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Biomedical subjects

D S Cole

Publications and source records attributed to D S Cole.

At least 19 recordsLinked to original sources

A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.

BACKGROUND: Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain. METHODS: We screened 6676 consecutive patients with 7001 myocardial infarctions confirmed by enzyme studies. A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction (ejection fraction, < or = 35 percent). On days 3 to 7 after infarction, 1749 patients were randomly assigned to receive oral trandolapril (876 patients) or placebo (873 patients). The duration of follow-up was 24 to 50 months. RESULTS: During the study period, 304 patients (34.7 percent) in the trandolapril group died, as compared with 369 (42.3 percent) in the placebo group (P = 0.001). The relative risk of death in the trandolapril group, as compared with the placebo group, was 0.78 (95 percent confidence interval, 0.67 to 0.91). Trandolapril also reduced the risk of death from cardiovascular causes (relative risk, 0.75; 95 percent confidence interval, 0.63 to 0.89; P = 0.001) and sudden death (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98; P = 0.03). Progression to severe heart failure was less frequent in the trandolapril group (relative risk, 0.71; 95 percent confidence interval, 0.56 to 0.89; P = 0.003). In contrast, the risk of recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk, 0.86; 95 percent confidence interval, 0.66 to 1.13; P = 0.29). CONCLUSIONS: Long-term treatment with trandolapril in patients with reduced left ventricular function soon after myocardial infarction significantly reduced the risk of overall mortality, mortality from cardiovascular causes, sudden death, and the development of severe heart failure. That mortality was reduced in a randomized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infarction.

Adult

Single dose cefotaxime plus metronidazole versus three dose cefuroxime plus metronidazole as prophylaxis against wound infection in colorectal surgery: multicentre prospective randomised study.

OBJECTIVE: To establish whether a single preoperative dose of cefotaxime plus metronidazole was as effective as a standard three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery. DESIGN: Prospective randomised allocation to one of two prophylactic antibiotic regimens in a parallel group trial. Group sequential analyses of each 250 patients were performed. SETTING: 14 District general and teaching hospitals. PATIENTS: 1018 Adults having colorectal operations were randomised, of whom 943 were evaluated. Demographic features, conditions requiring surgery, and operative procedures were similar in the two groups. Most patients had surgery for carcinoma of the colon or rectum. INTERVENTIONS: Group 1 received cefotaxime 1 g intravenously plus metronidazole 500 mg intravenously preoperatively. Group 2 received cefuroxime 1.5 g intravenously plus metronidazole 500 mg intravenously preoperatively, followed by cefuroxime 750 mg intravenously plus metronidazole 500 mg intravenously eight hours and 16 hours postoperatively. MAIN OUTCOME MEASURES: Development of surgical wound infection (as evidenced by the presence of pus), death, or discharge from hospital. RESULTS: Wound condition was scored on a five point scale on alternate days until discharge or for up to 20 days postoperatively. Wound infection rates were: group 1, 32/453 (7.1%; 95% confidence interval 4.7% to 9.4%); group 2, 33/454 (7.3%; 95% confidence interval 4.9% to 9.6%). Death rates (group 1: 26/470 (5.5%); group 2: 31/471 (6.6%], the incidence of postoperative complications, the median duration of hospital stay (12 days), and antibiotic tolerance were all similar in the two groups. Pooled data from groups 1 and 2 showed that wound infections were more frequent when minor faecal contamination had occurred at operation and when the duration of operation exceeded 90 minutes (greater than 90 min 11.2% of cases; less than 90 min 4.8%) and were associated with an extended hospital stay. CONCLUSIONS: A single preoperative dose of cefotaxime plus metronidazole is an efficacious as a three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery and has practical advantages in eliminating the need for postoperative antibiotics.

Adolescent

A randomised prospective comparison of cefotaxime versus netilmicin/penicillin for treatment of suspected neonatal sepsis.

In an open prospective study performed in 2 neonatal units, infants with suspected neonatal sepsis (SNS) of unknown microbial cause were randomly allocated to receive treatment with either cefotaxime (CTX) or netilmicin plus penicillin (N + P). 236 patients were entered into the trial, of whom 222 were evaluable. The number of 'definitely' and 'probably' infected babies was similar in both groups. There was no difference in clinical outcome between patients in the 2 treatment groups and no side effects were recorded for either of the antibiotic regimens. Antibiotic sensitivity testing of bacterial isolates from peripheral sites showed almost universal sensitivity of potential pathogens to both antibiotic regimens at the start of treatment in all infants. Thereafter, organisms resistant to CTX were isolated from patients in both treatment groups, possibly reflecting the antibiotic sensitivity profile of the colonising bacteria in both neonatal units. The results of this study indicate that either CTX or N + P are suitable, in our units, for the 'blind' treatment of early SNS. In units where listerial infections are prevalent, specific cover should be added to CTX. For SNS developing after admission, the choice of antibiotics will depend upon the background antibiotic sensitivity profile of the colonising bacteria.

