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Biomedical subjects

T W Meade

Publications and source records attributed to T W Meade.

At least 37 records · Page 2Linked to original sources
PubMed2000

Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.

BACKGROUND: Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease. METHODS: 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels. RESULT: At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024). CONCLUSIONS: Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.

Aged↗
PubMed1999

Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study.

OBJECTIVE: To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women's stated willingness to participate. DESIGN: Quasirandomised, interview based study. SETTING: 10 group practices in the Medical Research Council's General Practice Research Framework. PARTICIPANTS: 436 postmenopausal women aged 45-64 who had not had a hysterectomy. MAIN OUTCOME MEASURES: Stated willingness to enter a trial and reasons for the decisions made. RESULTS: Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health. CONCLUSION: For preventive trials the inclusion of a placebo arm may reduce patients' willingness to participate.

Algorithms↗
PubMed1999

Haemostatic function, arterial disease and the prevention of arterial thrombosis.

Recent years have seen the expansion of information linking raised plasma levels of individual clotting factors and evidence of disturbances of fibrinolytic activity with the risk of thrombotic manifestations of arterial disease, both in community-based, apparently healthy populations and in patients with known atherosclerosis. Some of these prothrombotic changes in the haemostatic system may result partly from underlying chronic inflammation or acute infection and may, in turn, contribute substantially to the thrombotic risk which accompanies these underlying processes. The importance of the coagulation system in the pathogenesis of arterial thrombosis is further illustrated by the benefit in the Thrombosis Prevention Trial of low-intensity, dose-adjusted warfarin in the primary prevention of ischaemic heart disease. Clinical trials of bezafibrate, which is being used for its fibrinogen-lowering as well as lipid-modifying properties, are in progress.

Animals↗
PubMed1999

HRT and cardiovascular disease.

Conclusions influencing clinical decisions about the effects of hormone replacement therapy (HRT) on cardiovascular disease have undergone major revisions over the last 30 years. Assumptions in the early 1970s that HRT would increase thromboembolic conditions were reversed in the 1980s, when the first formal studies seemed to indicate a cardioprotective effect. The Heart and Estrogen/progestin Replacement Study (HERS) has, however, very recently suggested that HRT does not affect the incidence of coronary heart disease (CHD) one way or the other. These roller-coaster changes of direction have made decisions by doctors and their patients about the long-term use of HRT extremely difficult and need to be replaced by the stability that only further randomised controlled trials (RCTs) can now provide.

Cardiovascular Diseases↗
PubMed1999

Clinical examination for abdominal aortic aneurysm in general practice: report from the Medical Research Council's General Practice Research Framework.

At the time of the 1992-1994 annual reviews in the thrombosis prevention trial, general practitioners (GPs) carried out clinical examination for aneurysms by abdominal palpation in 4171 men. When an aneurysm was suspected, the patient was referred to hospital for further investigation. Aneurysm was suspected in 60 men (1.4%) and confirmed in 25 (0.6%), the mean diameter of confirmed aneurysms being 5.0 cm (range = 3.1-8.0 cm). Of the 25 men in whom aneurysm was confirmed, 10 (40%) underwent elective surgery and one died while under investigation. Examination by abdominal palpation for aortic aneurysm, which is not widely used in either general practice or in hospital practice, other than vascular surgery, is clinically worthwhile even though not all aneurysms will be detected by this means.

Aged↗
PubMed1998

Associations of protein C and protein S with serum lipid concentrations.

Difficulties in the laboratory measurement of protein C and protein S levels cause problems in the diagnosis of deficiency states in individual patients and may complicate estimation of the prevalence of these states in the general population. Some difficulties may be due to unappreciated influences affecting the measured levels of proteins C and S. We measured protein C activity and antigen, total and free protein S antigen, and serum total cholesterol, high-density cholesterol and triglyceride in a community-based study of 150 adults (73 male, 77 female), age range 23-80 years. Participants were identified from the list of a single general practice by stratified random sampling within sex and decade of age. Protein C activity and antigen were strongly associated with serum lipids, mean levels increasing by approximately 0.25 u/ml as total cholesterol and triglyceride concentration each rose from the 5th to 95th centile. Total protein S antigen concentration was associated with total cholesterol, the mean rising by over 0.1 u/ml as total cholesterol increased from the 5th to the 95th centile, whilst a similar rise in triglyceride was associated with an increase in mean free protein S of more than 0.3 u/ml. Overall, physiological variation in total cholesterol and triglyceride concentration was associated with significant variation in protein C and protein S levels, independent of age and sex, suggesting that it is important to take serum lipids into account when investigating patients for protein C or protein S deficiency. Failure to do so may be misleading in some circumstances.

Adult↗
PubMed1998

The psychological impact of screening for risk of coronary heart disease in primary care settings.

