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Biomedical subjects

A E Fletcher

Publications and source records attributed to A E Fletcher.

120 records · Page 7Linked to original sources
PubMed1988

The relationship between a low treated blood pressure and IHD mortality: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The suggestion that treating blood pressure to below a certain level may increase IHD mortality is controversial. We investigated the influence of treated blood pressure on mortality in the DHSS Hypertension Care Computer Project. Mortality was examined by quintiles of treated diastolic blood pressure (DBP) in 2,145 patients treated for a minimum period of one year and subsequently followed for an average of four years. One hundred and seventy five patients died; 71 from IHD. In men and women all cause mortality increased with level of treated DBP. In men IHD mortality showed a U-shaped distribution with an age-adjusted rate of 15.2 per 1,000 person years in the lowest fifth (DBP less than 86 mmHg) comparable to that of 15.6 per 1,000 in the upper (DBP greater than or equal to 103 mmHg). A similar pattern could not be established in women due to very few IHD deaths. IHD mortality was further examined separately for men by prior history of IHD. An increase in IHD deaths in the lowest fifth of treated blood pressure was found for men both with and without a history of IHD. No similar pattern of IHD mortality was obtained for untreated DBP or treated systolic pressure. However, we cannot exclude the possibility that the risk of low treated DBP is secondary to ischaemic heart disease.

Age Factors↗
PubMed1987

Evaluation of quality of life in clinical trials of cardiovascular disease.

There is an increasing interest in the use of quality of life methods to assess the benefits of treatment in cardiovascular disease. When selecting dimensions of quality of life and the instruments to measure these dimensions, the key issue is the detection of a response to treatment during the trial. The sensitivity of a variety of instruments appropriate to hypertension, angina and congestive heart failure is reviewed. Quality of life should be assessed in double blind randomized controlled trials. A Health Index must be included to take into account any mortality and morbidity occurring during the trial. Data are presented on the measurement of quality of life in patients taking placebo prior to entering trials of antihypertensive treatment. The variation with age, sex and nationality is discussed. Also reported are the results arising from observer bias in a single-blind trial.

Angina Pectoris↗
PubMed1986

Atrial natriuretic factor receptors and stimulation of cyclic GMP formation in normal and malignant osteoblasts.

Synthetic rat atrial natriuretic factor (Ile-ANF-26) stimulated cyclic GMP formation by up to several hundred-fold in osteoblast-rich cultures from newborn rat calvaria and in clonal osteogenic sarcoma cells (UMR 106-01) which are phenotypically osteoblast. ANF had no effect on the cyclic AMP response to parathyroid hormone in the same cells. Specific, high-affinity binding sites for ANF were identified in both cell types, with Kd and receptor numbers in normal osteoblasts of 1.2 +/- 0.1 X 10(-10) M and 42 +/- 4 X 10(3) per cell, and in UMR 106-01 cells of 1.4 +/- 0.1 X 10(-10) M and 22 +/- 4 X 10(3) per cell.

Animals↗
PubMed1986

Basal and stimulated release of calcitonin gene-related peptide (CGRP) in patients with medullary thyroid carcinoma.

Calcitonin gene-related peptide (CGRP) is a recently discovered peptide whose existence was first predicted following sequence analysis of the rat calcitonin gene. In the present study, plasma levels of CGRP were measured in patients with medullary thyroid carcinoma, both basally and following calcium or pentagastrin stimulation. Using a sensitive radioimmunoassay for CGRP, 19 of 21 patients with medullary thyroid carcinoma had elevated plasma levels of immunoreactive CGRP (median value 114 pmol/l) while 23 normal subjects had plasma CGRP levels below the detection limit of the assay (less than 10 pmol/l). Calcium or pentagastrin infusion in medullary thyroid carcinoma patients were potent stimuli to CGRP release, increasing plasma levels two- to five-fold. Chromatographic characterization using high pressure liquid chromatography of the CGRP immunoreactivity in plasma from two patients with medullary carcinoma of the thyroid demonstrated the presence of two molecular forms, neither of which co-eluted with synthetic human CGRP. The role of CGRP in the pathophysiology of medullary thyroid carcinoma is not clear but it may contribute to some of the clinical features associated with the disease. Furthermore, measurement of CGRP in conjunction with calcitonin could help in determining the prognosis of these patients.

