Comparative effects of levosulpiride and cisapride on gastric emptying and symptoms in patients with functional dyspepsia and gastroparesis.

BACKGROUND: The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well-established in patients with functional dyspepsia, but formal studies comparing different prokinetic drugs are lacking. AIM: To compare the effects of chronic oral administration of cisapride and levosulpiride in patients with functional dyspepsia and delayed gastric emptying. METHODS: In a double-blind crossover comparison, the effects of a 4-week administration of levosulpiride (25 mg t.d.s.) and cisapride (10 mg t.d.s.) on the gastric emptying rate and on symptoms were evaluated in 30 dyspeptic patients with functional gastroparesis. At the beginning of the study and after levosulpiride or cisapride treatment, the gastric emptying time of a standard meal was measured by 13C-octanoic acid breath test. Gastrointestinal symptom scores were also evaluated. RESULTS: The efficacy of levosulpiride was similar to that of cisapride in significantly shortening (P < 0.001) the t1/2 of gastric emptying. No significant differences were observed between the two treatments with regards to improvements in total symptom scores. However, levosulpiride was significantly more effective (P < 0.01) than cisapride in improving the impact of symptoms on the patients' every-day activities and in improving individual symptoms such as nausea, vomiting and early postprandial satiety. CONCLUSION: The efficacy of levosulpiride and cisapride in reducing gastric emptying times with no relevant side-effects is similar. The impact of symptoms on patients' everyday activities and the improvement of some symptoms such as nausea, vomiting and early satiety was more evident with levosulpiride than cisapride.

Effect of D2-dopamine receptor antagonist levosulpiride on diabetic cholecystoparesis: a double-blind crossover study.

BACKGROUND: Abnormal gall-bladder motility has been reported in diabetics. The objective was to evaluate the effect of chronic D2-dopamine receptor inhibition on gall-bladder emptying in diabetic patients. METHODS: Under double-blind placebo-controlled conditions and according to a crossover design, patients were randomly assigned to receive either 4 weeks treatment with levosulpiride 25 mg t.d.s. or 4 weeks treatment with placebo, with an interval of 15 days. Twenty-three consecutive long-standing, insulin-treated diabetics with autonomic neuropathy were studied. MEASUREMENTS: At the beginning of the study and after levosulpiride or placebo treatment, gall-bladder emptying was measured ultrasonically by evaluating the gall-bladder volume in basal conditions and every 15 min for 90 min after the ingestion of a standard meal. Statistical analysis of the results was performed by means of analysis of variance. RESULTS: Levosulpiride treatment reduced the basal mean gall-bladder volume from 21.6 +/- 2.3 to 18.6 +/- 2.3 mL (P < 0.05). Furthermore, the residual gall-bladder volume (9.3 +/- 1.4 mL) was significantly reduced compared to the corresponding pre-treatment volume (14.6 +/- 1.5 mL (P < 0.05). In placebo-treated patients, no significant differences were observed in gall-bladder volumes before and after treatment. CONCLUSION: These results show that chronic oral administration of the D2-dopamine antagonist levosulpiride has a significant effect on gall-bladder motility in diabetic patients.

The effects of omeprazole 20 and 40 mg twice daily on intragastric acidity in duodenal ulcer patients.

BACKGROUND: The combination of omeprazole with amoxycillin or clarithromycin is used as treatment against Helicobacter pylori. It seems likely that the antibacterial activity of the antibiotic may be improved by increasing gastric pH towards neutrality, and a twice daily regimen of omeprazole is probably needed. AIM: To assess the effects of twice daily administration of omeprazole 20 and 40 mg. METHODS: Twelve duodenal ulcer patients in remission were randomized to receive in single-blind fashion either placebo, omeprazole 20 mg or omeprazole 40 mg twice daily (08.00 and 20.00 h). On the sixth day of dosing they underwent 24-h gastric pH-metry. RESULTS: Omeprazole 20 and 40 mg b.d. produced marked decreases (P < 0.001) of 24-h gastric acidity (pH 5.4 +/- 0.9 and pH 5.7 +/- 0.6, respectively, vs. a basal pH of 1.4 +/- 0.2) and kept gastric pH at levels higher than 3.0 for almost 24 h. Gastric pH was kept above 5.0 for about 18 h and above 6.0 for about 10 h, while the time spent above 7.0 did not exceed 3 h. There were no significant differences between the two omeprazole dosages at any pH threshold. CONCLUSION: Omeprazole 20 mg b.d. is sufficient to render the gastric milieu as anacidic as possible in duodenal patients.

