Biomedical subjects

A E Fletcher

Publications and source records attributed to A E Fletcher.

At least 91 records · Page 5Linked to original sources

PubMed1992

Cognitive function and angiotensin-converting enzyme inhibitors in comparison with other antihypertensive drugs.

This review mainly considers randomized studies where angiotensin-converting enzyme (ACE) inhibitors were compared with other antihypertensive drugs in terms of objectively assessed cognitive function, subjectively evaluated cognitive function, work performance, and general vitality. An overall assessment of the data suggests that ACE inhibitors may improve performance on tests of alertness but it is unlikely that they produce either deleterious or beneficial effects on memory. On the other hand, methyldopa interferes with cognitive function and work performance. Propranolol was also associated with impairment of activity and satisfaction at work. In subjective evaluation of cognitive function, two trials suggest an increased reporting of impairment with nifedipine but this has not yet been confirmed. Vitality was reduced on both methyldopa and propranolol. It is concluded that the ACE inhibitors, in common with atenolol and verapamil, do not appear to have any major effects on cognitive function in hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed1992

Quality of life with three antihypertensive treatments. Cilazapril, atenolol, nifedipine.

A multicenter, randomized double-blind study of 6 months' duration was performed in 540 patients (average age 54 years, 57% male) with mild-to-moderate essential hypertension to determine the relative effects on quality of life of cilazapril, atenolol, and nifedipine retard. Quality of life was assessed by using both a self-administered and an interviewer-administered questionnaire; the assessment included a complaint score (symptoms checklist), Health Status Index, assessment of work satisfaction, Psychological General Well-being Index, Profile of Mood States subscales, and life satisfaction assessment. Psychomotor function was measured by the Reitan Trail Making test B. At the end of the trial, diastolic blood pressure had fallen by an average of 15 mm Hg in all three groups, but significantly (p = 0.01) more patients taking cilazapril required the addition of a diuretic (36%) compared with those taking atenolol (25%) or nifedipine retard (24%). No significant differences in quality of life were observed between cilazapril and atenolol during the trial. Symptomatic complaints increased on nifedipine retard (p = 0.02) and contributed to a higher discontinuation rate (21% discontinued treatment compared with 13% and 14% taking atenolol and cilazapril, respectively, p = 0.04). However, a possible improvement in the fatigue subscale (p = 0.04) was also observed on nifedipine retard. The 95% confidence intervals showed that none of the drugs in this trial produced an effect equivalent to that previously reported between captopril and methyldopa in the Psychological General Well Being Index or between captopril and methyldopa or propranolol in Trail Making test B.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Relation between blood pressure and stroke mortality.

The relation between stroke mortality and blood pressure was investigated in 10,186 hypertensive patients followed up in the Department of Health Hypertension Care Computing Project for an average of 9 years. An untreated blood pressure measurement was available in 3,472 men and 3,405 women. The age-adjusted risk of stroke death increased by 1% for every 1 mm Hg increase in untreated systolic blood pressure. The relative hazard rate was 1.014 (95% confidence interval [CI], 1.007, 1.021) in men and 1.009 (1.003, 1.016) in women. The corresponding increases for 1 mm Hg for untreated diastolic blood pressure were almost 3% in men and again 1% in women (relative hazard rate 1.026 [95% CI, 1.014, 1.038] in men and 1.010 [1.000, 1.021] in women). Treated blood pressure measurements were available in 3,073 men and 3,148 women. Stroke mortality increased by 2% for a 1 mm Hg increase in treated systolic pressure and 3% for the corresponding increase in diastolic blood pressure. The relation between stroke mortality and blood pressure was similar over and under the age of 65, although the increase in mortality with pressure was greater for treated diastolic blood pressure in women under the age of 65 than over this age. There was no evidence for a J-shaped relation between stroke mortality and either systolic or diastolic pressure in men. In women there was a suggestion of such a relation, but since this relation was also observed for untreated pressures, any increase in risk at lower pressures is unlikely to be a result of treatment.

Blood Pressure↗

PubMed1992

Pharmacoeconomic evaluation of risk factors for cardiovascular disease: an epidemiological perspective.

