Twelve patients admitted for elective resection of carcinoma of colon or rectum were allocated at random to experimental and control groups (six in each) and received a total parenteral nutrition regimen providing 230 mg N/kg and 166 KJ/kg daily over the first 5 postoperative days. In the experimental group the parenteral fluid was supplemented with a synthetic glutamine-containing dipeptide, L-alanyl-L-glutamine (54 mg peptide-N/kg per day) and the control group received corresponding amounts of alanine-N and glycine-N. On each postoperative day nitrogen balance was better in the experimental group; mean daily nitrogen balance with alanyl-glutamine was -1.5 (SE 0.4) g N/day and with the control solution -3.6 (0.2) g N/day. The cumulative nitrogen balances on the fifth postoperative day were -7.1 (2.2) and -18.1 (1.7) g N, respectively. With the peptide-containing solution intramuscular glutamine concentration remained close to the preoperative value whereas with the control solution it decreased from 19.7 (SE 0.9) to 12.0 (0.6) mmol/l intracellular water.

From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.

The frequency of new primary cancers was studied in 1846 postmenopausal patients included in a randomised trial of tamoxifen as an adjunct to primary surgery for early breast cancer. The median follow-up was 4.5 years (range 0.5-10.5 years). The number of new cancers in the tamoxifen group (n = 57) did not differ significantly from that in the control group (n = 70). However, in tamoxifen patients second breast cancers occurred less often and endometrial cancer occurred more often than in the controls. The increase in endometrial cancers was probably related to the agonistic oestrogenic effects of tamoxifen and was most pronounced in those treated for over 2 years.

Meta-analysis was used to study patients' preference in 37 crossover trials that compared indomethacin with newer non-steroidal, antiinflammatory drugs (NSAIDs). 3 reports did not present numerical data. Patients who withdrew from the trial were included in the analysis. The difference between the proportion of patients who preferred the new drug and the proportion who preferred indomethacin (the therapeutic gain) was 14%. After exclusion of 2 unreliable studies the therapeutic gain was only 7%, and when 4 preliminary reports were also ignored, the gain was 5% (95% confidence interval 0 to 10%). In two additional analyses in which the 2 outlying results were excluded, the gain was also 5%. The findings do not support the trend to replace indomethacin with newer NSAIDs.

A rapid diagnostic test for malaria based on acridine orange staining of centrifuged parasites in a microhaematocrit tube ('QBC' tube) was compared with the thick blood smear in 12 volunteers experimentally infected with Plasmodium falciparum, 408 residents of a malaria endemic area, and 180 hospital patients with suspected malaria. In the experimentally infected volunteers, the QBC tube test and the thick blood smear were comparable and the QBC tube could detect as few as 4 parasites/microliter blood. When used for mass screening in the field study, the test had a sensitivity of 70% for the diagnosis of malaria compared with 92% for a single thick blood smear. However, when used to diagnose malaria in hospital patients, the test detected as few as 3 parasites/microliter in 91 of 92 patients with asexual parasitaemia. For the three studies, the QBC tube was highly specific (98.4%), indicating malaria in only 8 of 487 subjects with negative blood films. The species of parasite was correctly identified in 77% of species. Processing the QBC tube was easier and much more rapid than was processing a thick blood smear, taking only 5 min for centrifugation and 5 min for examination. The QBC tube is not a substitute for the blood smear, but its speed and ease of use make it an important new tool for the diagnosis of malaria.

A transdermal nicotine patch, which delivers 0.7 mg/cm2 per 24 h and is available in sizes of 10, 20, and 30 cm2 was tested in subjects from 21 general medical practices in a 3-month, placebo-controlled randomised double-blind study. The nicotine group (n = 100) and the placebo group (n = 99) were similar at entry. Participants who smoked more than 20 cigarettes a day were treated with the 30 cm2 patch and the others with the 20 cm2 patch. When abstinence, defined as smoking 0-3 cigarettes per week and verified by CO measurement, was achieved, the next smallest patch was applied. After 1, 2, and 3 months of treatment 41, 36, and 36%, respectively, in the nicotine group were abstinent. The corresponding figures in the placebo group were 19, 20, and 23%. The differences were significant for all 3 months. Body weight did not increase in the nicotine group, but in the placebo group the mean increase was 4.4 kg. Craving and withdrawal symptoms decreased more with nicotine substitution for cigarettes. The patches were generally well tolerated, although 25% of subjects in the nicotine group and 13% in the placebo group had transient local erythema after application of the patch; 5 members of the nicotine group withdrew because of poor cutaneous tolerance.

