Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study

Aim:

To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria.

Methods:

Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored.

Results:

The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0% vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups, but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators’ global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01).

Conclusions:

Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/discomfort) more than placebo does.

     

Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly

Background:

Small bowel bacterial overgrowth secondary to drug-induced hypochlorhydria may be of particular importance in the elderly, in whom anti-ulcer drugs are commonly prescribed and the consequences of malabsorption may be severe.

Methods:

Duodenal aspirates were obtained from elderly individuals before (n=24) and during a 2-month treatment course with either omeprazole (20 mg daily; n=8) or ranitidine (300 mg b.d.; n=6), and from six patients with small bowel bacterial overgrowth who had diarrhoea and malabsorption.

Results:

Before treatment, duodenal bacterial counts were normal (< 10⁴ colony forming units/mL) in 23 elderly subjects (96%). However, six of 14 patients (43%) treated with omeprazole (5 of 8) or ranitidine (1 of 6) developed bacterial counts> 10⁵ cfu/mL. All remained asymptomatic and had normal lactulose breath H₂ profiles during treatment.

Conclusion:

Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly but, in the short term, this bacterial overgrowth is not associated with malabsorption.

     

The influence of cisapride on gastric tone and the perception of gastric distension

Background:

Delayed gastric emptying, impaired gastric accommodation to a meal and hypersensitivity to gastric distension have been implied in the pathophysiology of functional dyspepsia. Dyspeptic patients are often treated with the prokinetic drug cisapride.

Aim:

To assess the effects of cisapride on perception of gastric distension and gastric accommodation to a meal.

Methods:

Eighteen healthy volunteers underwent a gastric barostat study on two occasions, after pre-treatment with placebo or cisapride 10 mg q.d.s. Graded isobaric and isovolumetric distensions were performed until the subjects reported discomfort. Volume and pressure changes were recorded and perception was scored by a questionnaire. In 10 volunteers, the amplitude of the gastric accommodation to a mixed liquid meal was also measured.

Results:

Pre-treatment with cisapride significantly lowered thresholds for perception and for discomfort, both during isobaric (4.3 ± 0.7 vs. 3.2 ± 0.7 and 12.2 ± 1.2 vs. 9.2 ± 0.9 mmHg above minimal distending pressure (MDP), respectively, P < 0.05) and isovolumetric (256 ± 46 vs. 200 ± 35 and 644 ± 36 vs. 511 ± 40 mL, respectively, P < 0.05) distensions. Cisapride significantly enhanced the size of the meal-induced fundus relaxation (143 ± 37 vs. 270 ± 50 mL, P < 0.05).

Conclusions:

Cisapride enhances both the perception of gastric distension and the gastric accommodation to a meal. These data suggest that cisapride may provide benefit to patients with impaired postprandial relaxation of the fundus.

     

Mebeverine decreases mass movements and stool frequency in lactulose-induced diarrhoea

Background:

In spite of its frequent use in the treatment of irritable bowel disease little is known about mebeverine’s mode of action in man.

Aim:

To examine mebeverine’s effect on transit though the gut during lactulose-induced diarrhoea.

Methods:

Nine healthy volunteers undertook a two-way randomized crossover study. Diarrhoea was induced using lactulose pre-treatment (20 m t.d.s., 4 days) and subjects received either mebeverine (135 mg t.d.s.) or no treatment. Transit of two enteric-coated capsules containing radiolabelled 8.4 mm tablets and 180–250 μM ion exchange resin were followed using gamma scintigraphy. Stool frequency and symptoms were assessed by diary cards.

Results:

Mebeverine reduced mean daily stool frequency associated with lactulose ingestion from a median of 2.25 (interquartile range (IQR) 1.75–2.75) to 1.5 (IQR 1.25–2.25) movements. Mebeverine significantly reduced the number of mass movements observed in the colon during the 11 h of the study from 2 (2–2) to 1 (1–2), and the number of retrograde movements from 1 (0–2) to 0 (0–0) (P < 0.05). Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9–3.2) to 2.8 (2.6–4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8–2.0) h to 1.0 (0.52–1.32) h, P = 0.02).

