In a prospective study, 12 intensive care patients, after abdominal surgery, received three alternate six-day courses of two enteral diets with identical nitrogen (0.3 g N/kg per day) and energy (60 kcal/kg per day) supply. The protein hydrolysate (PH) diet contained enzyme-hydrolysed casein and lactoserum (60% small peptides), while the non-degraded protein (NDP) diet contained a nitrogen source of similar amino acid composition, but in the form of non-degraded proteins. The patients were randomised to receive either PH-NDP-PH or NDP-PH-NDP. Parameters reflecting protein metabolism were assessed in the plasma, urine, and stomal effluent on days 1, 6, 12, and 18, three hours after stopping the nutrition (t0), and one hour after restarting it (t1). Comparisons of t1 and t0 values showed that 13 amino acids (including the eight essential amino acids) increased significantly with the protein hydrolysate diet, but only two increased with the non-degraded protein diet. Similarly, with protein hydrolysate, insulin-aemia at t1 was significantly higher than at t0 and correlated with plasma leucine, phenylalanine, alanine, and lysine concentrations. In addition, significant improvements in plasma albumin, transferrin, and retinol binding protein concentrations were seen with protein hydrolysate, together with a significant decrease in the plasma phenylalanine/tyrosine ratio and urinary 3-methylhistidine excretion. We conclude that in patients in intensive care after abdominal surgery enteral support containing small peptides is more effective than an equivalent diet containing whole proteins in restoring plasma amino acid and protein levels.

Whole gut perfusion in humans was used to compare the effect on intestinal water and electrolyte transport of the World Health Organisation oral rehydration solution (solution II, composition in mmol/l: glucose 111, sodium 90, bicarbonate 30, potassium 20; 308 mOsm/kg); a hypertonic commercial oral rehydration solution (solution III, glucose 188, sodium 50, bicarbonate 20, potassium 20 mmol/l; 335 mOsm/kg); and three experimental bicarbonate free, hypotonic oral rehydration solutions: solution IV (glucose 111, sodium 60, potassium 20 mmol/l; 260 mOsm/kg), solution V (glucose 80, sodium 60, potassium 20 mmol/l; 219 mOsm/kg), and solution VI (glucose 80, sodium 30, potassium 20 mmol/l; 177 mOsm/kg). Perfusion of the intestine with a standard cleansing solution (solution I, sodium 125, potassium 10, bicarbonate 20, sulphate 40, mannitol 80 mmol/l; 275 mOsm/kg) confirmed published data on minimal water and sodium absorption. Experimental solution VI produced maximum water absorption (mean (SE) +1660.0 (29.8) ml/h) significantly greater than solution II (+1195.3 (79.5) ml/h), III (+534.7 (140.3) ml/h), IV (+1498.0 (42.7) ml/h), and V (+1327.7 (24.4) ml/h; p less than 0.05). Sodium absorption was significantly greater with solution II (+97.4 (7.9) mmol/h) compared to VI (+43.3 (7.8) mmol/h; p less than 0.01) but not compared to IV (+67.2 (13.0) mmol/h). A hypotonic oral rehydration solution such as solution VI may provide optimal replacement treatment for patients with acute diarrhoea.

The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence.

Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms.

Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease.

Endoscopic palliation with biliary endoprostheses is now an established treatment for benign and malignant strictures of the biliary tree. These endoprostheses, however, tend to clog with time. We investigated this problem by undertaking in vitro studies on stents of different designs made of different polymer materials. The stent that performed best was then tested in an in vivo trial. There was a direct relation in vitro between the frictional coefficient of a polymer and the amount of encrusted material. Catheters perfused in bacterially contaminated bile, irrespective of material and design, accrued significantly more sludge than catheters perfused with sterilised bile. The presence of side holes significantly increased the amount of sludge in the stents, but eliminated any differences between the various materials. We therefore investigated the effect of omitting side holes in a clinical trial which consisted of two groups of 20 patients each. The group treated with conventional stents accrued significantly more sludge in the stents than the group treated with experimental stents without side holes (p less than 0.05). The absence of side holes did not cause incomplete drainage or increase morbidity. Side holes are detrimental to stent patency, which is adversely affected by other factors including bacteria and proteins.

