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Biomedical subjects

G D Murray

Publications and source records attributed to G D Murray.

At least 127 records · Page 7Linked to original sources
PubMed1989

Retrospective analyses for hypothesis generation. A commentary on the PACK trial (prevention of atherosclerotic complications with ketanserin).

Publication of the results of a large-scale randomized control trial (RCT) of the anti-serotonin drug ketanserin in patients with intermittent claudication offers an opportunity to examine the validity of retrospective subgroup analyses to generate hypotheses for further validation. This was prompted by an unanticipated adverse interaction which occurred in a subgroup of patients receiving both ketanserin and potassium-losing diuretics. The quality of the study ranked it in the 99th percentile of over 400 RCTs evaluated by a quality scoring system. The subgroup analysis resulted from the emergence during the study of a highly significant excess mortality in the patients on diuretics (relative risks 0.88 for those on ketanserin alone, 0.95 on potassium-sparing and 2.44 for those on potassium-losing diuretics (P = 0.007). External validity was evident from data in the literature indicating that a rare tendency of the many drugs that prolong the QT interval to cause torsade de pointes and fatal arrhythmias is exacerbated by hypokalemia of the degree caused by potassium losing diuretics. When the ketanserin and placebo treated patients also on potassium-losing diuretics are removed from the analyses there is a 23% reduction in endpoints which the power is no longer sufficient to detect as significant. There is also an apparent lag phase. Further study of the drug is clearly indicated.

Adult↗
PubMed1989

Twice-daily low-dose captopril in diuretic-treated hypertensives.

Twice-daily captopril (25 mg) and placebo were compared in ten hypertensive patients who were already receiving bendrofluazide. After six weeks therapy, captopril produced significant antihypertensive effects one to six hours after dosing but these did not persist at eleven to twelve hours. Plasma renin concentration was increased for twelve hours after captopril but inhibition of angiotensin II activity was lost by twelve hours. During the period when captopril reduced blood pressure significantly, effective renal plasma flow and hepatic blood flow were unchanged although renal vascular resistance was reduced. There was no evidence that captopril altered plasma sodium, potassium or magnesium concentrations following bendrofluazide. Thus, in thiazide-treated patients, captopril 25 mg produces significant blood pressure reduction for at least six hours after dosing, without impairing renal or hepatic blood flow. However, twice-daily low-dose captopril does not adequately control blood pressure throughout the dosage interval.

Adult↗
PubMed1988

The task of a statistical referee.

The results are presented of an audit of the statistical standard of papers published in The British Journal of Surgery. A number of deficiencies are highlighted, many of which stem from an over-emphasis on statistical significance at the expense of any assessment of the clinical relevance of research findings. The flaws in the design of published studies, and in particular the many instances of inadequate sample sizes, emphasize that statistical input should be sought at the beginning of a research project rather than at the end.

General Surgery↗
PubMed1988

Correcting for the bias caused by drop-outs in hypertension trials.

A major source of bias in hypertension trials can arise from patients who are withdrawn during the course of the trial because of inadequate blood pressure control. We develop a mechanism which allows for such withdrawals while preserving the potential to make an unbiased comparison of the treatment effects. The approach is illustrated using data from a large multicentre trial of two anti-hypertensive agents in patients with mild to moderate essential hypertension.

Clinical Trials as Topic↗
PubMed1988

Outcome of aneurysmal subarachnoid hemorrhage in patients 66 years of age and older.

The outcome at three months after aneurysmal SAH in a group of older patients and a group of younger patients is compared. The patients were admitted within 72 hours of their SAH. Of 61 patients 66 years of age and older, comprising 13% of the whole patient group, 52% died, 12% remained dependent and 36% became independent. In the younger group, 55% had an independent outcome (p less than 0.01). In contrast to what we expected in the older patient group, not extracranial, but intracranial events (re-bleeds, infarcts, hydrocephalus) were by far the most frequent cause of deterioration.

Age Factors↗
PubMed1988

Statistical pitfalls in the analysis of age-related effects in antihypertensive therapy.

