Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis.

BACKGROUND: Systemic corticosteroids are effective in ulcerative colitis but commonly cause side effects. AIM: To compare the safety and efficacy of a sparingly absorbed formulation of prednisolone metasulfobenzoate (Predocol) with a conventional tapering course of oral prednisolone. METHOD: In a double-blind randomized study, 59 active ulcerative colitis patients received Predocol 40 mg/day for 6 months, 61 received Predocol 60 mg/day for 6 months and 61 received prednisolone 40 mg/day for 2 weeks, tapered to week 8, followed by placebo until 6 months. RESULTS: Steroid-related side effects assessed using a 10-cm visual analogue scale were fewer at 2 months with Predocol 40 mg [VAS 8.1 cm (2.6), mean (s.d.)], or 60 mg [8.1 (2.1)] compared with prednisolone [6.7 (2.7); P = 0.01]. Mood changes affected 43% receiving prednisolone at 4 weeks vs. 8% for Predocol 40 mg (P = 0.001). Remission rates (Powell-Tuck < or =2) at 2 months were Predocol 40 mg 46%, Predocol 60 mg 28% and tapering prednisolone 41% (P = 0.13). Visual analogue scale for efficacy also showed non-inferiority for Predocol 40 mg/day. Remission rates at 6 months were Predocol 40 mg 51%, Predocol 60 mg 38% and tapering prednisolone 32% (P = 0.08). CONCLUSION: Predocol 40 mg/day has similar efficacy but markedly fewer side effects than a conventional tapering prednisolone regimen (ISRCTN14133410).

Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis.

BACKGROUND: As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis. METHODS: Patients (n = 209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily (n = 98) or placebo (n = 111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance. RESULTS: On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P < 0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P < 0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P < 0.01). A greater reduction in anxiety occurred in the omeprazole group (P < 0.05). CONCLUSION: Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.

A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture. Restore Investigator Group.

BACKGROUND/AIMS: Dilatation combined with subsequent pharmacological control of gastroesophageal reflux represents a logical but poorly documented approach to the management of benign esophageal stricture. This large trial (366 patients) aimed to assess whether omeprazole as the most effective available medication for gastroesophageal reflux disease prevents recurrent stricture formation. METHODS: Patients (n = 366) were randomized in a double-blind study to undergo either omeprazole (20 mg once daily; 180 evaluable patients) or ranitidine therapy (150 mg twice daily; 185 evaluable patients) for 1 year after dilatation to 12-18-mm diameter (36-54F gauge). Subsequently, endoscopy and dilatation were performed when clinically indicated and endoscopy on completion. Symptoms were assessed at clinic visits every 3 months and using weekly diary cards. RESULTS: Fewer patients undergoing omeprazole therapy required redilatation compared with those on ranitidine (43 of 143 [30%] vs. 66 of 143 [46%] by 12 months; P < 0.01), and patients in the omeprazole group needed fewer redilatations during the year (0.48 vs. 1.08; P < 0.01). On completion, symptom relief favored omeprazole: 76% of patients in the omeprazole group were free of dysphagia (compared with 64% in the ranitidine group; P < 0.05); 83% were able to accept a normal diet (69%; P < 0.01); and 65% were completely asymptomatic (43%; P < 0.001). CONCLUSIONS: Omeprazole, 20 mg once daily, was more effective than ranitidine, 150 mg twice daily, as prophylaxis against stricture recurrence and in providing symptom relief.

Treatment of active Crohn's disease by exclusion diet: East Anglian multicentre controlled trial.

Elemental diet is as effective in producing remission of Crohn's disease (CD) as is corticosteroid treatment, but most patients relapse soon after resumption of a normal diet. We have investigated the efficacies of dietary modification and oral corticosteroids in maintaining remission achieved with elemental diet. In a multicentre trial, 136 patients with active CD were started on elemental diet and other treatment was withdrawn. 43 (31%) declined to continue elemental diet for 14 days, but 78 (84%) of the remaining 93 achieved remission and were randomly assigned corticosteroids (38) or diet (40). Corticosteroid treatment started at 40 mg prednisolone daily, which was tapered and stopped after 12 weeks; that group received dietary advice on healthy eating. The diet group received "tapered" placebo and were instructed to introduce one new food daily, excluding any that precipitated symptoms. Assessment of progress for up to 2 years was made by physicians unaware of group assignment. Intention-to-treat analysis showed median lengths of remission of 3.8 (interquartile range 5.0) months in the corticosteroid group and 7.5 (15.3) months on diet, and relapse rates at 2 years, adjusted for withdrawals, of 79% and 62%, respectively (p = 0.048). Clinical improvement in the diet group was associated with significant changes in plasma albumin and alpha 1-antichymotrypsin concentrations and erythrocyte sedimentation rate. Food intolerances discovered were predominantly to cereals, dairy products, and yeast. Diet provides a further therapeutic strategy in active Crohn's disease.