Circulating concentrations of interleukin-2 (IL-2) and a soluble or shed form of the IL-2 receptor (sIL-2R) were determined by enzyme-linked immunosorbent assays (ELISA) in 61 patients with chronic active Crohn's disease (CD) initially and during a three month placebo controlled trial of cyclosporin 5-7.5 mg/kg/day. The baseline median (25-75% range) plasma IL-2 concentration was 0.6 ng/ml (0.3-2.85 ng/ml) in patients who did not receive prednisolone, 0.5 ng/ml (0.23-3.4 ng/ml) in patients who did (not significant), and 0 ng/ml (0-0.07 ng/ml) in control subjects (p less than 0.00001). The corresponding median serum sIL-2R concentrations were 747 U/ml (580-1287 U/ml), 540 U/ml (422-616 U/ml) respectively in CD patients (p = 0.006) and 320 U/ml (268-406 U/ml) in control subjects (p less than 0.00001). Increased concentrations of plasma IL-2 and serum sIL-2R were seen in 66% and 81% of the patients, respectively. A fall in serum sIL-2R was only seen in patients who improved with cyclosporin treatment (p = 0.006). At month 3 the median serum sIL-2R concentration was 440 U/ml (400-668 U/ml) v 801 U/ml (534-1067 U/ml) in patients not responding to cyclosporin (p = 0.003). No changes occurred in the placebo group. These results suggest that the IL-2 dependent pathway of immune activation is upregulated in vivo in CD and that cyclosporin may interfere with this process.

A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer.

We conducted a prospective randomised controlled trial of 137 patients with massive peptic ulcer haemorrhage over a period of 12 months to compare the haemostatic effects of endoscopic heat probe thermocoagulation and pure alcohol injection. Seventy eight patients (56.9%) were in shock at the time of randomisation to the trial. The age, sex, number of patients in shock, haemoglobin value at the time of entry to the trial, number of patients with severe medical illness, location of bleeders, and stigmata of recent haemorrhage were comparable among the heat probe, pure alcohol, and control groups. The initial haemostatic effect of the heat probe was better than that of the pure alcohol injection (44 of 45 v 31 of 46, p = 0.0004). The ultimate haemostasis achieved by the heat probe group (41 of 45) was better than that of the pure alcohol group (31 of 46, p = 0.012) and of controls (24 of 46, p = 0.0001). The duration of hospital stay was shorter for patients in the heat probe group than for the control group (6.2 days v 13.8 days, p less than 0.05). The incidence of emergency surgery was less for the heat probe than the control group (three of 45 v 12 of 46, p = 0.027). The mortality rate was less in the heat probe than in the control group (one of 45 v seven of 46, p = 0.031). We suggest that heat probe thermocoagulation should be the first treatment of choice for arrest of massive peptic ulcer haemorrhage.

Vancomycin hydrochloride (2 g daily) was administered to 12 patients with cirrhosis and lactulose resistant portal systemic encephalopathy in a double blind crossover trial. All 12 patients showed a remarkable clinical improvement after vancomycin treatment. The mean (SE) electroencephalographic (EEG) frequency changed from 6.3 (0.2) to 8.5 (0.2) cps (p less than 0.001) and the mean arterial ammonia concentration from 152 (4) micrograms/ml to 97 (8) micrograms/ml (p less than 0.001). Their clinical condition deteriorated when treatment was switched to lactulose, returning to the previous slower EEG frequency and high arterial ammonia concentrations. Vancomycin seems to be effective in chronic portal systemic encephalopathy in patients who are not helped by lactulose alone.

