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Biomedical subjects

J Webster

Publications and source records attributed to J Webster.

At least 217 records · Page 12Linked to original sources

General anesthesia for intrauterine placement of human conceptuses after in vitro fertilization.

General anesthesia has been used for the replacement of human conceptuses after in vitro fertilization (IVF). Two adjuvants, enflurane and halothane, have been compared. Halothane significantly reduced the incidence of implantation compared to enflurane. In 356 replacements, the incidence of implantation for enflurane and halothane was 34 and 17%, respectively (P = 0.005). Sixty-four percent of all replacements had three conceptuses; the incidence of implantation for enflurane and halothane in this group was 43 and 19%, respectively (P = 0.002). The incidence of multiple pregnancy was similar for both anesthetic agents (20%) and the demise of implantation sacs 5 weeks postovulation was 11% for enflurane and 12% for halothane.

Adult↗

Aspirin and other antiplatelet drugs in the prophylaxis of thrombosis.

Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. After a myocardial infarction it reduces the risk of death by about 10% and of coronary incidence (coronary death or definite myocardial infarction) by about 25%. These effects appear to be additive with those of beta-blocking drugs. Aspirin also reduces the risk of occlusion of aortocoronary saphenous vein grafts by about half. In transient cerebral ischaemia, aspirin may reduce the risk of stroke and death by 50%. In most clinical trials to date the daily dose of aspirin ranges from 325 mg to 1400 mg. Interest in very low doses of aspirin (less than 60 mg daily) is considerable but has yet to be translated into proven clinical benefit. Dipyridamole has not been shown to be effective as an antithrombotic when used alone. Its antiplatelet action ex vivo may be enhanced by combination with aspirin but clinical trials have shown relatively little advantage of the combination over aspirin alone. Sulphinpyrazone has not become established as a first line antithrombotic drug. Epoprostenol is useful in extracorporeal circulations to prevent platelet consumption and possibly in severe inoperable peripheral vascular disease.

Aspirin↗

Antihypertensive effect of single doses of enalapril in hypertensive patients treated with bendrofluazide.

This study was designed to investigate the validity of the then current recommendations for initiation of therapy with enalapril in hypertensive patients on treatment with a diuretic. Enalapril in single doses of 10 and 20 mg was given to 13 hypertensive patients on treatment with bendrofluazide 5 mg daily in a randomised, crossover, placebo controlled study. The mean maximal reduction in blood pressure was similar with both doses (35/20 mmHg supine, 38/20 mmHg standing), occurred on average within 6 h of tablet ingestion, and was not accompanied by any significant change in heart rate. Three patients experienced symptomatic hypotension. In one patient this was incapacitating after 10 mg and precluded exposure to 20 mg. This study shows that in hypertensive patients receiving treatment with diuretics, the addition of enalapril should be undertaken with caution. An optimal starting dose of enalapril in such patients remains to be confirmed.

Adult↗

Sorbinil pharmacokinetics in male and female elderly volunteers.

Sorbinil pharmacokinetics were studied, following a single oral dose, in eight male and eight female healthy, elderly volunteers. Elimination half-life tended to be longer in males than in females. There was no sex difference in AUC or renal clearance. The long elimination half-life of sorbinil in the elderly suggests that accumulation is likely to occur with chronic dosing.

Aged↗

Once daily amlodipine in the treatment of mild to moderate hypertension.

1. The antihypertensive efficacy of once-daily amlodipine was studied in a group of 30 patients with mild to moderate hypertension in a double-blind, placebo controlled parallel group study. The dose range of amlodipine was 2.5-10 mg daily titrated at 2 weekly intervals for a total treatment period of 8 weeks. 2. Amlodipine produced a significant reduction in blood pressure compared with placebo, the mean difference between baseline and 8 weeks (corrected for placebo effect) being 16/12 mm Hg supine, 14/4 mm Hg standing. 3. Blood pressure returned to baseline values during a terminal 4 week washout period on placebo. 4. There were no significant effects on heart rate. 5. Two patients experienced slight ankle oedema while receiving amlodipine 10 mg daily but the active drug was otherwise well tolerated. 6. Plasma concentration of amlodipine, sampled 24 h after the preceding dose, increased as the dose titration sequence was followed, averaging 2.5 ng ml-1 on 2.5 mg, 4.9 ng ml-1 on 5 mg and 10.5 ng ml-1 on 10 mg.

