Cure of Helicobacter pylori-positive active duodenal ulcer patients: a double-blind, multicentre, 12-month study comparing a two-week dual vs a one-week triple therapy. GISU (Interdisciplinary Group for Ulcer Study).

AIMS: To compare a two-week dual therapy to a one-week triple therapy for the healing of duodenal ulcer and the eradication of the Helicobacter pylori infection. PATIENTS AND METHODS: A total of 165 patients with active duodenal ulcer were enrolled in the study. At entry, endoscopy, clinical examination and laboratory tests were performed. Histology and the rapid urease test were used to diagnose Helicobacter pylori infection. Patients received either lansoprazole 30 mg plus amoxycillin 1 g bid for two weeks (two-week, dual therapy) or lansoprazole 30 mg plus amoxycillin 1 g plus tinidazole 500 mg bid for one week plus lansoprazole qd for an additional week (one-week, triple therapy). Two and twelve months after cessation of therapy, endoscopy and clinical assessments were repeated. RESULTS: Duodenal ulcer healing and Helicobacter pylori eradication were both significantly greater (p<0.0001) in the triple therapy group (healing: 98.6%; Helicobacter pylori cure rate: 72.6%) than in the dual therapy group (healing: 77.3%; Helicobacter pylori cure rate: 33.3%). Ulcers healed more frequently in Helicobacter pyloricured than in Helicobacter pylori-not cured patients (94.9% vs. 77.2%; p<0.0022). After one year, Helicobacter pylori eradication was re-confirmed in 46/58 patients previously treated with the triple therapy and in 10/40 patients treated with the dual therapy [p<0.0001]. Only three duodenal ulcer relapses were observed throughout follow-up: all were in Helicobacter pylori-not cured patients. CONCLUSIONS: Triple therapy was more effective than dual both in curing Helicobacter pylori infection and healing active duodenal ulcers. The speed of ulcer healing obtained after only 7 days of antibiotics and 14 days of proton pump inhibitors confirmed that longer periods of anti ulcer therapy were not necessary. Helicobacter pylori -not cured patients had more slowly healing ulcers which were more apt to relapse when left untreated.

Maintenance therapy with pantoprazole 20 mg prevents relapse of reflux oesophagitis.

BACKGROUND: Proton pump inhibitors can be effective as maintenance therapy in reducing the relapse rate of reflux oesophagitis at a dose lower than that used for acute healing. PATIENTS AND METHODS: Patients (n=396, 18-88 years old) with healed reflux oesophagitis (grade II or III before healing) were included in this multinational, prospective, parallel-group, randomized double-blind study. They took oral pantoprazole 20 mg (n=203) or 40 mg (n=193), once daily for up to 12 months. Scheduled endoscopies were performed at entry, after 6 and 12 months, or when symptoms of at least moderate intensity were perceived on 3 consecutive days; symptoms were assessed every 3 months. The primary efficacy parameter was the time until endoscopically proven relapse of reflux oesophagitis occurred; the secondary parameters included tolerability, safety and time until symptomatic relapse occurred. RESULTS: Analysis was performed using the 'all-patients-treated' approach. Endoscopic relapse rates in the 20 mg group after 6 and 12 months were 16 and 29%, respectively; in the 40 mg group, they were 7 and 19%, respectively. Symptomatic relapse rates after 6 and 12 months were 14 and 21% in the 20 mg group and 10 and 17% in the 40 mg group, respectively. Pantoprazole 20 mg and 40 mg were well tolerated throughout the study; the type and frequency of adverse events reported were similar for both treatment groups. CONCLUSION: The 20 mg dose was proven to be 'at least equivalent' to the 40 mg dose with respect to endoscopic and symptomatic relapse. The 20 mg once daily dose represents an effective and safe maintenance regimen for the majority of patients with healed reflux oesophagitis.

Ranitidine bismuth citrate with either clarithromycin 1 g/day or 1.5 g/day is equally effective in the eradication of H. pylori and healing of duodenal ulcer.

