Antacids can reduce gastroduodenal acidity for long periods if taken in substantial quantities after food. Their healing effect on gastric ulcer is minimal, if present at all, and easily overwhelmed by the benefit obtained from admission to hospital. Intensive antacid therapy appears effective in healing duodenal ulcer and preventing haemorrhage from stress ulcer, and is comparable in these respects with cimetidine but with a higher incidence of side-effects. Clinical impression strongly suggests that antacids relieve pain in peptic ulcer but objective confirmation is lacking.

A total of 179 adult patients with displaced intra-articular fractures of the distal radius was randomised to receive indirect percutaneous reduction and external fixation (n = 88) or open reduction and internal fixation (n = 91). Patients were followed up for two years. During the first year the upper limb musculoskeletal function assessment score, the SF-36 bodily pain sub-scale score, the overall Jebsen score, pinch strength and grip strength improved significantly in all patients. There was no statistically significant difference in the radiological restoration of anatomical features or the range of movement between the groups. During the period of two years, patients who underwent indirect reduction and percutaneous fixation had a more rapid return of function and a better functional outcome than those who underwent open reduction and internal fixation, provided that the intra-articular step and gap deformity were minimised.

AIM: To investigate the effects of leptin (1-20 microg/kg) on acidified ethanol (AE)- and indomethacin (Indo)-induced gastric lesions in rats and compare it with ranitidine, lanso-prazole, and omeprazole and to determine its mechanisms of actions. METHODS: Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors (PPIs) lansoprazole and omeprazole, or H(2)-receptor antagonist ranitidine 30 min before AE or Indo was evaluated. A radioimmunoassay was used to determine the PGE(2) concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content. RESULTS: Subcutaneous administration of leptin, two PPIs lansoprazole and omeprazole or H(2)-receptor antagonist ranitidine 30 min before AE or Indo produced a dose-dependent and reproducible inhibition of gastric ulcers (GUs). This inhibition was found to be more potent than other antagonists used. In N(G)-nitro L-arginine methyl ester (L-NAME)-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced, compared to rats without L-NAME pretreatment. However, the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE(2) level in the gastric glandular tissues. Leptin also increased mucus secretion. CONCLUSION: The results of the present study show that leptin inhibits GU formation by AE or Indo in a dose-dependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.

BACKGROUND: Concomitant aspirin use is a risk factor for nonsteroidal anti-inflammatory drug (NSAID)-associated upper gastrointestinal toxicity. In high-risk individuals, such as those with a history of NSAID-related gastric ulcer bleeding, gastroprotective therapy with a proton pump inhibitor has been reported to reduce the risk of recurrent aspirin-associated gastroduodenal ulcer bleeding. OBJECTIVE: This analysis compared the efficacy of misoprostol, lansoprazole, and placebo in reducing the risk of gastric or duodenal ulcer recurrence in patients taking NSAIDs and low-dose aspirin. METHODS: This post hoc subanalysis was based on a previous multicenter, prospective, randomized, double-blind, placebo-controlled, 12-week study in patients who had a history of gastric ulcer, were Helicobacter pylori negative, required chronic NSAID therapy, and were free of gastric or duodenal ulcer on baseline endoscopy. The study treatments were misoprostol 200 microg QID or lansoprazole 15 or 30 mg OD. The subanalysis included data from patients in the intent-to-treat cohort who took aspirin at an amount <or=325 mg/d. The end point was the cumulative rate of gastric ulcers, as assessed by serial endoscopy at 4, 8, and 12 weeks. RESULTS: Of 535 intent-to-treat patients from the primary study, 70 (40 men, 30 women; mean [SD] age, 64.7 [10.0] years; age range, 40-83 years) met the criteria for inclusion in the subanalysis. The proportions of patients who were free of gastric ulcers at the end of 12 weeks were 96% in the misoprostol group, 93% in the lansoprazole 15-mg group, 100% in the lansoprazole 30-mg group, and 35% in the placebo group (P <or= 0.008, each active treatment vs placebo). Adverse events considered possibly or probably related to treatment occurred in 5 (20.0%) misoprostol recipients (4 episodes of diarrhea, 1 episode of abdominal pain), 1 (14.3%) recipient of lansoprazole 30 mg (1 episode of pharyngitis), and 3 (13.6%) placebo recipients (1 episode each of abdominal pain, palpitations, and dyspepsia). CONCLUSIONS: In this subgroup analysis in patients at high risk for recurrence of gastric ulcer, use of cotherapy with misoprostol 200 microg QID or lansoprazole 15 or 30 mg OD significantly lowered the risk for gastric ulcer recurrence.

