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.

     

Iron absorption in patients with Zollinger–Ellison syndrome treated with long-term gastric acid antisecretory therapy

Background:

Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores.

Aim:

To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger–Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs.

Methods:

One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters.

Results:

Eighty-nine patients were taking omeprazole, nine patients were taking histamine H₂-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7–12.5 years) and total duration of any treatment was 10.1 years (range 0.7–21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency.

Conclusions:

Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B₁₂ in such patients is needed, such monitoring for iron parameters is not necessary.

     

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients

Summary

Background

Proximal acid reflux is common in gastro‐oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton‐pump inhibitors.

Aim

To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux.

Methods

Thirty seven consecutive gastro‐oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24‐h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis.

Results

At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non‐hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Δ + 2.5 min (95% confidence interval: 0.4–4.5); P < 0.02].

Conclusions

The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro‐oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.

     

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Summary

Background

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes.

Aim

To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro‐oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms.

Methods

Thirty‐two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24‐h pH‐metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full‐dosage PPI therapy (esomeprazole 40 mg/day) was prescribed.

Results

In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus–heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01).

Conclusions

This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

     

Pantoprazole 20 mg is effective for relief of symptoms and healing of lesions in mild reflux oesophagitis

Aim:

To investigate the efficacy of a low dose of pantoprazole, a gastric proton pump inhibitor, for the relief of symptoms and healing of lesions in mild gastro-oesophageal reflux disease (GERD), and to compare it with the efficacy of ranitidine.

Methods:

Patients with endoscopically established GERD (Stage I, Savary–Miller classification) were enrolled into a randomized, double-blind, parallel-group and multicentre study (intention-to-treat n = 209, age range 19–82 years). They were treated once daily with oral pantoprazole 20 mg or ranitidine 300 mg, for up to 8 weeks. End-point parameters included relief of symptoms (heartburn, acid regurgitation, pain on swallowing) and the healing of GERD lesions. Relief from symptoms was assessed after 2 and 4 weeks, and endoscopically confirmed healing of lesions after 4 and 8 weeks.

Results:

The proportion of patients reporting complete relief from symptoms after 2 weeks was greater in the pantoprazole than in the ranitidine group (69 vs. 48%, P < 0.01), with further improvements seen in the pantoprazole group after 4 weeks (80 vs. 65%, P < 0.05, Cochran–Mantel/Haenszel test). Healing of lesions was confirmed in 70/87 (80%) patients after 4 weeks (pantoprazole group), as compared with 55/86 (64%) patients (ranitidine group) (P < 0.05, per protocol population); after 8 weeks the respective results were 78/87 (90%) and 63/86 (73%) patients (P < 0.01). Both study medications were well tolerated.

Conclusion:

Low-dose pantoprazole (20 mg) is clinically superior to ranitidine (300 mg) in providing fast relief from symptoms and healing of lesions in patients with mild GERD.

     

Anti-diarrhoeal effects of seirogan in the rat small intestine and colon examined in vitro

Background:

Seirogan is a beechwood extract composed of guaiacol, creosol and other related phenolic compounds which is widely used as an anti-diarrhoeal agent in Asia. Abnormalities in water and electrolyte transport are often the cause of diarrhoea, but the mechanism of action of seirogan on small intestinal and colonic mucosal ion transport is unknown.

Aim:

To examine the effect of seirogan on electrogenic ion transport in vitro.

Methods:

Sheets of rat jejunum and colon were mounted in Ussing chambers, and transmural potential difference (PD) was used as an electrical marker of changes in mucosal ion transport. Hypersecretory conditions were induced by acetylcholine (ACh).

Results:

Serosal or mucosal application of seirogan (0.1–100 μg/mL) decreased basal jejunal transmural PD. Pre-treatment of the tissue with the neurotoxin, tetrodotoxin, did not inhibit the seirogan-induced changes in basal electrical activity. Seirogan had no effect on basal transmural PD in the ileum and colon. Under ACh-induced hypersecretory conditions in the small intestine and colon, addition of serosal or mucosal seirogan produced antisecretory effects determined indirectly by measurement of transmural PD.