BACKGROUND: No randomized double-blind studies have been performed to compare clarithromycin 1 g/day with higher doses of the macrolide (1.5 g/day) when combined with ranitidine bismuth citrate (RBC). AIM: To compare H. pylori eradication and ulcer healing rates of RBC 400 mg b.d. for 4 weeks combined for the first 2 weeks either with clarithromycin 500 mg b.d. (Group A) or clarithromycin 500 mg t.d.s. (Group B). METHODS: Two hundred and seventy-three patients with H. pylori-positive active duodenal ulcer were included. H. pylori infection was detected by CLO-test and histology on antral and corpus biopsies before and at least 4 weeks after the end of therapy. Eradication was assumed if both CLO-test and histology results were negative for H. pylori. RESULTS: Eradication/healing rates according to intention-to-treat and per protocol analysis were 76/82% and 87/92% for Group A and 78/85% and 88/95% for Group B, respectively (P = N.S.). Adverse events were reported by 7% and 12% of patients in Groups A and B, respectively, and they were generally mild. CONCLUSIONS: RBC in co-prescription with clarithromycin 500 mg b.d. is as effective as RBC plus clarithromycin 500 t.d.s. in eradicating H. pylori and healing duodenal ulcers.

A new 1-week therapy for Helicobacter pylori eradication: ranitidine bismuth citrate plus two antibiotics.

BACKGROUND: One-week triple regimens are currently the most recommended therapy for the eradication of Helicobacter pylori. No previous study has evaluated the efficacy of a short-term regimen combining ranitidine bismuth citrate with two antibiotics. METHODS: Seventy-two consecutive H. pylori-positive dyspeptic patients were recruited for this randomized, three-centre, open, parallel-group study. They were subdivided into two groups receiving either ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (group A) or ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s (group B) for 1 week. H. pylori infection was assessed by CLO-test and histology on both antral and corpus biopsies before and at least 4 weeks after the end of therapy. The bacterium was considered eradicated when both tests were negative. Eradication rates and the number of side-effects were evaluated in each group. The Chi-squared test was used for statistical analysis. RESULTS: One patient with only CLO-test positivity was erroneously randomized to group B and four patients dropped out of the study (two in group A and two in group B), mainly because they refused the second endoscopy. In group A, H. pylori was eradicated in 31 of 36 patients (intention-to-treat = 86%; 95% CI = 71-95% and per protocol 31/34 = 91%; 95% CI = 76-98%). Side-effects occurred in 10 patients (27%) and they were generally mild. In group B, H. pylori was eradicated in 29 of 35 patients (intention-to-treat = 83%; 95% CI = 66-93%; and per protocol 29/33 = 88%; 95% CI = 72-97%). Seven patients (20%) complained of modest side-effects. There was no significant difference between the two treatment arms (P = N.S.): no severe adverse events occurred and none of the patients was withdrawn from the study because of them. CONCLUSIONS: The co-administration of ranitidine bismuth citrate plus clarithromycin at low dosage and metronidazole in twice daily doses for 1 week is a short, effective and well-tolerated regimen for the eradication of H. pylori. These findings should provide the impetus for large-scale investigations.

Gastric Peristalsis Control by Mono Situ Electrical Stimulation: a Preliminary Study.

BACKGROUND: This study was initiated 3 years ago when antral gastric stimulation was first used successfully to reduce free feeding in swine. METHODS: Three swine weighing 45 kg each were implanted with one subserosal bipolar electrode, positioned in the antrum, close to the pylorus, at the anterior side of the lesser gastric curvature. RESULTS: During 4 hours of kethamine anesthesia we paced the stomach by various patterns of electrical stimulation and obtained both forward and backward peristalsis, as well as gastric peresis. CONCLUSION: Variations in antral electrical stimulation produce characteristic patterns of forward and reverse peristalsis.

Long-term Effects of Gastric Pacing to Reduce Feed Intake in Swine.

