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Biomedical subjects

R G Wilcox

Publications and source records attributed to R G Wilcox.

At least 19 recordsLinked to original sources

Gallopamil slow release: a double blind study of twice daily versus once daily treatment in chronic stable angina.

The clinical efficacy of a new slow release preparation of the calcium antagonist gallopamil was assessed in 20 patients by diary cards and treadmill exercise tests. A single blind phase of two week periods of placebo, gallopamil 100 mg o.d. and gallopamil 100 mg b.i.d., blinded to the patient, was followed in 18 patients by a double blind comparison of gallopamil 100 mg od versus 100 mg b.i.d. Angina frequency and trinitrin consumption per week were both significantly less on high dose (2.7 and 1.7) than on low dose (5.4 and 3.4) respectively. Treadmill total exercise time was longer on high dose (523s) than low dose (449s). Other exercise test parameters showed similar improvements on high dose treatment. Gallopamil was well tolerated. PR interval correlated best with plasma gallopamil level, while exercise test parameters correlated best with the log plasma level of its major metabolite nor-gallopamil.

Adult

Ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) in suspected acute myocardial infarction.

Continuous electrocardiography during the first 24 hours of a stay in a coronary care unit was used to record ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) or placebo. Recordings were made on 378 of the 436 patients admitted to a double blind trial of alteplase or placebo in one participating centre of the Anglo-Scandinavian study of early thrombosis (ASSET), patients being selected according to the availability of recorders. Of these, 309 (158 given alteplase and 151 placebo) had greater than 5 hours of analysable data. Most of the arrhythmias were recorded in patients with an in hospital diagnosis of myocardial infarction. Ventricular couplets and ventricular tachycardia were significantly more common in the patients treated with alteplase. Further, in patients with myocardial infarction who had ventricular extrasystoles, couplets, or ventricular tachycardia type a, the number of hours in which each arrhythmia was recorded was significantly higher in the alteplase group. The various ventricular arrhythmias in the alteplase group tended to cluster in the first 4-12 hours of the recordings. During the first 24 hours admission there were four episodes of ventricular fibrillation in the alteplase group and five in the placebo group of taped patients. By one month there had been 18 deaths in these 309 patients (alteplase four, placebo 14). These bore no relation to any recorded arrhythmia. Clinical records for the patients with no or minimal tape data yielded six further episodes of ventricular fibrillation during the first 24 hours (three in the alteplase group and three in the placebo group). Of the total 436 patients, 10 of the 218 patients in the alteplase group had died by one month compared with 22 of the 218 patients treated with placebo. The use of alteplase increases the incident of non-life threatening ventricular arrhythmias. These results, however suggest that arrhythmia after thrombolysis in the pre-hospital phase may be less of a problem than it is perceived to be.

Adolescent

A comparison of same day and separate day injection protocols for myocardial perfusion SPECT using 99Tcm-MIBI.

Three dose administration protocols for 99Tcm-MIBI were applied to groups of 15 patients with known or suspected ischaemic heart disease. Firstly, injections were given on consecutive days, with 300 MBq at rest and 500 MBq 24 h later at exercise. Secondly, both injections on the same day with 200 MBq at rest followed 1.5 h later by 1000 MBq during exercise. Finally, both injections on the same day with 200 MBq at rest followed 1.5 h later by 600 MBq during exercise. The diagnostic accuracy was significantly better when the administrations were on separate days than when given on the same day. There was no difference in diagnostic accuracy between the two same day protocols. The same day protocols gave a significantly higher false negative reporting rate than the separate day protocol.

Adult

Effects of alteplase in acute myocardial infarction: 6-month results from the ASSET study. Anglo-Scandinavian Study of Early Thrombolysis.

