In a prospective controlled clinical trial, 70 patients with normal gastrointestinal function were randomised to receive either an elemental diet based on Vivonex HN or an isonitrogenous isocalorie polymeric diet based on Clinifeed 400, administered by continuous 24 hour nasogastric infusion. The two groups of patients were well matched for age, sex, diagnosis, prior starvation, duration of feeding, initial nutritional status, and metabolic status. Nitrogen losses were significantly less on the polymeric feed, despite similar intakes. Serum transferrin rose significantly (1.85 +/- 0.2 to 2.30 +/- 0.2 g/l, p less than 0.05) only in the Clinifeed group, but nutritional parameters were otherwise maintained in both groups. The incidence of diarrhoea (Vivonex, 23.5%; Clinifeed, 30.6%) was not significantly different and was attributable to antibiotics in most cases. Hypokalaemia, which occurred in nearly half the patients, was equally distributed in the two groups, but hypophosphataemia occurred more often in the Vivonex group (p less than 0.05). Liver enzyme disturbances were similar in both groups. The present findings, therefore, provide no evidence that chemically defined 'elemental' diets containing free amino acids as their nitrogen source are in any way superior to polymeric diets containing whole protein and fat when administered to patients with normal gastrointestinal function.

It has been suggested that consumption of refined carbohydrate foods (notably sugar and white flour) increases bile cholesterol saturation and hence the risk of cholesterol gall stone formation. To test this hypothesis, 13 subjects with probable cholesterol gall stones ate refined and unrefined carbohydrate diets, each for six weeks in random order. On the refined carbohydrate diet, subjects ate more refined sugar (mean = SEM: 106 +/- 7 vs 6 +/- 1 g/day, p less than 0.001), less dietary fibre (13 +/- 1 vs 27 +/- 3 g/day, p less than 0.001), and had a higher energy intake (9.17 +/- 0.66 vs 7.16 +/- 0.64 MJ/day, p less than 0.001). After each diet, the lipid composition of duodenal bile and bile acid kinetics was determined. The cholesterol saturation index of bile was higher on the refined carbohydrate diet in all but one subject, with a mean value of 1.50 +/- 0.10 compared with 1.20 +/- 0.12 on the unrefined diet (p less than 0.005). On the refined carbohydrate diet, bile contained relatively less cholic acid and slightly more deoxycholic acid. There were, however, no significant differences in total or individual bile acid pool sizes. There were also no differences in the rates of primary bile acid synthesis or fractional turnover on the two diets. Consumption of carbohydrate in refined form increases bile cholesterol saturation. The risk of gall stones might be reduced by avoidance of refined carbohydrate foods.

A randomised double-blind trial of thioctic acid (alpha-lipoic acid), 300 mg/day versus placebo was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a six month period. Twenty patients received the active drug and 20 placebo. Twenty-two of the 40 patients (55%) abstained from alcohol and showed significant improvements (p less than 0.01) in mean values for serum aspartate transaminase, serum glutamyl transpeptidase, and mean corpuscular volume. Seventeen of the 22 (77%) showed overall histological improvement on liver biopsy. The remaining 18 patients (45%) continued to drink but significantly reduced their mean daily alcohol intake (p less than 0.001). No significant changes occurred in their laboratory indices, but five of the 18 (28%) showed overall histological improvement. Changes occurred irrespective of treatment with thioctic acid, which suggested that, over six months, this drug did not influence the course of alcohol-related liver disease.

The therapeutic efficacy of orally administered branched-chain amino acids in patients with liver cirrhosis and chronic encephalopathy was examined in a double blind, randomised crossover study. Seven patients with manifest hepatic cirrhosis and encephalopathy of six months' duration or longer ingested 30 g branched-chain amino acids or placebo during two 14-day periods. Psychometric tests and electroencephalograms were used to evaluate cerebral function. Neither clinical observations nor psychometric testing or electroencephalogram indicated a significant difference in the patients' response to branched-chain amino acids as compared with placebo. In four patients given branched-chain amino acids for longer periods (five to 22 weeks), psychometric tests also remained unchanged. The plasma concentrations of these acids after oral intake increased significantly, demonstrating adequate absorption. Basal plasma amino acid concentrations were unchanged, however, after branched-chain amino acid therapy. No side-effects were seen, which indicates that these amino acids are well tolerated as an extra protein supply in patients with chronic hepatic encephalopathy. As compared with placebo, however, no effect of branched-chain amino acids on the encephalopathy could be detected.

