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R Collins

Publications and source records attributed to R Collins.

At least 127 records · Page 7Linked to original sources
PubMed1994

Randomization.

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Data Interpretation, Statistical↗
PubMed1994

Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease.

Most evidence about the effects of blood pressure on the risks of cardiovascular disease derives from two principal sources: prospective non-randomised observational studies of the associations between blood pressure and the incidence of stroke and of coronary heart disease, and randomised trials of antihypertensive drug therapy. The focus of the first part of this chapter concerns the evidence from observational studies, which--despite the possibility of confounding by other risk factors--may be more relevant to the eventual effects of prolonged blood pressure differences on stroke and coronary heart disease risk. The focus of the second part concerns the evidence from randomised trials of antihypertensive drug treatment, which are more relevant to assessing how rapidly, and to what extent, the epidemiologically expected reductions in stroke or in coronary heart disease are produced by suddenly lowering blood pressure in middle and old age.

Adult↗
PubMed1994

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study.

We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Randomized controlled trial of oral captopril, of oral isosorbide mononitrate and of intravenous magnesium sulphate started early in acute myocardial infarction: safety and haemodynamic effects. ISIS-4 (Fourth International Study of Infarct Survival) Pilot Study Investigators.

The purpose of this randomized controlled study was to assess the haemodynamic effects, safety and tolerability in acute myocardial infarction (AMI) of one month of oral captopril, one month of oral isosorbide mononitrate and 24 h of intravenous magnesium. It was carried out in four United Kingdom and six Polish hospitals in consecutive phases: oral captopril vs oral mononitrate vs placebo were compared among 400 patients in a 'three-way' study; and then oral captopril vs placebo and oral mononitrate vs placebo were compared among 474 patients in '2 x 2' and '2 x 2 x 2' factorial studies (with 208 patients in the latter study also randomized between intravenous magnesium and open control). The factorial studies differed from the three-way study in that one group of patients was allocated both oral captopril and oral mononitrate, a higher maintenance dose of captopril was used (following the same initial dose), and once daily controlled-release mononitrate was used. In the three-way study, the mean of the lowest systolic blood pressures recorded during the first 4 h after randomization were (mmHg +/- standard error): 104 +/- 2 captopril vs 105 +/- 1 mononitrate vs 112 +/- 2 placebo (P < 0.001 for captopril or for mononitrate vs placebo), and in the factorial studies were 105 +/- 1 captopril vs 110 +/- 1 placebo (P < 0.01) and 106 +/- 1 mononitrate vs 108 +/- 1 placebo (NS). There was an excess of hypotension recorded among patients allocated active treatment (captopril > mononitrate > placebo) and there was a small, but significant, excess of cardiogenic shock with captopril compared with control in the factorial study. However, in these studies, neither captopril nor mononitrate were associated with any overall increase in the incidence of hypotension considered severe enough to lead to treatment being stopped. No other serious complications were observed, and compliance with study tablets at hospital discharge was not significantly different between the active and placebo groups. Patients allocated magnesium in the 2 x 2 x 2 factorial study had a slightly lower mean systolic blood pressure just after the initial 15 min bolus injection (126 +/- 2 magnesium vs 134 +/- 3 control; P < 0.05) but there were no significant differences during the subsequent 24 h maintenance infusion period. Apart from some facial flushing, magnesium did not appear to be associated with any complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Captopril↗
PubMed1993

A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.

Adult↗
PubMed1993

Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer.

OBJECTIVE: To determine whether prolonged infection with hepatitis B virus is associated with a lower blood cholesterol concentration. DESIGN: Cross sectional study. SETTING: 81 villages in rural China with a high prevalence of chronic infection with hepatitis B virus. SUBJECTS: 1556 apparently healthy men aged 35-64 years, randomly selected. MAIN OUTCOME MEASURES: Hepatitis B virus carrier state; plasma concentrations of cholesterol, apolipoprotein B, and apolipoprotein A I. RESULTS: 238 (15%) of the men were positive for hepatitis B surface antigen, indicating that they were chronic carriers. Plasma concentration of cholesterol was 4.2% (0.11 mmol/l) lower among carriers (that is, positive for hepatitis B surface antigen) than among non-carriers (95% confidence interval 0.6% to 8.0% (0.01 to 0.21 mmol/l), p < 0.05), and apolipoprotein B concentration was 7.0% (0.036 g/l) lower (2.8% to 11.2% (0.014 to 0.058 g/l), p < 0.001). In contrast, no association was observed between plasma concentrations of cholesterol or apolipoprotein and hepatitis B that had been eradicated (that is, patient positive for hepatitis B core antibody but negative for hepatitis B surface antigen). CONCLUSIONS: Chronic hepatitis B virus infection, which usually starts in early childhood in China, seems to lead not only to a greatly increased risk of death from liver disease but also to a somewhat lower cholesterol concentration in adulthood. This common cause produces an inverse association between cholesterol concentration and risk of death from liver cancer or from other chronic liver diseases.

Adult↗
PubMed1993

Hemodynamic effects of captopril and isosorbide mononitrate started early in acute myocardial infarction: a randomized placebo-controlled study.

