bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: clinical pharmacology of alosetron
Authors: Gunput M.D.
Published: March 2003

Alosetron, a new 5‐HT3 antagonist is in development for the treatment of the irritable bowel syndrome. A series of randomized placebo‐controlled double‐blind clinical pharmacology studies have been performed in healthy volunteers and irritable bowel syndrome patients to evaluate the pharmacokinetics and some of the pharmacodynamic properties of this drug. Alosetron was shown to dose‐dependently inhibit the 5‐HT‐induced skin flare response, increase colonic transit time and increase basal jejunal water and electrolyte absorption, in healthy volunteers. In irritable bowel syndrome patients, alosetron increased colonic compliance. Alosetron had no effect on the perception of gastric distension or on meal‐stimulated gastric acid secretion. Orally alosetron has ≈ 60% bioavailability and a half‐life of 1.5 h. At doses of 1 mg or more, it has a pharmacodynamic duration of action which justifies twice a day dosing. These data support the potential use of alosetron in the treatment of irritable bowel syndrome.
Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index
Authors: Talley  , Haque  , Wyeth  , Stace  , Tytgat  , Stanghellini  , Holtmann  , Verlinden  , Jones
Published: March 2003

Background:

There is not at present a suitable disease‐specific health‐related quality of life instrument for uninvestigated dyspepsia and functional (non‐ulcer) dyspepsia.

Aim:

To develop a new multi‐dimensional disease‐specific instrument.

Methods:

The Nepean Dyspepsia Index (NDI) was designed to measure impairment of a subject’s ability to engage in relevant aspects of their life and also their enjoyment of these aspects; in addition, the individual importance of each aspect is assessed. A 42‐item quality of life measure was developed and tested, both in out‐patients presenting to general practice with upper gastrointestinal complaints (n = 113) and in a randomly chosen population‐based sample (n = 347).

Results:

Adequate face and content validity was documented by an expert panel. Factor analysis identified four clinically relevant subscales: interference with activities of daily living, work, enjoyment of life and emotional well‐being; lack of knowledge and control over the illness; disturbance to eating or drinking; and disturbance to sleep because of dyspepsia. These scales had high internal consistency. Both symptoms and the quality of life scores discriminated dyspepsia from health.

Conclusion:

The Nepean Dyspepsia Index is a reliable and valid disease‐specific index for dyspepsia, measuring symptoms and health‐related quality of life.
Helicobacter pylori eradication with proton pump inhibitor‐based triple therapies and re‐treatment with ranitidine bismuth citrate‐based triple therapy
Authors: Rinaldi  , Zullo  , Francesco  , Hassan  , Winn  , Stoppino  , Faleo  , Attili
Published: March 2003

Background:

It has been suggested that short‐term triple therapy comprising a proton pump inhibitor, plus clarithromycin and amoxycillin be used as first choice in treating H. pylori infection, while eradication failure patients should be further treated with a quadruple therapy. Nevertheless, conflicting results have been reported using these treatment regimens in different countries.

Methods:

A total of 278 patients with H. pylori infection were randomised to receive one‐week triple therapy, comprising clarithromycin 500 mg b.d., amoxycillin 1 g b.d., and either omeprazole 20 mg b.d. (OAC; 90 patients), or pantoprazole 40 mg b.d. (PAC; 95 patients), or lansoprazole 30 mg b.d. (LAC; 93 patients). H. pylori infection at entry, and eradication 4–6 weeks after therapy had ended, were assessed by rapid urease test and histology on biopsies from the antrum and the corpus. When eradication did not occur, patients were given a 2‐week treatment comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s. and tinidazole 500 mg b.d. (RBTT). Eradication in these patients was assessed 4–6 weeks after conclusion of treatment by a further endoscopy.

