The degree of stenosis was estimated visually. The mean extent of raised lesions and clacification and the median value of stenosis score, which expressed the degree of stensosi in the coronary arterial tree, were significantly higher in all age groups in persons who died of coronary heart disease than in those who died violently. A marked overlapping between the individuals in the two series was, however, found in both for the exent of raised lesions and the severity of stenosis score. Raised lesions in coronary patients were calcified to about the same extent as those in persons ten years older in the series of violent deaths. Coronary atherosclerosis was most severe in coronary patients who had had symptomatic heart disease and had an old myocardial infarct and least severe in those in whome sudden death was the first manifestation of coronary heart disease from violent deaths as regards the extent of the raised lesions or prevalence of occlusion. The degree of coronary stenosis in coronary patients was closely related to the total extent of advanced coronary atherosclerosis.

Adult

What middle-aged men know of their parents' cause of death and age at death. A comparison between history and death certificate.

Middle-aged men's knowledge of the circumstances of their parents' diseases and death is reliable to such an extent that it can be used when appropriate for therapeutic purposes in familial diseases. This conclusion is based on findings in a health examination survey of 441 middle-aged men in Uppsala, Sweden where the men were asked whether their parents were dead and, if so, the known cause of death and at what age they had died. The information reported was then compared with the official data kept by the authorities. In 87% of cases it was possible to perform such a comparison. The study showed good conformity of the two sources, in general.

Accidents

Death after legally induced abortion. A comprehensive approach for determination of abortion-related deaths based on record linkage.

The sources for determination of abortion-related deaths in Georgia are the cause of death listed on the death certificate and reports from informal reporting channels. Although Georgia residents 10-44 years of age obtained 19,877 induced abortions in 1975, no deaths related to abortion were found through these two usual sources. To determine the sensitivity of this system, all abortion certificates for 1975 were compared with all death certificates of Georgia females aged 10-44 who died in 1975 and the first 2 months of 1976. Based on the age and racial distribution of the women who received abortions, approximately 13 deaths (from all causes) would be expected to have subsequently occurred during the period of time studied. The authors found only 10. From national death-to-case rates for legal abortion, the expected number actually atrributable to abortion was 0.78 death. Of the 10 deaths, 2 were potentially related to the previous abortion, but a causal relationship to the preceding abortion was not clearly evident for any of the 10 deaths. The data, therefore, tend to support the assertion that no large numbers of deaths related to abortion are undiscovered and that current measurements of abortion mortality are accurate.

Abortion, Legal

Deaths from ischaemic heart disease in Helsinki in the years 1959-1968. Vital statistics and medico-legally autopsied sudden deaths.

According to the official vital statistics, altogether 10910 deaths from ischaemic heart disease (IHD) occurred in persons resident in Helsinki during the 10-year period 1959-68. A significant increase was found in the incidence of IHD deaths in both sexes even though changes in the structure of the population were taken into account. The increase in the age-dependent incidence of IHD deaths was most conspicuous at middle age in both sexes and in young males. Altogether 3044 IHD deaths occurring unwitnessed or within 24 hours of the onset of the fatal attack were autopsied medico-legally during the 10-year period of the study. The medico-legally autopsied cases obviously represented a high proportion of sudden IHD deaths occurring outside hospitals in Helsinki. A clear male preponderance was found in the autopsy material as compared with all IHD deaths. The prevalence of cases of acute myocardial infarction varied in different years from 27 to 49 percent at medico-legal autopsies. No significant change occurred during the 10-year period in the distribution of the medico-legally autopsied IHD deaths into social groups, in the suddenness or place of death. The home was the most common place of death. From 1963 onwards the patients dying from an ischaemic heart attack during transportation to hospital or in an outpatient department constituted 6-7 percent of all annual IHD deaths.

Acute Disease

Inhibition of programmed cell death by cyclosporin A; preferential blocking of cell death induced by signals via TCR/CD3 complex and its mode of action.