Effect of gastric acid suppression on 13C-urea breath test: comparison of ranitidine with omeprazole.

BACKGROUND: The assessment of the effect of H2 antagonists on the results of the urea breath test has produced controversial results. AIM: To assess whether standard doses of both omeprazole and H2 blockers can adversely influence the accuracy of the urea breath test. METHODS: Sixty dyspeptic patients with ascertained Helicobacter pylori infection were recruited for this prospective, open study. They were randomized to receive either omeprazole 20 mg at 08:00 hours (n = 30) or ranitidine 300 mg at 22:00 hours (n = 30) for 14 days. The urea breath test was performed at baseline, on day 14, while patients were still taking the antisecretory drugs, and on day 21, 1 week after their cessation. Duplicate breath samples were collected after ingestion of 75 mg 13C-urea + citric acid. A delta value > 5 per thousand was considered positive. RESULTS: On day 14 the median delta values had declined, but not significantly (P = 0. 07) compared to baseline (13.79 vs. 22.39) with omeprazole, while they had increased (P = 0.27) with ranitidine (27.21 vs. 19.46). On the same day there were five out of 30 (17%) and five out of 28 (18%) false-negative results in the omeprazole and ranitidine groups, respectively. All these cases became positive again on day 21. However, in eight cases treated with omeprazole and 13 treated with ranitidine, there was an increase of 14-day delta values compared to baseline. CONCLUSIONS: Our study shows that both omeprazole and ranitidine at standard doses are able to negatively affect the results of the urea breath test. Their adverse effect resolves within 7 days of drug cessation and therefore the withdrawal of these drugs 7 days before testing seems to be sufficient to avoid false-negative results. The surprising finding that both antisecretory drugs reduce delta values in one group and increase them in another group of patients deserves further study.

Stool antigen assay (HpSA) is less reliable than urea breath test for post-treatment diagnosis of Helicobacter pylori infection.

BACKGROUND: The diagnostic yield of the stool antigen test (HpSA) in evaluating the results of Helicobacter pylori eradication therapy is controversial, but many studies have used only the 13C-urea breath test (13C-UBT) as a gold standard which has greatly reduced their relevance. AIM: To compare the reliability of HpSA and 13C-UBT in patients post-treatment using biopsy-based methods as reference tests. METHODS: A total of 100 consecutive dyspeptic patients (42 male and 58 female; mean age, 56 +/- 18 years) were enrolled in our study. All patients were H. pylori positive on the basis of at least two biopsy-based methods, and underwent 1 week of treatment with various triple therapies. They were again endoscoped 4 weeks after completing therapy and six biopsy specimens were taken from the gastric antrum and corpus for rapid urease test, histology and culture. HpSA and 13C-UBT were also performed within 3 days of the second endoscopy. RESULTS: On the basis of biopsy-based tests, infection was eradicated in 77 patients but continued in 23. Three false negatives were observed with HpSA and two with 13C-UBT. In contrast, the number of false positives was significantly higher (P < 0.01) with HpSA than with 13C-UBT (nine vs. one), confirming the lower specificity of the former test. The overall accuracy of HpSA was 88% vs. 97% for 13C-UBT (P < 0.02). CONCLUSIONS: HpSA has lower diagnostic value than 13C-UBT in the evaluation of the outcome of anti-H. pylori therapy. 13C-UBT remains the first-line diagnostic method to monitor eradication results. The use of HpSA should be reserved for those settings in which 13C-UBT is not available.

Optimal duration of therapy combining ranitidine bismuth citrate with clarithromycin and metronidazole in the eradication of Helicobacter pylori infection.

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 13C-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.

Head-to-head comparison of 1-week triple regimens combining ranitidine or omeprazole with two antibiotics to eradicate Helicobacter pylori.

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.

Comparison of the main oesophageal pathophysiological characteristics between short- and long-segment Barrett's oesophagus.