Over the past 30 years the identification of high blood pressure and hypercholesterolaemia as major predictors of cardiovascular disease has led to an increasing expenditure on healthcare costs in pharmacological treatment of these risk factors. Most of the cost has been due to antihypertensive treatment, but evidence from randomised trials of the benefits of cholesterol-lowering drugs, along with the introduction of therapies with fewer side effects, suggests that expenditure on cholesterol treatment will rise dramatically. Cost-effectiveness analyses can aid decision making in the use of these treatments. For both hypertension and hypercholesterolaemia, the most favourable cost-effectiveness ratios were found in late middle age, in men compared to women, at the highest level of the risk factor, and in subjects with multiple risk factors. The most cost-effective treatments appear to be those which were the cheapest and which also produced the largest reductions in the risk factor. However, certain findings were based on assumptions which may be invalid. The most important of these in hypertension, and to a lesser extent in hypercholesterolaemia, is that different treatments have similar effects on morbidity and mortality for a given level of risk reduction. Experimental evidence that might confirm or refute this is not available for most treatments of hypertension. Moreover there are no trials in women or in the elderly of cholesterol-lowering treatments. The burden of disease due to these risk factors has been underestimated, and further research is required to establish the benefits of treatment on prevention of conditions such as heart failure, peripheral vascular disease, and vascular dementia.

Adult↗

PubMed1992

Quality of life evaluation of antihypertensive drugs.

Eleven studies (10 randomised controlled trials and 1 large open study) that evaluated quality of life (QOL) are reviewed. The areas of QOL measured by the studies are compared and a consensus is reported that health-related QOL measures in patients with hypertension should include: symptomatic and psychological well-being, activity (work, leisure, sleep, sexual activity and social participation), cognitive function and life satisfaction. Recommended methods for measuring these aspects of QOL are noted. Seven studies included atenolol as 1 of the treatments and the effects of this drug on QOL are reviewed. The drug appears to maintain QOL as well as the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril and cilazapril. One trial also suggests that verapamil maintains QOL as well as atenolol, although this was not suggested by the nonrandomised study. Nifedipine slow release (SR) and propranolol both fared worse than atenolol in 2 separate trials, but 1 trial suggested that nifedipine gastrointestinal therapeutic system (GITS) was preferred to atenolol in terms of QOL. In the latter study, however, only patients completing the prescribed therapy revealed a preference for nifedipine GITS; this was absent in an intention-to-treat analysis. The rate of discontinuation of nifedipine therapy was high, underlining the necessity for an intention-to-treat analysis in trials assessing QOL.

Antihypertensive Agents↗

PubMed1992

Aging, blood pressure and mortality.

UNLABELLED: POPULATION STUDIES: We reviewed population studies that relate mortality to blood pressure in the elderly. A positive relationship between blood pressure and mortality at the age of 60-69 years was weaker over the age of 75 and became a negative relationship over the age of 85, with hypertensive subjects living longer. This negative relationship probably reflects cardiac, respiratory and neoplastic disease in very elderly subjects with low blood pressure. Therefore, in very elderly hypertensive subjects we cannot conclude that a reduction in blood pressure will not be beneficial, for example in reducing stroke events. CLINICAL TRIALS: The results of clinical trials of antihypertensive treatment in the elderly provide inadequate evidence to assess the benefit of treating hypertensive subjects over the age of 80 years. A randomly allocated controlled trial is required in this age group.

Aged↗

PubMed1992

Prevalence of venous disease: a community study in west London.

OBJECTIVE: To find out the prevalence of venous disease in patients aged between 35 and 70 years. DESIGN: Self-administered questionnaire. SETTING: Community study in west London, England. SUBJECTS: A random sample of 2,103 patients aged between 35 and 70 years who were registered with three general practices. RESULTS: 1,338 (64%) subjects filled in the questionnaires. Of these, 323/1,303 (25%) said that they had varicose veins, 81/1,338 (6%) had a deep vein thrombosis or pulmonary embolism, and 52/1,336 (5%) said that they had had phlebitis. In addition, 94/1,326 (7%) had worn support stockings, and 84/1,304 (6%) had been treated with anticoagulants at some time; 31% of responders reported that they had had some form of venous disease. CONCLUSIONS: Increased age and female sex were independent risk factors for varicose veins and phlebitis. Thrombosis and pulmonary embolism were both significantly associated with the presence of diabetes, female sex, and increased age. The facts that a quarter of the sample had varicose veins, and that nearly a third had had venous disease of some kind at some time, suggest that venous disease may place a heavier burden on health resources than had been realised.

Adult↗

PubMed1992

A questionnaire to assess risk factors, quality of life, and use of health resources in patients with venous disease.