Cyclosporin A (CsA) is reported to inhibit programmed cell death. We confirmed this by using T-cell hybridomas which are inducible to programmed cell death by activation with immobilized anti-CD3 antibody or with anti-Thy 1.2 antibody. Cell death and DNA fragmentation, characteristic features of programmed cell death, were almost completely blocked by CsA or FK506. To investigate whether CsA inhibits only the cell death through the signals via the TCR/CD3 complex or all of the programmed cell death induced by various reagents, we further established CD4+8+ thymic lymphomas which result in programmed cell death after activation with calcium ionophore, dexamethasone, cyclic AMP or anti-CD3 antibody. It was revealed that CsA could block only the cell death mediated by the TCR/CD3 complex. For the clarification of the site of action of CsA, Ca2+ influx and endocytosis of receptors after stimulation with anti-CD3 antibody were monitored in the presence of CsA, and no significant effects of CsA were observed. Furthermore, prevention of cell death was examined by adding CsA at various periods of time after initiation of culture. CsA was found to exert its effect even when added after 4 h of cultivation, and the kinetic pattern of suppression was similar to that of the suppressive effect on IL-2 production. These observations indicate that in the events of programmed cell death, the major site of action of CsA will not be the inhibition of the immediate membrane events after activation of the TCR/CD3 complex but rather the interference in the function of molecules that transmit signals between membrane events and the activation of genes in the nucleus.

Animals

Precursors of sudden coronary death. Factors related to the incidence of sudden death.

Precursors of sudden death were sought in men--1838 civil servants in Albany, New York, and 2282 residents of Framingham, Massachusetts--under continuous surveillance for 16 years. In men 45-74 years old there were 234 deaths attributed to coronary heart disease (CHD) of which 109 occurred within one hour of onset of symptoms. More than half of all deaths due to CHD occurred outside the hospital and about 80 per cent of these were sudden. Most were unheralded by prior symptoms of CHD. Persons at high risk of death from CHD, including sudden death, can be identified long before the terminal unexpected catastrophe. The same precursive stigmata exist in persons subject ot coronary attacks whether or not immediately fatal. The risk of sudden death in these two populations was positively correlated with high blood pressure, the electrocardiographic pattern of left ventricular enlargement, obesity, and heavy cigarette usage. Sudden death is a common and possibly incidental expression of lethal coronary heart disease. The potential candidate for sudden death cannot be confidently distinguished from the individual who succumbs more slowly of myocardial infarction. The inescapable conclusion is that the prevention of sudden death requires the prevention of coronary attacks.

Adult

Activation-driven T cell death. II. Quantitative differences alone distinguish stimuli triggering nontransformed T cell proliferation or death.

Clonal deletion is the major mechanism by which T cell tolerance is achieved in vivo. The process of activation-driven cell death, originally characterized with T cell hybridomas, likely represents the mechanism of clonal deletion because it shares a number of properties with the in vivo process, especially the ability to be triggered in an Ag-specific manner, the cell-autonomous nature of the response, and its sensitivity to the drug cyclosporin A. We now have extended our analysis of activation-driven cell death to clonal populations of nontransformed T cells. Activation-driven cell death can be induced in nontransformed T lymphocytes by combinations of mitogenic stimuli. In particular, two mitogenic stimuli at high dose, one a lymphokine and the other delivered via the TCR or another activation structure, are required to induce activation-driven cell death. Activation-driven cell death is an active cell suicide process with attributes typical of physiological cell death, including early nuclear disintegration and a requirement for macromolecular synthesis, and is distinct from death by factor deprivation. Susceptibility to the induction of cell death by antigenic or activating stimulation is a common aspect of most T cells and is consistent with observations that clonal deletion can occur throughout T cell ontogeny. Most importantly, the alternative cellular responses of cell death and cell proliferation in nontransformed T cells appear to be triggered solely as a function of quantitative differences in the doses of identical stimuli. This can be viewed as a dose-dependent switch that determines cell fate. Developmental regulation of this switch may explain the processes of positive and negative selection during T cell ontogeny and also provide a mechanistic rationale for a strategy of selective anti-tumor therapy.

Animals

Susceptibility to cell death is a dominant phenotype: triggering of activation-driven T-cell death independent of the T-cell antigen receptor complex.