Vogt-Koyanagi-Harada syndrome, a rare association of Hodgkin's disease.

Vogt-Koyanagi-Harada syndrome (VKHS) is a well-documented clinical entity. We report the case of a 24 year old man who, within 5 months of the diagnosis of VKHS, developed Hodgkin's disease. Like VKHS, the aetiology of Hodgkin's disease is unknown. A viral factor has been suspected in the pathogenesis of both conditions. Similar immunological abnormalities have been described in both, and may be important predisposing factors.

Omeprazole provides quicker symptom relief and duodenal ulcer healing than ranitidine.

In a double-blind, parallel-group clinical trial in 248 patients with symptomatic duodenal ulcers [97% greater than 5 mm diameter], 126 were randomized to receive omeprazole 20 mg once daily in the morning and 122 were randomized to receive ranitidine 300 mg once daily at night for 2 wk and if the ulcers were unhealed for a total of 4 wk. When ulcer healing was assessed on an intention-to-treat basis, 79% of those receiving omeprazole had healed ulcers after 2 wk compared with 62% of those receiving ranitidine (p less than 0.005; therapeutic gain for omeprazole, 18%; 95% confidence intervals, +6% to +29%). At 4 wk the figures were 91% (omeprazole) and 80% (ranitidine) (p less than 0.05). After 2 wk, 77% of omeprazole-treated and 59% of ranitidine-treated patients were free of ulcer pain (p = 0.005). Assessed by diary cards (successfully completed by 92% of patients), daytime pain resolved more quickly in omeprazole-treated patients than in those receiving ranitidine (p less than 0.01). Omeprazole-treated patients took fewer antacids (p less than 0.05) over the first 2 wk. Omeprazole, 20 mg each morning, provides more rapid relief of the symptoms of duodenal ulcer and heals a greater proportion of duodenal ulcers within 2 and 4 wk than ranitidine, 300 mg each night.

Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding.

We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.

Palliative intubation of oesophagogastric neoplasms at fibreoptic endoscopy.

Of one hundred and twenty-one patients with neoplastic obstruction of the oesophagus or cardia 118 underwent palliative intubation at fibreoptic endoscopy on a total of 135 occasions. Sixty had adenocarcinoma, 49 had squamous carcinoma, and in nine the oesophagus was involved by a growth arising elsewhere. Satisfactory swallowing ws restored in 112 patients. Thirteen patients died in hospital shortly after the procedure. Five fatal and 10 non-fatal perforations were sustained in 135 intubation procedures. Complications of tube function included food blockage on 26 occasions, tumour overgrowth on seven occasions, displacement on 16 occasions, disappearance of the tube in two patients, and late oesophageal perforation on nine occasions. Fifty-six patients survived for three months, 33 for six months, and 10 for a year after intubation. Comparison with series in the literature of patients who underwent surgical palliative intubation suggests that endoscopic palliation has lower mortality and morbidity, and an increased survival time, and is now the method of choice for palliation of oesophagogastric neoplasms.

Outcome of endoscopy and barium radiography for acute upper gastrointestinal bleeding: controlled trial in 1037 patients.

A study was conducted to find whether the higher diagnostic yield of endoscopy compared with barium radiography improves management or survival in patients with acute upper gastrointestinal bleeding. A total of 1037 patients were entered into a randomised study comparing the outcomes after each investigation. The diagnostic yield in patients who underwent endoscopy was 73% (382 of 526 cases) and in those examined by radiography 55% (280 of 511 cases). A fifth of the patients in the radiology group and a tenth of those in the endoscopy group subsequently underwent the alternative investigation; in most cases, however, no additional diagnostic information was obtained. Operation rates were similar in two groups, though patients in the endoscopy group were generally operated on sooner. Mortality rates were also similar in the two groups, though postoperative mortality was higher in the endoscopy group. Endoscopy may be a more accurate means of diagnosis than radiography, but it offers no short-term benefits in management.

Comparison of surgical and medical management of bleeding peptic ulcers.

