We report the case of a 73-year-old woman who was hospitalized for mild abdominal pain after her referral following a diagnostic assessment of acute lithiasic cholecystitis. After the spontaneus regression of her painful symptoms and fever and several days of well-being, her clinically acute abdominal features suddenly showed an obstruction of the upper gastrointestinal tract. An emergency esophagogastroduodenoscopy (EGDS) confirmed that a large gallstone completely obstructed the pylorus as previously demonstrated by an ultrasound examination of the gallbladder. During the course of endoscopy, removal of the gallstone from the duodenum was achieved by pulling it into the stomach; the patient underwent an operation, the gallstone was removed, and the cholecystoduodenal fistula resolved. Postoperative procedures and recovery were rapid and favorable.

BACKGROUND:Chronic Obstructive Pulmonary Disease (COPD) is a profoundly disabling disease managed predominantly by General Practitioners (GPs). We planned this prospective trial to evaluate the applicability of Italian GP-directed guidelines in routine practice and whether adherence to them improves treatment efficacy, with respect to decreased exacerbations, hospital admissions, drug use, and out-patient appointments and improved quality of life (QoL).METHODS:In a cluster randomised trial, 22 GPs were randomly put into two groups: one group was asked to follow the guidelines (YES-GL), the other to continue normal clinical practice (NO-GL). These GPs enrolled 123 patients with COPD and followed them for one year.RESULTS:Patients managed by the YES-GL GPs had more outpatient appointments and specialist consultations and a higher probability of being classified as having severe COPD. The QoL was fairly low in both groups, and all other clinical outcomes taken into consideration, were not affected by application of the guidelines.CONCLUSION:The guidelines did not substantially alter the clinical evolution of COPD patients, even though some facets of management improved.

AGAA1319tive, randomised, multicenter study were to evaluate the efficacy of "shorttherapy" with Pantoprazole (P) for two weeks and the efficacy of C low-dose on healing of DU and H.pylori eradication.Patients and Methods: 207 pts with endoscopically proven DU and HP+ve were randomised as follows:GROUP 1 (100 pts, MIF 67/33, mean age r Sl) 46.0::':12.4yrs) received P 40 mg o.m. for two weeks plus A I gr bid and M 500 mg bid for one week; GROUP 2 (107 pts, MIF 75/32, mean age::':SD 46.0::': 12.1 yrs) received P 40 mg o.m. for two weeks plus A I gr bid and C 250 mg bid for one week.EGDS and Rapide Urease test were performed in basal conditions and after four weeks.Results are shown in the table.Conclusions: Pantoprazole for two weeks is effective to heal duodenal ulcer.Clarithromycin low-dose is less effective than metronidazole to eradicate H. pylori infection.

There is growing interest in the relationship between H. pylori infection and gastro-oesophageal reflux disease (GORD). However, this relationship is complex, as yet not fully elucidated, and probably based on a multiplicity of factors. The prevalence of H. pylori infection in patients with GORD is similar, more often lower than in matched controls. There is a negative correlation between H. pylori infection and the severity of GORD. There are many hypothetical mechanisms by which H. pylori infection may protect from the development of GORD. Conversely, there are many possible mechanisms by which H. pylori infection could theoretically foster the GORD. Patients after H. pylori eradication may develop GORD, and this seems to suggest a protective role of H. pylori infection, but other possible explanations include weight gain after H. pylori eradication, changes in dietary habits and smoking, and pre-existing GORD. H. pylori infected patients treated by various acid-inhibiting therapies such as proton pump inhibitors (PPIs), H2-receptors antagonists (H2-RA) or vagotomy, have an increase of their corpus gastritis severity, both in the activity of inflammation and in the density of organisms. Long-term therapy of GORD in H. pylori infected may lead to rapid progression of atrophic gastritis intestinal metaplasia and dysplasia, and increase the risk of developing gastric cancer. More recently it has been shown that H. pylori infection may interfere with the acid suppressive therapies used for treating GORD. In our opinion the progression of gastritis depends on the threshold of acid output at which H. pylori can 'flourish'. Recently interest is growing on gastric transitional zones and Helicobacter ecology. Any decrease of acid secretion changes the behaviour of H. pylori: the activity of gastritis improves in the antrum, but it deteriorates in the body. During proton pump inhibitor treatment, H. pylori redistribution occurs within the stomach, from an antral to a corpus or fundus prevalent pattern; corpus-fundus gastritis, exacerbated by PPI therapy, may result both in a diminished acid secretion and gastro-oesophageal reflux. The interest in Barrett's oesophagus is growing due to the associated risk of adenocarcinoma. The literature seems to demonstrate that the prevalence of H. pylori infection of the stomach in Barrett's oesophagus patients is not different from that exhibited by controls, roughly one-third of the subjects. Intestinal metaplasia of the gastric cardia seems to be equally frequent in patients with and without GORD. Finally, it appears unlikely that a causal relationship exists between H. pylori infection and Barrett's-associated adenocarcinoma.