OBJECTIVES: The aim of this study was to study the hemodynamic effects of orally administered captopril and isosorbide mononitrate in suspected acute myocardial infarction. BACKGROUND: Early treatment with converting enzyme inhibitors and nitrates in acute myocardial infarction may limit infarct expansion and prevent left ventricular dilation. METHODS: In a double-blind study, 81 patients were randomized within 36 h of the onset of symptoms of suspected acute myocardial infarction to 1 month of oral captopril (6.25 mg initial dose, followed 2 h later by 12.5 mg and continuing with 12.5 mg three times daily), isosorbide mononitrate (initial dose 20 mg followed by 20 mg three times daily) or matching placebo. The effects of treatment on changes from baseline in mean arterial blood pressure, heart rate, stroke volume, cardiac output and systemic vascular resistance were assessed noninvasively using Doppler echocardiography 1 h after the first dose, 1 week after infarction and at 6 weeks (that is, 2 weeks after the scheduled end of trial treatment). RESULTS: One hour after the start of treatment, blood pressure was reduced by approximately 10% with both captopril and isosorbide mononitrate, but this difference did not persist at 1 week. Captopril was associated with a significant increase in cardiac output compared with placebo of 13 +/- 3% at 1 h (p < 0.01), 23 +/- 5% at 1 week (p < 0.001) and 22 +/- 6% (p < 0.05) at 6 weeks (2 weeks after the end of trial treatment). This increase in cardiac output with captopril was mainly due to a substantial and sustained increase in stroke volume, although there was also a small increase in heart rate at 1 week. Both captopril and isosorbide mononitrate reduced systemic vascular resistance within 1 h of the start of treatment, but only the effect of captopril was sustained (perhaps because the three-times daily nitrate regimen induced tolerance). Study treatment was well tolerated, and the incidence of withdrawal of study treatment for hypotension was not significantly different from that with placebo. CONCLUSIONS: This study indicates that the hemodynamic effects of both captopril and isosorbide mononitrate are well tolerated in the acute phase of myocardial infarction and that captopril favorably influences cardiac function.

Aged↗
PubMed1993

Short report: high-dose omeprazole and amoxycillin in the treatment of Helicobacter pylori-associated duodenal ulcer.

Thirteen consecutive patients with active duodenal ulcer disease were assigned to a treatment schedule with high-dose omeprazole and amoxycillin. Duodenal ulcer was diagnosed endoscopically in all patients, at which time antral biopsies were taken for culture and histology. All were positive for Helicobacter pylori and histological gastritis. Treatment was for 2 weeks: 80 mg omeprazole daily plus 500 mg amoxycillin syrup t.d.s. in the first week, followed by 40 mg omeprazole daily in the second week. Repeat gastroscopy was performed 4 weeks after completion of treatment in all patients. Duodenal ulcer healing occurred in 4/13 patients. H. pylori eradication was achieved in 2/4 patients with healed ulcers and in 3/9 patients with persistent ulceration. This study suggests that a short period of treatment with high-dose omeprazole and amoxycillin achieves low rates of ulcer healing and H. pylori eradication.

Adult↗
PubMed1993

Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics.

Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81% (35/43) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re-infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer relapse than omeprazole alone.

Adult↗
PubMed1993

Effects on ventricular arrhythmias of oral captopril and of oral mononitrate started early in acute myocardial infarction: results of a randomised placebo controlled trial.

OBJECTIVE: To assess the effects of oral vasodilator treatment on ventricular arrhythmias in acute myocardial infarction. SETTING: Coronary care units at the John Radcliffe Hospital, Oxford, and the Royal Infirmary, Edinburgh. PATIENTS: 100 patients with suspected acute myocardial infarction entered the study at a mean of 13 hours from symptom onset. DESIGN OF INTERVENTION: Double blind randomisation to 4 weeks treatment with captopril (12.5 mg three times a day after a 6.25 mg test dose (n = 32)) or isosorbide mononitrate (20 mg three times a day (n = 31)) or placebo control (n = 37). OUTCOME MEASURES: Ventricular arrhythmic events assessed by 48 hours of Holter monitoring starting at the time of randomisation. RESULTS: The number of ventricular extrasystoles/hour for captopril, mononitrate, and placebo was respectively (median and range) 6 (0-162), 4 (0-38), and 10 (0-932) (2p < 0.02 mononitrate v placebo). The number of episodes of multiple extrasystoles/hour was 0.2 (0-22), 0.3 (0-4), and 0.5 (0-19); (2p < 0.02 mononitrate v placebo). Episodes of ventricular tachycardia showed a non-significant decrease in the captopril and mononitrate groups (mean (SEM) 3.2 (0.8), 2.4 (0.7), and 4.7 (1.3) for the 48 hour period). The incidence of idioventricular rhythm was also reduced in both active treatment groups (28%, 19%, and 46% (2p < 0.05 mononitrate v placebo)). CONCLUSIONS: Oral mononitrate (and perhaps also captopril) seems to reduce the incidence of ventricular arrhythmias in the early phase of acute myocardial infarction. The effects on life-threatening arrhythmias, such as ventricular fibrillation, and on death can only be assessed in a much larger trial.

Administration, Oral↗