AIM: To assess the oesophageal manometric characteristics and 24-h pH profiles of patients with both short-segment and long-segment Barrett's oesophagus and compare them with those of patients with reflux oesophagitis and controls. METHODS: Seventy-nine patients who had undergone upper digestive endoscopy were recruited: 16 had short-segment Barrett's oesophagus, 13 had long-segment Barrett's oesophagus, 25 had grade III oesophagitis according to the Savary-Miller classification and 25 were used as controls. The diagnosis of Barrett's oesophagus was based on the histological detection of specialized intestinal metaplasia, which extended < 3 cm into the oesophagus in patients with short-segment disease and > 3 cm in patients with long-segment disease. All subjects underwent oesophageal manometry and basal 24-h oesophageal pH monitoring. RESULTS: The lower oesophageal sphincter pressure was significantly lower in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus than in controls (P=0.0004-0.0001), but there was no difference among the three reflux groups. The peristaltic wave amplitude of patients with long-segment Barrett's oesophagus was significantly lower than that of controls (P=0.002) and patients with short-segment Barrett's oesophagus (P=0.02), but was no different from that of patients with reflux oesophagitis. The percentage of non-propagated wet swallows was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus when compared with that of controls (P=0.0004-0.0001). The total percentage of time the oesophagus was exposed to pH < 4.0 was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus (P=0.0001) than in controls, and was higher in patients with long-segment disease than in those with short-segment disease (P=0.01). CONCLUSIONS: Long-segment Barrett's oesophagus is characterized by a greater impairment of peristaltic wave amplitude and a higher oesophageal acid exposure than is short-segment Barrett's oesophagus. However, both forms are linked to increased acid reflux.

Helicobacter pylori infection is not involved in the pathogenesis of either erosive or non-erosive gastro-oesophageal reflux disease.

BACKGROUND: The majority of reflux patients have non-erosive reflux disease. AIM: To evaluate the influence of Helicobacter pylori on oesophageal acid exposure in patients with both non-erosive and erosive reflux disease and in a group of controls. The pattern and distribution of chronic gastritis were also assessed. METHODS: One hundred and twelve consecutive patients with symptoms of gastro-oesophageal reflux disease agreed to undergo both upper gastrointestinal endoscopy and 24-h oesophageal pH-metry. Patients were grouped as H. pylori-positive or H. pylori-negative on the basis of both CLO-test and histology, and as cases with or without oesophagitis on the basis of endoscopy. The controls consisted of 19 subjects without reflux symptoms and with normal endoscopy and oesophageal pH-metry. RESULTS: H. pylori was positive in 35 patients (31%) and in six controls (31%); oesophagitis was found in 44 patients (39%) and non-erosive reflux disease in 68 (61%). The prevalence of chronic gastritis in the antrum and corpus was higher in H. pylori-positive than in H. pylori-negative patients (P < 0.001), but was more frequently mild (P < 0.001) than moderate or severe. The percentage total time the oesophageal pH < 4.0 was higher in patients than in controls (P < 0.008-0.001), but there was no difference between H. pylori-positive and H. pylori-negative patients (12.3% vs. 12%, P = 0.43) or H. pylori-positive and H. pylori-negative controls (1.07% vs. 1.47%, P = 0.19). CONCLUSIONS: H. pylori infection had the same prevalence in reflux patients and in controls. It did not affect oesophageal acid exposure, as there was no difference between H. pylori-positive and H. pylori-negative individuals. The high prevalence of mild body gastritis in H. pylori-positive patients suggests that H. pylori eradication is unlikely to lead to gastric functional recovery, which might precipitate or worsen symptoms and lesions in patients with gastro-oesophageal reflux disease.

Circadian pattern of intragastric acidity in patients with non-erosive reflux disease (NERD).

BACKGROUND: Most patients with gastro-oesophageal reflux disease have non-erosive reflux disease. Proton pump inhibitors are less effective than expected in these patients, but no previous study has measured their 24-h gastric pH values. AIMS: To evaluate whether there are differences in 24-h intragastric acidity between reflux patients with and without oesophagitis and controls. The influence of Helicobacter pylori on the gastric pH of reflux patients was also assessed. METHODS: Sixty-three consecutive patients with gastro-oesophageal reflux disease symptoms who agreed to undergo endoscopy and 24-h pH-metry were recruited. Twenty-five (39%) had erosive oesophagitis and 38 (61%) did not. H. pylori was diagnosed by CLO test, histology and 13C-urea breath test. Gastric pH was also measured in 30 controls without digestive symptoms. RESULTS: H. pylori was found in seven of the 25 (28%) patients with oesophagitis and 14 of the 38 (37%) patients with non-erosive reflux disease. Oesophageal pH-metry was abnormal in 21 of the 25 (84%) patients with oesophagitis and in 32 of the 38 (84%) patients with non-erosive reflux disease. The median gastric pH did not differ between patients with and without oesophagitis or between them and controls during the 24 h (P = 0.8) and other time intervals (P = 0.2-0.4). The gastric pH did not differ between infected and non-infected patients with oesophagitis (P = 0.2-0.4) or non-erosive reflux disease (P = 0.3-0.8). CONCLUSIONS: The circadian pattern of intragastric acidity does not differ between patients with non-erosive reflux disease and oesophagitis. Moreover, the study confirms that H. pylori infection does not affect the gastric pH in either group of reflux patients.