In a randomised, controlled trial 2514 patients with suspected acute myocardial infarction received 100 mg intravenous alteplase (recombinant tissue plasminogen activator [rt-PA]) plus heparin within 5 h of onset of symptoms, and 2499 similar controls received placebo plus heparin. At 1 month the overall mortality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval [CI] 11-39%). At 6 months the mortality rates were 10.4% (alteplase) and 13.1% (placebo), a relative reduction of 21% (95% Cl 8%-32%, p = 0.0026). 6-month mortality rates in patients with proven myocardial infarction were 12.6% and 17.1%, respectively (relative reduction 26%; 95% Cl 14-37%); this effect was similar for anterior (15.6% vs 21.2%) and inferior (7.7% vs 12.8%) myocardial infarction. 6-month mortality rates were lower in those treated with alteplase irrespective of other recognised cardiac risk factors. However, treatment with alteplase made no difference to subsequent cardiac events after one month (readmissions, reinfarctions, death) nor to treatment for angina or heart failure. Product limit estimates of one year mortality are 13.2% with alteplase and 15.1% with placebo. The corresponding figures for patients with an index diagnosis of myocardial infarction are 15.7% and 18.9%, a relative reduction of 16.9%.

Adolescent

Thrombolysis with tissue plasminogen activator in suspected acute myocardial infarction. The ASSET Study.

Intravenous rtPA (total dose, 100 mg over 3 h) was compared with placebo in a prospective, randomized, double-blind trial in 5,011 patients with suspected AMI of less than 5 h duration. No ECG or enzymatic confirmation of the diagnosis was required for study entry. At 1 month 9.8% of patients given placebo had died compared with 7.2% of those who received rtPA (2.6% actual reduction, 26% relative reduction, with 95% confidence intervals of 11-39%). The majority of deaths occurred in patients who had an in-hospital diagnosis of MI (72% in both groups), with a 1-month infarct mortality of 13.1% in the placebo limb and 9.4% in the rtPA limb (relative reduction 28%, 95% CI, 14-41%). Approximately 18% of patients in both groups had a normal ECG on entry to the trial, and at 1 month the fatality was 1.6% in the rtPA group and 3.0% in the placebo group. Treatment with rtPA did not reduce the number of patients with normal ECGs from developing MI (28% rtPA vs 24% placebo). Treatment with rtPA was associated with significantly more bleeding episodes, the vast majority of which were clinically minor. The risk of all strokes in the rtPA group was similar to that in the placebo group (1.1% vs 1.0%). Treatment with rtPA was unaccompanied by either allergic or hypotensive episodes, and, among rtPA treated patients, there was no increase in clinically important ventricular dysrhythmias. Neither age nor time from onset of symptoms reduced the benefit from rtPA.

Aged

Verification of smoking history in patients after infarction using urinary nicotine and cotinine measurements.

Urinary concentrations of nicotine and its major metabolite cotinine were measured in volunteers whose smoking habits were known to test the reliability of the measurements as indicators of current smoking. In the non-smokers detectable concentrations were always below the confidence limits set for the method, while in smokers the concentrations were always above these limits. After subjects stopped smoking cotinine appeared in the urine for longer than nicotine and was still detectable at least 36 hours after the last cigarette had been smoked. When this method was used to verify the smoking histories given by patients attending an infarction clinic it was estimated that 46-53% of previous smokers had actually stopped smoking compared with the 63% who said that they had done so. It is suggested that simultaneous assays of urinary nicotine and cotinine may be a useful means of verifying patients' current smoking habits.

Cotinine

Effect of beta-blockers on arrhythmias during six weeks after suspected myocardial infarction.

Twenty-four-hour electrocardiographic tape-recording was used to investigate the incidence of arrhythmias in patients with suspected myocardial infarction who were receiving either propranolol, atenolol, or placebo. Recordings begun within 24 hours after admission to a coronary care unit showed that 76% of patients eventually found to have had a myocardial infarction had ventricular arrhythmias of a type generally regarded as serious, whereas of patients in whom myocardial infarction was not substantiated, only 24% had such arrhythmias. At one and six weeks after admission the incidence of arrhythmias ranged from 25% to 33% irrespective of diagnosis. Of patients monitored at both one and six weeks, however, only 5% had arrhythmias on each occasion. Patients treated with propranolol and atenolol showed a similar incidence of arrhythmias to those taking placebo. There was no difference in the incidence or type of arrhythmias recorded between patients who died and those who were still alive at six weeks.These results confirm that "serious" ventricular arrythmias occur in most patients during the acute phase of myocardial infarction and suggest that they do not constitute an independent risk factor. Beta-blockers showed little evidence of useful antiarrhythmic action in the dosage used, but increasing the dosage in suspected myocardial infarction is not practicable because of the risk of hypotension. The findings raise grave doubts about the value of studying arrhythmias to assess drugs intended to reduce mortality from myocardial infarction.