The effect of oxmetidine 800 mg/day, a new histamine H2-receptor antagonist, on duodenal ulcer healing was compared with cimetidine 1000 mg/day in a two-centre double-blind trial. Ninety-nine patients completed the study. After four weeks, ulcers were healed in 74% of the cimetidine-treated patients and in 78% of the oxmetidine-treated patients (p greater than 0.05). Healing rates after eight weeks increased to 90% in the cimetidine group and to 94% in the oxmetidine group. Healing rates after four weeks were, however, different in the two centres (p less than 0.01): in centre 1 88% of the cimetidine-treated, but 63% of the oxmetidine-treated patients healed, in centre 2 rates were 60% (cimetidine) and 92% (oxmetidine). Analysis of patient data revealed that in the two centres treatment success was inversely correlated (p less than 0.01) with the percentage of smokers in each treatment group. Smoking significantly influences duodenal ulcer healing with histamine H2-receptor antagonists.

Fifty patients with endoscopically proven gastric ulcers completed a one month double-blind randomised trial of tripotassium dicitrato bismuthate (TBD) (DeNol) compared with an identical placebo. Ulcer healing occurred in 18 (72%) of the 25 patients given TDB and in nine (36%) of the patients given placebo. The TDB group experienced significantly less pain than the placebo group. During a follow-up of 29 patients with healed ulcers for up to 44 months, relapse occurred in 13 (45%). It was highest in the first three months (27%) and had risen to 41% at two years.

A controlled trial of 44 patients was undertaken to evaluate the use of dexamethasone (32 mg stat, 8 mg qds) in preventing, and intravenous mannitol (1 g/kg) in reversing the cerebral oedema of fulminant hepatic failure. Diagnosis of cerebral oedema was based on intracranial pressure recordings or the presence of defined clinical signs. Cerebral oedema developed in 34 patients with similar frequency in those treated with and without dexamethasone (16 of 21 and 18 of 23 respectively). In those 34 patients episodes of cerebral oedema resolved significantly more frequently in the 17 patients who received mannitol than in the 17 patients who did not (44 of 53 and 16 of 17 respectively, p less than 0.001). Dexamethasone did not affect survival but among patients who developed cerebral oedema those who received mannitol had a significantly better survival than those who did not receive it (47.1% and 5.9% respectively, p 0.008, Fisher's one-tail test).

One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily). Ulcer healing was assessed after six weeks' treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks' treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year's maintenance treatment, and there have been four ulcer recurrences in each group (14%).

During a double-blind randomised clinical trial of cimetidine and ranitidine in the management of duodenal ulcer, the response of patients' peripheral blood lymphocytes to optimal mitogenic stimulation in vitro has been measured. Treatment with cimetidine, but not ranitidine, was associated with a significant increase in the proportion of peripheral blood lymphocytes responding to this optimal mitogenic stimulation. We conclude that these effects of cimetidine may not be mediated at classical histamine H2-receptors.

The aim of this study was to determine whether bedtime administration and a low cholesterol diet reduce the minimum effective dose of chenodeoxycholic (chenic) acid, defined as the dose giving a mean cholesterol saturation index of 0.8. Dose response studies were carried out in 10 patients with radiolucent gallstones in a functioning gallbladder during three different treatment regimens. On each regimen, all patients received three different doses of chenodeoxycholic acid in random order for one month each. Bedtime chenic acid plus a low cholesterol diet gave the greatest reduction in saturation index. A significant dose/response relationship was found on each regimen. On the conventional regimen of mealtime chenic acid, the minimum effective dose was 14 mg/kg/day; on bedtime chenic acid it was 12.4 mg/kg/day; and on bedtime chenic acid plus low cholesterol diet it was further reduced to 8.4 mg/kg/day (p less than 0.01). There was a dose-related increase in bowel frequency, which was absent at 10.6 mg/kg/day and below. We conclude that administration of chenic acid at bedtime with a low cholesterol diet enables the minimum effective dose for gallstone dissolution to be approximately halved, thus preventing diarrhoea and reducing the cost of treatment.

