Famotidine vs. omeprazole: a prospective randomized multicentre trial to determine efficacy in non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Several studies in Western countries showed that proton-pump inhibitors are superior to histamine2-receptor antagonists or placebo in the treatment of non-erosive gastro-oesophageal reflux disease. The efficacy of acid-suppressive drugs for non-erosive gastro-oesophageal reflux disease in Japan, in which the prevalence of Helicobacter pylori infection is higher compared with Western countries, is unknown. AIM: To compare the efficacy of famotidine and omeprazole in Japanese patients with non-erosive gastro-oesophageal reflux disease by a prospective randomized multicentre trial. METHODS: A total of 98 patients received either famotidine 20 mg b.d. (n = 48) or omeprazole once daily (n = 50). Frequency of gastro-oesophageal reflux disease symptoms and health-related quality of life were evaluated at baseline and after 4 weeks of treatment. Complete relief was defined as no gastro-oesophageal reflux disease symptoms during the 7-day interval in week 4. RESULTS: Complete relief was achieved in 23 (48%) of patients receiving famotidine and 28 (56%) of patients treated with omeprazole. In the famotidine group, complete relief rate in H. pylori-negative patients was significantly lower than H. pylori-positive patients (35% vs. 64%). Both famotidine and omeprazole improved most scales of health-related quality of life. Omeprazole significantly improved reflux score irrespective of H. pylori infection while famotidine significantly improved reflux score in H. pylori-positive patients but not in H. pylori-negative patients. CONCLUSIONS: Omeprazole is more effective than famotidine for the control of gastro-oesophageal reflux disease symptoms in H. pylori-negative patients, while similar efficacy is observed in H. pylori-positive patients with non-erosive gastro-oesophageal reflux disease.

Diagnostic application of CD44 variant expression in pancreatic juice for detection of pancreatic neoplasm.

Recently, increased and disorganized expression of CD44 variant exons (CD44v) has been demonstrated in several types of human malignancy. We tried to investigate CD44v expression in pancreatic juice from patients who underwent endoscopic retrograde pancreatography. We analyzed 24 patients with pancreatic neoplasms diagnosed histologically (adenocarcinoma, 17; adenoma, 7) and 15 patients with non-neoplastic lesions. The expression of CD44v mRNA in pancreatic juice was detected by using the reverse-transcription polymerase chain reaction technique followed by Southern hybridization with exon-specific probes. Of 17 patients with adenocarcinoma, 14 (82%) showed expression of CD44v6 mRNA and 11 (65%) showed expression of CD44v2 mRNA. Of 7 patients with adenoma, 6 (86%) were positive CD44v6 mRNA expression and 2 (29%) for CD44v2 mRNA expression; while, out of 15 patients with non-neoplastic lesion, 5 (33%) showed positive findings for CD44V6 mRNA and 3 (20%) for CD44v2 mRNA. Comparing of diagnostic accuracy among CD44v6, CD44v2 and cytological examination, the sensitivities for adenocarcinoma were 82%, 65% and 41% respectively. However, the specificity was lower in CD44v6 (50%), CD44v2 (77%) than in cytology (100%), because CD44v was positive in adenoma cases and normal cases. A combination of RT-PCR analysis for the expression of CD44v with cytological examination in the pancreatic juice may increase the accuracy of diagnosis for pancreatic cancer.

[A study of hypertriglyceridemia occurring in patients with chronic hepatitis C during administration of interferon beta].

The prevalence and risk factors of hypertriglyceridemia during the administration of interferon (IFN) were examined in 78 patients with chronic hepatitis C who were treated with 6 MU of IFN-beta once or 3 MU of IFN-beta twice a day for 6 weeks. Hypertriglyceridemia (serum triglyceride (TG) above 150 mg/dl) was found before the start of IFN treatment in 9% of the patients. During the administration of IFN, elevation of serum TG above 150 mg/dl was found in 82% of patients. In addition, serum TG level exceeded 500 mg/dl at least once during the administration of IFN in 13% of patients. On stepwise multiple regression analysis, three risk factors, high serum TG value before the administration of IFN, high ALT value before the administration of IFN, and divided administration of IFN-beta twice daily were found to be associated with hypertriglyceridemia during IFN administration.

Rebamipide prevents recurrence of gastric ulcers without affecting Helicobacter pylori status.

Rebamipide, a gastroprotective drug developed in Japan, accelerates ulcer healing and reduces recurrence of experimental gastric ulcers. We examined the effects of rebamipide, given during healing of human gastric ulcers infected with Helicobacter pylori, on the quality of ulcer healing and ulcer recurrence. Sixty H. pylori-positive patients with gastric ulcers were randomly allocated to three treatment groups: group O (N = 20) received 20 mg of omeprazole every day for eight weeks, group OR (N = 20) received the same dose of omeprazole and 300 mg of rebamipide three times a day for eight weeks, and group OA (N = 20) received the same dose of omeprazole for eight weeks and 1500 mg of amoxicillin three times a day for the first two weeks. After this treatment was completed no other medication was given. Endoscopic examinations were performed at the end of therapy (for healing rate), one month later (for rate of H. pylori eradication) and every three months for follow-up (for ulcer recurrence rate). At the end of therapy, biopsy specimens were taken from the gastric ulcer scar and examined under the microscope for neutrophil and mononuclear cell infiltration. The ulcer healing rate of the three groups was almost the same; H. pylori in group OA was 65% and that of the other two groups was 0%. The number of patients with a flat ulcer scar pattern (good quality of ulcer healing) was increased and the neutrophil infiltration was significantly improved in groups OR and OA compared to group O. The ulcer recurrence rate was significantly lower in group OA and group OR than in group O. In conclusion, rebamipide is almost equipotent to amoxicillin plus omeprazole for the reduction of ulcer recurrence. The decreased recurrence rate by rebamipide may be due to improvement of the quality of ulcer healing, reflected as in the suppression of inflammatory cell infiltration in the scar, which results from either cure of H. pylori infection and/or treatment with a gastroprotective drug such as rebamipide.