Conclusion:

Mebeverine reduces the diarrhoeal effect of lactulose by decreasing the mass movements induced in the ascending colon. This effect may contribute to its clinical effect in irritable bowel syndrome.

     

Comparison of 24-h control of gastric acidity by three different dosages of pantoprazole in patients with duodenal ulcer

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.

     

Nizatidine in combination with amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection

Background:

The efficacy of H₂-antagonists in combination with antibiotics in curing Helicobacter pylori infection remains controversial, and it is uncertain whether double dose H₂-antagonist therapy is superior to standard dose.

Aim:

To determine the efficacy of two doses of nizatidine in combination with two antibiotics in the treatment of H. pylori.

Methods:

A randomized controlled trial was conducted in 160 patients comparing nizatidine l50 mg with 300 mg b.d. (standard vs. double dose), in combination with clarithromycin (500 mg) and amoxycillin (1000 mg) b.d. for 14 days, in Australia and Taiwan. Compliance was based on a clinical assessment and pill count. H. pylori status was determined by histology (antrum and corpus) and CLO-test.

Results:

Baseline clinical and endoscopic findings were similar in both arms of the study. Based on an intention-to-treat analysis, cure of H. pylori was achieved in 78% (95% CI: 70.4–85.4%) in the standard nizatidine dose arm and 70% (95% CI: 61.6–78.2%) in the double dose arm (P = 0.2). Similar cure rates were observed in ulcer and non-ulcer patient groups. Compliance was excellent in the single and double dose arms (85 and 91%, respectively).

Conclusions:

The combination of nizatidine in standard or double dose with clarithromycin and amoxycillin is similarly efficacious in curing H. pylori infection.

     

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions

Summary

Background

Zollinger–Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long‐term maintenance.

Aims

The safety and efficacy data for short‐term (6‐month) treatment of Zollinger–Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years.

Methods

The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid‐reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h.

Results

Twenty‐four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90–100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported.

Conclusions

Maintenance oral pantoprazole therapy up to 3 years at dosages of 40–120 mg b.d. was effective and well tolerated in patients with Zollinger–Ellison syndrome and other hypersecretory conditions.

     

Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients

Background:

The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested.

Aim:

To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H. pylori-positive duodenal ulcer.

Methods:

In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithomycin 250 mg b.d. H.?pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4–6 weeks after the end of treatment, confirmed 4 weeks later by ¹³C-urea breath test.

Results:

Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2–97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7–93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).

Conclusions:

One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.

     

Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders

Aim:

To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea.

Source:

Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these.

Results:

In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT₃ antagonists.

Conclusion:

Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.

     

Effects of two anticholinergic drugs, trospium chloride and biperiden, on motility and evoked potentials of the oesophagus

Background:

Anticholinergic drugs are known to impair the motor function of the oesophagus but their effects on the oesophageal afferent pathways are unknown.

Aim:

To determine the effects of a peripherally-acting (trospium chloride) and a centrally-acting (biperiden) anticholinergic drug on the motility and the evoked potentials of the oesophagus.

Methods:

Nine healthy volunteers were randomized to receive 1.2 mg trospium chloride (TC), 5 mg biperiden (BIP) or saline i.v. Primary peristalsis was elicited by swallowing a 5 mL water bolus and secondary peristalsis by insufflation of 20 mL air, 10 times each. Oesophageal potentials were evoked by electrical stimulation in the distal and proximal oesophagus (30 stimulations at 0.4 Hz, two runs).

Results:

Both anticholinergic drugs reduced by a similiar amount the contraction amplitudes (TC 17 mmHg, BIP 25 mmHg, saline 67 mmHg; P < 0.01) and the rate of secondary contractions (TC 60%, BIP 70%, saline 95%; P < 0.01). In contrast, only biperiden prolonged the latencies of the evoked potentials (N1 peak, distal oesophagus: BIP 191 ms, TC 102 ms, saline 101 ms; P < 0.01; P1 peak: BIP 322 ms, TC 161 ms, saline 144 ms; P < 0.01).