Much of the literature concerning age-related effects in antihypertensive therapy suffers from serious deficiencies in statistical design and analysis. The problems include those relating to the choice of a suitable control group, the measurement of response to treatment, response to baseline blood pressure, interpreting post hoc analyses, and the pooling of data from a number of related studies. These problems are discussed and we attempt to identify solutions that give a satisfactory balance between scientific validity and the real-life problems of conducting clinical trials. We conclude by outlining a protocol for future studies in this area.

Aged↗
PubMed1988

Interpreting age-related aspects of antihypertensive treatment: statistical defects and their remedy.

Much of the literature concerning age-related effects in hypertension and its treatment suffers from serious deficiencies in statistical design and analysis. The problems include the measurement of response to treatment, the lack of a suitable control group, the way response is related to baseline blood pressure, the interpretation of post hoc analyses and the pooling of data from related but different studies. We discuss these problems and attempt to identify solutions which give a satisfactory balance between scientific validity and the practical issues of conducting clinical trials in hypertension.

Age Factors↗
PubMed1988

Does therapeutic reduction of diastolic blood pressure cause death from coronary heart disease?

Mortality data from 3350 patients who attended the Glasgow Blood Pressure Clinic between 1968 and the end of 1982 were used to examine the hypothesis that lowering diastolic blood pressure (DBP) below 85 mmHg causes death from coronary heart disease (CHD). Analysis of 257 coronary deaths in quintiles of treated DBP showed a significantly nonlinear relation, with the lowest mortality from CHD occurring in the middle quintile (91-98 mmHg). This finding persisted after adjustment for risk at entry, and was independent of sex and pre-existing CHD. In contrast, the relations between treated systolic blood pressure and death from CHD, and treated DBP and death from stroke were linear. For 2355 patients who were untreated at referral there was no relation between the change in DBP during treatment and death from CHD. In our view, however, these findings do not necessarily support the hypothesis that lowering of DBP below 85 mmHg with treatment causes death from CHD. Evidence for this is indirect and inconsistent, and should not, at present, be used as a basis for any change in treatment practice.

Antihypertensive Agents↗
PubMed1987

Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes.

1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink. 2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol. 3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels. 4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink. 5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol. 6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin-angiotensin systems after alcohol.

Adolescent↗
PubMed1987

Dietary sodium deprivation raises blood pressure in the rat but does not produce irreversible hyperaldosteronism.

It is reported that dietary deprivation of sodium in young rats produces changes of sodium balance and aldosterone excretion which persist when normal sodium intake is restored. To test this further, sodium intake was reduced 10-fold in rats. In the first experiment sodium intake was reduced for 5 weeks in rats aged 3 weeks. Systolic blood pressure, heart rate and plasma renin concentration increased and growth rate was reduced. Sodium intake was then increased for 10 weeks. Blood pressure, heart rate and plasma renin concentration fell and growth rate increased but body weight did not regain control values. As compared with controls, plasma concentrations of aldosterone and corticosterone did not increase after the 10-week period. Thus, sodium depletion did not produce an irreversible change in aldosterone but it did raise arterial pressure. Further experiments confirmed the pressor effect in young and adult rats. Blood pressure was measured in the tail in these experiments but the increase in pressure was not a technical artifact as measurements made in the tail correlated well with measurements made simultaneously by intra-arterial catheter. Catheters were inserted under general anaesthetic for this comparison of pressure and rats previously deprived of sodium showed a significantly higher mortality rate due to the anaesthesia and surgery involved. Thus, a 10-fold reduction of dietary sodium raises blood pressure in young and adult rats and it may increase mortality from a minor surgical procedure. It does not produce irreversible changes in aldosterone.

Aldosterone↗
PubMed1987

Clinical and biochemical effects of the renin inhibitor H142 in humans.

The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose, or with H142 at 1.0 or 2.5 mg/kg/h, for 30 min while supine and thereafter with dextrose for 1.5 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after H142 infusion was stopped. In contrast, total renin concentration as measured by radioimmunoassay rose while ANG I and II fell, subsiding after H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited: plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.

Adult↗
PubMed1987

Effects of calcium antagonism and beta-blockade on haemodynamic responses to stress.

The influences of verapamil, propranolol and their combination on blood pressure and heart rate during cold pressor testing and isometric exercise were examined in 13 patients with essential hypertension. Verapamil modified the peak pressor responses to each stimulus while the major action of propranolol was on heart rate. Together the drugs attenuated both haemodynamic responses. Combined calcium antagonism and beta-blockade may modify favourably surges in blood pressure and heart rate in ambulant hypertensives.

