The VAMP Research multi-purpose database in the U.K.
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Biomedical subjects
Publications and source records attributed to Y Lis.
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The initial results are reported of a case-control study undertaken on the VAMP multi-purpose database and designed to estimate the risk for first-time occurrence of myocardial infarction in users of hormone replacement therapy (HRT). The findings currently available relate to the computerized data and show 2- to 5-fold increases in risk in smokers and those with diabetes mellitus, hypertension or hyperlipidaemia. With any form of HRT, a non-significant protective effect [adjusted odds ratio = 0.83 with 95% CI (confidence intervals) of 0.66-1.03, p = 0.089] has been shown. However, the protective effect of HRT in the data available to date appears to be confined to non-smokers in whom the odds ratio in the absence of other risk factors is 0.70 (95% CI of 0.49-1.00). The comparable odds ratio in smokers is 1.05 (95% CI of 0.71-1.53). These results should be interpreted with caution as smoking status was unknown for about half of the subjects and was more complete among the cases than controls.
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1. A total of six hundred and eighty three new chemical entities (NCEs), were marketed in the UK between 1960 and 1987. The number of NCEs introduced annually onto the UK market declined to an average of 20 per year in 1964 and subsequently to only 7 in 1985. 2. Average development times have increased fourfold since 1960 to a peak value of 13 years in 1984. The concomitant decline in effective patent life has resulted in a mean effective patent life of less than 10 years since the mid 1960s and no more than 6 years since the early 1980s, except for the cohort marketed in 1987. 3. The largest contribution to total development time was made by the clinical phase. For NCEs marketed in the mid 1960s it was 3.3 years increasing to a peak of almost 8 years in the early 1980s, and representing on average two-thirds of research and development time. 4. Between 1960 and the early 1970s total development time for central nervous system (CNS) agents, cardiovascular products and anti-infectives had doubled to 9, 8 and 7.3 years respectively. By the 1980s it was averaging 13 years for CNS agents and was 54% and 28% longer than for anti-infectives and cardiovascular compounds respectively.
1 A total of three hundred and nineteen new chemical entities (NCEs) were investigated in man for the first time between 1964 and 1985 by seven UK-owned pharmaceutical companies. The majority (96.2%), were self-originated by the UK company or one of its overseas subsidiaries. 2 There was an increase in the number of NCEs investigated each year in man, doubling from an average of 12 per year up to 1980, to over 20 per year between 1981 and 1985. The majority of first drug evaluations in human volunteers were carried out in the UK (92.2%), in contrast to evaluation of new medicines in patients, where 42.9% were first tested outside the UK. 3 The majority of NCEs evaluated in man (78%), were in four therapeutic classes: anti-infectives (32%), anti-allergics (22%), drugs acting on the central nervous system (13%) and cardiovascular system agents (11%). 4 By the end of 1985, 49 (15.4%) of these NCEs had been marketed in the UK and 198 (62.0%) discontinued from further development. The main reasons for termination were inappropriate pharmacokinetics in man (39.4%), and lack of clinical efficacy (29.3%). 5 Average development times increased from less than 2 years between 1964 and 1965, to around 8 years in the 1980s with a consequent reduction in the effective patent life.
Human mitral valves (32 floppy and 17 rheumatic) obtained at surgery were analysed and compared with 35 normal (autopsy) valves. Total amounts of collagen, proteoglycan and elastin were increased approx. 3-fold in floppy and rheumatic valves. The water content of rheumatic cusps was lower than normal. The most significant changes in floppy valves were the 59% increase in mean value of the proteoglycan content, a large increase in the ease of extractability of proteoglycans from 26.7 to 57.2% of the total and a 62% increase in mean value of the elastin content in the anterior cusps. Normal human mitral valve cusps contained a mean proportion of 29.3 (and chordae 26.6) type III collagen (as % of total types III + I collagen), the values increasing significantly to 33.2 and 36.3% respectively in chronic rheumatic disease. The ratio observed in floppy valves depended on the extent of secondary surface fibrosis, which could be demonstrated histologically; in valve cusps with considerable secondary fibrosis, the percentage of type III increased significantly (to 34.4%), whereas it decreased significantly (to 25.2%) when fibrosis was negligible. It is concluded that the ratio of collagen types in floppy valves reflects the extent of secondary fibrosis rather than the pathogenesis of the disrupted collagen in the central core of the valve.
A preliminary double-blind, placebo-controlled study of the effects of a 48-h intravenous infusion of nitroglycerin (NG) in 140 patients with acute myocardial infarction has been carried out. The patients were randomised to placebo or active treatment within 12 h of the onset of symptoms. Those patients treated with nitroglycerin showed a significant reduction on both days in systolic blood pressure, haemoglobin concentration, and packed cell volume. There was also a significant reduction in diamorphine usage in the first 24 h. There was a higher incidence (non-significant) of dysrhythmia in the placebo group despite an increased usage of antidysrhythmic therapy. The mortality rate in the placebo group was 13%, and 7.8% in the active treatment group, but this difference was not significant. At the 3-month follow-up, 83% of treated patients as opposed to 60% of placebo group were able to resume normal or near-normal activities. Preliminary findings suggest that intravenous NG may be useful treatment for patients with acute myocardial infarction and a larger-scale trial is warranted.
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On polyacrylamide slab electrophoresis two ferritin species, termed fast and slow, were present in three control and four iron-loaded human hearts. The ratio of the fast to slow species varied between hearts and correlated with the distribution of isoferritins, which had pI values ranging from 4.8 to 5.6. The acidic isoferritins were prominent in all hearts, but one control and the four iron-loaded hearts contained, in addition, basic isoferritins. All ferritins were composed of two subunits, an acidic H type and a more basic HL type, which was the main subunit in normal liver. Hearts with the highest proportions of acidic isoferritin contained the highest proportion of the H subunit.
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Metamizole sodium continues to be used extensively as an analgesic in Poland. This study was the first undertaken to quantify the incidence of agranulocytosis associated with metamizole sodium in Poland, and to compare the findings with those from other countries. Based on data obtained retrospectively from medical records covering the period 1997-2001 in six haematology centres representative of Poland as a whole, the crude estimate obtained was a rate of 0.2 cases per million person-days of use. This is the same order of magnitude as the value from an epidemiological study covering several countries (0.3-4.0).