Conclusions:

Both anticholinergic drugs depress oesophageal motility, but only the centrally-acting anticholinergic drug biperiden modifies the oesophageal evoked potentials, suggesting a central cholinergic transmission of the oesophageal afferent pathways.

     

Acid-inhibitory effects of omeprazole and lansoprazole in Helicobacter pylori-negative healthy subjects

Background:

Omeprazole 20 mg once daily (o.d.) and lansoprazole 30 mg o.d. have similar acid-inhibitory effects in healthy Helicobacter pylori-positive subjects. However, little is known about the acid-inhibitory effects of the o.d. and twice daily (b.d.) doses in H. pylori-negative subjects.

Aim:

To compare the decrease in gastric acidity of omeprazole 20 mg (o.d. and b.d.) with lansoprazole 30 mg (o.d. and b.d.) in healthy H. pylori-negative subjects on day 6–7 of dosing.

Methods:

A randomized, investigator-blind, crossover study design was used. Intragastric pH was measured continuously with glass electrodes positioned in the gastric corpus. Sixteen H. pylori-negative subjects, whose intragastric acidity fell below pH 4 for 70% of a 24-h baseline period, were entered in the study.

Results:

Both dosing regimens of omeprazole and lansoprazole significantly increased median gastric pH and percentages of time above pH 4 during the entire 24-h period, night- and daytime, compared to baseline. There were no significant differences in median gastric pH values or time above pH thresholds 3, 4 and 5 between the o.d. dosing regimens. During the night the percentage of time spent above pH 3 and 4 was significantly higher with omeprazole 20 mg b.d. than with lansoprazole 30 mg b.d.

Conclusions:

This comparative study demonstrates that daily doses of omeprazole 20 mg and lansoprazole 30 mg are equally effective in raising intragastric pH in H. pylori-negative subjects on day 6 of dosing. During the night, omeprazole 20 mg b.d. provides superior gastric acid suppression compared to lansoprazole 30 mg b.d.

     

Eradication of Helicobacter pylori with lansoprazole, roxithromycin and metronidazole—an open pilot study

Background:

The most extensively studied Helicobacter pylori eradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested.

Aim:

To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre out-patient care in an open pilot study.

Methods:

163 patients with duodenal ulcer and proven H. pylori infection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily. H. pylori status was determined by urease quick test, histology, microbiology and ¹³C-urea breath test before starting and at least 4 weeks after completing treatment.

Results:

150 patients were available for evaluation; H. pylori was successfully eradicated in 84.7% (127/150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by ¹³C-urea breath test; and in 75.3% (113/150), at least two tests were negative. Side-effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of the H. pylori isolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%).

Conclusions:

For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.

     

Omeprazole, azithromycin and either amoxycillin or metronidazole in eradication of Helicobacter pylori in duodenal ulcer patients

Background

Azithromycin is a new generation, acid stable, macrolide antibiotic that achieves remarkably high concentrations in gastric tissue (above the minimal inhibitory concentration for Helicobacter pylori) after oral administration.

Aim

To establish whether azithromycin plus omeprazole in association with either amoxycillin or metronidazole are useful in curing H. pylori infection in patients with a duodenal ulcer.

Methods

One hundred patients with active duodenal ulcers and H. pylori infection were treated with omeprazole (days 1–10, 40 mg b.d.; days 11–24, 40 mg o.m.; days 25–42, 20 mg o.m.) plus azithromycin 500 mg o.m. for the first 6 days. Patients were randomly assigned to receive either amoxycillin 1 g b.d. (OAzA group; n = 50) or metronidazole 400 mg t.d.s. (OAzM group; n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before the treatment and 6 weeks after completion of therapy.