Arrhythmias, Cardiac

Dexamethasone in acute stroke.

Over 13 months 118 patients admitted to hospital with acute stroke were allocated at random to treatment with either dexamethasone or placebo. At one year there was no significant difference in the numbers of survivors or in the quality of life between the two groups. The results suggest that there is no indication for the routine administration of dexamethasone to a heterogeneous group of patients with stroke.

Acute Disease

Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension.

Atenolol was compared with five other beta-blockers and a thiazide diuretic in a randomised cross-over trial of once-daily treatment of essential hypertension. Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects. Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects, suggesting that further increases in dosage might be effective and well tolerated. Labetalol proved ineffective when given once daily, and the high incidence of side effects, equalled only by pindolol, would probably prohibit further increases in dosage. Bendrofluazide was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure, and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension.

Acebutolol

Serum lipid concentrations and blood pressure in obese women.

In 70 obese women no correlation was found between body weight and serum cholesterol or triglyceride concentrations, but there was a significant correlation between weight and blood pressure. Weight reduction by diet or jejunoileal shunt was not accompanied by any significant change in serum lipid concentrations other than the decrease in serum cholesterol expected after intestinal bypass. Twelve months after bypass surgery was carried out on 14 patients, however, both systolic and diastolic blood pressures were significantly reduced and at levels appropriate to the patients' new weights. These results suggest that obesity in women cannot be taken to indicate the presence of hyperlipidaemia and that sustained weight loss may lower blood pressure.

Adolescent

Contribution of atenolol, bendrofluazide, and hydrallazine to management of severe hypertension.

The efficacy of various combinations of atenolol, bendrofluazide, and hydraliazine given twice daily was assessed in a double-blind trial on 39 patients with moderate to severe essential hypertension. Concurrent treatment with all three drugs proved most effective and produced a mean reduction in blood pressure of 43/31 mm Hg. In the dosage used, hydrallazine affected only the diastolic blood pressure, and when added to either bendrofluazide or bendrofluazide plus atenolol it produced a further mean reduction in pressure of 6 mm Hg. Once-daily treatment with atenolol and bendrofluazide was as effective in reducing blood pressure as the same combination given twice daily, and the hypotensive effect was still present at least 24 hours after the last dose of tablets. A combined tablet of atenolol and bendrofluazide taken once daily would be a simple regimen to follow and would provide almost as much hypotensive effect as a twice-daily regimen incorporating a modest dose of hydrallazine. The hypotensive effect of atenolol was equal to that of bendrofluazide on systolic pressure but significantly better than that of bendrofluazide on diastolic pressure. Atenolol reduced plasma renin and urate concentrations but increased plasma potassium levels. The biochemical effects of atenolol, therefore, may be an advantage over those of bendrofluazide when deciding on first-line treatment for essential hypertension.

Bendroflumethiazide

Intravenous urography in the management of acute retention.

A retrospective analysis of the frequency of requests for an intravenous urogram (I.V.P.) in men with acute retention of urine showed that this investigation was performed in 82%. In no instance, however, did the urographic findings influence the decision to operate or the type of operation performed. The introduction of a specialised urological service did not reduce the number of I.V.P.s requested because most referrals to the urologist were made after the I.V.P. Patients who had an I.V.P. waited on average 8 days from admission to operation compared with 3-5 days for those who did not. We conclude that no purpose is served by a routine I.V.P. in every male patient admitted to hospital with acute retention of urine.

Acute Disease

Triiodothyronine, T.S.H., and prolactin in obese women.

Basal levels of thyroid-stimulating hormone and prolactin and their response to thyrotrophin-releasing hormone are normal in obese women. Serum thyroxine and triiodothyronine are also normal and do not correlate with body-weight in healthy non-dieting women. After jejunoileal bypass, serum-triio-dothyronine levels fall, and this fall appears to depend more on the reduction in calorie intake after the operation than on the reduction in body-weight per se.

Adult