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.

Bolus infusion of famotidine: effects on gastric pH by repeated 12-hour doses of 20 mg in postoperative patients.

This study was carried out to assess the efficacy of intravenous (IV) famotidine in suppressing gastric secretion over a 48-hour period. Twenty postoperative patients requiring a nasogastric tube received famotidine 20 mg IV every 12 hours and gastric pH was measured continuously by means of an indwelling probe. A baseline recording was performed over the first 4 hours and then the drug was infused every 12 hours (q12h) over a 15-minute period for the subsequent 48 hours. The mean pH value achieved during each time segment under active treatment was significantly higher (P < .001) than the mean basal value. Also the density distributions of minutes spent at the various pH units confirm that famotidine is highly effective (P < .001) in raising and maintaining gastric pH above 4.0 units during most of the drug-related period (44 hours). It can be concluded that repeated intravenous boli of famotidine 20 mg every 12 hours allow us to obtain an effective control of intragastric acidity. The antisecretory action is consistent over the total 48-hour period examined and therefore the use of intermittent infusion of famotidine seems to be advisable, as opposed to the recommended continuous IV administration of cimetidine and ranitidine. There is, however, a considerable intersubject variability in the antisecretory response to the drug.

Are clinical patterns of dyspepsia a valid guideline for appropriate use of endoscopy? A report on 2253 dyspeptic patients.

We studied 2253 consecutive dyspeptic patients, without clinical evidence of organic disease, who were referred to our open access endoscopy service. The aim was to assess whether the various clinical patterns of dyspepsia can be considered a valid guideline for the appropriate use of endoscopy. According to the symptomatological patterns, our patients were defined as sufferers from 1) ulcer-like (973 patients), 2) reflux-like (857), and 3) dysmotility-like dyspepsia (423). In our patient population, which reflects the general population of our city, the dysmotility-like type of dyspepsia was the least frequent (19%), whereas the ulcer-like (43%) and the reflux-like (38%) dyspepsia were almost equivalent. A negative endoscopy (35.7%) occurred significantly (p < 5 x 10(-4)) more often in dysmotility-like than in ulcer-like (26.3%) and reflux-like dyspepsia (25.7%). Furthermore, in dysmotility-like dyspepsia, we observed no malignancies in patients less than 60 yr old, and no gastric ulcers in patients less than 50 yr old. In the latter subgroup of patients (under 50 yr), duodenal ulcers and esophagitis were rare (occurring in only one and five, respectively, out of 145 patients). In ulcer-like and reflux-like dyspepsia, abnormal endoscopic findings occurred frequently (in 73.5% and 74.1%, respectively), and no relationship with patients' age was observed. Our data indicate that patients under 50 yr old with dysmotility-like dyspepsia can be considered a kind of population for which endoscopy is inappropriate. However, because the prevalence of dysmotility-like dyspepsia was 19% (423/2253) in our patient sample, and only 7.15% of them were under 50 yr old (161/2253), we can obtain only a small percentage of reduction in endoscopic service load if the guideline of age < 50 yr is adopted.

Open access endoscopy: a large-scale analysis of its use in dyspeptic patients.

We examined 2,253 consecutive dyspeptic patients referred to our endoscopy service by general practitioners ("open" group) and hospital clinicians ("clinic" group) to study the prevalence of the various endoscopic findings according to patient age and the route of endoscopic referral. The results obtained are representative of that specific population. Normal endoscopic findings progressively lessened as patients' age increased, and the overall rate was as low as 26.5% in the open and 30.3% in the clinic groups. Erosive prepyloric changes and duodenitis were the most frequently noted abnormalities in patients < 40 years of age (16.9% and 20.1%, respectively, in the open and 11.6% and 14.2% in the clinic groups). Chronic gastritis was prevalent in patients > 60 years of age. Duodenal ulcer decreased from 9.7% (open) and 18% (clinic) in patients < 40 to 2% and 1.1% in patients > 60. No malignancy was found in patients < 40, while only approximately 1% of those < 60 had neoplasms. All our endoscopic findings, both in the open and the clinic groups, were not significantly different. No significant differences in symptoms were observed among patients with different endoscopic findings. We conclude that (a) endoscopy is really useful only in a small group of patients < 40 years of age; (b) individual symptoms alone have a poorly discriminant diagnostic power; and (c) restriction of open access endoscopy is not justified.