Adult↗

Single doses of enalapril and atenolol in hypertensive patients treated with bendrofluazide.

Enalapril in single doses of 5 and 10 mg and atenolol in a single dose of 50 mg were given to 16 hypertensive patients on long-term treatment with bendrofluazide, 5 mg daily, in a double-blind randomized crossover placebo controlled study. Both doses of enalapril and atenolol produced similar effects on blood pressure. The mean maximal reduction in blood pressure from baseline with all three active treatments was approximately 32/18 mmHg both supine and standing and occurred on average at 6 h after tablet ingestion. Both supine and standing heart rate fell significantly after atenolol, but no significant change occurred after enalapril. This study establishes that 5 mg enalapril is the maximal starting dose that need be used in hypertensive patients already on diuretic treatment. Even this dose may be hazardous in some patients. The study also serves to emphasize that such combination-therapy studies should be carried out at an early stage in drug development, prior to widespread prescription to patients, in order to avoid unnecessary overdosage with new agents.

Adult↗

Angiotensin converting enzyme inhibitors in the clinic: first-dose hypotension.

A fall in blood pressure occurs, in most patients, within a few hours of a single dose of an angiotensin converting enzyme (ACE) inhibitor. While a serious fall in pressure is unusual in previously untreated essential hypertension, some patients are at risk of severe first-dose hypotension. These include those with treated heart failure, severe hypertension on polypharmacy, 'renin-dependent' renovascular hypertension and the occasional elderly patient. In such groups of patients the incidence of severe, symptomatic first-dose hypotension approaches 10%. This effect is not specific for ACE inhibitor therapy and may well occur as frequently with other drugs in such patients. First-dose hypotension may not be accompanied by tachycardia, possibly as a result of a parasympathomimetic action that may contribute to the first-dose effect. It is generally not possible to predict patients at risk, although plasma renin and angiotensin II concentrations show a modest positive correlation with the initial fall in blood pressure. The maximum initial hypotensive effect of ACE inhibitors is not clearly dose related but the duration of effect may be. Therefore such drugs should be started at minimum effective dosage. High-risk patients should be observed closely for at least 6 h. Symptomatic hypotension usually responds to supine rest although infusion of angiotensin II, atropine and occasionally saline may be required.

Atenolol↗

Bovine alloreactive cytotoxic cells generated in vitro detect BoLA w6 subgroups.

Alloreactive cytotoxic T cells (CTL) were generated in mixed lymphocyte culture against cells bearing subgroups of BoLA w6, as well as in BoLA w4, w10 and w16. Primary cultures were restimulated at weekly intervals with irradiated stimulator cells and tested in a 51Cr-release assay with target cells derived from Theileria annulata-infected cell lines. Generation of CTL was accelerated in animals that had been previously primed in vivo by skin grafting. CTL were generated that were specific for BoLA w6 subgroups and not w6. With w6.1 the specific killing was significant at the 5% level, and with w6.2, 6.3 and 6.4 it was significant at the 0.1% level. Where CTL were potentially generated against two BoLA-A locus allele products at the same time (i.e. with heterozygous stimulator cells), one of which was a w6 subgroup, there was similar CTL activity against both products when w6.4 and w16 or w6.1 and w4 were the combinations involved. In two generations against w10 and either w6.1 or w6.2 there was significantly more killing of w10-bearing targets than those with the w6 subgroup.

Animals↗

Atenolol or propranolol in hypertensive patients poorly controlled on captopril and frusemide.