Bacterial Infections

Digoxin and cimetidine: investigation of the potential for a drug interaction.

The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. In a repeated-dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance.

Adult

A single-blind comparative study of auranofin and hydroxychloroquine in patients with rheumatoid arthritis.

Forty patients with rheumatoid arthritis were randomly allocated to treatment with auranofin 3 mg b.d. or hydroxychloroquine 200 mg b.d. Twenty patients received each drug. Efficacy was analysed by comparing patients with available data at weeks 12, 24, 36 and 48 with baseline within each treatment group, and between treatment groups at each of these same time points. There were statistically significant improvements in all measured parameters of clinical efficacy among hydroxychloroquine treated patients, and in all efficacy parameters except one (time to onset of fatigue) in the auranofin treatment group. There were no significant differences between the treatment groups for any parameter of clinical efficacy. Of the laboratory parameters measured, only auranofin treatment produced statistically significant decreases in the concentration of IgA, IgG and IgM, with significant differences between treatments being detected in the case of IgA and IgG. Eight auranofin-treated and three hydroxychloroquine-treated patients were withdrawn because of adverse reactions before completing 48 weeks treatment. The commonest reason for stopping auranofin treatment was diarrhoea (5 cases). Three hydroxychloroquine-treated and two auranofin-treated patients were withdrawn from the study because of inefficacy of the trial drug. Auranofin had a more 'potent' biochemical profile than hydroxychloroquine, although more patients tolerated one year of treatment with the latter drug.

Adult

Light and electron microscopic studies of phrenic nerves after long-term electrical stimulation.

Light and electron microscopic evaluation were carried out on canine phrenic nerves subjected to long-term electrical stimulation. A total of 34 stimulated and 19 control nerves were studied by light microscopy, and 10 stimulated and five control nerves were evaluated by electron microscopy. Except in a few cases in which a higher current was used, the current used for stimulation was between 1 and 2 mA. The pulse width was 150 microseconds. The typical charge per pulse was 0.22 microC and charge density per pulse 1.125 microC/sq cm of real area. The total number of days of electrical stimulation in individual phrenic nerves ranged from 4 to 374. No morphological changes in the phrenic nerve that could be attributed to the electrical stimulation were observed by light or electron microscopic study. There were, however, two phrenic nerves cuffed with bipolar electrodes which showed focal demyelination at the electrode level, but these changes were caused by factors other than the electrical stimulation. The results of the studies have direct clinical implications to long-term stimulation of phrenic nerves.

Animals

Chelation therapy.

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Arteriosclerosis

Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate?

Cimetidine 1 g daily is often continued for a fixed period beyond the time of healing of duodenal ulcer on the assumption that it might reduce the subsequent relapse rate. To test this, 194 patients whose ulcers had healed after one month of cimetidine 1 g daily were allocated at random to three groups for further treatment with cimetidine 1 g daily for two months (n = 63) or five months (n = 66) or placebo (n = 65). Thereafter all patients received placebo. Endoscopy was done routinely every three months, or earlier if symptoms recurred. During follow-up in the placebo phase, which lasted for up to 25 months, the estimated total proportions of patients in the three groups with symptomatic recurrences of ulcer were 80%, 90%, and 77%, respectively; the corresponding proportions with silent plus symptomatic relapses were 92%, 90%, and 100%. The relapse rates were also similar in all three groups. Statistical analysis showed a significant variation in relapse rate but the differences were regarded as clinically unimportant. These findings show that full-dose cimetidine continued for several months beyond the time of healing of duodenal ulcer dose not decrease the risk of subsequent relapse.

Adult

Effects of beer, wine, and liquor in coronary deaths.

For a series of 568 married men who died of coronary heart disease and an equal number of matched control subjects, information was collected on a large number of variables, including daily alcohol consumption classified by type of beverage, namely, beer, wine, or liquor. Daily consumption of small to moderate amounts of alcohol (2 oz [59.2mL] or less daily) was inversely related to coronary death. This inverse relation was present in both crude and adjusted matched-pair analyses and was similar for each type of alcohol, as indicated by adjusted relative risks of 0.3 for beer, 0.3 for wine, and 0.2 for liquor. In contrast, for heavy drinking, there was no association with coronary death in either crude or adjusted analyses.

Adult

Daily alcohol consumption and fatal coronary heart disease.

For a series of 568 married white men who died from coronary heart disease (CHD) and an equal number of matched controls, information was collected on a large number of variables, including daily alcohol consumption. The crude matched pair ratio estimate for any versus no daily drinking was 0.6 (95% confidence limits 0.4 to 0.7). After controlling for additional confounding variables the risk ratio for any versus no daily alcohol consumption was 0.6 (0.5--0.8). This preventive effect was restricted to light drinkers, defined as those who drank less than or equal to 59.2 ml (2 oz) of alcohol daily. These data provide strong evidence against a causal role of daily alcohol consumption in fatal CHD and are consistent with a small preventive effect of any versus no daily drinking which is attributable only to light but not heavy drinkers.

Adult