Duration of acid suppression in H2-antagonist nonresponders.

We monitored 24-hour gastric acidity in 16 resistant duodenal ulcer patients treated with ranitidine 300 mg hora somni (9 cases) and famotidine 40 mg hora somni (7 cases) for 3 months. Data obtained in these patients were compared with those of a group of unselected duodenal ulcer patients who responded to a 4-week course of the same H2-antagonist regimens. In the time window 22.00-07.59 h there was a reduced effectiveness of ranitidine in nonresponder patients in terms of both mean pH levels (4.8 +/- 0.9 vs. 5.6 +/- 0.7, p < 0.04) and the mean duration of the antisecretory effect defined as the time spent in minutes above pH 3.0 (403 +/- 73 vs. 490 +/- 59, p < 0.02). Also, the action of famotidine was diminished in nonresponder patients in the same time interval as regards both pH values (4.1 +/- 1.6 vs. 5.7 +/- 0.6, p < 0.03) and the duration in minutes (329 +/- 163 vs. 473 +/- 45, p < 0.05). The analysis of all individual nonresponder patients shows that there was a certain variability in the duration of acid suppression: the majority of them had an adequate nocturnal acid inhibition, while in some cases of both the ranitidine and the famotidine subgroups, acid inhibition lasted only few hours or did not occur at all. At present, it is not possible to distinguish with certainty two different subsets of H2-antagonist nonresponders because of the small size of the population studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability in individual response to various doses of omeprazole. Implications for antiulcer therapy.

This study was carried out in order to perform a combined prospective assessment of the individual pharmacodynamic response and of duodenal ulcer healing in patients treated with three different doses of omeprazole. Ninety-nine patients with endoscopically proven duodenal ulcers were subdivided into three parallel groups of 33 cases, who were randomly assigned to receive orally at 0800 hr, in single blind fashion, either 10 mg, 20 mg, or 40 mg of omeprazole. All of them underwent continuous intragastric pH monitoring both in basal conditions and on the fifth day of each dose regimen; ulcer healing was then assessed endoscopically after four weeks of treatment. All three doses of omeprazole caused pH values to increase significantly (P < 0.001) over the whole 24-hr period. In patients treated with omeprazole 10 mg, the individual responses showed the highest variability: the acid inhibition, expressed in terms of time spent above pH 3.0, lasted for more than 16 hr in 42% of cases, for more than 8 hr in 28%, and for less than 6 hr in 30%. In patients treated with omeprazole 20 mg, the pharmacological response was more marked and uniform and lasted for more than 16 hr in 79% of cases; however, it is worth noting it lasted for less than 6 hr in three patients (10%). In patients treated with omeprazole 40 mg, the individual response was excellent (more than 16 hr) in 94% of cases, and it lasted for less than 6 hr in only one patient (3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Negative effect of ranitidine on the results of urea breath test for the diagnosis of Helicobacter pylori.

OBJECTIVES: In analogy with proton pump inhibitors, H2-antagonists may also be responsible for false-negative results on urea breath test for the detection of Helicobacter pylori. In this study we assessed the frequency and duration of false-negative urea breath tests in patients given different doses of ranitidine. METHODS: A total of 120 consecutive dyspeptic patients infected with H. pylori on the basis of concomitant positive results of CLO-test, histology and urea breath test were recruited for this prospective, open, parallel-group study performed in an urban university gastroenterological clinic. They were randomized to receive an acute treatment with either ranitidine 300 mg once a day in the evening, ranitidine 300 mg once a day in the morning, ranitidine 150 mg b.i.d., or ranitidine 300 mg b.i.d. for 14 days. The urea breath test was performed on day 14 while patients were still taking ranitidine, and on day 21, 1 wk after completion of therapy. The test was repeated on day 28 in those patients who were still negative on day 21. Duplicate breath samples were collected after ingestion of 75 mg 13C-urea plus citric acid. A delta value >5/1000 was considered positive. RESULTS: Of 118 patients infected with H. pylori, 15 (13%) had a negative urea breath test on day 14. The false-negative results were equally distributed among the four groups of ranitidine dosage. Nine of these patients reverted to positive at 7 days and the remaining six at 14 days after completion of therapy. CONCLUSIONS: Our study shows that ranitidine negatively affects the results of urea breath testing, independent of the given dosage. Patients undergoing this examination for H. pylori diagnosis should discontinue use of H2-antagonists 2 wk before testing.