Effect of rebamipide on Helicobacter pylori infection in patients with peptic ulcer.

This study was designed to assess whether the gastroprotective drug, rebamipide, aids in eradication of H. pylori. One hundred twenty patients, endoscopically diagnosed with gastric or duodenal ulcers and H. pylori infection, were randomly allocated to two treatment groups. Sixty patients received 40 mg of omeprazole twice a day, 1500 mg of amoxicillin three times a day, and 300 mg of rebamipide three times a day (group OAR); the other 60 patients received the same dosage of omeprazole and amoxicillin but no rebamipide for two weeks (group OA). All patients subsequently received an H2-receptor antagonist for six weeks. At the end of the treatment, endoscopy was performed to assess the status of the ulcers as well as the extent of H. pylori infection. In the intent-to-treat (73.3 vs 51.7%, P = 0.014) and per-protocol analyses (75.9 vs 55.3%, P = 0.021) the cure rates for H. pylori infection in group OAR were found to be significantly higher than those in group OA. Our findings suggest that rebamipide aids in curing H. pylori infection. This drug does not induce formation of resistant colonies and has few side effects.

Quality of ulcer healing influences the relapse of gastric ulcers in humans.

The usefulness of dye-contrast endoscopy for the evaluation of the quality of gastric ulcer healing and the prediction of relapse was investigated. Sixty consenting patients whose ulcers healed during 3 months of treatment underwent endoscopy for the identification of the pattern of mucosal regeneration. Patients were monitored for relapses for up to 18 months after antiulcer therapy had ended. The pattern of regeneration was flat in 24 patients, nodular in 25 and intermediate in 11. Internal hypoechoic areas seen by endoscopic ultrasonography were less common and histological maturity was better in the patient group with the flat pattern compared with the patient group with the nodular pattern of mucosal regeneration. Prostaglandin E2 synthesis was highest in the group with the flat pattern of mucosal regeneration and the relapse rate was lowest in this group. We conclude that the evaluation of the quality of ulcer healing is possible and that findings in individuals may aid the prediction of relapse for particular patients.

[Percutaneous microwave coagulation therapy for hepatocellular carcinoma--study on its therapeutic effect in surgical cases].

Six patients with hepatocellular carcinoma were subjected to percutaneous microwave coagulation therapy (PMCT) by ultrasonic guiding. The size of the main tumor in the present cases was limited to not more than 2 cm. From 18 to 48 days after PMCT, each patient was subjected to surgery and pathological examination. By macroscopic observation, the PMCT area including both non-tumor and tumor regions looked yellowish white, and the boundary was clearly recognized. In the histological examination, the coagulation area surrounded by fibrous capsule was found, and deletion of nuclei and changes in stainability were observed in the marginal region. These changes indicated obvious coagulation necrosis, but the changes became less intense toward the center in the area, and in some portions, the tissue was indistinguishable from viable cells by light microscopy. In 2 cases out of the 6, part of the tumor remained outside the coagulation area. Since only the area determined by the microwave electrode is coagulated to cause necrosis on PMCT, sufficient safety margin should be required.

Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2.

The effects of zinc L-carnosine on ethanol-induced damage and the correlation of these effects with endogenous prostaglandin E2 were evaluated in rat gastric mucosa in vivo and in vitro. When given either intragastrically or intraperitoneally, zinc L-carnosine (10 or 30 mg/kg) prevented gross visible damage to gastric mucosa caused by ethanol without affecting the mucosal prostaglandin E2 level. This protective effect of zinc L-carnosine was not inhibited by indomethacin. Histological assessment showed that zinc L-carnosine inhibited deep mucosal necrosis, as did 16,16-dimethyl prostaglandin E2. Zinc L-carnosine (10(-6) or 10(-5) M) inhibited the damage caused by ethanol to gastric cells isolated from rat gastric mucosa in vitro; this effect was not inhibited by indomethacin. The results suggested that zinc L-carnosine protects the gastric mucosa and enhances cellular resistance to ethanol without the mediation of endogenous prostaglandins.

Roles of endogenous leukotrienes and prostaglandins in the healing of gastric ulcers induced by acetic acid in rats.

We investigated the roles of endogenous leukotrienes (LTs) and prostaglandins (PGs) in the healing of gastric ulcers induced by acetic acid in rats. The mucosal levels of LTB4 and sulfidopeptide LT at the ulcer edge had increased by one day after the induction of ulcers. AA-861, a selective inhibitor of 5-lipoxygenase, did not affect the ulcer healing. Indomethacin delayed the healing. Cimetidine did not affect this delay, but ornoprostil, a PGE1, derivative, prevented it. These results suggest that endogenous LTs are not related to the healing of gastric ulcers and that a deficiency in endogenous PGs may be involved in the persistence of gastric ulcers.