Results

Ninety-seven patients completed the study. H. pylori infection was eradicated in 85% (41/48) of patients in the OAzA group (intention-to-treat analysis 82%) vs. 74% (36/49) of patients in the OAzM group (intention-to-treat analysis: 72%) (N.S.). All ulcers had healed after 6 weeks of omeprazole treatment. Side-effects, usually minor, were recorded in 13% (OAzA group) and 47% (OAzM group) of patients (P < 0.001), but therapy was discontinued for only one patient in the OAzA group (N.S.).

Conclusion

Ten days of treatment with omeprazole plus (for the first 6 days) azithromycin and either amoxycillin or metronidazole provides effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.

     

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study

Background

Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated.

Aim

To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components.

Methods

One hundred and twenty-eight patients (68 males, 60 females, age 22–80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clari-thromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the ¹³C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities.

Results

All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT.

Conclusions

(i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

     

Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin

Background:

Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication.

Aim:

To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies.

Methods:

Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14–17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site).

Results:

Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73–98% (1 week), 78–99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal.

Conclusion:

An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.

     

Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine

Background:

Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (⁷⁵Selenium HomotauroCholic Acid Test) can accurately diagnose this condition.

Aim:

To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine.

Method:

Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed.

Results:

Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3–12.6). Their median daily faecal weight was 285 g (range 85–676) and median faecal fat output was 17 mmol/24 h (range 8.3–38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea.

Conclusions:

Idiopathic bile acid malabsorption, once suspected, especially by documenting true ‘large volume’ watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.

     

Influence of clarithromycin dosage on pantoprazole combined triple therapy for eradication of Helicobacter pylori

Background:

Low-dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known.

Aim:

To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole.

Methods:

One hundred and sixty-three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.), metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the ¹³C-urea breath test.

Results:

One-hundred and thirty-nine patients completed the study. Based on a per protocol analysis, successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention-to-treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%).

Conclusions:

Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.

     

Low rate of emergence of clarithromycin-resistant Helicobacter pylori with amoxycillin co-therapy

Background:

Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance.

Aim:

To assess pre- and post-treatment antibiotic resistance in three double-blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin.

Methods:

Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4–6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and ≥ 2 negative tests. Susceptibility testing was performed using the Etest.

Results:

In the 91 patients with pre-treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin-susceptible H. pylori isolates. In the 10 patients with pre-treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates.

Conclusions:

Use of amoxycillin co-therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin-containing regimen.

     

The role of osmolality in the absorption of a nutrient solution

Background:

Loss of water during enteral nutrition following massive intestinal resection may be severe. Low osmolality of oral rehydration solutions has recently been shown to mediate an increase in water absorption.

Aim:

To evaluate the effect of osmolality of a nutrient solution on the intraluminal duodenojejunal water flow, and the net absorption rates of total nitrogen and carbohydrate.

Methods:

Eight healthy volunteers with a mean age of 27 (range 25–29) years participated in the study. Enteral nutrition (17% protein, 59% carbohydrate, 24% lipid plus 5 g/L PEG 4000) was infused (5 mL/min 2.64 kcal/min) into the descending duodenum either as a hypotonic (160 mOsmol/kg) or as an isotonic solution in a random order. Intestinal samples were aspirated 20 and 45 cm distally to the infusion point.

Results:

Intraluminal water flow rates were significantly lower with the hypotonic solution than with the isotonic solution, both in the duodenum (4.9 ± 0.3 vs. 6.7 ± 0.5 mL/min; P < 0.02) and the upper jejunum (3.0 ± 0.1 vs. 3.9 ± 0.2 mL/min; P < 0.005). The net absorption rates of total nitrogen and carbohydrate were similar with both solutions.

Conclusion:

Low osmolality of a nutrient solution decreases intraluminal water flow rates in the upper intestine without affecting the absorption rates of total nitrogen and carbohydrate. Compared with an isotonic solution, the use of a hypotonic solution might lower the water loss in patients with extensive short bowel intestinal resection.