OBJECTIVE: To test the accuracy and usefulness of a questionnaire to assess risk factors and symptoms of venous disease, quality of life, and dependence on health and social services. DESIGN: Case-control study. SETTING: Multicentre study in three general practices. SUBJECTS: Patients drawn from a larger investigation of prevalence of venous disease. RESULTS: Patients who had venous disease were taller and heavier and had spent more time standing at work than those who did not. It was strongly associated with both number of pregnancies and number of children. There were weak but not significant associations with the wearing of a corset, constipation, and a family history of venous problems. CONCLUSIONS: The questionnaire was able to pick out recognised risk factors, and is suitable for use in studies of patients with venous disorders. It may also provide information about factors that have not yet been accepted. The case-control study is an appropriate way of assessing not only risk factors, but also signs and symptoms, quality of life, and use of health resources in patients with venous disease.

Case-Control Studies↗

PubMed1992

Quality of life on antihypertensive therapy: a double-blind trial comparing quality of life on pinacidil and nifedipine in combination with a thiazide diuretic. European Pinacidil Study Group.

The quality of life (QL) was evaluated in a 6 month double-blind trial in six European countries. Patients with a sustained supine diastolic blood pressure (SDBP), phase V, of 95 mm Hg or more on bendrofluazide, 5 mg daily (or an equivalent dose of a thiazide diuretic) were randomised to additional pinacidil (n = 127), 25 mg up to 100 mg daily, or nifedipine (n = 130), 20 mg up to 80 mg daily. The treatment groups were similar at entry for QL scores, average DBP of 103 +/- 6 (SD) mm Hg, and average age of 56 +/- 10 (SD) years. Eighteen patients on pinacidil and 12 on nifedipine withdrew due to side effects, such as oedema (both drugs) and flushing (nifedipine). The maximum antihypertensive effect was achieved within 6 weeks and maintained, resulting in a significant fall in SDBP of 13.7 mm Hg on pinacidil and 15.5 mm Hg on nifedipine at the end of the trial. There was no significant difference in the antihypertensive effect. The target SDBP was achieved in 57% of pinacidil-and 63% of nifedipine-treated patients. The average number of symptomatic complaints fell in both groups, with significant decreases in the reporting of blurred vision and headaches on nifedipine. Complaints of growth of body and facial hair increased on pinacidil but there were no significant between-drug comparisons with respect to side effects. In measures of psychological well being, patients on pinacidil showed a significant (p less than 0.05) improvement in total and cognitive function scores compared to nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Epidemiological aspects of cardiovascular disease in the elderly.

BACKGROUND: Cardiovascular disease is the leading cause of death in the elderly in industrialized societies. However, in the elderly, unlike middle-aged subjects, little attention has been paid to strategies for reducing morbidity and mortality from this disease. OBJECTIVES: To review studies of risk factors for cardiovascular diseases in the elderly and the evidence, if any, of risk factor modification. FINDINGS: Overall, the evidence suggests that the established risk factors for cardiovascular disease in middle-aged subjects persist into old age. Several studies have shown that serum cholesterol is positively associated with a risk of coronary heart disease. In the very elderly, U-shaped distributions have been reported for the relationship between cholesterol and total mortality, probably as a result of other confounding factors. At present there is little experimental evidence of benefits from lowering cholesterol in the elderly. In contrast, several randomly allocated, placebo-controlled trials have established the benefits of blood pressure reduction (systolic or diastolic) up to the age of 84 years. A high blood pressure in the very old probably remains a risk factor, but prospective studies have reported non-linear relationships. Smoking has been reported to be a risk factor in the elderly in some, but not all studies. CONCLUSIONS: At present, only the treatment of high blood pressure can be definitively recommended in the elderly. The effects of both dietary and pharmacological modification of cholesterol need to be investigated.

Aged↗

PubMed1991

Structure-activity relationships in calcitonin gene-related peptide: cyclic AMP response in a preosteoblast cell line (KS-4).