BACKGROUND:Triple therapies containing omeprazole and ranitidine have been shown to be equivalent in eradicating H. pylori infection, but have been assessed either separately or head-to-head, only in small trials.AIM:To carry out a large randomized controlled study comparing omeprazole and ranitidine combined with two antibiotic combinations for 1 week.METHODS:Three hundred and twenty H. pylori-positive patients were randomly subdivided into four equal-sized groups and received one of the following treatments: OAM = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; RAM = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; OAC = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s.; RAC = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s. The assessment of H. pylori status was performed before and 4 weeks after the end of therapy by means of CLO-test and histology. H. pylori infection was considered to be eradicated when both tests were negative.RESULTS:OAM and RAM eradicated H. pylori in 89% and 85% of cases on per protocol (P = 0.48) and in 77% and 75% of cases on intention-to-treat analyses (P = 0.71). OAC and RAC eradicated H. pylori in 67% and 70% of cases on per protocol (P = 0.68) and in 57% and 64% of cases on intention-to-treat analyses (P = 0.41). In contrast, there was significant difference between OAM and OAC (P<0.01) and between RAM and RAC (P<0.05). Side-effects occurred in 15%, 10%, 17% and 16% of patients with respect to the above four subgroups.CONCLUSIONS:Omeprazole and ranitidine combined with two antibiotics for 1 week are equally effective in the eradication of H. pylori infection, and these results question the role of profound acid suppression in the eradication of the bacterium.

Background: Ranitidine bismuth citrate (RBC) co‐prescribed with clarithromycin and metronidazole for 1 week has been shown to be an effective eradicating regimen for Helicobacter pylori . Aim: To determine the optimal duration of this regimen. Methods: A series of 165 dyspeptic patients were recruited for this randomized, open, parallel‐group study. They were subdivided into three groups receiving RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. for three different periods (4, 7 and 10 days). H. pylori infection was assessed by the concomitant positivity of CLO‐test and histology performed at the pre‐entry endoscopy. The bacterium was considered eradicated on the basis of a negative 13 C‐urea breath test performed at least 28 days after the completion of treatment. Results: The three subgroups were well matched and 16 patients dropped out of the study for many reasons (six in the 4‐day, five in the 7‐day and five in the 10‐day treatment regimens). Intention‐to‐treat cure rates were 60%, 84% and 85%, and the per‐protocol rates 67%, 92% and 94% in the 4‐day, 7‐day and 10‐day treatment regimens, respectively. There was a significant difference, P = 0.003−0.006 on intention‐to‐treat and P = 0.001−0.002 on per protocol analysis between the 4‐day and the 7‐day and the 4‐day and the 10‐day periods, respectively. The 7‐day and 10‐day periods did not differ from each other. Side‐effects were reported in 9%, 14% and 20% of the 4‐, 7‐ and 10‐day regimens. They led to stopping treatment in four cases (one in the 7‐day and three in the 10‐day period). There was no statistical difference among them. Conclusions: Reducing the duration of RBC‐based triple therapy to 4 days provides a low and unacceptable rate of H. pylori eradication. As there is no difference between 7 and 10 days of treatment, 1 week represents the optimal time period for this kind of treatment, based on RBC plus two antibiotics.

BACKGROUND:It is now clear that the extent to which gastric acid secretion must be suppressed varies with the clinical condition being treated.AIM:To assess the 24-h control of gastric acidity and the individual response variability of three different doses of pantoprazole.METHODS:Sixty-four duodenal ulcer patients were recruited for this prospective, randomized, multicentre, double-blind, parallel-group study. They were subdivided into three well-matched groups treated with 20 mg o.m., 40 mg o.m. and 40 mg b.d. of pantoprazole, respectively. Endoscopy and intragastric pH monitoring were performed in each patient before and after 14 days of treatment.RESULTS:Fifty-five patients were eligible for final analysis (17 treated with 20 mg o.m., 18 with 40 mg o.m. and 20 with 40 mg b.d. pantoprazole). The ulcer crater healed in 94, 88 and 95% of cases, respectively. The three dosages of pantoprazole produced significant increases in gastric pH compared to basal levels (P < 0.0001). There was also a clear dose-dependent pharmacodynamic effect, which augmented on moving from the lowest dosage of 20 mg o.m. pantoprazole to the highest dosage of 40 mg b.d. (P < 0.01-0.001). The inter-individual response variability within the three treatment groups was more marked with the dose of 20 mg than with the two higher doses of pantoprazole.CONCLUSIONS:All three doses of pantoprazole we tested are highly effective in decreasing gastric acidity and there is a clear dose-dependent pharmacodynamic effect on moving from the lowest to the highest dosage. The greatest inter individual variation in the degree of acid inhibition was seen with pantoprazole 20 mg o.m., while the majority of patients responded adequately to the two higher doses of the drug.