Results:

Six patients were lost to the follow‐up. At the end of the first course of treatment, the overall H. pylori eradication rate was 78% (95% CI: 73–83) and 79% (95% CI: 75–84) at ‘intention‐to‐treat’ (ITT) and ‘per protocol’ (PP) analysis, respectively, without any statistically significant difference between treatment regimens, although a trend for better results with the omeprazole combination was observed. Moreover, H. pylori eradication was achieved in 82% (95% CI: 75–97) (ITT) and 86% (95% CI: 69–94) (PP) of 38 patients re‐treated with RBTT regimen.

Conclusions:

Our data found that this short‐term triple therapy is not a satisfactory treatment (< 80% eradication rate) for H. pylori infection. The 2‐week triple therapy used as re‐treatment in eradication failure patients yielded more promising results.
The colonic mesenteric margin is most susceptible to injury in an experimental model of colonic ulceration
Authors: ANTHONY  , DHILLON  , POUNDER  , WAKEFIELD
Published: March 2003

Background

: Crohn's disease ileal ulcers and indomethacin‐induced jejunal ulceration in the rat tend to occur in the mucosa nearest to the mesentery (mesenteric margin), an area of the bowel wall that has a critical blood supply. Mercuric chloride induces caecal and colonic ulceration in the Brown Norway rat.

Aim

: To examine whether the mesenteric margin is more sensitive to injury by a substance known to be vasculotoxic in the caecum and colon.

Methods

: Brown Norway rats received a single subcutaneous dose of either mercuric chloride 1 mg/kg or saline. The gastrointestinal tract was examined macro‐ and microscopically for lesions 48 h later. The vascular anatomy of the normal rat colon and caecum was also examined using the carbon ink perfusion technique.

Results

: Mercuric chloride induced caecal and colonic ulceration preferentially along the mesenteric margin of the bowel wall. Histologically, the lesions showed mucosal necrosis and neutrophil infiltration. There was also extensive vascular degeneration/necrosis with microaneurysm formation and extensive submucosal haemorrhage. Cellular infiltration of the vasculature was not a feature. The caecal and colonic mesenteric margins in control rats were supplied by small end arteries.

Conclusions

: The colonic and caecal mesenteric margins are susceptible to injury by mercuric chloride, a chemical known to induce haemorrhagic vasculopathy in the rat gastrointestinal tract. The large bowel mesenteric margin may be susceptible to injury by mercuric chloride because of the critical blood supply to that side of the bowel wall.
Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection—comparison with omeprazole and lansoprazole
Authors: Miwa H. , Ohkura R. , Murai T. , Sato K. , Nagahara A. , Hirai S. , Watanabe S. , Sato N.
Published: March 2003

Background

: A recent trend in curative therapy for Helicobacter pylori infection is the so‐called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials. Various regimens employing this triple therapy have been reported. However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy.

Aim

: To validate its usefulness by comparing rabeprazole with omeprazole and lansoprazole, in combination with amoxycillin and clarithromycin.

Patients and methods

: 221 H. pylori‐positive patients with peptic ulcer disease were randomized to receive one of three different proton pump inhibitor/amoxycillin–clarithromycin (PPI/AC) regimens for 7 days. (i) OAC regimen (n = 75): omeprazole 20 mg b.d., amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (ii) LAC regimen (n = 74): lansoprazole 30 mg b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d.; and (iii) RAC regimen (n = 72): rabeprazole 20 mg b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d. Cure of the infection was determined by the 13C urea breath test 1 month after completion of the treatment.

Results

: Intention‐to‐treat based cure rates for OAC, LAC and RAC regimens were 85% (95% CI, 75–92), 84% (95%, CI 73–91) and 88% (95% CI, 78–94), respectively, and per protocol based cure rates of these regimens were 88% (95% CI, 78–94), 91% (95%, CI 82–99) and 93% (95% CI, 84–98), respectively. Adverse effects in the entire study population, which included diarrhoea, glossitis or skin rash, were reported by 15% of the patients, and complete compliance was achieved in 95% of these patients.