Conclusion:

The ability of seirogan to decrease basal transmural PD in the jejunum, and inhibit the ACh-induced electrical responses, may contribute to its anti-diarrhoeal action.

     

A comparison of omeprazole, lansoprazole and pantoprazole in the maintenance treatment of severe reflux oesophagitis

Background:

Proton pump inhibitors are effective for the healing of oesophagitis. Standard doses of omeprazole, lansoprazole or pantoprazole are sufficient for healing in mild to moderate cases of oesophagitis.

Aim:

To compare the efficacy of double the standard doses of omeprazole, lansoprazole or pantoprazole for maintenance treatment of severe oesophagitis complicated by a stricture.

Methods:

Thirty-six patients with reflux oesophagitis and stricture confirmed by endoscopy were included in a prospective study comparing three maintenance therapies. In all cases weekly dilatation of the stenosis was performed and patients were treated with omeprazole 20 mg b.d. until healing of oesophagitis and dysphagia relief were achieved. Thirty participants responded to therapy and were then randomly assigned to 4 weeks of maintenance treatment with omeprazole (20 mg b.d.; n=10), lansoprazole (30 mg b.d.; n=10) or pantoprazole (40 mg b.d.; n=10). Subsequently, endoscopies were performed—the endoscopists were blinded to the therapy assignment. The endpoints were defined as the absence of oesophagitis, oesophageal stricture and complaints.

Results:

After 4 weeks of treatment, the number of patients remaining in remission (no oesophagitis or stricture and no symptoms) was nine out of 10 (90%) in the omeprazole group, two out of 10 (20%) in the lansoprazole group (P < 0.01) and three out of 10 (30%) in the pantoprazole group (P < 0.01).

Conclusions:

In our study omeprazole was superior to either lansoprazole or pantoprazole in the maintenance treatment of complicated gastro-oesophageal reflux disease.

     

Comparison of simple tests for the non-invasive diagnosis of clinically silent cirrhosis in chronic hepatitis C

Summary

Background

Biopsy is the gold standard for assessing cirrhosis in patients with chronic hepatitis C virus infection, but it is expensive and at risk of complications. Alternative non‐invasive methods have been developed but their usefulness remains uncertain.

Aim

To compare the accuracy of five non‐invasive scores in detecting cirrhosis.

Methods

We reviewed the charts and liver biopsies of 228 consecutive, treatment‐naïve, hepatitis C virus‐positive patients, 13.2% of whom with histological diagnosis of cirrhosis. The five alternative scores were age‐platelet index, cirrhosis discriminant score, aspartate transaminases to platelet ratio index, Pohl's index, and aspartate transaminases/alanine transaminases ratio.

Results

The specificities of the scores were good (87–100%), but not so their sensitivities (17–67%). Accordingly positive likelihood ratios were generally good but negative likelihood ratios were suboptimal. Combinations of the scores independently related to cirrhosis only slightly change this diagnostic accuracy. Using double cut‐offs to exclude/diagnoses cirrhosis, cirrhosis discriminant score classified 21% of patients without misdiagnoses and aspartate transaminases to platelet ratio index classified 85% of case with 9% of misdiagnoses.

Conclusions

The five scores showed variable sensitivities and specificities in detecting liver cirrhosis, both individually and in combination. The use of double cut‐off points may make the cirrhosis discriminant score and aspartate transaminases to platelet ratio index useful to reduce the number of patients submitted to liver biopsy.

     

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.

     

Interdigestive antroduodenal motility and gastric acid secretion

Background:

In humans, interdigestive acid secretion and antroduodenal motility are closely related with cyclic variations in acid secretion, synchronous with the various phases of the migrating motor complex (MMC). Duodenal acidification inhibits antral motility, but little is known about the effect of acute acid inhibition on antroduodenal motility.

Aim:

To study the effect of acute acid inhibition on antroduodenal motility.

Subjects:

Ten healthy volunteers (four men and six women; age range 20–31 years).