The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.

Animals

The use of beta-agonists and the risk of death and near death from asthma.

BACKGROUND: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS: The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS: An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.

Administration, Inhalation

[Medico-legal studies on the deaths from coal-mine accidents. 3. Causes of death (author's transl)].

Thirty-four deceased who were killed from twenty cases of coal-mine accidents during fourteen years from 1965 to 1978 were autopsied in our laboratory and their causes of death have been discussed. In the explosion of methane gas and coal dust chemical energy stored in coal or methane is converted to mechanical energy and thermal energy which act upon the human bodies to bring about seven sorts of causes of death. Deaths are caused more frequently by thermal energy directly or indirectly than by mechanical energy. It is a characteristic found in the explosions of coal mines which are large and closed underground spaces consisting of inflammable material. In gas spurt major cause of death is asphyxia from the lack of oxygen resulting from the substitution of air by methane gas and the effects of mechanical energy developed by gas spurt is slight in degree. In the coal-mine accidents the causes of death are so much concurred that is is difficult to certify the cause of death. A new concept of a cause of death has been proposed to solve such a problem.

Accidents, Occupational

Occurrence of coronary ostial stenosis in a necropsy series of myocardial infarction, sudden death, and violent death.

A postmortem coronary angiography technique employing aortic injection of contrast medium and double contrast visualization of the aortic bulb and large epicardial coronary trunks was applied to the study of coronary ostia in a series of 124 deaths from acute myocardial infarction and a series of 89 sudden deaths without recent infarction and 42 violent deaths. A stenosis of 50 per cent or more of the lumen was found in the right ostium in 45 per cent and in the left ostium in 8 per cent of infarct cases. The corresponding figures in sudden deaths were 37 per cent on the right and 4.5 per cent on the left side, and in violent deaths 7 per cent in the right ostium and none in the left. Most ostial stenoses were caused by coronary atherosclerosis. In 9 patients, two with a recent infarct and 7 sudden deaths, an ostial stenosis was the only stenosed site in the coronary arterial tree. Of theses 9 patients, 7 were known to have suffered from symptomatic heart disease during life, chest pain on effort and arrhythmias being the most common complaint.

Adult

[Studies on mortality in diabetics in a circumscribed region: age and death, length of diabetes and causes of death].

Studies were carried out in regard to the age at death, duration of diabetes mellitus at the time of death and cause of death in an unselected evaluation of the findings in all 1694 diabetics who died in Erfurt and environs over an 11-year period. The The mean age of the patients at the time of death was 70.6 years, with virtually no difference between the sexes. Only six patients died prior to the age of 40. In accordance with the age structure of diabetics in a circumscribed area, the average survival time was 6.5 years. The interval between the first manifestation of the disease and death was 0 to 4 years in 45% of the patients; only every fifth patient survided for 10 or more years. These results are interpreted as being a reflexion of the frequent incidence of preceding or simultaneously-occuring atherosclerosis in these diabetics. Cardiovascular incidents affecting, above all, the coronary and cerebral vessels, account for about 60% of the deaths. Differences between these results and other statistical analyses can be explained on the basis of the unselective nature of the case material in the present study which was, moreover, collected in a defined region over a definite period of time.

Adult

A validation of cause-of-death certification in 1,156 deaths.

Swedish twins have been followed for mortality since 1961, when the Swedish Twin Registry was formed. During the years 1961-73 there were 1290 deaths among twins born in 1901-25. In 1156 cases the cause of death could be established from collected records and classified according to the 1965 revision of ICD. Using the review of records as the standard, rates of detection and confirmation relating to the death certificate diagnoses were calculated. It is concluded that Swedish death certificate data are fairly valid for use in epidemiological studies and mortality statistics with regard to most cancer forms, cerebrovascular disease, ischemic heart disease, bronchitis, asthma and emphysema, accidents and suicides, but not for diabetes mellitus, alcoholism, mental diseases, rheumatic heart diseases and other heart diseases. However, in selected clinical-epidemiological studies it is often necessary to collect all available documents prior to judging the cause of death.

Aged