Conclusion

: 1‐week proton pump inhibitor/AC regimens for H. pylori infection were effective in the Japanese population. Rabeprazole can be considered as equivalent to omeprazole and lansoprazole in the PPI/AC triple therapy.
Short‐term triple therapy with lansoprazole 30 mg or 60 mg, amoxycillin and clarithromycin to eradicate Helicobacter pylori
Authors: Sieg  , Sellinger  , Schlauch  , HÖrner  , Fuchs
Published: March 2003

Background

: We investigated the efficacy of 30 vs. 60 mg lansoprazole daily in a 1‐week triple therapy for eradication of Helicobacter pylori in a prospective randomized study.

Methods

: Two hundred and fifteen consecutive out‐patients with peptic ulcer disease or non‐ulcer dyspepsia, in whom H. pylori infection was confirmed by histology and/or a urease biopsy test, were randomly assigned to a 1‐week treatment with either 15 mg lansoprazole b.d. (LAC15 group) or 30 mg lansoprazole b.d. (LAC30 group) in combination with 1 g amoxycillin b.d. and 500 mg clarithromycin b.d.

Results

: Eradication of H. pylori was successful in 87% (per protocol) and 82% (intention‐to‐treat) of the patients with LAC15 and in 94% (per protocol) and 87% (intention‐to‐treat) of the patients with LAC30. The difference was not significant. In both treatment groups, all peptic ulcers were healed at the check‐up. Adverse effects were seen in 11 patients of the LAC15 group and 10 patients of the LAC30 group: they caused discontinuation of the therapy in four of the LAC15 group and two patients of the LAC 30 group.

Conclusions

: A 7‐day triple therapy using lansoprazole (LAC15) is an efficient and economical regimen for the eradication of H. pylori.
The effect of Helicobacter pylori eradication on gastro‐oesophageal reflux
Authors: Tefera  , Hatlebakk  , Berstad
Published: March 2003

Background

: Increased prevalence of oesophagitis has been reported following eradication of Helicobacter pylori. We hypothesized that H. pylori eradication might increase gastro‐oesophageal acid reflux in patients with reflux oesophagitis.

Methods

: Twenty‐five consecutive patients (13 male, 12 female) with H. pylori infection and reflux oesophagitis grade I (22 patients) or II (three patients) were enrolled; mean age 49.9 (range 33–75) years. Twenty‐four hour intra‐oesophageal pH recording was performed before and 12 weeks after eradication of H. pylori, which was achieved using bismuth subnitrate suspension 150 mg q.d.s., oxytetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s. for 10 days. Eradication was confirmed by 14C‐urea breath test 12 weeks after completion of treatment. The patients did not receive acid‐suppressive medication.

Results

: All patients had abnormal gastro‐oesophageal reflux before anti‐H. pylori treatment. After treatment, there was no significant change in the percentage of total time oesophageal pH < 4 (P=0.46) in the 23 patients in whom the infection had been cured. Nine of the cured patients had increased acid exposure, whereas 14 had decreased acid exposure. No significant change in reflux symptom scores was found. There was no relationship between change in acid exposure and symptom improvement.

Conclusions

: Twelve weeks after H. pylori eradication there was no consistent change in gastro‐oesophageal acid reflux in patients with mild or moderate reflux oesophagitis.
Randomized trial of omeprazole and clarithromycin combined with either metronidazole or amoxycillin in patients with metronidazole‐resistant or ‐susceptible Helicobacter pylori strains
Authors: Houben  , Hensen  , Rauws  , Hulst R. W. M. Van Der , Hoff B. W. M. Van‘T , Ende A. Van Der , Kate F. J. W. Ten , Tytgat
Published: March 2003

Background

: The impact of metronidazole resistance on the efficacy of proton pump inhibitor based triple therapies remains unclear.

Aim

: To study whether metronidazole resistance affects Helicobacter pylori eradication rates in patients treated for 1 week with either omeprazole 20 mg b.d., metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC), or omeprazole 20 mg b.d., amoxycillin 1000 mg b.d. and clarithromycin 500 mg b.d. (OAC).