Methods:

Antroduodenal motility (perfusion manometry) and gastric acid secretion (continuous aspiration with recovery marker) were measured simultaneously. Each subject was studied twice in random order during (1) intravenous infusion of saline for one–two complete MMC cycles and (2) during acute acid inhibition with intravenous famotidine (bolus 20 mg, continuous infusion 4 mg/h) for one–two complete MMC cycles or at least 240 min.

Results:

In the saline study, acid output in phase III (2.1 ± 0.3 mmol/10 min) and late phase II (1.7 ± 0.2 mmol/10 min) was significantly (P < 0.05) increased over early phase II and phase I (1.2 ± 0.2 and 1.2 ± 0.2 mmol/10 min, respectively). Famotidine increased gastric pH to above pH 6 within 30 min. After acid inhibition, duration of MMC cycle during famotidine (106 ± 8 min) was not significantly different from the saline experiment (133 ± 14 min). Phase distribution of the MMC cycle was not significantly different between famotidine (I, II and III: 12 ± 3, 82 ± 3 and 5 ± 1%) and saline (I, II and III: 13 ± 3, 83 ± 3 and 4 ± 1%).

Conclusions:

Gastric acid secretion varies cyclically with interdigestive antroduodenal motility. Acute acid inhibition with intravenous famotidine does not significantly affect interdigestive antroduodenal motility.

     

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.

     

Meta-analysis: the adjuvant role of thymopentin on immunological response to hepatitis B virus vaccine in end-stage renal disease

Summary

Background

It has been calculated that 30–40% of dialysis patients fail to produce antibodies to HBsAg antigen after vaccination towards hepatitis B virus. Several authors have reported on the benefit of thymopentin (TP5) as adjuvant to vaccine against hepatitis B virus in patients receiving regular dialysis. However, consistent information on this issue is still lacking.

Aims

To evaluate efficacy and safety of thymopentin as adjuvant to hepatitis B vaccine in dialysis patients by performing a systematic review with a meta‐analysis of clinical trials.

Methods

We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses.

Results

We identified 11 studies involving 272 unique patients with end‐stage renal disease. Only prospective, controlled trials were included. Pooling of study results did not show a significant increase in seroresponse rate among study (thymopentin plus hepatitis B virus vaccine) vs. control (hepatitis B virus vaccine alone) patients; the pooled odds ratio of failure to respond to hepatitis B virus vaccine was 0.677 (95% confidence intervals: 0.285–1.605); no heterogeneity was found (P = 0.0001). Thymopentin significantly improved the seroresponse rate in the subgroup of trials based on greater thymopentin doses (OR: 0.184; 95% CI: 0.085–0.398).

Conclusions

Our meta‐analysis showed that thymopentin significantly improved the seroresponse rate towards hepatitis B vaccine only in dialysis patients treated with higher thymopentin doses. The limited number of patients precluded definitive conclusions.

     

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.

     

Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial

Summary

Background

Enteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment.

Aim

To evaluate nitazoxanide, a thiazolide anti‐infective agent, in treating viral gastroenteritis in adults and adolescents.

Methods

50 out‐patients at least 12 years of age (mean 33.5 years) presenting with diarrhoea and stool‐positive by enzyme‐linked immunosorbent assay for norovirus, rotavirus or adenovirus were enrolled in a double‐blind, placebo‐controlled clinical trial. Patients were randomly assigned either nitazoxanide 500 mg or placebo twice daily for 3 days. The primary end point was time from first dose to resolution of symptoms. Analysis was modified intent‐to‐treat for 45 patients, excluding five patients with other identified enteropathogens at baseline.

Results

The median time from first dose to resolution of symptoms was 1.5 days (IQR: 0.5–2.5) for nitazoxanide‐treated patients and 2.5 days (IQR: 1.5–4.5) for the placebo group. Significant reductions in time to resolution of symptoms were observed for all patients analysed (P < 0.0001) and for subsets of patients with rotavirus (P = 0.0052) and norovirus (P = 0.0295). The number of patients with adenovirus (n = 5) was too small to draw any conclusion. No significant adverse events were reported.

Conclusions

Nitazoxanide may play an important role in managing viral gastroenteritis in adults.