We studied omeprazole and ranitidine in promoting duodenal ulcer healing in a multicentre trial by comparing the proportion of healed ulcers after two, four, and eight weeks of treatment. Altogether, 194 patients (143 men) were randomly allocated according to a prearranged treatment schedule to either drug and were treated double blind. Each received 40 mg omeprazole in the morning and a ranitidine placebo morning and evening or 150 mg ranitidine morning and evening with an omeprazole placebo in the morning. A total of 188 patients (94 taking omeprazole, 94 taking ranitidine) completed the trial. Sixty four (68%) omeprazole treated and 45 (48%) ranitidine treated patients had healed ulcers at two weeks, 91 (99%) omeprazole treated and 79 (88%) ranitidine treated had healed ulcers by four weeks, and 91 (100%) omeprazole treated and 86 (97%) ranitidine treated patients had healed ulcers by eight weeks. The overall difference in healing rates was significant (p = 0.0008, Mantel-Haenszel test). The differences were significant also at two weeks (20%, 95% confidence interval 5.6 to 34.4, p less than 0.01) and at four weeks (11%, 95% CI 3.7 to 17.3, p less than 0.01), but not at eight weeks (3%, 95% CI -0.5 to + 7.3, p = 0.25), using the chi 2 statistic, the study having a power to detect a 20% difference on 90% of occasions. After two weeks of treatment complete symptom relief was observed in 70 (74%) patients receiving omeprazole and in 58 (62%) receiving ranitidine. Diary cards showed a significantly lower percentage of days with pain in the omeprazole treated group (7.4% v 21.4%, p < 0.02) when assessed over either the first two weeks or over weeks three and four treatment. A total of 144 patients with healed duodenal ulcer were followed up, with no treatment, for six months. At the end of this period 19 (26%) of 74 patients healed with omeprazole and 17 (24%) of 70 patients healed with ranitidine were still in remission. A similar protocol was used for 46 patients (25 men) with gastric ulcer who were randomly allocated to treatment with omeprazole or ranitidine as described above. Forty patients (16 omeprazole, 24 ranitidine) completed trial. Thirteen (81%) omeprazole treated and 14 (58%) ranitidine treated patients had healed ulcers at four weeks; at eight weeks 14 (93%) omeprazole treated and 20 (87%) ranitidine treated patients had healed ulcers. These differences were not significant at four weeks (p = 0.25) or eight weeks (p = 0.96). Twenty seven gastric ulcer patients were followed up for six months and seven (58%) of the 12 omeprazole healed and five (33%) of the 15 ranitidine healed patients were in remission at six months. Unwanted adverse events were trivial except for one fatality in a 67 year old women, who died from bronchopneumonia and myocardial ischaemia while receiving treatment with omeprazole, which was judged to be unrelated to her death.

The majority of upper gastrointestinal bleeds stop spontaneously despite the low pH and proteolytic activity of gastric juice which inhibit coagulation and platelet aggregation. In order to investigate this paradox six healthy male volunteers received intragastric infusions of 160 ml autologous venous blood or 160 ml egg white acting as control in random order on separate days. Basal acid output was calculated before infusion, net acid secretion and gastric volume emptied were calculated after intragastric infusions. Serum gastrin concentrations were also measured before and after intragastric infusions and expressed as the integrated gastrin response. Basal acid output (mmol/h) was 4.7 (1.9) (mean (SEM)) before egg white infusion and 5.9 (2.6) before venous blood infusion. After egg white infusion net acid secretion (mmol/20 min) increased to 5.6 (3.1) compared with 2.3 (1.3) after venous blood infusion (p less than 0.05). The gastric volume emptied (ml/20 min) was less after venous blood infusion at 105 (28) compared with 321 (66) after egg white infusion (p less than 0.03). Integrated gastrin response was similar after venous blood and egg white infusion. When compared with an equivalent protein meal intragastric blood stimulates less acid secretion and delays gastric emptying. This effect may facilitate haemostasis after gastric bleeding.

This study investigates whether aspirin injury to the human gastric mucosa can be prevented by profound acid suppression with omeprazole, in a randomised, double blind, crossover design according to latin square. It was concluded that profound acid suppression can prevent aspirin induced gastric mucosal injury in normal subjects. This approach may prevent the development of peptic ulcers and their complications in patients taking aspirin and other non-steroidal anti-inflammatory drugs.

This double blind, double dummy study compares the rate of healing of erosive reflux oesophagitis, assessed endoscopically, with four and eight weeks treatment using omeprazole or cimetidine, and the effect of four and eight weeks treatment of reflux oesophagitis with omeprazole or cimetidine on reflux symptoms, microscopic healing, and in a subgroup of patients, oesophageal pH measurements. Omeprazole 40 mg once daily achieves (i) greater and more rapid symptom relief, (ii) more rapid and sustained endoscopic and histological healing, and (iii) greater reduction of oesophageal acid exposure than cimetidine 400 mg four times daily.

The aim of this study was to determine the effect of colloidal bismuth subcitrate (De Nol) on symptoms and gastric histology in patients with non-ulcer dyspepsia. In a single centre trial, patients with food related upper abdominal pain not caused by ulcer disease were randomised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks. Seventy three patients were entered and 51 completed the trial: 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group. Overall there was no difference between the two groups in terms of symptom relief. Among patients with histological gastritis (n = 23), however, those who took colloidal bismuth subcitrate used fewer antacid tablets (for three of four fortnightly periods) and were more likely to become asymptomatic (eight of 11 v three of 12, p less than 0.05); their gastritis was more likely to resolve (five of 10 v 0 of 12, p less than 0.025) and their gastric biopsies more likely to become negative for Helicobacter like organisms (eight of nine v 0 of 12, p less than 0.001) when compared with patients taking placebo. In contrast, patients who did not have gastritis in their index biopsies (n = 28) fared similarly whether they received colloidal bismuth subcitrate or placebo. Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without.