2787 women who were aged 35 years or more at expected date of delivery were randomised to chorionic villus sampling (CVS) at 9-12 weeks gestation or amniocentesis at 15-17 weeks for the detection of a chromosomal abnormality in the fetus. 396 women were excluded after randomisation because of a non-viable fetus, a multiple pregnancy, or infection or because the pregnancy was too far advanced (more than 12 completed weeks). Among all women eligible at the time of the first study procedure there were 89/1169 (7.6%, 95% confidence interval [CI] 6.2-9.3%) total losses (spontaneous and induced abortions and late losses) in the CVS group and 82/1174 (7.0%, CI 5.6-8.6%) in the amniocentesis group for an excess of 0.6% for those women undergoing CVS, with a tendency to later losses in the CVS group. Approximate 95% CIs indicate that this difference is most unlikely to be greater than 2.7%. Mean birthweights for each week of gestation were similar in both groups, with no evidence of excess small-for-gestational age babies in the CVS group. The proportion of preterm births were similar in both groups. Perinatal mortality was greater in the CVS group, the greatest imbalance being beyond 28 weeks. Preliminary analysis has not disclosed an obvious recurrent event in the CVS group which might explain a cause-and-effect relationship for these late fetal losses. There is no evidence of any excess intrauterine growth retardation babies in the CVS group. Maternal morbidity was similar in both groups. 103/1037 (9.9%) women eligible for CVS had a further amniocentesis; 32 of these second procedures were needed to complete the cytogenetic diagnosis. More problems such as confined mosaicism and maternal cell contamination occurred in the interpretation of the CVS samples, but these were clarified by amniocentesis when appropriate.

105 patients who had chronic low back pain without clinical signs of lumbar nerve root compression or radiological evidence of spondylolysis or osteomalacia were randomised to three treatments: 30 sessions of intensive dynamic back extensor exercises over three months; a similar programme at one-fifth the exercise intensity; or one month of thermotherapy, massage, and mild exercises. The results consistently favoured intensive exercise, which had no adverse effects. Since these exercises can be conducted in groups, the intensive programme is no more costly than conventional strategies that require individual attention.

100 consecutive patients with both duodenal ulcer and Campylobacter pylori infection were followed up to see whether eradication of C pylori affected ulcer healing or relapse. Patients were randomly assigned to 8 weeks of treatment with cimetidine or colloidal bismuth subcitrate (CBS), with tinidazole or placebo being given concurrently from days 1 to 10, inclusive. Endoscopy, biopsy, and culture were done at entry, in weeks 10, 22, 34, and 62, and whenever symptoms recurred. There was no maintenance therapy. C pylori persisted in all of the cimetidine-treated patients and in 95% of those treated with cimetidine/tinidazole, but was eradicated in 27% of the CBS/placebo group and 70% of the CBS/tinidazole group. When C pylori persisted, 61% of duodenal ulcers healed and 84% relapsed. When C pylori was cleared 92% of ulcers healed (p less than 0.001) and only 21% relapsed during the 12 month follow-up period (p less than 0.0001).

In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.

The efficacy, safety, and tolerability of simvastatin (20 mg twice a day) in the treatment of hyperlipidaemia due to unremitting nephrotic syndrome was compared with that of cholestyramine (8 g twice a day) in a crossover trial in ten patients. Two patients were taken off the protocol, one because he could not tolerate cholestyramine and one because of non-compliance with the cholestyramine regimen. No clinical or laboratory adverse experiences were noticed during the study in the other eight patients. Simvastatin was significantly more effective than cholestyramine in reducing the hyperlipidaemia--it produced a 36% decrease in total cholesterol and a 39% decrease in low density (LDL)-cholesterol, whereas cholestyramine reduced total cholesterol by 8% and LDL-cholesterol by 19%. With simvastatin the apolipoprotein B level decreased by 30%, whereas the apolipoprotein A level increased by 10%.

A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.

In laboratory animals, non-steroidal anti-inflammatory drugs (NSAIDs) are reported to inhibit diet-induced gallstone formation. To see if these drugs had a similar effect in man, 82 patients who had taken part in a comparison of ursodeoxycholic acid, placebo, and diet for prevention of gallstone recurrence were sent questionnaires about their use of NSAIDs during the period of the trial. 75 replied. After a mean follow-up of 33 (SEM 4) months none of the 12 regular users of NSAIDs had had gallstone recurrences, compared with 20 of the 63 who never or rarely used these drugs (p less than 0.02).