During 1975-80, 908 patients admitted to Nottingham hospitals with gastrointestinal bleeding and found to have gastric or duodenal ulcers were analysed retrospectively for short-term outcome of treatment. Overall one-quarter of all patients underwent operation, but when the years 1975-7 were compared with 1978-80 the operation rate fell from one in three to just over one in five. Death rates were much lower in patients treated medically than in those who underwent operation, and the risks of operation were greater for patients with gastric ulcer. Less conventional operations were attended by greater mortality. Almost all patients who died during medical treatment and three-quarters of those who died after operation were over 65. No differences in age or clear variations in haemoglobin concentrations or transfusion requirements were found between the earlier and later periods. Reduction in operation rates had no appreciable effect on mortality, despite the accepted view that early operation is advisable.

Neutrophil function in chronic liver disease.

Neutrophil locomotion, phagocytosis and killing of Candida albicans, and plasma opsonization of brewer's yeast were studied in 44 out-patients with chronic liver disease. There were four diagnostic groups: alcoholic liver disease (ALD), chronic active hepatitis (CAH), primary biliary cirrhosis (PBC) and cryptogenic cirrhosis (CC). Results were compared with a control group of patients with non-malignant disorders of the upper alimentary tract. Neutrophil locomotion induced by zymosan-activated autologous plasma was significantly depressed in patients with ALD and, to a lesser extent, in cryptogenic cirrhosis. With plasma from healthy donors, the patients' neutrophils showed normal locomotion. Plasma from patients with CAH gave slightly but significantly reduced phagocytosis of both Candida albicans and brewer's yeast, but the patients' cells had normal phagocytic and killing activity in the presence of normal plasma. Thus, no intrinsic abnormality in neutrophil function was found in these patients, but plasma defects, which differed in cirrhoses of different underlying aetiology, led to impaired neutrophil locomotion or phagocytosis. No correlations were found between these plasma defects and circulating levels of C3, C4, immune complexes or IgA.

Cimetidine in treatment of reflux oesophagitis with peptic stricture.

Twenty patients with reflux oesophagitis causing a tight peptic oesophageal stricture entered a randomised double-blind crossover trial in which they received cimetidine, 1.6 g daily, and matching placebo each for six months. The gross endoscopic appearances of oesophagitis, though not the grades of histopathological changes, showed significant improvement during treatment with cimetidine. The need for dilatation of the strictures, however, was not reduced.

Controlled trial of maintenance cimetidine treatment in healed duodenal ulcer: short and long-term effects.

Forty-two patients with endoscopically diagnosed duodenal ulcer were studied in a double-blind trial after their ulcers had been healed with cimetidine. Cimetidine was effective in preventing relapse, only five of the 20 patients allocated to cimetidine 400 mg twice daily relapsing during the six months' treatment, compared with 16 of the 22 on placebo treatment (P less than 0.01). Cimetidine was safe in the dosage and duration used, no symptomatic, haematological, or biochemical abnormalities occurring during the trial. Subsequent follow-up at the end of the trial when treatment had been stopped showed that relapse was frequent, particularly in the cimetidine group, making the cumulative relapse rate eight months after completion of the trial similar in the two groups (75% in the cimetidine group, 86% in the placebo group). It seems likely that maintenance cimetidine treatment has to be continued indefinitely in patients with duodenal ulcer, and, until such treatment is shown to be safe and effective, surgical treatment remains a logical option for many patients.

Effect of different operation policies on mortality from bleeding peptic ulcer.

The outcome in bleeding gastric and duodenal ulcer has been compared in two hospitals in Nottingham which take their patients randomly from a common source according to a fixed daily admission rota. Bleeding seemed equally severe in the two groups but 66 (32%) of 206 patients were operated upon at hospital A compared with 44 (46%) of 96 at hospital B (P=0.03), where operations also tended to be done earlier. Postoperative mortality-rates were virtually identical at the two hospitals, but at hospital B the overall death-rate from bleeding ulcer was higher, partly because of its higher operation-rate. The value of an aggressive surgical policy in bleeding peptic ulcer is questionable.

Comparative trial of sulphasalazine and oral sodium cromoglycate in the maintenance of remission in ulcerative colitis.

Patients with ulcerative colitis in remission were randomly allocated to treatment with sulphasalazine (2 g/day) or oral sodium cromoglycate (160 mg/day or 2 g/day), and the relapse rates in these treatment groups were compared during continued treatment for one year. The percentage cumulative relapse rate after 12 months' treatment was 30% in the 33 patients treated with sulphasalazine compared with 71% in the 25 treated with high dose sodium cromoglycate, a highly significant difference (P less than 0.01). Patients allocated low dose sodium cromoglycate were only treated for a maximum of six months, and the relapse rate in these 12 patients was similar to that in patients on the high dose. These results suggest that oral sodium cromoglycate is considerably less effective than sulphasalazine in maintaining remission, and by analogy with results in other trials may be no more effective than placebo tablets.