Circadian gastric acidity and Helicobacter pylori infection in patients with chronic pancreatitis.

A high prevalence of duodenal ulcer has been reported in patients with chronic pancreatitis. Data from previous studies on gastric acid secretion in these patients have provided conflicting results, and the potential role of H. pylori infection has been poorly investigated. The aim of this study was to assess the circadian pattern of gastric acidity and the prevalence of H. pylori infection in a group of patients suffering from this disease. Thirty-five patients with chronic pancreatitis ascertained by means of pancreatic calcifications or ductal alterations revealed by ERCP were recruited for this prospective study. They underwent 24-hr gastric pH-metry with glass minielectrodes positioned in the gastric corpus, and their profile of gastric acidity was compared with that of 35 healthy subjects, matched for age and sex. H. pylori infection was diagnosed by means of serology. There was no statistical difference (P = NS) in gastric pH of circadian, nocturnal, daytime, and postprandial periods between healthy subjects and patients with chronic pancreatitis. The prevalence of H. pylori infection was rather low (31%) in our patients and similar to that of a comparable control population (37%) in our geographical area. In conclusion, our study shows that patients with chronic pancreatitis have a circadian pattern of gastric acidity similar to that of normal subjects. Moreover, the prevalence of H. pylori infection is low in this population. These findings greatly differentiate the ulcer diathesis in chronic pancreatitis from that of patients with ordinary duodenal ulcer and suggest that other factors are implicated in the ulcerogenic process.

Circadian acidity pattern in prepyloric ulcers: a comparison with normal subjects and duodenal ulcer patients.

We used continuous 24-h pH monitoring to compare the circadian intragastric acidity of 36 patients with prepyloric ulcers (PPU) with that of 101 normal subjects (NS) and that of 206 patients with duodenal ulcer (DU). The ulcer crater was endoscopically ascertained in all cases, and PPU were located within an area up to 2 cm proximal to the pylorus. The pH curve pertaining to DU patients ran below that of NS during most of the circadian period, whereas the pH profile of PPU patients was higher than that of NS, and this was particularly true during the evening and the night. The acidity of PPU patients was significantly lower (p < 0.01) than that of NS during the night only, whereas it was lower (p < 0.05-0.001) than that of DU patients during each time interval analysed (24 h, nighttime, and daytime). Our findings show that the gastric acidity of PPU patients differs greatly from that of DU patients, since it is lower throughout the whole 24-h period, and particularly during the night. Thus these two entities are pathophysiologically different with regard to the acidity pattern and should be considered two distinct subgroups of peptic ulcer disease instead of being incorporated, as usually happens, in the clinical group 'duodenal ulcer disease'.

Antisecretory effects of three omeprazole regimens for maintenance treatment in duodenal ulcer.

This study was carried out to assess the antisecretory effects and their possible changes over time of three different dose regimens of omeprazole that could be proposed for maintenance treatment in duodenal ulcer. Forty-five patients with endoscopically proven duodenal ulcer were studied by means of 24-hr gastric pH-metry both in basal conditions and on the fifth day of acute treatment with omeprazole 20 mg in the morning. Ulcers healed after four weeks (in three cases after eight weeks) and afterwards, 15 patients were randomized to receive orally at 0800 hr in single-blind fashion omeprazole 10 mg daily (group A), 15 to receive omeprazole 40 mg on Saturday and Sunday followed by a five-day period without medication (group B), and 15 to receive omeprazole 20 mg every other day (group C) for up to three months. On the 20th and 80th days of these maintenance treatments 24-hr gastric pH-metry was repeated to assess the antisecretory effectiveness of each regimen over a two-month period. In patients of group B these tests began at 1700 hr on Friday, the last of five days off treatment, and in those of group C at 1700 hr of the day off medication. All three dose regimens of omeprazole were able to raise pH values significantly (P < 0.01-0.001) compared to basal levels. Omeprazole 20 mg every other day was more effective (P < 0.01) than omeprazole 40 mg weekend, but did not differ significantly from omeprazole 10 mg daily. The durations of acid inhibition (pH > 3.0 units/24 hr) were 12.44, 10.00, and 17.38 hr with groups A, B, and C, respectively. There was no significant difference between the pH profiles of the 20th and 80th days with every dose regimen. It is concluded that all three dose regimens of omeprazole are effective in reducing gastric acidity and their pharmacodynamic action does not change with time. Therefore they are suitable to be assessed in large clinical trials aimed at verifying the prevention of duodenal ulcer recurrence for longer periods.