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Biomedical subjects

L E Ramsay

Publications and source records attributed to L E Ramsay.

At least 19 recordsLinked to original sources
PubMed1992

Investigation of selected patients with hypertension by the rapid-sequence intravenous urogram.

The rapid-sequence intravenous urogram (IVU) has tended to fall from favour for investigating hypertension because of its perceived imprecision for detecting renovascular disease. However, no study has examined the value of the IVU as a screening test in appropriately selected patients. We have analysed the diagnostic yield of the rapid-sequence IVU in hypertensive patients selected for features suggesting renal or renovascular disease in a retrospective review of case records from a hypertension clinic. The IVU was abnormal in 27% (95% CI 21-32%) of 241 consecutive patients. The most common abnormalities were chronic pyelonephritis (6%); proven renovascular disease (5%); stone (4%); possible renovascular disease and simple cyst (each 3%); hydronephrosis (2%); and tumour and active tuberculosis (each 1%). The IVU led to intervention aiming to correct hypertension in 5% (95% CI 2-8%) of patients, and revealed an abnormality needing intervention in its own right in 4% (95% CI 2-6%). The IVU led to unnecessary invasive investigation in 3% of cases. Individual abnormalities could not be predicted from the clinical or laboratory features. The initial investigation in hypertensive patients with suspected renal or renovascular disease should be a general purpose test able to detect a wide range of abnormalities. The rapid-sequence IVU is the only single test capable of satisfying this requirement. In patients with features suggesting renovascular disease, a normal rapid-sequence IVU excludes renovascular disease with 93% probability, but is an imperfect screening test since it fails to diagnose about 20% of cases. Renal arteriography should be done despite a normal IVU when it is essential to exclude renovascular disease.

Female↗
PubMed1992

Diabetes, impaired glucose tolerance and insulin resistance with diuretics.

There is a definite relation of diuretic treatment to impaired glucose tolerance and biochemical diabetes, and a probable relation to insulin resistance. The effect of diuretics on glucose tolerance is dose-related. Spironolactone does not impair glucose tolerance even at high dosage, but apparent differences between other diuretics may well be due to comparison at doses which are not equivalent. Diuretic-induced changes in carbohydrate metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs when relatively low doses of thiazide are combined with potassium-sparing agents. The effect of diuretics on glucose tolerance is largely and possibly wholly reversible. These disturbances of carbohydrate homeostasis have been detected by detailed biochemical testing, and their clinical importance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In non-diabetic subjects diuretics may rarely cause or trigger a serious hyperosmolar non-ketotic diabetic syndrome. This apart, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long-term. It is now established that biochemical diabetes, glucose intolerance and insulin resistance probably do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes, otherwise they remain an excellent choice for first-line antihypertensive therapy.

Blood Glucose↗
PubMed1992

Influence of diuretics, calcium antagonists, and alpha-blockers on insulin sensitivity and glucose tolerance in hypertensive patients.

Treatment with thiazide diuretics causes impaired glucose tolerance, biochemical diabetes, and insulin resistance. The effect of diuretics on glucose tolerance is clearly dose-related. Spironolactone does not impair glucose tolerance, even at high dosage, but differences among other diuretics could be due to comparisons at doses that are not equal. Diuretic-induced changes in glucose metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs even when relatively low doses of thiazide are combined with potassium-sparing agents. The effects of diuretics on glucose homeostasis are in large part and probably entirely reversible. These disturbances of glucose metabolism have been detected only by detailed biochemical testing, and their clinical relevance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In nondiabetic subjects, diuretics rarely cause or trigger a serious hyperosmolar nonketotic diabetic syndrome. Otherwise, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long term. Evidence from large outcome trials suggests that biochemical diabetes, glucose intolerance, and insulin resistance do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes unless their use is essential. Otherwise, a low dose of thiazide remains as excellent choice for first-line antihypertensive therapy. Dihydropyridine calcium antagonists, diltiazem, and verapamil appear to have no important effects on glucose homeostasis. There is very limited evidence that selective alpha-antagonists increase insulin sensitivity. The importance of metabolic differences between drug classes will be established only by comparative outcome trials with coronary events as the end point.

Adrenergic beta-Antagonists↗
PubMed1992

Thiazide diuretics: first-line therapy for hypertension.

