This multinational trial aimed to compare the efficacy of two doses of pantoprazole with the recommended dose of omeprazole for the prevention of recurrence of reflux esophagitis. Methods: Recruited were patients with esophagitis grade 2-4 (SavarylMiller) and symptoms of heartburn with or without regurgitation who at completion of a run-in phase during treatment with pantoprazole 40 mg once daily for 4-8 weeks (Gastroenterology 1999;116:GI011) had symptomatic relief and healed esophagitis (grade 0-1) demonstrated by endoscopy. A total of 639 patients from 60 centres in Austria, Belgium, Denmark, Finland, Greece, Norway, Sweden and Switzerland were allocated at random to double-blind maintenance treatment with pantoprazole 20 mg (n=211), pantoprazole 40 mg (n=218) or omeprazole 20 mg (n=21O) in the morning for up to 12 months. The patients had assessment of symptoms three-monthly and repeat endoscopy at 3 and 12 months, and in-between, if indicated by recurrence of symptoms. For the primary efficacy analysis (ITT population) patients with unknown endoscopic status at the time when they left the trial were considered as relapsed. Results: The treatment groups were well matched with regard to demographic and disease characteristics at baseline (such as gender; age; smoking habits; and severity and duration of reflux disease), and proportions of drop-outs and withdrawals in the groups were comparable. The endoscopic relapse rates were 23%, 17%, and 19% in the pantoprazole 20 mg, pantoprazole 40 mg, and omeprazole groups, respectively. The difference (and 95% confidence interval) between relapse rates in the pantoprazole 40 mg and omeprazole groups was -2% (-10% to 6%). Corresponding differences between pantoprazole 20 mg and omeprazole, and between pantoprazole 20 and 40 mg, were 4% (-4% to 12%), and 6% (-2% to 14%), respectively. Neither of the treatment differences was statistically significant. Absence of symptoms was highly predictive of maintenance of healing. All treatment regimens were well tolerated and no serious adverse events were attributed to treatment. Conclusion: Once daily 20-40 mg pantoprazole and 20 mg omeprazole were equally effective and safe for preventing recurrence of reflux esophagitis.

BACKGROUND:Previous studies have suggested abnormal copper metabolism in patients with primary sclerosing cholangitis (PSC). In the present work the trace element metabolism was studied in a group of 32 patients with PSC.METHODS:Hepatic copper and selenium concentrations were determined with a sensitive electrothermal atomic absorption technique. Serum concentrations of copper and zinc were determined by conventional atomic absorption.RESULTS:For the patient group serum copper values (20.3 +/- 4.5 mumol/l) were higher than those for the control group (14 +/- 3 mumol/l), and average hepatic copper concentrations were greater by a factor of four. Serum selenium values were slightly lower, although the average hepatic selenium was significantly higher than in the healthy control group. Previous studies have discussed possible toxic effects of hepatocellular copper accumulation, which may be accompanied by formation of activated oxygen species and depletion of glutathione. In the present study, however, it could not be demonstrated that the concentration of the lipoperoxidation product, malonic dialdehyde, was higher than normal in blood. Furthermore, blood concentrations of glutathione and glutathione peroxidase were not abnormal.CONCLUSION:Although a protective effect of the raised selenium concentrations in the liver might be discussed, it is apparent that the copper accumulation in the liver cells described here did not induce detectable changes in the indices studied.

In the present study the prophylactic effect of concentrated wheat fibre on duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or placebo was added to an ordinary Norwegian diet for 1 year after endoscopic healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37 patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side effects were infrequently seen. A concentrated wheat fibre supplement seems to have no preventive effect when given to duodenal ulcer patients living on a traditional Norwegian diet.

A method for the direct determination of copper in human liver biopsy specimens is described. The addition of a mixed Mg-Pd nitrate modifier is shown effectively to delay the volatilization of copper both from aqueous standards and the powered NIST Bovine Liver to an appearance time comparable with the solid biopsy specimens. Calibration against solid liver reference materials is preferable compared with aqueous copper standard solutions. A number of copper absorption lines provide a wide range of sensitivities; the less sensitive Cu-line 222.6 nm was found optimal in the determination of copper concentrations in the range of 20-200 mg/kg in liver biopsy specimens.The copper concentrations measured in liver biopsy specimens from patients suffering from sclerosing cholangitis were considerably higher than those reported for a group of healthy persons.

Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology, characterized by fibrosis and inflammation of the intra- and extrahepatic bile ducts. PSC is usually seen in association with inflammatory bowel disease, particularly in younger patients with extensive ulcerative colitis. Crohn's disease is seen in more than 10% of all patients with PSC. The bowel disease may produce no symptoms in some patients, and the clinical course is usually silent. The development and widespread use of endoscopic retrograde cholangiopancreaticography (ERCP) have enabled us to diagnose the disease far more often than was possible only a decade ago, and also to recognize that PSC has a much wider clinical and pathologic spectrum than previously realized. Most patients with concomitant ulcerative colitis and persistently abnormal liver function tests are likely to have PSC. Patients with PSC usually have a cholestatic biochemical profile, whereas the histologic features of the liver biopsy are variable and often nonspecific. Cholangiography displaying strictures and beading is diagnostic of the disease. The prognosis is variable, with a benign clinical course in many patients. However, an increased rate of cholangiocarcinoma is found in PSC, as is an increased rate of colonic cancer in patients with PSC and ulcerative colitis.