Methods

: A randomized, single blind, single centre study with parallel groups was conducted. H. pylori positive patients were enrolled in a metronidazole‐resistant (MR; MIC > 8 μg/mL) or a metronidazole‐susceptible group (MS; MIC < 4 μg/mL), as determined by E‐test. Within the strata patients were randomized to either OAC or OMC.

Results

: One hundred and twenty‐two patients were included. The per protocol cure rate for OAC was 52 out of 57 (91%) (MS 23 out of 26 (89%); MR 29 out of 31 (94%)) and for OMC 46 out of 55 (84%) (MS 19 out of 22 (86%); MR 27 out of 33 (82%)).

Conclusions

: One‐week OAC and OMC are effective therapies. OAC and OMC were equally effective in patients with metronidazole‐susceptible strains of H. pylori. Using the OMC regimen, neither equality nor significant differences in treatment outcome could be shown between patients with metronidazole‐resistant or –susceptible strains of H. pylori.
A double‐blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency
Authors: Halm  , LÖser  , LÖhr  , Katschinski  , MÖssner
Published: March 2003

Background

: Modern pancreatin preparations consist of enteric‐coated microspheres to protect the enzymes from gastric acid. There are, however, no clinical trials comparing different sizes of pancreatin microspheres with regard to fat excretion and fat intake.

Aim

: To prove both equivalent efficacy and safety of conventional pancreatin microspheres and smaller pancreatin minimicrospheres in patients with exocrine insufficiency due to chronic pancreatitis.

Methods

: In this prospective, randomized, double‐blind, multicentre, crossover trial, patients with a stool fat excretion of > 7.5 g/day during a placebo period were randomly assigned either to the minimicrosphere/microsphere treatment sequence or vice versa. The primary end‐point was the coefficient of fat absorption, which was calculated from fat excretion and fat intake during the course of a standardized diet. Stool weight, clinical symptoms and the safety of the preparations were also evaluated.

Results

: Thirty‐seven patients entered the study, of whom 23 fulfilled the criteria for the crossover period. In the per protocol analysis (n=18), the 90% confidence intervals for the coefficient of fat absorption of both crossover periods lay entirely within the equivalence range (P=0.02). The intention‐to‐treat analysis revealed similar results, but the equivalence range was slightly missed (P=0.07). Similar results were obtained for the secondary parameters and the reported adverse events.

Conclusions

: Pancreatin minimicrospheres have been shown to be equally effective as microspheres in improving the coefficient of fat absorption in patients with exocrine insufficiency due to chronic pancreatitis.
Double‐blind comparison of lansoprazole 15 mg, lansoprazole 30 mg and placebo as maintenance therapy in patients with healed duodenal ulcers resistant to H2‐receptor antagonists
Authors: Kovacs  , Campbell  , Richter  , Haber  , Jennings  , Rose
Published: March 2003

Background

: Maintenance antisecretory therapy is often used to prevent duodenal ulcer recurrence and control symptoms. This study compared the efficacy and safety of lansoprazole 15 mg and 30 mg daily with placebo in preventing ulcer recurrence in patients with a recent history of duodenal ulcer disease.

Methods

: Fifty‐six patients were treated with either lansoprazole 15 mg, 30 mg or placebo o.m.

Results

: Within 1 month of study initiation, 27% (four out of 15) of placebo‐treated patients experienced ulcer recurrence as compared to 13% (two out of 15) and 6% (one out of 18) of lansoprazole 15 mg and 30 mg treated patients, respectively. Median time to first ulcer recurrence was > 12 months in lansoprazole patients. At Month 12, significantly (P < 0.001) more lansoprazole 15 mg patients (70%) and lansoprazole 30 mg patients (85%) remained healed. Eighty‐two per cent of lansoprazole 15 mg and 76% of lansoprazole 30 mg patients remained asymptomatic during the entire study period. All placebo patients became symptomatic, experienced ulcer recurrence, or withdrew from the study by month six. The incidence of adverse events was comparable among the three treatment groups.