We have determined the relative importance of day and night time gastric acid inhibition for duodenal ulcer healing by comparing the anti-ulcer efficacy of a single morning with that of a single bedtime dose of ranitidine. One hundred and thirty patients with active duodenal ulcer were randomly assigned to a double-blind therapy with ranitidine 300 mg at 8 am or the same dose at 10 pm for up to eight weeks. The antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring in 18 of these patients. At four weeks ulcers had healed in 41/61 (67%) of patients taking the morning dose and in 47/63 (75%) of those receiving the nocturnal dose (95% CI for the difference -0.09 +0.25; p ns). At eight weeks, the corresponding healing rates were 82% and 85.5%, respectively (95% CI for the difference -0.11 +0.17; p ns). Both treatments were significantly superior to placebo in raising 24 h intragastric pH, although the effects of the morning dose were of shorter duration than those of the nocturnal dose. These findings suggest that suppression of nocturnal acidity is important but not essential to promote healing of duodenal ulcers; a prolonged period of acid inhibition during the day (as obtained with a single large morning dose of H2-blockers) may be equally effective.

We have evaluated the effect of cisapride on interdigestive antroduodenal motility during a prolonged oral therapy in 20 consecutive dyspeptic subjects. Individuals with less than two migrating motor complexes (MMCs) starting from the antral region in 240 minutes and without evidence of upper gastrointestinal tract diseases were randomly treated with either cisapride (10 cases), or placebo (10 cases) for 15 days. Computerised manometry of antroduodenal region was performed for 240 minutes, in basal conditions and on the 15th day of therapy. Symptomatic evaluation of patients was also performed before and after treatment. After cisapride administration, a significant increase in the incidence of antral migrating motor complexes was noticed (p = 0.022); likewise, the motility index, calculated for phase-2 periods, appeared to be significantly higher both in the antrum and in the duodenum (p less than 0.001). Symptomatic improvement was observed in both groups, with a hardly significant (p = 0.049) reduction of dyspeptic symptoms severity only but not of frequency in cisapride treated patients v controls. We conclude that longterm oral therapy with cisapride improves interdigestive antroduodenal motor activity.

The aim of this study was to evaluate the efficacy of cimetropium bromide, a new antimuscarinic compound, in relieving symptoms of patients with irritable bowel syndrome over a three month period. Seventy consecutive outpatients were given cimetropium (50 mg tid) or placebo according to a double blind, randomised, parallel groups design. Symptoms were evaluated initially and at monthly intervals up to the end of the study period. One patient receiving placebo withdrew because of treatment failure. Pain score decreased by 40, 66, 85% in the cimetropium group, at the end of the first, second and third months respectively, compared with 26, 32 and 52% reductions among controls (p = 0.0005). At the end of treatment there was a 86% reduction in the number of abdominal pain episodes per day in the cimetropium group compared with 50% in the placebo group (p = 0.001). Constipation and diarrhoea scores decreased by 59 and 49% in the cimetropium treated patients, compared with 37 and 39% in controls, the differences between being not significant. At the end of the study 89% of the patients treated with cimetropium considered themselves as globally improved as opposed to 69% in the placebo group (p = 0.039). The corresponding 95% confidence intervals for the differences between the proportion of improved patients in the two groups were from 11% to 29%. Six patients taking cimetropium complained of slight dry mouth. The results of this study showed that cimetropium bromide is effective in relieving pain in patients with irritable bowel syndrome.

Eighty patients with reflux oesophagitis were randomised to receive either Pyrogastrone five tablets daily or cimetidine 400 mg twice daily for six weeks, extended to 12 if necessary. At six weeks, 49% of the Pyrogastrone treated subjects and 37% of the cimetidine treated subjects were healed. After 12 weeks the cumulative healing rates were 64% for Pyrogastrone and 66% for cimetidine. Compared with baseline both drugs achieved similarly significant improvements in symptom score, endoscopic and histological grading even in those who did not heal completely. Response was not related to length of symptoms or initial severity of oesophagitis. Eleven of 25 (44%) patients healed with Pyrogastrone relapsed within one year compared with 15 of 27 (56%) healed with cimetidine. Although this trend in favour of Pyrogastrone was not significant at one year the early relapse rate was significantly greater in cimetidine treated subjects. At six weeks, five cimetidine treated subjects had relapsed compared with none in the Pyrogastrone group (p = 0.05). This study shows that Pyrogastrone and cimetidine are equally effective in the healing of oesophagitis and raises the possibility that Pyrogastrone has marginal benefits in terms of time to relapse.