Synthetic analogs of chicken and human CGRP were used to define structure-function relationships in a murine osteoblast precursor cell line, KS-4, that exhibits a substantial cyclic AMP response to CGRP but no response to calcitonin. Human CGRP had 40% of the activity of chicken CGRP, but [Asp-14]-human CGRP was equipotent with chicken CGRP. Similar observations were made previously for calcium- and phosphate-lowering effects. Des-1-Ala,deamino CGRP compounds of both human and chicken origin were three-fold more potent than the respective native CGRPs. The [4-F-Phe)-37]-chicken CGRP analog had a four-fold enhanced activity. In all of the 13 analogs either truncated amino-terminally or missing the (2-7)-disulfide bridge, biologic activity was greatly reduced (0.1% of chicken CGRP), as it was in chicken CGRP-(1-36)-OH, which lacks the C-terminal amino acid. The same analog has been shown to retain a hypocalcemic effect, which is most likely mediated through calcitonin receptors. In confirmation of their antagonistic effect reported in liver, analogs that lack the N-terminal ring structure exhibited significant antagonistic activity. The data illustrate the specificity of CGRP receptors in promoting cyclic AMP formation in osteoblast-like cells. Such CGRP analogs will be useful in investigating structure-function relationships of CGRP.

Animals↗

PubMed1991

The effects of two centrally-acting anti-hypertensive drugs on the quality of life.

The objectives of this study were to compare the effects of two centrally-acting antihypertensive drugs on measures of quality of life in a three-month double-blind trial of hypertensive patients randomized to methyldopa (n = 79) or rilmenidine (n = 78). We studied men and women aged over 21 y attending eight hospital out-patient clinics in the United Kingdom. They had average diastolic blood pressures between 95 and 110 mm Hg and systolic pressures below 210 mm Hg after a 4-week placebo run-in period. The doses ranged from 1 to 2 mg daily of rilmenidine and 500 mg to 1 g of methyldopa. Hydrochlorothiazide (25 mg daily) was added after 8 weeks when the diastolic blood pressure remained at 90 mm Hg or more in 29% of patients on rilmenidine and 35% of those on methyldopa. Quality of life was assessed from self-completed questionnaires using standardized instruments. Both drugs reduced blood pressure, but at the end of the trial the fall in the methyldopa group (19.3/13.0 mm Hg) was significantly greater than in the rilmenidine group (13.2/10.0 mm Hg). Ten patients in the methyldopa group withdrew from the trial compared with three in the rilmenidine group, primarily because of adverse effects. In both groups there was a significant increase in the overall reporting of adverse effects. Reports of dry mouth increased on both drugs, and sleepiness on rilmenidine but not methyldopa. There was no significant difference between the drugs in the overall reporting of adverse effects or of individual adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1991

Adverse treatment effects in the trial of the European Working Party on High Blood Pressure in the Elderly.

Adverse treatment effects were assessed in 840 elderly hypertensive patients randomly assigned to active treatment (a combination of triamterene and hydrochlorothiazide) or placebo; methyldopa was added to the regimen in one third of the treated patients. Symptoms of dry mouth, nasal stuffiness, and diarrhea were reported by significantly more treated patients than placebo control subjects. More patients receiving diuretics plus methyldopa than diuretics alone reported dry mouth and diarrhea. Significantly more treated patients than control subjects showed evidence of a high serum creatinine level, mild hypokalemia, and gout. More treated patients tended to have diabetes. The benefits of treatment outweighed these adverse treatment effects.

Aged↗

PubMed1991

The assessment of the relationship between blood pressure and sodium intake using whole-day, daytime and overnight urine collections.

The usefulness of whole-day, daytime (waking to retiring time) and overnight urine samples for assessing the relationship between blood pressure and sodium intake was examined in 301 male London civil servants, aged from 37 to 58 years old. Systolic blood pressure (SBP)/diastolic blood pressure (DBP) averaged 126/78 mmHg and the 24-h urinary excretion of sodium and potassium was 174 and 73 mmol, respectively. There was poor consistency between day- and night-time urine samples with respect to both sodium and potassium content. The urinary excretion of sodium and potassium was lower (P less than 0.001) in overnight than in daytime samples. After standardization for creatinine, the night: day ratio was 0.79 for sodium output and 0.55 for potassium excretion. Blood pressure, adjusted for age and body mass index, was significantly and positively correlated with overnight sodium excretion (SBP/DBP: slope = 0.061/0.046 mmHg/mmol) whereas the correlations with sodium excretion in daytime (0.010/0.004 mmHg/mmol) and whole-day (0.024/0.016 mmHg/mmol) urine samples were not significant. Blood pressure was significantly correlated with the sodium:potassium ratio in whole-day urine (1.941/1.968 mmHg/unit). As the agreement between daytime and overnight urine samples was low with respect to both sodium and potassium content, and due to the fact that the relationship between blood pressure and sodium in overnight samples may at least partially reflect pressure diuresis, overnight urinary sodium, even if related to sodium intake, cannot be employed to assess the association between salt in the diet and blood pressure.