Conclusions

: Lansoprazole safely and effectively reduces duodenal ulcer recurrence and ulcer‐related symptoms.
Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis—a 2‐year follow‐up
Authors: Van Rensburg C. J. , Honiball  , Van Zyl J. H. , Grundling H. DE K. , Eloff  , Spies  , Simjee  , Theron  , Fischer  , Louw
Published: March 2003

Background

: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+‐ATPase, necessary for the final step in gastric acid secretion.

Aim

: To assess safety and efficacy of oral pantoprazole (40 mg o.d.) used as a prophylaxis against relapse in patients with healed reflux oesophagitis during an open‐label, 2‐year study.

Methods

: Outpatients (n=157) with healed stage II or III reflux oesophagitis (Savary–Miller classification) were enrolled into a long‐term, multicentre maintenance study. Endoscopy was performed at entry into the study, after 12 and 24 months, or when disease‐specific symptoms occurred on more than three consecutive days. Symptoms were assessed at 3‐monthly intervals. Endoscopically confirmed relapses (at least stage I) were evaluated as treatment failures.

Results

: Of the 178 adverse events, experienced by 88 (56%) patients (intention‐to‐treat population), 12 (7%) were assessed by the investigators as possibly related to the study medication. Median serum gastrin levels increased from a baseline of 46 ng/L to 90 ng/L, reaching a plateau after 9 months. For the intention‐to‐treat population the endoscopic remission rates after 12 and 24 months were 87% and 76%, respectively (Life‐Table survival analysis, Kaplan–Meier).

Conclusion

: Pantoprazole 40 mg proved to be safe and efficacious during a 2‐year prophylaxis treatment in patients with healed reflux oesophagitis.
One‐year follow‐up of newly diagnosed irritable bowel syndrome patients
Authors: RuigÓmez  , Wallander  , Johansson  , RodrÍguez L. A. GarcÍA
Published: March 2003

Background

: Irritable bowel syndrome is the most common functional gastrointestinal disorder seen by general physicians.

Methods

: We followed up a population‐based cohort of newly diagnosed irritable bowel syndrome patients aged 20–79 years, to examine patterns of treatment, comorbidity and healthcare utilization. We used the UK General Practice Research Database as the source population. Individuals with other gastrointestinal diseases, cancer and pregnant women were not included. There were 2956 patients in our final cohort.

Results

: Irritable bowel syndrome patients were mainly young and middle‐aged; only 12% were 60 years or older. The majority of patients were women (74%). There were no marked differences in terms of use of healthcare services or comorbidity status in the year before irritable bowel syndrome diagnosis as compared to the year after. Fourteen per cent of irritable bowel syndrome patients received no drug treatment at all. Among those treated, the first choice was an antispasmodic. Elderly patients (> 60 years old) were more likely to receive drug treatment. Females had a slightly higher probability of being treated than men, except for the category of anti‐diarrhoeal drugs.

Conclusion

: This study has shown that irritable bowel syndrome patients are mainly young and female. We also found that treatment pattern varied according to age and gender. Elderly patients and females were at a higher risk of receiving drug treatment.
The effect of omeprazole dosing on the isolation of Helicobacter pylori from gastric aspirates
Authors: Williams  , Sercombe  , Lawson  , Slater  , Owen  , Pounder
Published: March 2003

Background

: Animal experiments suggest that omeprazole dosing increases shedding of Helicobacter into the gastric lumen, and hence into gastric juice.

Aim

: To assess the effect of omeprazole dosing on the yield of H. pylori from gastric aspirates of infected volunteers.