Adult↗
PubMed1987

The effect of chronic prazosin therapy on the response of the renin-angiotensin system in patients with essential hypertension.

Changes in plasma active and inactive renin and angiotensin II in response to tilt and intravenous frusemide were assessed in ten patients with essential hypertension, before treatment and again during chronic therapy with the alpha 1-adrenoceptor antagonist prazosin. During prazosin treatment blood pressure in the patients fell from mean levels 172/108 mmHg to 149/88 mmHg (P less than 0.05). Both before and during prazosin, tilt and frusemide each led to significant elevation of plasma active renin (P less than 0.001) and angiotensin II (P less than 0.05). Inactive renin tended to fall with tilt, and fell significantly following frusemide (P less than 0.05). Active renin (P less than 0.05) and angiotensin II (P less than 0.01) were lower 15 hours after dosing during chronic prazosin therapy than before treatment, but changes after tilt and frusemide were not attenuated during treatment. Chronic prazosin administration does not appear substantially to affect changes in active renin or angiotensin II in response to two standard stimuli, and may be useful in controlling hypertensive patients pending investigation of their renin-angiotensin system.

Adult↗
PubMed1987

Secondary hypertension in a blood pressure clinic.

The prevalence, reversibility, and mortality of secondary hypertension among 3783 patients with moderately severe nonmalignant hypertension attending the Glasgow (Scotland) Blood Pressure Clinic were assessed. Underlying causes of hypertension were found in 297 patients (7.9%). Eighty-seven patients (2.3%) were considered to have a potentially reversible cause for their hypertension, including the oral contraceptive pill (38 patients), renovascular disease (27 patients), and primary hyperaldosteronism (ten patients), but of these only 33 patients (0.9% of total clinic population) were cured by specific intervention. Two hundred ten patients (5.6%) had irreversible renal parenchymal disease and significantly higher mortality than men and women with other causes of hypertension. Excess deaths in the renal group were attributed to renal failure (International Classification of Diseases [ICD] 580 to 589) and vascular causes (ICD 390 to 458) but not to cancer (ICD 140 to 208; 235 to 239) or other nonvascular disease. These results suggest that investigation of hypertension for an underlying cause will reveal a small number of patients with treatable disorders, of whom only a few will be cured by specific intervention, and a moderate number with irreversible disease who are at high risk of myocardial infarction and stroke.

Adult↗
PubMed1986

Retinal changes in malignant hypertension.

To assess the diagnostic and prognostic importance of papilloedema in malignant hypertension a two part study was undertaken. Four observers reviewed 56 photographs of fundi from patients with grade 3 or 4 hypertensive retinopathy. Complete agreement on the presence or absence of haemorrhages was recorded in 52 cases and on exudates in 53 cases. Opinion on papilloedema, however, was divided, all four observers agreeing in only 34 cases. In the second part of the study survival in 139 consecutive hypertensive patients with bilateral retinal haemorrhages and exudates was examined by life tables. Ten year survival was 46% in patients with bilateral haemorrhages and exudates alone (n = 43) and 48% when papilloedema was also present (n = 96). Multivariate analysis confirmed that papilloedema was not related to survival. These results suggest that papilloedema is an unreliable physical sign and does not adversely influence prognosis in hypertensive patients who already have bilateral retinal haemorrhages and exudates when effective treatment is available. Papilloedema should no longer be regarded as a necessary feature of malignant hypertension.

Actuarial Analysis↗
PubMed1986

Potassium supplementation in blacks with mild to moderate essential hypertension.

Potassium chloride (KCl) salt (65 mmol) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study. The fall in BP was independent of the order of randomization and was significant for systolic (SBP; P less than 0.01) and diastolic (DBP; P less than 0.05) pressure after 4 weeks. Analysis of the 95% confidence intervals in this and in five other studies, two of which were reported as showing no beneficial effect, suggests that potassium supplementation does lower BP, but that the change is small and within the confidence levels of all six trials. Thus, apparent discrepancies in the literature are not genuine statistically.

Adult↗