AIMS: To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro-mucosal inflammation after eradication. METHODS: Two hundred and six H. pylori-positive patients with active gastric ulcer underwent 8-week based therapy (OA) consisting of 2-week amoxicillin with omeprazole and subsequent 6-week omeprazole. They randomly received either rebamipide (OA-R) or placebo (OA-P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically. RESULTS: Per Protocol Set analysis showed no significant difference in eradication rate between OA-R (64.6%; 95% confidence interval, 54.3-75.0%) and OA-P (67.9%; 95% CI, 57.6-78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement (P = 0.017) in inflammation scores in OA-R (1.84 +/- 0.41) compared with that in OA-P (2.02 +/- 0.39) after 16-weeks of treatment. This suppressive effect on inflammation was observed even in the OA-R patients unsuccessfully eradicated. CONCLUSION: Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate.

BACKGROUND: Studies that report prevention of ulcer recurrence among long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs) that do not stratify for Helicobacter pylori status may not be generalizable to the large population of individuals without H pylori. METHODS: This was a prospective, double-blind, multicenter, active- and placebo-controlled study among 537 patients without H pylori who were long-term users of NSAIDs and who had a history of endoscopically documented gastric ulcer. Patients were randomized to receive placebo, 200 microg of misoprostol 4 times a day, or 15 or 30 mg of lansoprazole once daily for 12 weeks. Ulcer status was determined by endoscopy at 4, 8, and 12 weeks. RESULTS: Patients receiving lansoprazole (15 or 30 mg) remained free from gastric ulcer longer than those who received placebo (P<.001) but for a shorter time than those who received misoprostol. By week 12, the percentages of gastric ulcer-free patients were as follows: placebo, 51%(95% confidence interval [CI], 41.1%-61.3%); misoprostol, 93%(95% CI, 87.2%-97.9%); 15-mg lansoprazole, 80%(95% CI, 72.5%-87.3%); and 30-mg lansoprazole, 82%(95% CI, 75.0%-89.6%). A significantly higher proportion of patients in the misoprostol group reported treatment-related adverse events and early withdrawal from the study. When the impact of withdrawals on ulcer development was considered (as failures), therapy was successful for 69% for each of the active treatment groups and 35% for the placebo group. CONCLUSIONS: Proton pump inhibitors such as lansoprazole are superior to placebo for the prevention of NSAID-induced gastric ulcers but not superior to misoprostol, 800 microg/d. When the poor compliance and potential adverse effects associated with misoprostol are considered, proton pump inhibitors and full-dose misoprostol are clinically equivalent.

BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers. METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d.(Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d.(Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment. RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2%(95% CI: 84.8-93.7%) and 86.4%(95%CI: 81.5-91.3%) in total in the full analysis set, 89%(95% CI: 84.3-93.7%) and 85.3%(95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both). CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