The efficacy of methylprednisolone (1 g daily or three days), which is effective in reversing transplant rejection, was assessed in a randomised controlled trial of 55 patients with severe acute alcoholic hepatitis, 34 of whom had encephalopathy. The clinical progress, frequency of bleeding and sepsis, and cause of death were similar in the treatment (27 patients) and control groups (28 patients). There was no significant difference in mortality rate between the two groups: 57% of the control group and 63% of the treatment group died during the study. Patients' survival depended on the presence of absence of the following features: encephalopathy, serum bilirubin concentration more than 340 micromol/l, serum creatinine concentration more than 250 micromol/l, and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis.

Neomycin, an antibiotic which is primarily active against the aerobic gut flora and hence reduces the endogenous production of ammonia, is a well-recognised form of treatment for acute or acute on chronic hepatic encephalopathy. This study suggests that metronidazole may be a useful alternative or even adjunctive treatment for such patients. Theoretical and practical justifications for the use of this drug are presented. The results of a week's prescription of each drug have been assessed by changes in clinical and biochemical criteria, including electroencephalograms and arterial ammonia sample. In the treatment of a series of 11 mildly or moderately, and seven severely affected, patients with histologically confirmed cirrhosis, metronidazole is shown to be as effective as neomycin.

In a double-blind, placebo controlled and randomised secretory study the effectiveness of pirenzepine, ranitidine, and their combination was compared intraindividually in eight healthy subjects receiving intravenous bolus injections. Pirenzepine (0.15 mg/kg) plus ranitidine (0.6 mg/kg) suppressed peptone-stimulated gastric acid secretion from 69 +/- 11 to 2 +/- 0.4 mmol H+/3 h; the mean percentage inhibition was 97%. Postprandial gastrin was unaffected. There were only minor side-effects in a few experiments (reduction of salivation, brief blurring of vision), but no prolactin stimulation after ranitidine or ranitidine plus pirenzepine. The combined application of ranitidine and pirenzepine inhibited meal-stimulated acid secretion more effectively and produced fewer side-effects than the combination of cimetidine plus pirenzepine studied previously.

One hundred and three outpatients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with either cimetidine 200 mg tds and 400 mg nocte, or ranitidine 150 mg bd for four weeks. The endoscopists were not aware of the treatment and took no part in the clinical management. On completion of treatment ulcers had healed in 43 of 51 (84%) patients given cimetidine and in 40 of 52 (77%) patients given ranitidine. There were no serious unwanted effects in either treatment group. The results show no significant difference between healing rates after four weeks of standard cimetidine therapy or ranitidine 150 mg bd.

Emergency endoscopy on 332 patients with acute upper gastrointestinal bleeding showed that 178 had peptic ulcers; 28 of these were actively bleeding (spurting) and 108 showed stigmata of recent haemorrhage (vessels or spots in the ulcer base) suggesting a risk of rebleeding. These 136 patients were randomly allocated to Argon laser photocoagulation or to no additional therapy (controls) at the time of initial endoscopy. All patients received conventional management, and the controlling clinicians did not know whether or not the laser had been used in any individual patients. The laser system proved both simple and safe in use. Initial haemostasis was achieved by the laser in 10 of 15 'spurting vessels', but four of 13 'control' spurting vessels also stopped bleeding spontaneously. Overall, there were no statistically significant differences between the laser treated and control groups in terms of rebleeding, the need for surgical intervention, or death. These results require amplification in larger trials, and comparison with other studies using different protocols and other haemostatic methods.