Calcitonin↗
PubMed1985

Quality of life in hypertensive patients on different antihypertensive treatments: rationale for methods employed in a multicenter randomized controlled trial.

In measuring the quality of life and other such end points in a trial, it is widely recognized that poor methods and observer and subject bias may invalidate the results. The measurement of two aspects of the quality of life, activity and well-being, is attempted using methods which include valid, repeatable assessments that are also sensitive to the actions of pharmaceutical agents. Methods are described for use in a randomized controlled trial to measure three aspects of well-being: symptoms, activity, and psychological status. These methods are employed in a single-blind randomized trial of a combination of oxprenolol plus diuretic compared with captopril plus diuretic in 97 patients with mild to moderate hypertension. The patients are from West German centers involved in a multicenter European study. In 34 (35%) of the patients, well-being was assessed from a self-administered questionnaire, and in the remaining 63 patients the investigators interviewed the patients and asked the same questions. Data are presented at entry to the trial. The methods appeared to be successful at that stage and the results were comparable with those for similar studies in London. Activity, well-being, and psychological status were sufficiently correlated to suggest that the methods are valid estimates of certain aspects of the quality of life. However, two major problems remain. Less disability was reported when the questionnaires were completed by the investigators; and after randomization their nonblindness must raise doubts about the objectivity of interviewer-derived data. The results of the trial may have to be assessed solely from self-administered questionnaires.

Adult↗
PubMed1985

Angiotensin converting enzyme inhibitors and quality of life: the European trial.

Two prospective multi-centre randomized trials were initiated to compare the relative efficacy and influence on quality of life of captopril, alone or in combination with hydrochlorothiazide, against either methyldopa, alone or in combination with hydrochlorothiazide, or oxprenolol in combination with chlorothalidone. The complaint rate, activity index and psychiatric morbidity were evaluated as indices of quality of life. Captopril was associated with a significantly (P less than 0.05) greater reduction in complaint rate compared with methyldopa and a tendency for less symptoms of depression compared with oxprenolol (P = 0.06), the latter drug being associated with an increase in depression scores. The trends in quality of life indices in the captopril-treated patients would suggest the need for double-blind placebo-controlled trials to investigate these apparent benefits.

Adult↗
PubMedDate not supplied

Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly.

BACKGROUND: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. METHODS: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. RESULTS: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). CONCLUSIONS: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

Aged↗
PubMedDate not supplied

Causes of death and risk factors in young and old diabetic patients referred to a retinopathy clinic.

The causes of death and associated risk factors are compared in young and old diabetic patients attending a retinopathy clinic. Mortality in those diagnosed under and over the age of 30 years is also examined in order to compare insulin-dependent with non-insulin-dependent patients. A defined cohort attending the Hammersmith Hospital Retinopathy Clinic was followed for an average of 11 years. Main outcome measures were standardized mortality ratios (SMRs) in different age/sex groups and relative hazard rates (RHRs) for possible risk factors related to mortality. The patients were divided into those aged under and over the age of 60 years at attendance at the clinic. The RHRs were smaller in the elderly for plasma urea [1.015 versus 1.107 (p < 0.01)]. Attenuation of risk was also suggested for systolic blood pressure (RHR of 1.005 in the elderly versus 1.015 in the younger patients) and for the effects of smoking [RHR of 1.17 (elderly patients) and 1.35 (younger patients)]. In those diagnosed under the age of 30 years, there were very high SMRs for renal disease, cerebrovascular disease (men only), ischemic heart disease, other heart disease, and respiratory disease (men only), but increased SMRs were also demonstrated in those diagnosed over the age of 30 years. The risk factors associated with poor survival were similar for those diagnosed over and under the age of 30 years: poor diabetic control, high systolic and diastolic blood pressure, and increased plasma urea. In conclusion, there was no evidence that blood sugar control or diastolic blood pressure were less important in older age groups. Plasma urea, systolic pressure, and being on insulin were less useful as predictors of mortality in the elderly, but were still important in patients diagnosed over the age of 30 years.

Adolescent↗