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Biomedical subjects

T W Meade

Publications and source records attributed to T W Meade.

At least 127 records · Page 7Linked to original sources
PubMed1988

Randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease in men at high risk: design and pilot study.

We report the pilot stage of a double-blind randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease (IHD) in men at high risk. The first objective was to see if levels of factor VII coagulant activity, VIIc, could be reduced without undue difficulty from a mean level of about 115% to about 70% (the level in patients on conventional warfarin doses being about 30%). This was accomplished with a mean daily dose of 4.6 mg warfarin. The international normalized ratio (INR) corresponding to a VIIc value of 70% was about 1.5. The second objective was to assess the risk of bleeding associated with the intended level of anticoagulation. There was no significant excess in the number of actively treated men ever reporting nose bleeds, possible haematuria, rectal bleeding or bruising, although there may have been an increase in the frequency of rectal bleeding in men who did report this symptom. The third objective was to establish the willingness of patients to take part in a trial of this kind. Of those invited to the initial screening examination, 72% attended. Of those invited to enter the treatment phase of the trial, 71% did so. Compliance with trial treatment was at a very high level. The rate of withdrawal from randomized treatment was within acceptable limits, at about 15% over a three- or four-year period. The scientific case for a full trial is strong and the pilot trial shows that it could be accomplished.

Aged↗
PubMed1987

Sources of variability in coagulation factor assays.

Estimates of the components of variation of a number of coagulation factor assays are presented and are compared with those for other haematological and biochemical variables. They have been derived from a study in which fourteen volunteers gave blood samples approximately bi-monthly for three years. The systematic between-batch variation was generally only a small component of the total variation. However, the proportion of the total variation due to differences between people ranged from about 15% in the case of two measures of antithrombin III to about 85% for cholesterol and haemoglobin. For factor VII activity and fibrinogen, the figure was just over 70%. These estimates of the components of variation are not generally available in the literature. In view of the increasing interest in the role of coagulation factors in the pathogenesis of arterial disease, estimates of this kind are needed both for the interpretation of observed relationships as well as for planning sample sizes for future studies.

Analysis of Variance↗
PubMed1987

Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease.

The Northwick Park Heart Study (NPHS) has demonstrated associations of high levels of factor VII coagulant activity (VIIc) and of plasma fibrinogen concentration with the risk of subsequent ischaemic heart disease (IHD). In cross-sectional data from the 2023 white men in NPHS, lifetime duration of smoking was a determinant of initial plasma fibrinogen levels. Fibrinogen levels had apparently begun to fall soon after smoking was discontinued but it was over 5 years before they had returned to levels found in life-long non-smokers. In prospective data, smoking cessation and the adoption or resumption of smoking were associated with a decrease or an increase, respectively, of about 0.15 g/l in plasma fibrinogen. These changes would lower or raise the risk of IHD by about 20%. A switch from cigarettes to cigars was associated with a large increase in fibrinogen. A substantial part of the relation between smoking and IHD appears to be mediated through the fibrinogen concentration. Following changes in body mass, VIIc rose in those who had given up smoking and fell in those who resumed.

Age Factors↗
PubMed1987

Phobic anxiety and ischaemic heart disease.

A prospective study of the relation between scores on the six subscales of the Crown-Crisp experiential index and subsequent incidence of ischaemic heart disease was undertaken among participants in the Northwick Park heart study. Results from 1457 white men aged 40-64 at recruitment showed that phobic anxiety was strongly related to subsequent major ischaemic heart disease (fatal and non-fatal events combined) when other associated variables were taken into account. The phobic anxiety score alone remained significantly associated with ischaemic heart disease when scores on all the subscales were included in the analysis. Phobic anxiety seemed to be particularly associated with fatal ischaemic heart disease but was not associated with deaths from other causes and was no higher in those with a pre-existing myocardial infarction at recruitment than in those without. There was a consistent increase in risk of fatal ischaemic heart disease with score on the phobic anxiety subscale. The relative risk for those whose score was 5 and above was 3.77 (95% confidence interval 1.64 to 8.64) compared with those whose score was 0 or 1. The 49 participants with evidence of myocardial infarction at recruitment had higher scores on the subscales for free floating anxiety and functional somatic complaint. The Crown-Crisp experiential index is simple to fill out and acceptable to patients. When the results are combined with other known risk factors it may be of use in defining high risk subjects and in planning strategies for prevention.

Adult↗
PubMed1987

Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations.

Three restriction fragment length polymorphisms (RFLPs) of the fibrinogen genes were used in 91 individuals to investigate the role of genetic variation at this locus in the determination of plasma fibrinogen. The strongest association was with a polymorphism detected with the beta-fibrinogen probe and the enzyme BclI. The probe detects two alleles, designated B1 and B2. The individuals with the genotype B1B1 had a mean fibrinogen of 2.74 g/l; those with B2B2 had a mean fibrinogen of 3.69 g/l (a level previously associated with a strongly increased risk of ischaemic heart disease); and those heterozygous for the two alleles, with the genotype B1B2, had a mean of 2.98 g/l. Genetic variation at the fibrinogen gene locus accounted for 15% of the total phenotypic variance in fibrinogen.

Female↗
PubMed1987

Increased factor VII coagulant activity in the rabbit following diet-induced hypercholesterolaemia. Evidence for increased conversion of VII to alpha VIIa and higher flux within the coagulation pathway.