Methods

: Six serial nasogastric aspirates, three before and three during dosing with omeprazole 40 mg b.d., were obtained for culture from 10 H. pylori infected volunteers and one uninfected volunteer. To reduce contamination, samples were diluted 1:10 with Maximum Recovery Diluent (MRD; pH 7.0) or HCl‐KCl buffer (pH 2.2) prior to culture on Columbia and Dent’s agar.

Results

: Undiluted gastric juice cultures were rapidly overgrown by upper respiratory tract flora. HCl‐KCl dilution resulted in isolation of H. pylori from 77% of infected subject aspirates before, and 67% of aspirates during dosing with omeprazole. The yields were significantly lower with MRD dilution, 47% and 10%, respectively. Omeprazole dosing significantly decreased the yield after MRD dilution, but not after HCl‐KCl dilution.

Conclusions

: Decreasing intragastric acidity, by dosing with omeprazole, decreases the isolation of H. pylori from routinely processed gastric aspirates. In vitro acidification of gastric aspirates, by HCl‐KCl dilution, increases the isolation of H. pylori both before and during omeprazole dosing.
Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5‐HT3 receptor antagonist
Authors: Camilleri  , Mayer  , Drossman  , Heath  , Dukes  , Mcsorley  , Kong  , Mangel  , Northcutt
Published: March 2003

Background

: No currently available treatment provides consistent relief of irritable bowel syndrome. Colonic sensory and motor function are modulated partly through 5HT3‐receptors.

Aim

: To evaluate effects of the 5HT3‐receptor antagonist, alosetron, in irritable bowel syndrome.

Methods

: Randomized, double‐blind, placebo‐controlled, dose‐ranging (1, 2, 4, 8 mg b.d. alosetron), 12‐week trial in 370 patients with diarrhoea‐predominant or alternating constipation and diarrhoea irritable bowel syndrome. Weekly measurement of adequate relief was the key end‐point; other irritable bowel syndrome symptoms were collected daily using an electronic phone system.

Results

: Alosetron (1 mg or 2 mg b.d.) significantly (P < 0.05 vs. placebo) increased the proportion of females, but not males, reporting adequate relief. Stool consistency, frequency and percentage days with urgency improved over placebo (P < 0.05) within the first month with all doses of alosetron, and persisted throughout the trial with all doses in female patients. With 1 mg b.d. alosetron, females had improved stool consistency and urgency within the first week, and adequate relief and improved stool frequency within the first 2 weeks. There was no consistent improvement in bowel function among male patients.

Conclusion

: In female irritable bowel syndrome patients with predominant diarrhoea or alternating constipation and diarrhoea, alosetron is effective in treatment of abdominal pain and discomfort and bowel‐related symptoms.
Effect of naproxen on the hamster gastric antrum: ulceration, adaptation and efficacy of anti‐ulcer drugs
Authors: Fitzpatrick  , Sakurai  , Le
Published: March 2003

Background

: Various animal models of non‐steroidal anti‐inflammatory drug (NSAID)‐induced gastric ulceration exist. These models have limitations, which make them less relevant to the human situation.

Aim

: To develop a more simple and more relevant model of NSAID‐induced gastric ulceration and adaptation.

Methods

: Gastric ulceration was evaluated following the orogastric administration of naproxen (80 mg/kg b.d.) to hamsters. The effects of misoprostol and famotidine on gastric acid secretion and ulceration were also determined. Gastric adaptation was evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemistry, in hamsters given naproxen for 3 weeks. Antral resistance to acute injury by NSAIDs and ethanol was also determined in these animals.

Results

: Naproxen caused primarily gastric antral ulceration, which decreased from day 3 to day 21. This gastric adaptation was accompanied by an increase in PCNA positive cells, particularly on days 7 and 14. The adapted gastric antral mucosa was resistant to acute damage by various agents. Misoprostol (1 or 100 μg/kg) prevented antral ulceration, without affecting gastric acid secretion. Despite decreasing acid output by>  90%, famotidine (30 mg/kg) failed to prevent ulceration.