BACKGROUND: The purpose of this study was to show the effect of chronic antral gastric electrical stimulation on the feeding behavior of swine. METHODS: Three groups of swine were investigated; first group control-group, second group- 8 months of electrical antral stimulation (10 Volts; 450 micros; Hertz 100; Mode: Cycling; on time 3.25 s; off time 5.15 s), the third group- 3 months of stimulation with modification of the following parameters- amplitude 8 Volts, Hertz 5. All animals were nourished with a commercial balanced dry feed ad libitum. RESULTS: Group one demonstrated continued increased weight gain. After 90 days of stimulation, group two noted a net decrease of food intake from 12% to 16%, followed by a net cyclical weight loss 30 days later (2 weeks of weight gain followed by 1 week of weight loss). The percentage difference between group one and two in increasing weight was- 12 to 29% respectively. The feed output of the stimulated group (group two) was 12.8 less compared with the control. Finally, group three was used to test a lower stimulation rate, resulting in a shorter rest during feeding and a 7% increase in consumption compared with control. CONCLUSIONS: Long-term antral gastric pacing influences the alimentary behavior of swine. We attempt to extrapolate this influence in humans for possible attendant applications in patients with consumption dysfunction (e.g. bulimia and/or anorexia).

Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients.

BACKGROUND: In a significant number of patients affected by the irritable bowel syndrome, an adverse reaction to food is proposed to be a causative factor. A diet that eliminates the offending foods is the obvious treatment for such adverse reactions. Compliance with a dietetic regimen is often poor and sometimes not completely free from risks. METHODS: Since the diarrheic type of irritable bowel syndrome seems mainly affected by food intolerance, and previous observations suggested that oral cromolyn sodium is effective in such patients, a multicenter therapeutic trial in the diarrheic type of irritable bowel syndrome was carried out in 346 of 409 patients with this disease, to evaluate the effects of oral cromolyn sodium and compare its efficacy with that of an elimination diet. RESULTS: Symptoms related to the irritable bowel syndrome improved in 60% of patients treated with elimination diet and in 67% of those treated with oral cromolyn sodium (1500 mg/day) for 1 month. Moreover, in both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones. CONCLUSIONS: These results confirm the high prevalence of adverse reactions to foods in diarrheic irritable bowel syndrome and the usefulness of cromolyn sodium treatment in these patients.

Pathogenesis of gastric ulcer.

The cause of gastric ulcer is still poorly understood, even though a certain number of pathophysiologic abnormalities have been described in subgroups of gastric ulcer patients. It is not known whether these abnormalities lead to ulceration or occur as a result of ulcers. Environmental factors, such as aspirin intake or stressful life events, may be related to gastric ulcer in some patients. The main pathophysiologic events (dismotility, prostaglandin formation, alteration in gastric mucosal barrier and blood flow, impaired gastric secretions), and the environmental factors involved in the development of gastric ulcer (cigarette smoking, alcohol consumption, drug ingestion, psychologic stress, infectious agents) are reviewed in this paper. Knowledge about the natural history of gastric ulcer has been increased by the availability of fiberoptic endoscopy and by controlled clinical trials, but ulcer pathogenesis still remains obscure, and perhaps multifactorial.

[Evaluation of the cost of maintenance therapy (6 months) with 150 mg ranitidine vs 20 mg omeprazole vs 20 mg omeprazole every other day in duodenal ulcer]. / Valutazione dei costi della terapia di mantenimento (sei mesi) con ranitidina 150 mg vs omeprazolo 20 mg vs omeprazolo 20 mg a giorni alterni nell'ulcera duodenale.

Prevention of ulcer relapse and of its complications is a problem which remains to be solved. Our study involved 250 patients, with healed duodenal ulcer. We evaluated efficacy and costs of three different maintenance therapies: ranitidine 150 mg/day, omeprazole 20 mg/day every other day and omeprazole 20 mg/day. Six months later, we found the incidence of relapse to be 24.4% (32/131) in the once-a-day ranitidine group, 19.7% (13/66) in the day every-other-day omeprazole group, and 3.8% (2/53) in the once-a-day omeprazole group. Further, we evaluated costs relative to relapsing patients, and total costs for each treatment group. From these data, we conclude that personalized maintenance therapy with omeprazole is the most cost-effective: a dosage of 20 mg/day is extremely effective in maintaining remission, and is therefore most indicated in patients at risk; omeprazole 20 mg/day every-other-day affords better compliance, lower costs and fewer relapses with respect to standard H2-antagonist dosages.

Efficacy of long-term therapy with low doses of omeprazole in the control of gastric acid secretion in Zollinger-Ellison syndrome patients.