The effect of gastric anacidity on the absorption of food-bound cobalamins is uncertain. Omeprazole, an inhibitor of the enzyme H-K-ATPase in the parietal cell, is the most potent inhibitor of gastric acidity known so far. In 17 healthy male volunteers the absorption of liver-bound cobalamins was assessed after a single intravenous dose of omeprazole (80 mg) or placebo in a double-blind, crossover manner. The effect of omeprazole on pH, gastric acidity, and intrinsic factor (IF) concentration was measured in aspirates of gastric juice 5 min before and 30 and 60 min after the administration of liver homogenate containing 0.74 nmol of 57Co-labelled cobalamins. Omeprazole treatment resulted in anacidity (pH values above 6.0) in 14 individuals 30 min after the liver dose and in 15 individuals after 60 min. The IF concentration was unchanged in the omeprazole experiment as compared with the placebo experiment. The absorption of liver-bound cobalamins was 310 pmol (189-501 pmol) in the omeprazole experiment as compared with 415 pmol (150-549 pmol) in the placebo experiment (median values and range, p = 0.5228). We suggest that anacidity induced by omeprazole does not reduce the absorption of liver-bound cobalamins.

A high frequency of a variety of autoantibodies has been found in sera from patients with primary sclerosing cholangitis (PSC). The prevalence of all types of autoantibodies in PSC was significantly higher than that in healthy controls and patients with isolated inflammatory bowel disease. The titres of the antibodies were rather elevated, particularly in females, and most of them were IgM. The most frequent type of antinuclear antibody was the ‘homogenous’ type, which is a marker of many autoimmune diseases. The overall prevalence of the antibody was 35%, whereas in female patients it reached 67%. No correlation was found between autoantibody positivity and any clinical parameter. The present findings support the hypothesis that immunological factors may be relevant in PSC.

During the 10-year period from 1 January 1975 to 31 December 1984, primary sclerosing cholangitis (PSC) was diagnosed in 45 patients. Twelve of the patients have died (26.7%), 10 of them of causes related to PSC. Inflammatory bowel disease was found in all patients; ulcerative colitis was found in 37, Crohn's disease in 6, and unclassified colitis in 2 patients. Of the patients alive, 27 were submitted to a follow-up study in 1985. At the follow-up examination no general progression of the liver disease, as measured on the basis of clinical examination and levels of transaminases, alkaline phosphatases, and bilirubin, was found. Cholangiographic evaluation in 24 patients showed that the stage of ductal changes progressed from mild to moderate in 3 patients; in the other patients the stage was not altered. Morphologic examination of liver biopsy specimens in patients with a benign clinical course usually showed portal inflammation, fibrosis, and minor signs of piecemeal necrosis, whereas widespread piecemeal necrosis was found in patients who deteriorated and died. The 50% survival since diagnosis of liver disease was calculated to be 17 years in patients with PSC and 50 years in a comparable group among the general population. The estimated survival curve in PSC was displaced to the left, indicating a reduced life expectancy of about 30 years.

Omeprazole is a potent inhibitor of gastric acid secretion, whereas its effect on intrinsic factor (IF) secretion is unknown, and its effect on pepsin secretion has been less extensively investigated.

In 10 healthy volunteers gastric acid output in response to a meal was significantly increased 60-64 h after cessation of 4 weeks of ranitidine treatment as compared with the response before treatment. Four to 6 weeks after discontinuation of treatment the acid secretory response to the meal had returned to values not significantly different from those seen before treatment. There was no change in pepsin output owing to ranitidine treatment.

The effect of an intravenous infusion of omeprazole (0.35 mg/kg) and placebo on basal and stimulated (pentagastrin 1.0 microgram/kg/h) secretion of gastric acid, intrinsic factor and pepsin was studied in 10 healthy male subjects. Omeprazole caused a marked inhibition of basal and stimulated acid output. The inhibition of pepsin output was less marked, but also significant. The output of intrinsic factor, however, showed no significant change. The results indicate that acid and intrinsic factor might have different secretory mechanisms within the parietal cell.

The damaging effect of enteric-coated and plain naproxen tablets on the gastric mucosa was studied in 12 healthy subjects before and after 7 days' treatment in a randomized, double-blind, double-dummy, cross-over trial. Both formulations of the drug caused mucosal lesions, but the extent of the damage was significantly decreased after enteric-coated naproxen as compared with plain tablets. The subjects' preference was significantly in favour of the enteric-coated naproxen tablets. The plasma naproxen concentration was significantly higher after treatment with enteric-coated naproxen than after treatment with plain tablets. In conclusion, the results of the study indicate that naproxen might damage the gastric mucosa by local and systemic effects and that the local effect might be prevented by enteric coating of the tablets.

TRH inhibits gastric secretion, gastric motility, and pancreatic enzyme secretion in man. We measured TRH immunoreactivity (TRH-IR) in mucosal and transmural biopsies from different parts of the stomach, pylorus, duodenum, and pancreas in patients undergoing surgery or gastroscopy. TRH-IR was found in pancreas (range, 1.64-3.27 pg TRH/mg protein) and in mucosa of the fundus (13.3 +/- 2.0 pg TRH/mg protein), antrum (22.5 +/- 4.5 pg TRH/mg protein), and duodenum (35.5 +/- 6.4 mg TRH/mg protein). Low levels of TRH-IR were found in transmural biopsies from fundus, antrum, and pylorus (range, 0.45-0.87 pg TRH/mg protein). Chromatography of gastrointestinal tissue extracts on a cation exchange column resulted in two different TRH-IR peaks, one eluted at pH 3.5 and the other eluted at pH 7.4. The peak at pH 7.4 corresponded to synthetic TRH. The presence and the action of TRH in human gut indicate a physiological role of TRH in the gastrointestinal tract in man.