BACKGROUND: The usefulness of nonsteroidal anti-inflammatory drugs (NSAIDs) is limited by adverse gastrointestinal tract events. OBJECTIVE: To identify the optimal antisecretory therapy for healing of gastric ulcer in patients using NSAIDs and the impact of concurrent Helicobacter pylori infection on ulcer healing. DESIGN: Prospective, double-blind, multicenter, parallel-group study. SETTING: Gastroenterology practices in ambulatory and referral center settings. PATIENTS: Three hundred fifty-three patients with an active, nonmalignant gastric ulcer at least 5 mm in diameter confirmed by endoscopy and biopsy and who continued to receive stable doses of NSAIDs. INTERVENTION: Patients were randomized to receive ranitidine hydrochloride, 150 mg twice daily, or lansoprazole, 15 mg or 30 mg once daily, for 8 weeks. MEASUREMENTS: Healing was assessed by endoscopy at 4 and 8 weeks in an intent-to-treat population. Helicobacter pylori status was assessed by histological examination. RESULTS: After 8 weeks of treatment, healing was observed in 61 (53%) of 115, 81 (69%) of 118, and 85 (73%) of 117 patients receiving ranitidine lansoprazole, 15 mg, and lansoprazole, 30 mg, respectively (P<.05 for ranitidine vs both lansoprazole doses; 95% confidence interval, 3.2-28.0 for ranitidine vs lansoprazole, 15 mg, and 7.4-31.8 for ranitidine vs lansoprazole, 30 mg). The gastric ulcer healing rates were similar between H pylori-infected and -noninfected patients, with a statistically significant increase with the use of lansoprazole vs ranitidine. CONCLUSIONS: In patients who require continuous treatment with NSAIDs, lansoprazole is superior to ranitidine for healing of NSAID-associated gastric ulcers. Healing is not delayed by the presence of H pylori infection.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79%(95% CI: 65-90%), OMC 86%(95% CI: 73-94%) and O 4%(95% CI: 0-14%). Eradication rates PP were OAC 83%(95% CI: 68-93%), OMC 93%(95% CI: 80-98%) and O 3%(95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

BACKGROUND: Helicobacter pylori infection is associated with idiopathic gastric ulcer in about 90% of the cases, but only a few controlled studies aimed at evaluating gastric ulcer healing and the natural history after Helicobacter pylori-eradication have been carried out. OBJECTIVE: The aim of the present study was to evaluate the efficacy of omeprazole coupled with amoxicillin in the eradication of Helicobacter pylori and healing and prevention of gastric ulcer recurrence. PATIENTS: Fifty-nine patients with active gastric ulcer were randomized under double-blind conditions to receive either omeprazole 20 mg twice daily for four weeks plus amoxicillin 3 g daily during the first and second week (29 patients, Group A) or omeprazole .20 mg twice daily for 4 weeks plus placebo for two weeks (30 patients, Group B). METHODS: Endoscopic studies were carried out at the end of the 4 weeks treatment (or after 8 weeks in non-healed patients) as well as 2, 6 and 12 months later. A total of 3 biopsies in the antrum, 3 in the gastric body and at least seven at the edge of the crater were taken at each endoscopic control for exclusion, of malignancy, histological detection of Helicobacter pylori and for evaluation of gastric histology according to the Sydney system. RESULTS: With intention to treat analysis, the percentage of healing after 4 and 8 weeks was 86% and 100% in Group A patients and 86% and 93% in Group B, respectively. Two patients dropped out in Group B for non medical reasons. The percentage of eradication was 63% in Group A and 7% in Group B. During a 12-month follow-up gastric ulcer relapsed in 20/32 (63%) of the persistently Helicobacter pylori positive patients. Only two out 20 (10%) Helicobacter pylori cured patients showed a gastric ulcer relapse and Helicobacter pylori reinfection. Twenty out of 30 patients, still healed after 12 months, underwent endoscopic control after two years. A gastric ulcer relapse was observed in three out of nine (33%) patients with persisting infection after treatment. No gastric lesions, but one case of erosive oesophagitis were observed in the 11 Helicobacter pylori-eradicated patients. CONCLUSIONS: In our experience, Helicobacter pylori eradication does not favour gastric ulcer healing but does positively influence the subsequent natural history.

Rabeprazole, a new proton pump inhibitor, was studied in patients with acid-peptic-related diseases (duodenal ulcer, gastric ulcer, GERD) in three placebo-controlled, double-blind, randomized clinical trials. Men and women over the age of 18 were enrolled if the presence of an active duodenal or gastric ulcer or erosive or ulcerative esophagitis was confirmed on upper gastrointestinal endoscopy. Patients were randomly allocated to either placebo or rabeprazole 20 mg or 40 mg in the duodenal and gastric ulcer protocols or to placebo or rabeprazole 10 mg, 20 mg, or 40 mg in the GERD protocol. All doses of rabeprazole in all three studies were statistically significantly superior to placebo in healing acid-related lesions. There were no treatment differences between the rabeprazole doses in healing active peptic lesions. The incidence of positive [13C]urea breath test for H. pylori was 53% in patients with duodenal or gastric ulcers. H. pylori status was not effected by treatment with rabeprazole.