Thirteen patients with Zollinger-Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7-34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger-Ellison syndrome patients. The drug was discontinued after 12-32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their 'initial basal acid secretion' after 5 days, while two patients who had been treated with omeprazole for a longer time (30-32 months) recovered only 38 and 40%, respectively, of their 'initial basal acid secretion' at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger-Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger-Ellison syndrome for a long period (10-30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole.

A comparison of nizatidine and ranitidine in the maintenance treatment of duodenal ulcer. A randomized, double blind, multicentre, 2-year study.

UNLABELLED: One hundred and eight patients with an endoscopically documented healed duodenal ulcer (DU) participated to a multicentre, randomized, double-blind, long-term study. The study was planned with the aim to compare the efficacy of nizatidine 150 mg with ranitidine 150 mg in preventing relapse during the 2 years following the DU healing. Fifty four patients were assigned to each treatment. Endoscopic examinations were scheduled at 6, 12 and 24 months. Clinical evaluations were performed every two months. Routine laboratory tests were investigated at the beginning of the study and at each of the scheduled endoscopies. STATISTICS: chi-squared test with Yate's correction, Student's t test for unpaired data, Wilcoxon Rank Sum test and Logrank test. Twenty five patients dropped-out: 15 in the nizatidine and 10 in the ranitidine group. The cumulative relapse rate was 18% for nizatidine and 21% for ranitidine treatment (p:ns). Both drugs resulted safe, as only minor side effects were registered. IN CONCLUSION: nizatidine is as effective and safe as ranitidine in the long-term (2 year) treatment of DU.

Treatment and prevention of NSAID induced gastroduodenal mucosal damage.

The use of aspirin and other nonsteroidal antiinflammatory drugs (NSAID) is associated with various degrees of gastroduodenal damage. The agents currently available for the treatment of NSAID induced gastric mucosal damage are histamine2-receptor antagonists, antacids, sucralfate and prostaglandin (PG) analogs. Although all of these agents are effective in healing gastric and duodenal injury if NSAID therapy is discontinued, currently available data suggest that there may be significant differences among these drugs in healing or preventing mucosal injury when NSAID therapy is continued. In particular, the synthetic PG misoprostol appears to be therapeutically superior to agents in the other drug classes in these settings.

Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis and rheumatoid arthritis.

The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant adverse effects on the integrity of the gastrointestinal (GI) mucosa. A unique, double-blind, placebo-controlled, randomized, multicentre study investigated the prophylactic co-therapy with misoprostol, a novel PGE1 analog, for the prevention of the NSAID-induced gastric and duodenal mucosal lesions. The study also investigated whether the co-therapy with misoprostol could interfere with the anti-rheumatic action of the NSAIDs using detailed rheumatological assessments. Patients with osteoarthritis or rheumatoid arthritis had to be free of symptoms and significant erosive and/or haemorrhagic lesions of the upper GI tract. The patients were randomized to co-therapy with misoprostol or its matching placebo. Follow-up endoscopy and symptoms assessment were carried out within 4 weeks and compared to pre-study findings. Misoprostol significantly reduced (p less than 0.01) the incidence of erosive and/or haemorrhagic gastric and duodenal mucosal lesions. Misoprostol also reduced the proportion of patients with epigastric pain (p less than 0.01). Misoprostol was well tolerated and did not interfere with the anti-rheumatic activity of the administered NSAID. We conclude that misoprostol is safe and effective in the protection against NSAID-induced gastric and duodenal mucosal lesions and symptoms.

Comparison of 150 mg nizatidine BID or 300 mg at bedtime, and 150 mg ranitidine BID in the treatment of gastric ulcer--an 8-week randomized, double-blind multicentre study.

One hundred and one active gastric ulcer patients concluded an 8-week, randomized, double-blind multicentre study, planned with the aim to compare the effectiveness of a new H2 blocker, nizatidine, with ranitidine. Thirty-three patients received 300 mg nizatidine at bedtime, 34,150 mg nizatidine b.i.d. and 34,150 mg ranitidine b.i.d. The three groups were well matched for the common clinical parameters. After 4 weeks, healing rates were 51.5% (confidence intervals 95%: 34.1-68.9%), 61.8% (41.2-82.4%), 76.5% (51-102%), respectively. At this check point ranitidine showed a significantly better outcome than did 300 mg nizatidine at bedtime (p less than 0.05). After 8 weeks, healing rates were 81.8% (54.1-109.5%), 88.2% (58.7-117.7%) and 88.2% (58.7-117.7%); these differences were not statistically significant. Age, sex, ulcer symptoms, alcohol and cigarette consumption, concomitant treatments, ulcer size and site and length of ulcer history were all found not to influence ulcer healing. Pain relief and antacid consumption were comparable in the three treatment groups. No clinically significant unwanted effects were recorded throughout the study. Nizatidine can, in our opinion, be successfully used in the treatment of active gastric ulcer.

