Randomised trials have shown that duodenal ulcers treated by H2 blockers heal faster if Helicobacter pylori is eradicated concurrently. It remains unknown whether eradication of H pylori without suppression of acid-secretion, is sufficient to allow healing. 153 patients with H pylori infection and duodenal ulcer were randomised to receive either a 1-week course of bismuth subcitrate, tetracycline, and metronidazole (76), or omeprazole for 4 weeks with the same three-drug regimen for the first week (77). Endoscopy and antral biopsies were done at entry and 4 weeks after treatment. 132 patients were suitable for analysis. Duodenal ulcers healed in 60 (92%; 95% CI 86-100%) patients taking bismuth, tetracycline, and metronidazole compared with 63 (95%; 88-100%) taking omeprazole in addition to the three other drugs. H pylori was eradicated in 61 (94%; 88-100%) who received only three drugs compared with 66 (98%; 96-100%) who received omeprazole as well. Symptoms were reduced more effectively during the first week in patients who received omeprazole (p = 0.003). We conclude that a 1-week regimen of bismuth, tetracycline, and metronidazole for patients with H pylori and duodenal ulcer eradicates the organism and heals the ulcer in most patients. Concurrent administration of omeprazole reduces ulcer pain more rapidly but has no effect on ulcer healing.

The use of long-term oral anticoagulant treatment after myocardial infarction remains controversial because of conflicting findings on mortality in previous trials and the increased risk of bleeding associated with anticoagulants. We have carried out a randomised, placebo-controlled, double-blind, multicentre trial in 3404 hospital survivors of myocardial infarction. Eligible patients were randomly assigned to anticoagulant (nicoumalone or phenprocoumon) or placebo treatment within 6 weeks of discharge. The target prothrombin time was 2.8-4.8 international normalised ratio. During mean follow-up of 37 (range 6-76) months there were 170 deaths among 1700 anticoagulant-treated patients and 189 in 1704 placebo-treated patients (hazard ratio 0.90 [95% CI 0.73-1.11]). Anticoagulant treatment led to significant reductions by comparison with placebo treatment in recurrent myocardial infarction (114 vs 242 patients; hazard ratio 0.47 [0.38-0.59]) and cerebrovascular events (37 vs 62; 0.60 [0.40-0.90]). Major bleeding complications were seen in 73 patients who received anticoagulants and 19 who received placebo. We conclude that long-term oral anticoagulant treatment after myocardial infarction in low-risk patients has a limited effect on mortality but achieves substantial benefit by reducing the risk of cerebrovascular events and recurrent myocardial infarction.

Recognition of heart failure (HF) may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction. Since increased secretion of the cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) occurs early in the course of HF, we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea, and compared values with left-ventricular ejection fraction (LVEF), a standard measure of left-ventricular function, by radionuclide angiography. Patients were enrolled prospectively. On the basis of clinical findings, conventional tests, and response to specific treatment, 20 of the 52 patients were classified as having primary lung disorder (PLD), 12 as HF alone, and 20 as HF with underlying PLD (HF/PLD). Compared with findings in PLD patients, LVEF was significantly depressed in HF and HF/PLD patients (p < 0.001), whereas both plasma ANP and BNP were significantly increased (p < 0.001). Admission plasma BNP concentration more accurately reflected the final diagnosis of HF (93% sensitivity and 90% specificity when BNP > or = 22 pmol/L) than LVEF or plasma ANP concentration. When all patients were considered together, there were strong negative correlations between LVEF and log BNP (r = -0.7, p < 0.001) and log ANP (r = -0.59, p < 0.001). Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD, suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea.

Adjuvant systemic treatment for resectable breast cancer changes the natural history of the disease but provides only a small and delayed effect on survival. Evaluation of the types of first relapse avoided by available treatments may explain why effects on mortality are small and appear late during follow-up. In randomised clinical trials done by the International Breast Cancer Study Group (IBCSG) between 1978 and 1985, 2108 patients with node-positive disease received more-effective treatments (6 or more cycles of cyclophosphamide, methotrexate, fluorouracil and prednisone; with or without tamoxifen, or tamoxifen and prednisone alone), and 722 patients received less-effective treatments (no treatment or a single cycle of chemotherapy). 3 main categories of first site of relapse were defined and evaluated by cumulative incidence analysis: local or regional, and distant soft tissue, bone, and viscera. The more-effective treatments reduced the cumulative incidence of first relapse in local or regional and distant soft tissue sites at 10 years from 36% to 18% (p = 0.0001); first relapse in bone and viscera was not altered by the more-effective treatments. These results were similar for premenopausal and postmenopausal women, and for patients with oestrogen-receptor-positive or oestrogen-receptor-negative tumours. Adjuvant systemic treatments in current use improve patient outcome mainly by reducing the incidence of first local or regional and distant soft-tissue relapses, while first recurrences in bone or viscera are influenced much less. More intensive treatments at present being tested in clinical trials might affect bone and visceral relapses and have a greater and earlier influence on survival.