PURPOSE: To compare low-dose thiazides to beta-blockers, angiotensin converting enzyme (ACE) inhibitors, calcium antagonists and alpha-blockers for simplicity, tolerability, efficacy, safety and cost-effectiveness as first-line treatment for hypertension. METHOD: Review of short-term comparative studies, and the outcome of long-term trials with vascular complications of hypertension as endpoints. SIMPLICITY: Among the advantages of thiazides are a flat dose-response; no dose titration; effectiveness when used once a day; no first-dose hypotension; and few contra-indications. TOLERABILITY: Thiazides are the best tolerated agents in patients over the age of 60 years and in younger women. They sometimes cause gout and impotence in younger men, in whom beta-blockers are equally acceptable first-line therapy. EFFICACY: Thiazide-based regimens have consistently reduced vascular complications of hypertension, the real measure of efficacy. There is little evidence that regimens based on other drugs are effective in this sense. SAFETY: Concerns that thiazide-induced biochemical changes cause coronary events are baseless. An overview of outcome trials shows that thiazide-based treatment reduces coronary events significantly, and the reduction is not significantly different from that predicted by epidemiological data. Thiazide-based therapy has also reduced coronary events significantly and substantially in elderly patients with isolated systolic hypertension. COST-EFFECTIVENESS: Low-dose thiazide treatment needs minimal monitoring, and has proved most cost-effective in formal analyses. CONCLUSION: Low-dose thiazide treatment is a clear first-line choice for patients aged over 60 years and younger women, except those with diabetes or gout. In younger men there is little to choose between thiazides and beta-blockers.

Adrenergic alpha-Antagonists↗
PubMed1991

beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination.

OBJECTIVE: To determine the effects of the beta 1 selective adrenoceptor blocker atenolol, the dihydropyridine calcium antagonist nifedipine, and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication. DESIGN: Randomised controlled double blind four way crossover trial. SETTING: Royal Hallamshire Hospital, Sheffield. SUBJECTS: 49 patients (40 men) aged 39-70 with chronic stable intermittent claudication. INTERVENTIONS: Atenolol 50 mg twice daily; slow release nifedipine 20 mg twice daily; atenolol 50 mg plus slow release nifedipine 20 mg twice daily; placebo. Each treatment was given for four weeks with no washout interval between treatments. MAIN OUTCOME MEASURES: Claudication and walking distances on treadmill; skin temperature of feet as measured by thermistor and probe; blood pressure before and after exercise; subjective assessments of walking difficulty and foot coldness with visual analogue scales. RESULTS: Atenolol did not significantly alter claudication distance (mean change -6%; 95% confidence interval 1% to -13%), walking distance (-2%; 4% to -8%), or foot temperature. Nifedipine did not alter claudication distance (-4%; 3% to -11%), walking distance (-4%; 3% to -10%), or foot temperature. Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance (-9%; -3% to -15% (p less than 0.003)) and skin temperature of the more affected foot (-1.1 degrees C; 0 to -2.2 degrees C (p = 0.05)). These effects on walking distance and foot temperature seemed unrelated to blood pressure changes. CONCLUSIONS: There was no evidence of adverse or beneficial effects of atenolol or nifedipine, when given singly, on peripheral vascular disease. The combined treatment, however, affected walking ability and foot temperature adversely. This may have been due to beta blockade plus reduced vascular resistance, which might also explain the reported adverse effects of pindolol and labetalol on claudication.

Adult↗
PubMed1991

Dietary reduction of serum cholesterol concentration: time to think again.

OBJECTIVE: To evaluate the long term efficacy of diets in lowering serum cholesterol concentration. DESIGN: Descriptive overview of 16 published controlled trials of six months' duration or longer. SETTING: Trials had been conducted in hospital clinics (6), industry (3), mental hospitals or institutions (3), and in general populations (4). PATIENTS: Trials had been conducted in high risk subjects (5), in unselected healthy subjects (6), or for secondary prevention in patients with coronary heart disease (5). Women were included in only four trials. INTERVENTIONS: Diets equivalent to the step 1 diet were employed in eight trials, with individual intervention by dietitians (3) or occupational physicians (2) or with population advice (3). Intensive diets which were more rigorous than the step 2 diet were employed in eight trials. MAIN OUTCOME MEASURES: Net change in serum total cholesterol concentration in subjects receiving treatment with diet compared with values in control subjects after six months to 10 years. RESULTS: In five trials with the step 1 diet as individual intervention the net reduction in serum cholesterol concentration ranged from 0% to 4.0% over six months to six years. In trials with population education reductions in cholesterol concentrations were 0.6-2.0% over five to 10 years. When population and individual dietary advice were combined changes in cholesterol concentration ranged from a fall of 2.1% to a rise of 1.0% over four to 10 years. Diets more intensive than the step 2 diet reduced serum cholesterol concentration by 13% over five years in selected high risk men in the population; by 6.5-15.1% over two to five years in hospital outpatients; and by 12.8-15.5% over one to four and a half years in patients in institutions. CONCLUSIONS: The response to a step 1 diet is too small to have any value in the clinical management of adults with serum cholesterol concentrations above 6.5 mmol/l. Current guidelines recommend screening of serum cholesterol concentration in healthy subjects, followed by treatment with a step 1 diet. The guidelines should be reviewed to provide a more realistic estimate of the effect of a step 1 diet and of the likely need for lipid lowering drugs.

Cholesterol↗
PubMed1991

Effect of sulindac on the cough reflex of healthy subjects.

