Investigation into use of drugs preceding death from asthma.

Copies of death certificates were provided by the Registrar General for all deaths attributed to asthma in persons aged 5 to 34 years which were registered in England and Wales in the last quarter of 1966 and the first quarter of 1967. Information was obtained from the relevant general practitioners about 177 of the 184 subjects, and necropsy data were obtained for 113 of the 124 cases in which a post-mortem examination was known to have been made. Ninety-eight per cent. of the subjects for whom evidence was obtained were known to have been suffering from asthma, and signs of severe asthma (overdistended lungs and small bronchi plugged with mucus) were found in 91% of necropsies (57% of all deaths). Evidence that death might have been due to any other pathological condition was rare. Death was sudden and unexpected in 81% of the subjects (137 out of 171), and 59% of all deaths were referred to coroners. In 39% of cases (67 out of 171) the practitioner had not regarded the patient as suffering from severe asthma in his terminal episode. Corticosteroids and sympathomimetic preparations were the only drugs to have been used by a large proportion of patients. Two-thirds of the patients had received corticosteroids before the terminal episode, but detailed information about their use provided no suggestion that excess use could have been responsible for any large proportion of the deaths. Eighty-four per cent. of the patients were known to have used pressurized aerosol bronchodilators, and several instances of their use in excess were described. Routine inquiries about their use in the hours immediately preceding death were not made, and further evidence is required before their effect can be assessed adequately.     

Randomised trial of prophylactic daily aspirin in British male doctors

A six year randomised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke, myocardial infarction, or other vascular conditions. Though total mortality was 10% lower in the treated than control group, this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infarction. Likewise, there was no significant difference in the incidence of non-fatal myocardial infarction or stroke—indeed, disabling strokes were somewhat commoner among those allocated aspirin. The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infarction, however, was a substantial 25% reduction. Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group, but as the control group was not given a placebo the relevance of these findings was difficult to assess. There was no apparent reduction in the incidence of cataract in the treated group.The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease.     

Hypothermia-inducing peptide promotes recovery of vesicular stomatitis virus from persistent animal infections.

A single injection of the hypothermia-inducing neuropeptide bombesin resulted in an excellent recovery system for reisolating viruses from Swiss albino mice infected with vesicular stomatitis virus even up to 90 days after infection. The virus was recovered from a cell homogenate prepared from whole brain tissue 24 h after intracerebral injection of bombesin; brain cells were cocultivated with BHK-21 cell monolayers and then plaqued on BHK-21 cells at 31 degrees C. All of the recovered viruses were identified as vesicular stomatitis virus by antibody neutralization and peptide analyses of some of the structural proteins. However, some of the recovered viruses were altered with regard to tryptic peptide maps, temperature sensitivity, and central nervous system disease induced compared with the viruses used to initiate the infection. Most of the recovered viruses induced a similar disease when reinoculated intracerebrally into mice, characterized by hind-leg paralysis 4 to 6 days after infection. Two of the recovered viruses were lethal, however, resulting in a relatively rapid generalized wasting disease and death in 3 to 4 days.     

Incidence of AIDS and excess of mortality associated with HIV in haemophiliacs in the United Kingdom: report on behalf of the directors of haemophilia centres in the United Kingdom.

OBJECTIVE--To estimate the cumulative incidence of AIDS by time since seroconversion in haemophiliacs positive for HIV and to examine the evidence for excess mortality associated with HIV in those who had not yet been diagnosed as having AIDS. DESIGN--Analysis of data from ongoing national surveys. SETTING--Haemophilia centres in the United Kingdom. PATIENTS--A total of 1201 men with haemophilia who had lived in the United Kingdom during 1980-7 and were positive for HIV. INTERVENTION--None. END POINTS--Diagnosis of AIDS; death in those not diagnosed as having AIDS. MEASUREMENTS AND MAIN RESULTS--Estimation of cumulative incidence of AIDS and number of excess deaths in seropositive patients not diagnosed with AIDS. Median follow up after seroconversion was 5 years 2 months. Eight five patients developed AIDS. Cumulative incidence of AIDS five years after seroconversion was 4% among patients aged less than 25 at first test positive for HIV, 6% among those aged 25-44, and 19% among those aged greater than or equal to 45. There was little evidence that type or severity of haemophilia or type of factor VIII or IX that had caused HIV infection affected the rate of progression to AIDS. Mortality was increased among those who had not been diagnosed as having AIDS, especially among those with "AIDS related complex." Thirteen deaths were observed among 36 patients diagnosed as having AIDS related complex against 0.65 expected, and 34 deaths in 1080 other patients against 22.77 expected; both calculations were based on mortality rates observed in haemophiliacs in the United Kingdom in the late 1970s. CONCLUSIONS--Rate of progression to AIDS depended strongly on age. There is a substantial burden of fatal disease among patients positive for HIV who have not been formally diagnosed as having AIDS.     

Mortality in relation to smoking: 40 years' observations on male British doctors.

OBJECTIVE--To assess the hazards associated with long term use of tobacco. DESIGN--Prospective study of mortality in relation to smoking habits assessed in 1951 and again from time to time thereafter, with causes sought of deaths over 40 years (to 1991). Continuation of a study that was last reported after 20 years'' follow up (1951-71). SUBJECTS--34,439 British male doctors who replied to a postal questionnaire in 1951, of whom 10,000 had died during the first 20 years and another 10,000 have died during the second 20 years. RESULTS--Excess mortality associated with smoking was about twice as extreme during the second half of the study as it had been during the first half. The death rate ratios during 1971-91 (comparing continuing cigarette smokers with life-long non-smokers) were approximately threefold at ages 45-64 and twofold at ages 65-84. The excess mortality was chiefly from diseases that can be caused by smoking. Positive associations with smoking were confirmed for death from cancers of the mouth, oesophagus, pharynx, larynx, lung, pancreas, and bladder; from chronic obstructive pulmonary disease and other respiratory diseases; from vascular diseases; from peptic ulcer; and (perhaps because of confounding by personality and alcohol use) from cirrhosis, suicide, and poisoning. A negative association was confirmed with death from Parkinson''s disease. Those who stopped smoking before middle age subsequently avoided almost all of the excess risk that they would otherwise have suffered, but even those who stopped smoking in middle age were subsequently at substantially less risk than those who continued to smoke. CONCLUSION--Results from the first 20 years of this study, and of other studies at that time, substantially underestimated the hazards of long term use of tobacco. It now seems that about half of all regular cigarette smokers will eventually be killed by their habit.     

Polymorphic arylamine N-acetyltransferase encoding gene (NAT2) from homozygous rapid and slow acetylator congenic Syrian hamsters

The nucleotide (nt) and deduced amino acid (aa) sequences were determined for polymorphic arylamine N-acetyl-transferase (NAT2) and its gene, NAT2, from homozygous rapid and slow acetylator congenic Syrian hamsters. The slow acetylator (NAT2^s) allele contained three point mutations which differed from the rapid acetylator allele (NAT2^r); two mutations were silent, and the third mutation resulted in a premature stop codon. The NAT2^r allele contained a truncated open reading frame of 726 nt encoding a 242-aa protein, which is 48-aa shorter than NAT2^r.