[Cigarette smoking and group I pepsinogen levels. Study in a normal population]. / Fumo di sigaretta e livelli di pepsinogeno del gruppo Io. Studio in una popolazione normale.

Several studies have shown an influence of cigarette smoking on serum pepsinogen group I (PGI) levels in duodenal ulcer patients and in control subjects. The elevation of PGI in smokers has just been interpreted as reflecting some degree of smoking-induced inflammation of the gastric mucosa. We have determined fasting serum PGI by radioimmunoassay in 163 healthy subjects investigated by a survey conducted on a sample population of an urban area in the North-East of Italy by means of a random selection based on the public registers of home addresses. The data reported confirmed that PGI levels are increased by smoking in a healthy population. The main contribution of this study consists in demonstrating in a non-selected population an increase of the only parameter up to date claimed to be a possible serological predictive index for ulcer disease.

Comparison between single morning and bedtime doses of 40 mg famotidine for the treatment of duodenal ulcer.

The aim of this study was to compare the duodenal ulcer healing effects of morning (08.00 hours) vs. single bedtime (22.00 hours) doses of 40 mg famotidine, bearing in mind that the known efficacy of bedtime doses of H2-antagonists is regarded as evidence of the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer. This randomized double-blind multicentre trial was conducted in a total of 127 patients with endoscopically proven active duodenal ulcer. Nine patients dropped out and thus 118 were included in the final analysis. The duration of treatment was 4 weeks, and this was extended to 8 weeks in patients whose ulcers failed to heal by week 4. The patients in the two treatment groups were well matched for age and sex. The therapeutic efficacy parameters were endoscopic healing of the ulcer lesion and disappearance of pain. Results were compared using the chi-square method. The 4- and 8-week (cumulative) ulcer healing rates in the patients treated with the morning dose of famotidine were 77.2% and 86%, respectively, compared with 78.6% and 91.8% in those who received the bedtime dose. The differences failed to prove statistically significant either at week 4 (P = 0.85) or at week 8 (P = 0.31). The percentages of patients with ulcer pain, evaluated weekly, were similar in the two treatment groups. The equivalent efficacy of the morning and bedtime famotidine regimens raises doubts concerning the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer.

Influence of cimetidine in low doses (less than ED50) on prostanoid production by human gastric mucosa in vitro.

Cimetidine has been defined as a cytoprotective agent and numerous studies have reported that it is able to influence prostaglandin production as well as mechanisms which protect the surface epithelium of the gastric mucosa. However, results have been contradictory and high drug concentrations contrasting the cytoprotection concept have been utilized. The present study tried to evaluate whether low concentrations (less than ED50) of cimetidine in vitro are able to modify prostanoids produced by gastric mucosa fragments. Thirteen patients without histological lesions were examined. Five mucosal biopsy specimens were obtained from the antrum in seven patients and from the body in another six patients. One biopsy was utilized for histological examination, while the remaining four specimens were incubated in the absence or in the presence of 5, 50 and 500 ng/ml of cimetidine, respectively. Concentrations of PGE2, 6-oxo-PGF1 alpha, PGF2 alpha and TXB2 in the incubate were determined by radioimmunoassay. Cimetidine at 50 ng/ml increased PGE2 production at the antrum level while 500 ng/ml of cimetidine increased PGF 2 alpha and TXB2 production at the body level. Furthermore, the drug dose was directly related to PGE2 production (at the antrum level) and TXB2 (at the body level). The differences in prostanoid production between the antrum and body could be due to the different cell composition of the two anatomical areas, and suggest that the effects of cimetidine are mediated through binding to H2-receptors. The authors conclude that cimetidine in low doses stimulates the net production of some but not all prostanoids, the observed effects varying with anatomical site.