Eighteen patients whose clinic blood pressure (BP) remained over 95 mmHg despite treatment with captopril 50 mg twice daily plus frusemide 40 mg twice daily were randomised in a crossover study to four weeks' treatment with once daily atenolol 100 mg, slow release propranolol 160 mg or placebo. The reduction in BP on atenolol was superior to that on both propranolol and placebo. The mean supine BP 24 hours post dosing were 177/110 mmHg (placebo), 173/109 mmHg (propranolol) and 164/100 mmHg (atenolol). The corresponding mean heart rates were 77 bpm (placebo), 63 bpm (propranolol) and 62 bpm (propranolol) and 62 bpm (atenolol). The difference in hypotensive efficacy between atenolol and propranolol is not readily explained but our study shows that atenolol has a clinically useful supplementary effect on BP. Refractory hypertension remains an important clinical problem and further studies are required to establish the optimum combination of drugs that should be used with captopril in order to achieve 'target' BP in patients with moderate to severe hypertension.

Aged↗

Association between dietary fat intake and plasma factor VII coagulant activity--a predictor of cardiovascular mortality.

Repeated measurements were made in 8 adults of factor VII coagulant activity (VIIc) and fibrinogen concentration (two haemostatic variables associated with cardiovascular mortality), together with factor VII concentration, factor X, prothrombin, and serum cholesterol and triglyceride concentrations, while the usual diet was recorded by precise weighing over 12-14 days. In 6 subjects measurements were continued while low-fat and high-fat diets were taken for a further 2 and 3 weeks respectively. Plasma VIIc was related positively and independently to fat and protein intake, whereas factor VII concentration was associated only with protein consumption. In a second study, consumption of 50% extra energy for one day increased VIIc significantly when taken mainly as fat but not when taken mostly as carbohydrate. The character of the VIIc response to fat intake suggested an association with post-prandial lipaemia. A high fat intake may lead not only to coronary atheroma but also to fibrin deposition and thrombus formation through direct activation of the coagulation system.

Adult↗

Effect of impaired glucose tolerance and type II diabetes on resting metabolic rate and thermic response to a glucose meal in obese women.

We examined the hypothesis that patients with impaired glucose tolerance or type II diabetes mellitus have reduced glucose-induced thermogenesis and that this perpetuates obesity in them by reducing energy expenditure. The thermic response after a 75-g glucose meal for 150 minutes was significantly lower in five obese women with diabetes (7.18 +/- 1.8 kcal) and five other obese women with impaired glucose tolerance (6.4 +/- 0.8 kcal) than in five obese women with normal glucose tolerance (16.7 +/- 2.4 kcal) and five lean healthy control subjects (14.0 +/- 2.2 kcal, P less than 0.05). However, obese women with diabetes or impaired glucose tolerance had a significantly higher resting metabolic rate (RMR) (307.0 +/- 9.7 mL O2/min) than predicted for them on the basis of their age, body weight, and total body potassium (274.8 +/- 8.0 mL O2/min, p less than 0.01). The predicted RMR in obese women with normal glucose tolerance test (GTT) (286.0 +/- 5.0 mL O2/min) was not different from their observed RMR (272.0 +/- 6.0). Thus the total energy expenditure during the meal of obese women with diabetes (254 +/- 32 kcal/150 min) and obese women with impaired glucose tolerance (221 +/- 5 kcal/150 min) was higher than that of obese women with normal glucose tolerance (201 +/- 9 kcal/150 min). All three obese groups had a higher total energy expenditure than the lean group (158 +/- 4 kcal/150 min, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transbronchial radioactive implantation using a Flexible Injector System. An improved technique for endobronchial brachytherapy.

A new implantation device for endobronchial brachytherapy is described. This implantation system is flexible and can be easily passed through the suction channel of a flexible bronchofiberscope (FBF) for radionuclide implantation of the tumor. All four patients implanted using this system, experienced excellent palliation of their symptoms. We think that the flexible system described is an improvement over the rigid system for endobronchial implantation in most patients.

Brachytherapy↗

A new transferrin allele in sheep.

An electrophoretic variant of sheep transferrin, TfL, has been described. Transferrin L has been shown to be controlled by a single codominant allele, TfL, at the Tf locus. Transferrin L is electrophoretically distinguishable from the very similar transferrin TfKCzech. The value of gradient polyacrylamide gel electrophoresis for transferrin phenotyping in sheep is discussed.

Alleles↗