Factor VII coagulant activity (VIIc) is considerably higher in rabbits fed a 1% cholesterol-supplemented diet than in rabbits fed a standard diet. This increase was statistically significant 4-6 days from the beginning of treatment and rose to about 300% during the 100 days of treatment. Treatment is also associated with a 20-fold increase in plasma cholesterol concentration with the major fraction of excess cholesterol associated with the very low and intermediate density lipoprotein fractions. In both groups of rabbits, the direction and extent of variation in VIIc generally coincided with variation in cholesterol, so that over time there were significant and positive correlations between plasma cholesterol concentration in both the rabbits fed the standard diet and the rabbits fed the cholesterol-supplemented diet. The increase in VIIc was due to a higher proportion of the more active alpha VIIa in the plasma of hypercholesterolaemic rabbits rather than to an increase in the concentration of the single-chain protein. The plasma concentration of factor X and prothrombin had increased in the hypercholesterolaemic rabbits by 10 days from the beginning of treatment and both proteins were maintained at 150-200% of the concentrations in the plasma of rabbits fed the standard diet. However, these differences were only seen when the factor X and prothrombin were assayed using synthetic substrates. The specific coagulation assays for these two factors revealed no differences between the groups of animals up to 100 days.

Animals↗
PubMed1987

Hypercoagulability and ischaemic heart disease.

Thrombogenesis is increasingly recognised as an immediate cause of most major clinical episodes of ischaemic heart disease (IHD) and the haemostatic system makes a significant contribution to the development of atheroma. It is therefore important to consider how far concepts of increased thrombotic tendency and hypercoagulability can be demonstrated in reality. A number of general observations do suggest that characteristics of the circulating blood influence the course of events in IHD--for example, the occurrence of IHD or stroke in young women using oral contraceptives in whom advanced arterial wall changes are not a feature. Epidemiologically, the coagulation system has been more rewarding than the study of platelets. The Northwick Park Heart Study (NPHS) has demonstrated a strong relationship between the level of factor VII activity and the later incidence of IHD. Several biochemical characteristics of factor VII suggest that this relationship may well be one of cause and effect. There is growing evidence that high levels of factor VII activity lead to high levels of thrombin production. In addition to NPHS, three other prospective studies have shown an association between high levels of plasma fibrinogen and IHD incidence. Again, there are several reasons for believing that this association, too, is of pathogenetic significance. Dietary fat intake is a major determinant of the factor VII activity level, and smoking of the fibrinogen level. Hypercoagulability determining IHD is best defined, on present evidence, as over-activity of procoagulatory influences (whereas hypercoagulability leading to venous thrombosis is predominantly manifested as underactivity of natural defence mechanisms).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Disorders↗
PubMed1987

Skinfold thickness and cardiovascular risk factors.

The relation of blood pressure, serum cholesterol, plasma fibrinogen, and coagulation factor VIIc with skinfold thickness at four sites (forearm, triceps, suprailiac, and subscapular) was examined in 2,948 white participants in the Northwick Park Heart Study. When considered separately, all four skinfolds were significantly associated with the four cardiovascular risk factors in males. Of the two limb skinfolds, forearm was consistently more strongly associated than triceps with the risk factors. The magnitude of the association between forearm skinfold and the risk factors was similar to that of the two trunk skinfolds, suprailiac and subscapular. Multiple regression analysis suggested an independent association of forearm skinfold with cholesterol and blood pressure in males when the other skinfolds were taken into account. There was no consistent difference in the strength of the associations of the two trunk skinfolds with the risk factors. With the exception of systolic blood pressure, the associations between the cardiovascular risk factors and skinfold thickness in males were stronger at younger ages. In the case of females the findings were somewhat different. The associations with the four risk factors were consistently stronger for the two trunk skinfolds than the limb skinfolds. Triceps was somewhat more strongly associated with the risk factors than forearm skinfold except for plasma fibrinogen. Thus there are sex differences in the association of the distribution of subcutaneous fat with cardiovascular risk factors.

Adolescent↗
PubMed1987

Relation between cigarette smoking and use of hormonal replacement therapy for menopausal symptoms.

The aim of this study was to characterise new users of hormonal replacement therapy (HRT) for the relief of menopausal symptoms and to compare these women with never-users of HRT; 402 new users and 804 never-users were studied. Hot flushes were the most common symptom in both users and non-users and were the most frequent reason for prescribing HRT. The prevalence of menopausal symptoms in non-users of HRT was high although substantially lower than that in users. HRT users were more likely to be current cigarette smokers than were never-users. There was also, within smokers, a significant relation between the number of cigarettes smoked and the likelihood of using HRT. This relation between HRT use and smoking could result from an anti-oestrogen effect of smoking, intensifying menopausal symptoms. Of potential clinical relevance is the suggestion that a proportion of women using HRT may be doing so in order to alleviate smoking-induced symptoms. Users of HRT were also more likely to have used oral contraceptives than were never-users; this relation was probably behavioural.

Climacteric↗
PubMed1986

Randomised trial of community-based centre versus conventional hospital management in treatment of alcoholism.

151 problem drinkers (105 men and 46 women) were recruited from the general medical and psychiatric services of a district general hospital and were allocated randomly to a community-based day centre (ACCEPT) or standard hospital inpatient and outpatient services. 115 patients (79%) were followed up at 12 months. The group as a whole showed improvement in all outcome indices at the 3-month follow-up, and this was maintained at 6 and 12 months. Patients assigned to ACCEPT services claimed to have reduced their alcohol intake (55%) more than their hospital counterparts (37%), and this was confirmed by their informants. Patients referred from the psychiatric services reduced their alcohol intake more than those from general medical services. It is concluded that treatment at a community day centre is at least as cost effective as hospital treatment of alcohol abuse.

Adolescent↗