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.

Peripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing different platelet function tests in this patient population. We have compared prospectively four tests for the measurement of in vivo platelet activation (plasma betaTG, plasma PF4, intraplatelet betaTG and urinary excretion of 11-dehydro-TXB2) and one in vitro platelet function test (ADP-induced platelet aggregation) in 63 well-characterized patients with intermittent claudication and in 18 age- and sex-matched healthy volunteers. No statistically significant difference was found between patients and controls for plasma betaTG (20.0 +/- 11.8 vs. 18.8 +/- 9.0 ng/ml, respectively), plasma PF4 (5.2 +/- 2.9 vs. 6.3 +/- 3.5 ng/ml), betaTG/PF4 ratio (4.0 +/- 2.9 vs. 3.6 +/- 1.8), intraplatelet betaTG (4503 +/- 1482 vs. 4059 +/- 1065 ng/ml), and threshold aggregatory concentration of ADP (1.7 +/- 0.72 vs. 1.45 +/- 0.56 microM). Urinary 11-dehydro-TXB2 was instead significantly higher in the PVD group (55.4 +/- 27.5 vs. 26.7 +/- 7.0 ng/h, p <0.001). Our study shows that urinary 11-dehydro-TXB2 is a more sensitive index of in vivo platelet activation than the measurement of either platelet specific proteins or of in vitro platelet aggregation in patients with PVD.

There is much experimental work on the occurrence of tolerance to the antisecretory effect of H2-receptor antagonists in healthy subjects, while data on its development in patients with duodenal ulcer are poor and conflicting. Moreover, this phenomenon has not been studied previously with 24 h gastric pH-metry in patients with active duodenal ulcer. For these reasons, we carried out a prospective pharmacodynamic investigation in 48 patients with endoscopically proven duodenal ulcer using the well-established once daily dosing schedule of H2 blockers. They were studied by means of 24 h continuous endoluminal pH-metry which was performed before, on d1 and d28 after receiving an oral bedtime dose (2200 hours) of either roxatidine 150 mg or ranitidine 300 mg, given in randomized and single-blind fashion. Eight patients did not complete the study for various reasons and 82% of ulcers healed after 4 weeks of therapy. Gastric pH was higher (P < 0.001) on d1 and d28 than basal values during all time periods, but the evening, with both H2 blockers. There was no significant difference between pH values of d1 and d28 in any time interval with both roxatidine and ranitidine. There was also no difference in pharmacodynamic data between the two active treatments. We conclude that tolerance does not develop after 1 month's treatment with a bedtime dose of H2 antagonist in patients with active duodenal ulcer and therefore data gathered on this phenomenon in healthy subjects are not applicable to ulcer patients.

BACKGROUND:Patients with reflux esophagitis have a high rate of relapse within one year after therapy is discontinued.METHODS:We enrolled 175 adults with endoscopy-confirmed reflux esophagitis in a prospective study comparing five maintenance therapies. All the patients were initially treated with omeprazole (40 mg orally once a day) for four to eight weeks, and healing was confirmed by endoscopy. Participants were then stratified according to their initial grade of esophagitis and randomly assigned to 12 months of treatment with one of the following: cisapride (10 mg three times a day), ranitidine (150 mg three times a day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a day), or omeprazole plus cisapride. Endoscopy was repeated after 6 and 12 months of treatment; the endoscopists were blinded to the treatment assignments. Remission was defined as the absence of esophageal lesions on scheduled or unscheduled follow-up endoscopy.RESULTS:In an intention-to-treat analysis, the numbers of patients in continued remission at 12 months were 19 of 35 (54 percent) in the cisapride group, 17 of 35 (49 percent) in the ranitidine group, 28 of 35 (80 percent) in the omeprazole group, 23 of 35 (66 percent) in the ranitidine-plus-cisapride group, and 31 of 35 (89 percent) in the omeprazole-plus-cisapride group. Omeprazole was significantly more effective than cisapride (P = 0.02) or ranitidine (P = 0.003), and combination therapy with omeprazole plus cisapride was significantly more effective than cisapride alone (P = 0.003), ranitidine alone (P < 0.001), or ranitidine plus cisapride (P = 0.03). Ranitidine plus cisapride was significantly better than ranitidine alone (P = 0.05).CONCLUSIONS:For maintenance treatment of reflux esophagitis, omeprazole alone or in combination with cisapride is more effective than ranitidine alone or cisapride alone, and the combination of omeprazole and cisapride is more effective than ranitidine plus cisapride.