     

Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study

Summary

Background

Although laxatives are a first‐line treatment for constipation, there are few randomized placebo‐controlled trials assessing their efficacy.

Aim

To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation.

Methods

55 patients (age 19–89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3‐day run‐in period. Patients recorded stool frequency and consistency and adverse events.

Results

In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl‐treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P = 0.0061). Mean stool consistency score improved from ‘hard’ (run‐in) to between ‘soft’ and ‘well‐formed’ during bisacodyl treatment, remaining between ‘moderately hard’ and ‘hard’ for placebo treatment (P < 0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups.

Conclusions

Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.

     

Evidence for impaired assimilation and increased colonic fermentation of protein, related to gastric acid suppression therapy

Background:

Although the role of gastric digestion (by acid-dependent pepsins) in overall protein assimilation has never thoroughly been studied, it is generally considered to be limited. Protein that escapes assimilation in the small intestine is intensely fermented by the colonic flora. Phenol and p-cresol are specific bacterial metabolites of tyrosine.

Aim:

To elucidate the role of gastric digestion of protein by evaluating the influence of acid suppression therapy on overall protein assimilation and fermentation.

Methods:

Protein assimilation was studied in 16 healthy subjects under basal conditions and after omeprazole treatment using the combined ¹⁴C-octanoic acid/¹³C-egg white breath test. The degree of protein fermentation was estimated by measuring the urinary output of phenol and p-cresol in 41 healthy volunteers and in 17 patients treated for more than 1 month with omeprazole because of peptic disease.

Results:

Protein assimilation was significantly impaired after omeprazole treatment. Gastric emptying, conversely, was not affected. The urinary output of phenol and p-cresol was increased in patients treated with omeprazole as compared to untreated controls.

Conclusion:

Gastric acid suppression therapy hampers protein assimilation and may promote protein malabsorption. Gastric digestion is likely to play a substantial role in overall protein assimilation.

     

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety

Summary

Background

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion.

Aim

To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.

Methods

A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked.

Results

Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea.

Conclusions

Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

     

Alternating bowel pattern: what do people mean?

Summary

Background

With the introduction of new therapies, the subgrouping of patients based on bowel pattern has become important. However, the appropriate definition of an alternating bowel pattern remains unclear.

Aim

To determine if specific symptoms are reported by people with an alternating bowel pattern.

Methods

Using the Rochester Epidemiology Project, a series of population‐based surveys were undertaken in which valid self‐report gastrointestinal symptom questionnaires were mailed to 4029 randomly selected members of the community. One question asked was ‘How would you describe your usual bowel pattern in the last year'?

Results

3022 subjects (74%) provided questionnaire data and 2718 were eligible for this analysis, the mean age was 57 years, with a range of 20–98 years (median = 61). Of these, 9.2%, 2.5% and 7.6% reported their usual bowel pattern as being constipated, diarrhoea, or alternating respectively. At least 50% of those reporting alternating bowel pattern reported incomplete evacuation (63%), urgency (57%), straining (55%) and loose stool (50%). The proportion of alternators reporting each individual symptom was between that of diarrhoea and constipation except for mucus and incomplete evacuation; however, no symptom was unique to alternators.

Conclusion

People who self‐report an alternating bowel pattern appear to represent a blend of constipation and diarrhoea symptoms, rather than a distinct subgroup.

     

Novel therapies for Helicobacter pylori infection

Background:

Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection.

Aim:

To evaluate orally administered novel therapies for the treatment of H. pylori infection.

Methods:

Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1–4Glc-(3′-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present.

Results:

None of the novel therapies appeared effective and no adverse events occurred.

Conclusion:

Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.

     

Gastrointestinal pH profiles in patients with inflammatory bowel disease

Background:

5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.

Aim:

To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen.

Methods:

Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn’s disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease).

Results:

The median gastric pH values in the patient groups (Crohn’s disease 2.4, range 1.5–4.1; ulcerative colitis 1.95, range 1.55–4.4) were significantly higher than those observed in the controls (1.55, range 0.95–2.6). In the small bowel and colonic segments, all the pH values of Crohn’s disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission.

Conclusions:

The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.