Long-term treatment of gastro-oesophageal reflux disease patients with frequent symptomatic relapses using rabeprazole: on-demand treatment compared with continuous treatment.

BACKGROUND: On-demand treatment may be an alternative in the long-term treatment of non-severe gastro-oesophageal reflux disease in patients with frequent symptomatic relapses. AIM: To compare the efficacy of on-demand treatment with rabeprazole 10 mg versus continuous treatment in the long-term treatment of patients with frequent symptomatic relapses of mild to moderate gastro-oesophageal reflux disease. METHODS: This randomized, open-label study enrolled patients diagnosed with non-erosive reflux disease or oesophagitis grade 1 or 2 (Savary-Miller classification) reporting frequent symptomatic relapses (requiring > or =2 courses of antisecretory therapy during the previous year), whose intensity is rated at least moderate (>2 on a 5-point Likert scale). After a 4-week selection phase with rabeprazole 10 mg once daily, patients reporting symptom relief (Likert score < or =2) were randomized to receive either rabeprazole 10 mg continuous treatment or on-demand treatment for 6 months. The main evaluation criterion was the rate of symptom relief (scored on the Likert scale) after 6 months. RESULTS: One hundred and seventy-six patients were enrolled in the 4-week selection phase (men, 53%; mean age, 49 years; non-erosive reflux disease, 36.4%; gastro-oesophageal reflux disease 1, 53.4%; gastro-oesophageal reflux disease 2, 10.2%). Rabeprazole relieved symptoms in 88.6% of patients. Of this group, 152 were randomized to the comparative phase to receive rabeprazole 10 mg continuous treatment (once daily) or on-demand treatment (continuous treatment, n = 81; on-demand treatment, n = 71). At month 6 (end point), the symptom relief rate was slightly higher for patients in the continuous treatment group compared with those in the on-demand treatment group: 86.4% versus 74.6%, respectively. This difference was not statistically significant (P = 0.065). For the overall quality of life score, there was no difference between the continuous treatment and on-demand treatment groups (86.25 and 84.94). Mean daily consumption of rabeprazole was significantly lower in the on-demand treatment group versus the continuous treatment group (0.31 tablets versus 0.96 tablets; P < 0.0001). CONCLUSION: On-demand therapy with rabeprazole 10 mg provides an alternative to continuous therapy in patients with mild to moderate gastro-oesophageal reflux disease suffering from frequent symptomatic relapses.

[Hepatitis caused by clometacin (Dupéran). Retrospective study of 30 cases. A model of autoimmune drug-induced hepatitis?]. / Hépatites à la clométacine (Dupéran). Etude rétrospective de 30 cas. Un modèle d'hépatite auto-immune médicamenteuse?

Thirty cases of clometacin-induced hepatitis were retrospectively collected over a nine-year period in hepatogastroenterological units of non university, public hospitals. There was a strong female predominance (90 percent). Clometacin (Dupéran) was taken because of arthritis in 8 out of 10 cases. Administration was continuous in 85 percent of cases and median duration was 445 days. median dose was 450 mg per day. Jaundice, fatigue, and weight loss were the most frequent symptoms, but edema, ascites and palmar erythema were not uncommon. Thrombopenia (38 percent) was the most frequent hematologic abnormality. Renal failure, always with benign course, was present in 1/4 of cases. Biochemical disorders indicated hepatocellular and cholestatic hepatitis in 3/4 and 1/4 of cases respectively. Hypoprothrombinemia below 50 percent was noted in 1 out of 6 cases, and was associated with death in half cases. Gamma-globulins were increased in 80 percent of cases, with a predominant increase of IgG. Antinuclear or anti-smooth muscle antibodies were present in 60 percent of cases, whereas antimitochondrial and antimicrosomes were absent. Histopathological examination of the liver biopsy specimens obtained in 25 patients showed acute hepatitis in 8 and chronic active hepatitis with fibrosis in 17--including 6 patients with cirrhosis; there were no epidemiological, clinical (except ascites), or biochemical differences between these two groups. Four of the 7 patients tested had HLA B8 antigens; they all had chronic active hepatitis, with autoantibodies in 3 cases. Median duration of hospitalization was 21 days. Hepatitis was directly responsible for death in 3 patients; biochemical sequelae (hypergammaglobulinemia or anicteric cholestasis) were present in 8 patients, 2 of whom most likely had cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man.

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.

Inhibition of rat basal pancreatic secretion by intraduodenal bile.

The effect on basal exocrine pancreatic secretion of diversion from and reintroduction into the duodenum of bile has been studied on conscious rats provided with pancreatic, biliary and duodenal fistulae. Diversion of bile from the intestine augmented protein output by 30%. After an eight-hour diversion recirculation of bile into the duodenum reduced pancreatic protein output by 30%; volume being not significantly modified. When either bile was diverted or the main bile duct was ligated, a similar inhibition of protein secretion was observed after intraduodenal injections of 20 mM solutions of taurocholate, taurochenodeoxycholate, chenodeoxycholate, and cholate, and of synthetic mixed micelles (bile salts, lecithin). Inhibitory action of bile salts on pancreatic secretion was seen equally whether or not the bile salts were in free or conjugated form or pancreatic juice returned to the intestine. We conclude that unlike man and the dog, bile as well as pancreatic juice inhibits the basal pancreatic exocrine secretion of the rat.