Alcohol intemperance and sudden death.

Ten years after a health screening examination was offered to 50 year old men 32 of the 2322 participants and 12 of the 454 nonparticipants had died of ischaemic heart disease. Of these, 26 and 11 respectively had suffered sudden death, for which necropsy was performed. Half of the men who had died suddenly had been registered for alcohol intemperance up to 1973, which was four times the prevalence of such registrations in the general population. Registration at both the Swedish Temperance Board and the Bureau of Social Services was associated with an odds ratio of 3.74 for sudden death as compared with not being registered at either. Logistic analysis including the classical risk factors for ischaemic heart disease together with registration for alcohol intemperance and at the Bureau of Social Services showed only the two types of registration and systolic blood pressure to be independent risk factors. On the other hand, there was no overrepresentation of subjects entered in the registers among those surviving a myocardial infarction. For non-fatal myocardial infarction blood pressure and serum triglyceride concentration were significant risk factors and serum cholesterol concentration, smoking, and body mass index probable risk factors; the two types of registration were not independent risk factors. Alcohol intemperance is strongly associated with an increased risk of sudden death after myocardial infarction.     

Animal models of sudden unexplained death

The etiology of sudden infant death syndrome (SIDS) is unknown but thought to be multifactorial. Several animal models have been developed that induce death without pre-existing symptoms and with pathology similar to that seen in SIDS infants; however, the relevance of these animal models to the events leading to SIDS remains elusive, in part because animal models are as varied as the potential causes of SIDS. In addition, it is difficult to find an animal model that can accurately reflect the genetic, developmental and environmental risk factors for SIDS. Comparisons between species can prove difficult but animal models provide a useful tool for evaluating potential mechanisms related to sudden unexplained death. This review focuses on models developed to examine the association of infection and inflammation with mechanisms proposed to explain sudden unexplained death.     

Risk stratification for sudden cardiac death

Recent advances in pharmacological and device-based therapies have provided a range of management options for patients at risk of sudden cardiac death (SCD). Since all such interventions come with their attendant risks, however, stratification procedures aimed at identifying those who stand to benefit overall have gained a new degree of importance. This review assesses the value of risk stratification measures currently available in clinical practice, as well as of others that may soon enter the market. Parameters that may be obtained only by performing invasive cardiac catheterisation procedures are considered separately from those that may be derived using more readily available non-invasive techniques. It is concluded that effective stratification is likely to require the use of composite parameters and that invasive procedures might only be justified in specific sub-groups of patients.     

Drugs, hERG and sudden death

Early recognition of potential QT/TdP liability is now an essential component of the drug discovery/drug development program. The hERG assay is an indispensable step and a high-quality assay must accompany any investigational new drug (IND) application. While it is the gold standard at present, the hERG assay is too labor-intensive and too low throughput to be used as a screen early in the discovery/development process. A variety of indirect high throughput screens have been used.     

Tracking the sudden oak death pathogen

Invasive species are, by definition, unwelcome and pathogenic ones, especially so. Tracing the origins and spread of Phytophthora ramorum, the devastating 'Sudden Oak Death' pathogen, in the forests and nurseries of Oregon has revealed differences between forest and nursery pathogen populations that suggest discrete sources of primary inoculum initiate each type of outbreak. New information on the ecology and evolution of this pathogen is presented that helps gauge the effectiveness of quarantine and eradication programmes.     

Interleukin-10 and sudden infant death syndrome

Uncontrolled pro-inflammatory responses to infections or bacterial toxins have been suggested to play a role in triggering the physiological events leading to sudden infant death syndrome (SIDS). We tested the hypothesis that these uncontrolled responses might be due to interactions between the gene polymorphisms inducing low levels of IL-10 and exposure to cigarette smoke. In vitro, the IL-10 (G-1082A) polymorphism was associated with low IL-10 levels and the -1082G allele was associated with high levels. The first objective was to assess the distribution of this polymorphism among SIDS infants, parents of SIDS infants and controls, and two ethnic groups: Aboriginal Australians who have a high incidence of SIDS; and Bangladeshis who in Britain have a low incidence of SIDS compared with Europeans. The second objective was to assess effects of human recombinant IL-10 on interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) responses of human leukocytes to staphylococcal toxins implicated in SIDS. The third objective was to assess IL-10 responses to endotoxin and toxic shock syndrome toxin (TSST) from leukocytes of smokers and non-smokers in relation to the IL-10 (G-1082A) polymorphism. There were major differences in the distributions of these polymorphisms between Europeans and Bangladeshis (p=0.00) and between Europeans and Aboriginal Australians (p=0.00); however, they were similar for the Bangladeshi and Aboriginal Australian subjects. There were no significant differences in the distribution of these polymorphisms among SIDS infants or parents of SIDS infants compared to control groups. IL-10 significantly reduced IL-6 and TNF-alpha responses to TSST and staphylococcal enterotoxins A and C. At 50 ng ml(-1), IL-10 significantly increased TNF-alpha but not IL-6 responses to TSST and enterotoxin A. Although IL-10 responses to endotoxin were lower from leukocytes of smokers who were homozygous for the G allele, the differences were not significant; however, significantly lower IL-10 responses were found for smokers who were homozygous for the A allele (p=0.01) and heterozygotes (p=0.04). The pooled data found smokers had significantly lower levels of IL-10 responses to TSST, but there were no significant differences for smokers compared with non-smokers for the three genotypes. The high incidence of SIDS and serious respiratory infections among Aboriginal Australian infants and the low incidence of these conditions among Bangladeshi infants might be explained in part by our findings of differences in IL-10 responses between smokers and non-smokers. The lowest levels of IL-10 responses were observed among smokers who were homozygous for the A allele which is most prevalent among the Aboriginal Australians (83%) and Bangladeshis (84%). The major difference between the risk factors for SIDS in these two groups is the level of exposure of infants to cigarette smoke associated with maternal smoking.