A randomised double-blind trial of (+)-cyanidanol-3(Catechin), 2 g/day versus placebo, was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a three month period. Twenty received the active drug and 20 placebo; one non-compliant patient in the treatment group was withdrawn. Forty-one per cent (16/39) abstained from alcohol and showed significant improvements (P < 0.005) in mean values for serum aspartate transaminase, serum gamma glutamyl transpeptidase, and mean corpuscular volume. Ten of the 16 showed overall histological improvement on liver biopsy. Fifty-nine pr cent (23/39) continued to drink, though significantly reducing their mean daily alcohol intake (P < 0.001). No significant changes occurred in this group in mean serum enzyme values, though the mean value for mean corpuscular volume improved significantly (P < 0.01) and 16 of the 23 showed overall histological improvement. Changes occurred irrespective of treatment with Catechin which suggests that, over a three month period, this drug did not influence the course of alcohol-related liver disease.

Thirty patients with distal colitis (proctosigmoiditis) in relapse were randonly allocated to twice daily treatment with traditional aqueous hydrocotrisone enemas (Cortenemas) or a suspension of hydrocortisone in an inert foam base (Colifoam). Each treatment contained the same amount of hydrocortisone. Clinical, sigmoidoscopic, and histological response was assessed after two weeks. Both agents were effective, and broadly similar in terms of objective improvement, but subjective improvement was greater with the foam preparation, and several patients expressed a preference to this mode of treatment.

Twenty patients with persistent diarrhoea participated in a randomised, double-blind trial of oral sodium cromoglycate and placebo. Eight patients noted significant improvement in their diarrhoea while taking sodium cromoglycate and this did not correlate with the presence of other atopic diseases, a history of food intolerance, or the presence of lactase deficiency. The results suggest that some patients with diarrhoea of unknown cause may have food allergy as a major contributing cause for their diarrhoea.

Fifteen patients with cystic fibrosis and pancreatic insufficiency were studied during four randomised seven day treatment periods in which they received only pancreatic supplement (Pancrelipase, 27 capsules per day) or supplement plus cimetidine (20 mg/kg body weight/24 h) or sodium bicarbonate (15 g/m2/24 h) alone or in combination. Dietary intake was not fixed but was restricted to foods of known fat and nitrogen content from which daily intakes could be computed. Faecal fat and nitrogen were calculated as g/24 h and percentage of intake. Addition of either cimetidine or bicarbonate resulted in significant improvement in fat and nitrogen excretion, which was not greater with the combination of both drugs. Cimetidine and sodium bicarbonate in these doses are therefore sufficient to produce maximal improvement in digestive activity of pancreatic supplements. Fat excretion per gram of intake fell with cimetidine and bicarbonate from 12 times the normal level, to normal, in patients consuming less than 120 g fat daily. Above this intake the dose of pancreatic supplement appeared to be inadequate. Faecal nitrogen excretion increased with nitrogen intake in all four periods, but, in contrast with fat excretion, the response to cimetidine and bicarbonate was not affected by the level of intake. Dietary intake appears to be a significant factor in determining the faecal output of fat and nitrogen in patients with pancreatic insufficiency and should be considered when determining the optimum amount of pancreatic supplementation.

Prostaglandins have been shown in animal laboratory studies to be capable of protecting the gastrointestinal tract against injury by exogenous agents. This study was conducted to determine if prostaglandin E2 (PGE2), which is native to the human gastric mucosa, could influence the increase in faecal blood loss associated with the ingestion of aspirin (ASA). A randomised double-blind study was performed on 27 healthy men. Faecal blood loss was measured by the 51Cr labelled red cell technique. ASA (600 mg four times daily) caused a significant increase in faecal blood loss. PGE2 (1 mg four times daily) had no effect on faecal blood loss when administered alone. When given in addition to ASA it resulted in a faecal blood loss not significantly different from control. No significant alteration in intestinal transit occurred. It is concluded that PGE2 protects man from the gastrointestinal injury associated with ASA.