The effects of a single dose of sulindac 200 mg and placebo on the capsaicin-induced cough reflex were studied in a two-phase double-blind crossover study in 18 healthy subjects. Sulindac increased the threshold for capsaicin cough response significantly, but did not alter D5, peak response, or the total cough response when compared with placebo values.

Adult↗
PubMed1991

Cough and enalapril: assessment by spontaneous reporting and visual analogue scale under double-blind conditions.

The incidence and prevalence of cough related to enalapril was assessed by spontaneous reporting and a visual analogue scale during a 6 month random double-blind parallel-group study comparing enalapril with nifedipine. Cough was reported spontaneously by 6.2% of enalapril-treated patients, and by none on nifedipine (NS). No patient had to discontinue enalapril because of cough. After 24 weeks treatment increases in visual analogue scale scores for cough frequency greater than or equal to 8 mm were more common for enalapril than nifedipine (difference 21.5%, 95% CI 7.3-35.7%). Increased cough frequency by visual analogue scale was present throughout the study in women, but less consistently in men. High scores for cough were not related to the dose of enalapril. Cough with enalapril was not an important problem during the 6 months of treatment. However increased cough frequency could be detected by visual analogue scale, with a frequency consistent with that observed in open clinic-based studies of longer duration. These findings suggest that ACE inhibitor-induced cough may increase in severity over time, and that even a period of 6 months treatment is too short to evaluate this side-effect adequately.

Adult↗
PubMed1991

Influence of debrisoquine oxidation phenotype on exercise tolerance and subjective fatigue after metoprolol and atenolol in healthy subjects.

1. The effects of single doses of metoprolol 50 mg, metoprolol 100 mg and atenolol 100 mg on exercise tolerance were compared with placebo in a double-blind random cross-over study in 12 healthy subjects. Nine subjects were extensive metabolisers of debrisoquine, and three were poor metabolisers. 2. Three hours after dosing beta-adrenoceptor blocker treatments significantly reduced exercise heart rate, prolonged time to complete exercise, and increased subjective fatigue measured by visual analogue scale. 3. Scores for subjective fatigue did not correlate with reduction in exercise heart rate or prolongation of exercise time. Exercise time prolongation was weakly but not significantly correlated with exercise heart rate reduction. 4. When compared with placebo, prolongation of exercise time and increased fatigue with metoprolol were not significantly related to debrisoquine oxidation phenotype or to the debrisoquine/4-hydroxydebrisoquine (D/4OH-D) ratio. 5. When metoprolol responses were compared with those for atenolol, changes in exercise time and fatigue scores were significantly related to oxidation phenotype. For metoprolol 100 mg, poor metabolisers required 20.8 s longer to complete exercise (P less than 0.05) and had higher fatigue scores by 78% (P less than 0.05) as compared with extensive metabolisers.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Adequacy of twice daily dosing with potassium chloride and spironolactone in thiazide treated hypertensive patients.

1. The effects of 4-6 weeks treatment with placebo, potassium chloride 32 mmol 12 hourly, and spironolactone 25 mg 12 hourly upon the plasma potassium concentration-time profile were examined in hypertensive patients taking bendrofluazide 5 mg daily. 2. When compared with placebo, potassium chloride increased peak plasma potassium concentration (P less than 0.05), 12 h AUC for plasma potassium (P less than 0.1), and 12 h urine potassium excretion (P = 0.002). Spironolactone increased peak plasma potassium concentration (P less than 0.05), and 12 h AUC for plasma potassium (P less than 0.05), compared with placebo values. 3. Potassium chloride and spironolactone did not differ significantly in any respect other than 12 h urine potassium excretion. The 12 h AUC for plasma potassium was 35% larger with spironolactone than potassium chloride (not significant). 4. With both active drugs peak plasma potassium was observed 2-3 h after dosing, and efficacy tended to wane towards 12 h. However, variability of plasma potassium within the dose interval was not increased markedly, and 12 hourly dosing is probably satisfactory for both potassium chloride and spironolactone at the doses studied.

Adult↗
PubMed1991

The association between haemospermia and severe hypertension.

The association between haemospermia and hypertension was examined in a case-control study comparing 5 hypertensive patients with haemospermia to 20 age-matched hypertensive men. Patients with haemospermia had much higher blood pressures than hypertensive controls (200/131 mmHg vs 147/90 mmHg; P less than 0.0005/P less than 0.0001), higher left ventricular voltage on ECG (P less than 0.02), and higher concentrations of serum creatinine, proteinuria and renovascular disease (all P = 0.06 vs controls). Haemospermia is associated with severe uncontrolled hypertension. It is not, however, associated with hypertension per se, as the prevalence of hypertension in published series of patients with haemospermia is no higher than that expected in the general population. Men presenting with haemospermia should have their blood pressure measured carefully as they may require antihypertensive treatment urgently.

Adult↗