Patients with a short bowel malabsorb dietary nutrients with loss of calories and weight. Malabsorbed carbohydrates are fermented by colonic bacteria to short-chain fatty acids, which are absorbed and supply energy. The maximum energy-consumption capacities in patients with short bowel were individually measured on 40:40% carbohydrate:fat diets. 8 patients with colon in continuity and 6 patients with jejunostomies were placed on isocaloric 60:20% or 20:60% carbohydrate:fat diets and faecal excretions of calories, carbohydrates, fat, nitrogen, and fluids were compared. The high-carbohydrate low-fat diet reduced faecal loss of energy by 2.0 MJ/day compared to the low-carbohydrate high-fat diet in patients with colon in continuity, and absorption of energy increased from 49 to 69% (p < 0.001). Faecal excretions of carbohydrates were low and not influenced by the change in carbohydrate intakes (26 g/day and 28 g/day, respectively) whereas faecal fat (46 g/day and 106 g/day) was highly dependent on dietary intakes and accounted for differences in faecal loss of energy. In contrast, patients with jejunostomies excreted equal amounts of calories on the high-carbohydrate diet (4.8 MJ/day) and the high-fat diet (5.9 MJ/day; p = 0.08); and the percentage of calories absorbed was not different (55% and 48%, respectively; p = 0.21). Furthermore, in patients without colon the excretions of carbohydrates (80 g/day and 42 g/day on high-carbohydrate and low-carbohydrate diets, respectively) and fat (69 g/day and 35 g/day on high-fat and low-fat diets, respectively) were proportional to the amounts ingested. The large intestine is important in the digestion of carbohydrates and hence in the salvage of calories in patients with short bowel and severe malabsorption.

Oxidative modification of low-density lipoprotein (LDL) may be atherogenic. We studied the time of onset of LDL oxidation (lag) in 18 postmenopausal women before and after intraarterial infusion of 17 beta-oestradiol, after 3 weeks' patch administration in 12 of these women, and 1 month after discontinuation in 10. The lag increased from baseline after acute infusion (from 134 [SD41] to 167 [36] min, p = 0.01) and after the patch (132 [31] to 178 [45] min, p = 0.009). After discontinuation of oestradiol, the lag returned to baseline. This study shows an antioxidant effect of physiological levels of 17 beta-oestradiol, which may contribute to an anti-atherogenic action.

Donor-specific bone marrow infusion after organ grafting can induce tolerance in animals. In this randomised controlled study we show it has no benefit in patients undergoing liver transplantation. Of 25 patients, 9 received bone marrow 5 days after a 10 day course of antithymocyte globulin. Immunosuppression was maintained with cyclosporin only. An average of 3.0 rejection episodes per patient was seen in the bone marrow group compared to 3.1 in the controls. Chimerism was not found in peripheral blood or bone marrow of recipients using erythrocyte antigen markers, PCR for donor class II DNA or Y-probe in-situ hybridisation in one female recipient of male liver and bone marrow.

The long-term benefits of Helicobacter pylori-eradication treatment (HET) in H pylori-associated duodenal ulcer are unclear. We followed up patients with duodenal ulcers from a trial of H pylori eradication in 1985-86. 63 of 78 patients (81%) were reviewed clinically and had upper gastrointestinal endoscopy with gastric antral biopsy. Of 35 patients previously rendered H pylori negative, 32 (92%) remained H pylori negative after 7.1 years (mean). All patients initially H pylori positive remained infected, unless HET was given in the interim. Duodenal ulceration was found in 20% (5 out of 25) of patients remaining H pylori-positive, compared with 3% (1 of 38) of H pylori-negative patients (p < 0.05). The reduction of duodenal ulcer relapse obtained from H pylori eradication in H pylori-associated duodenal ulcer extends to at least 7 years after treatment, and is likely to be due to freedom from H pylori infection. However, duodenal ulcer may recur in patients rendered H pylori negative, due to factors other than reinfection with H pylori.

Nicotine-replacement therapy (NRT) by gum, transdermal patch, intranasal spray, or inhalation is expensive but how effective is it? We have done a meta-analysis of controlled trials to see how effects on abstinence rates are influenced by the clinical setting, the level of nicotine dependency, the dosage of NRT, and the intensity of additional advice and support offered. Published or unpublished randomised controlled trials of NRT that have assessed abstinence at least 6 months after the start of NRT were identified and 53 trials (42 gum, 9 patch, 1 intranasal spray, 1 inhaler), with data from 17,703 subjects, were included in the analyses. Use of NRT increased the odds ratio (OR) of abstinence to 1.71 (95% confidence interval 1.56-1.87) compared with those allocated to the control interventions. The ORs for the different forms of NRT were 1.61 for gum, 2.07 for transdermal patch, 2.92 for nasal spray, and 3.05 for inhaled nicotine. These odds were non-significantly higher in subjects with higher levels of nicotine dependence but they were largely independent of the intensity of additional support provided or the setting in which NRT was offered. We conclude that the currently available forms of NRT are effective therapies to aid smoking cessation.

Although laparoscopic cholecystectomy has rapidly become routine practice in the UK, there has been no rigorous comparison of it with open cholecystectomy. In our trial, 302 patients were randomised to laparoscopic or minilaparotomy cholecystectomy. Recovery after surgery was assessed by length of hospital stay, outpatient review at 10 days and 4 weeks, and patient questionnaires 1, 4, and 12 weeks after surgery. The mean operation time was 14 min shorter for minilaparotomy, while median post-operative hospital stay was 2 days shorter after laparoscopic cholecystectomy. The hospital costs were about 400 pounds greater for the laparoscopic procedure. Laparoscopic patients returned to work in the home sooner; at 1 week, they had better physical and social functioning, were less limited by physical problems, and had less pain and depression. At 4 weeks, only physical functioning and depression scores were better in the laparoscopic group, and by 3 months there were no differences. Laparoscopic patients were more satisfied with the appearance of their scars. The incidence of complications after both procedures was 20%. Compared to minilaparotomy cholecystectomy, laparoscopic cholecystectomy results in shorter hospital stay, less postoperative dysfunction, and quicker return to normal activities, but is more costly.