AIMS: A prospective study was conducted to identify the psychological impact of labelling middle-aged men as having above average risk for coronary heart disease. A second aim was to find out the psychological effect of participation in a subsequent clinical trial. METHODS: 5813 men attended nine special screening clinics in England and Scotland for baseline measurement of psychological symptoms and coronary disease risk factors. Each man was later informed of his risk status by letter as either above average risk (high-risk) or no special risk (low-risk). In three clinics some men also received an intermediate risk (moderate-risk) between high-risk and low-risk. Follow-up psychological measurements were made after labelling and 3 months later. RESULTS: Men who received either the high-risk label (n=838) or the low-risk label (n=3114) showed a decrease in reported psychological symptoms after labelling. Men receiving the unexpected intermediate risk (moderate-risk) label, which communicated specific test abnormalities, increased their psychological symptoms to 'case' levels on the General Health Questionnaire; relative risk (compared with low-risk) was 1.80 (95% confidence interval 1.19-2.71) after adjustment for confounding factors. Compliers with a subsequent clinical trial decreased their risk of becoming cases and, if ill at trial entry, increased their case remission rate. CONCLUSIONS: The ascription of an 'above average risk' label for coronary disease to middle-aged men does not adversely affect the psychological state of those who receive it if they have received preparation for risk labelling. However, communicating abnormal coronary disease test results without adequate preparation confers short-term psychological harm. Non-specific support from familiar general practice professionals received by participants in a clinical trial reduces the risk of psychological ill-health. All coronary disease screening programmes should include adequate pre-labelling preparation for all risk labels and abnormal results.

Aged↗
PubMed1998

Sex differences in the determinants of fibrinolytic activity.

Impaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice. Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein. Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only "global" measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.

Adult↗
PubMed1997

Community studies of the health service implications of low back pain.

STUDY DESIGN: Retrospective study using primary care physician case notes and a self-report questionnaire on the same randomly selected population sample. OBJECTIVES: To assess the prevalence, management, and outcomes of low back pain in the community, comparing, in the same random sample of registered patients, self-report questionnaire data and primary care physicians' records. SUMMARY OF BACKGROUND DATA: The financial and resource implications of low back pain are extensive. Data on consultations, investigations, and the management of low back pain are fragmentary and there are no comparisons estimating prevalence from case notes and self-report. METHODS: A retrospective study of prevalence, management, referral, and outcome covering the previous 12 months was carried out in three general practices using case notes and a self-report postal questionnaire on a sample of 900 patients over 18 years. RESULTS: Lifetime prevalence of low back pain was 62%. Annual prevalence was 48%, with 16% reporting low back pain at the time of report. Twenty-four percent consulted their primary care physician for low back pain, of whom 17% were referred to a hospital specialist. The annual consultation rate of patients with low back pain was similar to the rate for patients with chronic conditions. The activities of daily living were restricted in less than half, with few taking sick leave. The general health status of those reporting recent low back pain was significantly lower than those not reporting low back pain. Most felt that low back pain was self-limiting and would not consult health professionals for future episodes. There were substantial discrepancies between case notes recorded at consultation with the primary care physician and self-report regarding consultation and investigations. CONCLUSIONS: Prevalence rates were comparable with those reported in other studies. The significant discrepancies between data sources suggest patient recall bias or underrecording in case notes. The low consultation rate, time off, and day-to-day disability indicate that most episodes are self-limiting.

Adolescent↗
PubMed1997

Plasminogen activator inhibitor-1, the acute phase response and vitamin C.

Epidemiologial studies suggest that elevated plasma plasminogen activator inhibitor-1 (PAI-1) activity is associated with ischaemic heart disease. Based on our earlier work suggesting a link between plasma fibrinogen, infection and low vitamin C status, we sought to determine whether similar relationships existed for PAI-1 activity. We performed a longitudinal study of cardiovascular disease risk factors in 96 volunteers aged 65-74 years, living in the community in Cambridge. Each subject was visited at home 7 times over a 14 month period. Plasma PAI-1 activity, serum ascorbate, markers of the acute phase response, serum lipids and other cardiovascular disease risk factors were measured on each occasion. In a multiple regression analysis, the three significant predictors of PAI-1 activity were body mass index (P = 0.0001), blood neutrophil count (P = 0.03) and, inversely, serum ascorbate (P = 0.003). The inverse relationship between PAI-1 activity and serum ascorbate persisted even when vitamin C supplement takers or smokers were excluded from the analysis. Serum ascorbate was strongly related to estimated dietary intake of vitamin C (P < 0.0001). Low serum ascorbate is associated with high PAI-1 activity which is, in turn, associated with increased ischaemic heart disease risk. We hypothesise that activation of the acute phase response by infection could increase PAI-1 activity and, consequently, also increase the risk of coronary artery thrombosis. Furthermore, we suggest that vitamin C could attenuate this response.

Acute-Phase Reaction↗
PubMed1997

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. The Oxford Cholesterol Study Group.

The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12.10% +/- 6.08 of standard; 2P < 0.05) and non-significantly lower factor VII coagulant activity (8.24% +/- 4.99 of standard) and fibrinogen concentrations (0.10 +/- 0.08 g. l-1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2.62 +/- 1.03 IU; 2P < 0.01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1.2, factor XII and C1 inhibitor). Total free fatty acid concentration was marginally significantly reduced (2P = 0.02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1.74 +/- 0.15 mmol.1(-1): 2P < 0.0001) but also in VLDL cholesterol (0.28 +/- 0.08 mmol.1(-1); 2P < 0.001) and IDL cholesterol (0.17 +/- 0.03 mmol.1(-1); 2P < 0.0001). There were also lower triglyceride levels associated with LDL (0.07 +/- 0.01 mmol.1(-1); 2P < 0.0001), IDL (0.03 +/- 0.01 mmol.1(-1); 2P < 0.01) and VLDL (0.27 +/- 0.14; 2P = 0.05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA reductase inhibitors (and of the newer fibrates which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.

Adult↗