BACKGROUND:The experience with long-term treatment of peptic ulcer with omeprazole is still scant, but the possibility cannot be excluded that its better pharmacodynamic effect on gastric acidity also has a positive result in the relapse rate. Moreover, this drug acts via a mechanism other than receptorial binding, and therefore its efficacy should not dissipate with time. This study was carried out to assess the pharmacodynamic properties and the possible changes with time of two dose regimens of omeprazole that could be suitable for long-term treatment in duodenal ulcer. METHODS:Twenty patients with endoscopically proven duodenal ulcer were studied by means of 24-h gastric pH-metry both in basal conditions and on the 5th day of acute treatment with 40 mg omeprazole in the morning. All the ulcers healed after 4 weeks, and thereafter 10 patients were randomized to receive orally 20 mg omeprazole daily at 0800 h in single-blind fashion (group A) and 10 to receive 20 mg omeprazole every other day (group B) for up to 6 months. At the end of the 1st, 3rd, and 6th month of these maintenance treatments 24-h gastric pH-metry was repeated to assess the antisecretory effect of each regimen over time. In group-B patients the test was performed on 2 consecutive days (without and with medication) at each time interval. The fasting gastrin values were also determined. The patients underwent esophagogastroduodenoscopy every 2 months. RESULTS:Three patients in group B were lost to follow-up for various reasons, and only seven remained eligible for final analysis. The two long-term regimens of omeprazole were able to increase significantly pH values (p < 0.02-0.001) and the times spent at and above pH 3.0 (p < 0.001) over 24 h compared with basal conditions. In group A the 24-h pH value obtained in the 6th month was higher (p < 0.02) than that in the 3rd month of maintenance treatment. In group B the pharmacologic effect tended to decrease on the day without medication compared with the day with medication, but the difference between them was significantly (p < 0.05) only at the 6-month interval. There was no significant difference between the gastrin levels of the two groups in the long-term treatment. No ulcer relapse was detected at any long-term endoscopic control in the two groups of patients. CONCLUSIONS:The two omeprazole regimens we tested are effective in reducing gastric acidity, and their pharmacodynamic action does not decrease with time. They are therefore suitable for maintenance treatment in acid-related disorders.

A 6-month, open, randomized study was performed to evaluate different dosage regimens for maintenance therapy with omeprazole in patients refractory to treatment with standard histamine2 (H2)-blockers. One hundred two patients with gastric and/or duodenal ulcers, unhealed after 8 weeks of full-dose H2-antagonist treatment but healed after a further 4 to 8 weeks of omeprazole 20–40 mg/d, were randomized into four treatment groups: omeprazole 20 mg once daily (group A), omeprazole 20 mg every other day (group B), omeprazole 20 mg twice weekly (group C), and ranitidine 150 mg at bedtime (control). Endoscopic and clinical examinations were performed at 3 and 6 months and at every symptomatic relapse. Eleven patients dropped out for reasons of noncompliance. Relapses were detected in 14.8% of 27 cases in group A, 19.4% of 31 cases in group B, 42.9% of 21 cases in group C, and 66.7% of 12 controls. The better outcomes in groups A and B, as compared with group C and the control group were statistically significant. These findings confirm the efficacy of omeprazole in maintenance therapy for refractory ulcers and suggest that drug administration should be daily or every other day, as twice-weekly dosages are less effective.

To the Editor: We reported (Feb. 4 issue)1 on the effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer within one year. Ulcers recurred in 1 of 46 patients in whom H. pylori had been eradicated, as compared with 45 of 53 in whom H. pylori persisted (2 percent vs. 85 percent, P<0.001). We now report two-year follow-up data. Endoscopy was repeated 24 months after initial therapy or if symptoms recurred. After successful eradication, reinfection with H. pylori developed in 5 of 46 patients (11 percent) within two years. This . . .