Adult↗

PubMed1991

Pharmacological specificity of novel, synthetic, cyclic peptides as antagonists at tachykinin receptors.

1. The interaction at tachykinin receptors of a series of novel cyclic hexapeptides has been examined by use of radioligand binding assays (NK1 and NK3 sites in rat cortex, NK2 sites in hamster urinary bladder) and functional pharmacological assays (guinea-pig ileum, rat vas deferens and rat portal vein for NK1, NK2 and NK3 receptors, respectively). 2. The compounds cyclo(GlnTrpPhe(R)Gly[ANC-2]LeuMet) (L-659,837) and cyclo(GlnTrpPheGly-LeuMet) (L-659,877) were powerful and selective displacers of NK2 binding (pIC50 6.9 and 8.0, respectively), and were competitive antagonists of responses to stimulation of NK2 receptors in rat vas deferens (pKB for antagonism of responses to eledoisin 6.7 and 8.1, respectively). Responses in the NK1 and NK3 pharmacological assays were blocked only weakly, if at all. 3. In the longitudinal muscle of the small intestine of the rat, responses to stimulation of the putative NK2 receptor by eledoisin, neurokinin A or neurokinin B were antagonized by both cyclo(GlnTrpPhe(R)-Gly[ANC-2]LeuMet) and cyclo (GlnTrpPheGlyLeuMet) in a manner consistent with the presence in this tissue of a uniform population of receptors, indistinguishable from the NK2 receptor of the rat vas deferens. 4. The compounds cyclo(GlnTrpPheGlyLeuMet) and the lactam-containing analogue are among the most selective antagonists for the NK2 receptor that have been described; their availability should be of value in the characterization of the receptors mediating responses to tachykinins, and in elucidating the physiological functions of the tachykinin receptors.

Amino Acid Sequence↗

PubMed1990

Economic assessments in randomized controlled trials.

When comparing costs and benefits of different medical strategies, cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis may be used. Both direct and indirect costs and benefits must be considered. Integrating survival with a measure of quality of life such as a health status index permits calculation of quality of life adjusted years of survival (QALYS). In any trial where it is expected that a more expensive treatment is the most effective, a full economic assessment should be made. Examples are provided from the use of verapamil and propranolol in hypertension, naftidrofuryl in stroke and auranofin in the treatment of rheumatoid arthritis.

Cost-Benefit Analysis↗

PubMed1990

Measuring costs and financial benefits in randomized controlled trials.

Economic assessment can be incorporated into clinical trials to evaluate and compare the costs and benefits of different health care programs. In this article the three main types of evaluation are discussed: cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis. The measurement of direct and indirect costs is described and specific examples are quoted. Full economic analyses are given for the use of naftidrofuryl in the treatment of acute cerebral hemisphere infarction and the use of auranofin in the treatment of rheumatoid arthritis. Economic evaluation is seen to be justified whenever a more expensive treatment is expected to produce greater benefit. Such analyses should consider quality of life and health status, as well as the more easily identifiable outcomes.

Arthritis, Rheumatoid↗

PubMed1990

Blood cadmium in London civil servants.

Blood cadmium was measured in 466 randomly selected London civil servants not exposed to heavy metals at work. Blood cadmium ranged from 3.6 to 75.6 nmol/L (0.4 to 8.5 micrograms/L) with a geometric mean of 6.4 nmol/L (0.7 micrograms/L) in nonsmokers and 13.6 nmol/L (1.5 micrograms/L) in smokers (p less than 0.001). Blood cadmium was higher in women than in men (9.5 versus 7.8 nmol/L) and was inversely correlated with employment grade (p less than 0.001). The associations with age, body weight and alcohol intake were not significant. After adjusting for gender and the number of cigarettes smoked per day, 36% of the variance of blood cadmium was explained, while the contribution of employment grade was not significant. There was an unexpected negative relationship between serum creatinine and blood cadmium in men (r = -0.16; p less than 0.01). This was not true in women (r = +0.03), but the correlation remained present in men after adjustment for age, body mass index and smoking. In contrast, in the two sexes, the correlations between blood pressure and blood cadmium were weak and not statistically significant. In conclusion, in unexposed subjects, gender and smoking are important determinants of blood cadmium. In addition, a low level of environmental exposure to cadmium is not associated with a deterioration of renal function or an increase in blood pressure.

Age Factors↗