Conclusion

: The administration of naproxen (80 mg/kg b.d.) to hamsters is a simple, reliable and relevant method for evaluating NSAID‐induced gastric antral ulceration and adaptation.
Review article: travellers’ diarrhoea
Authors: De Las Casas  , Adachi  , Dupont
Published: March 2003

In this review we will briefly consider the important aetiological agents and clinical expressions in travellers’ diarrhoea, then we will review the prevention and therapy of the illness.
Pantoprazole, amoxycillin and either azithromycin or clarithromycin for eradication of Helicobacter pylori in duodenal ulcer
Authors: Včev  , Štimac  , Ivandić  , Včeva  , Takač  , Pezerović
Published: March 2003

Background:

Studies have shown that 1‐week triple therapy consisting of a proton pump inhibitor, amoxycillin and clarithromycin may cure Helicobacter pylori infection in the majority of patients.

Aim:

To establish whether pantoprazole plus amoxycillin in association with either azithromycin or clarithromycin is useful in curing H. pylori infection in patients with a duodenal ulcer.

Methods:

One hundred and ten patients with active duodenal ulcers and H. pylori infection were treated with pantoprazole (days 1–7, 40 mg b.d.; days 8–28 40 mg o.d.) plus amoxycillin 1 g b.d. for the first 7 days. Patients were randomly assigned to receive either azithromycin 500 mg o.d. for the first 6 days (PAAz group; n=55) or clarithromycin 500 mg b.d. for the first 7 days of treatment (PAC group; n=55). H. pylori status was determined by urease test and histology before the treatment, and again 4 weeks after cessation of any medication.

Results:

One hundred and three patients completed the study. H. pylori infection was eradicated in 78% (39/50) of patients in the PAAz group (ITT analysis: 71%, 95% CI: 61–83%) vs. 81% (43/53) of patients in the PAC group (ITT analysis: 78%, 95% CI: 69–90%) (N.S.). All ulcers had healed.

Conclusion:

Our study shows that 1‐week triple therapy with pantoprazole, amoxycillin and either azithromycin or clarithromycin is not satisfactory (<80% ITT H. pylori eradication rate).
Five‐day regimens containing ranitidine bismuth citrate plus high‐dose clarithromycin and either amoxycillin or tinidazole for Helicobacter pylori infection
Authors: Cammarota  , Cannizzaro  , Ojetti  , Cianci  , Pastorelli  , Armuzzi  , Gentiloni  , Gasbarrini  , Pirozzi  , Gasbarrini
Published: March 2003

Background:

Ranitidine bismuth citrate (RBC)‐based triple therapies for a period of 7 days have proved to be an effective treatment for Helicobacter pylori.

Aim:

To investigate the eradication efficacy, safety profile and patient compliance of two RBC‐based triple therapies given for 5 days.

Methods:

Eighty H. pylori‐positive patients with dyspeptic symptoms, referred to us for gastroscopy, were consecutively enrolled in this prospective, randomized, open‐label study. These patients were randomly assigned to receive a 5‐day course of RBC 400 mg b.d. plus clarithromycin 500 mg b.d. and either tinidazole 500 mg b.d. (RBCCT group) or amoxycillin 1 g b.d. (RBCCA group). The H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C‐urea breath test 8 weeks after the completion of treatment.

Results:

All enrolled patients completed the study. Thirty‐seven of 40 patients treated with RBCCT (both PP and ITT analysis: 93%; 95% CI: 80–98%) and 35 of 40 in the RBCCA group (both PP and ITT analysis: 88%; 95% CI: 73–96%) returned H. pylori‐negative. Slight or mild side‐effects occurred in 4/40 patients (10%) in the RBCCT group and in 5/40 (12%) in the RBCCA group.

Conclusions:

This is the first study demonstrating the efficacy of RBC‐based triple therapies given for only 5 days. RBC regimens containing high‐dose clarithromycin and either amoxycillin or tinidazole prove to be well tolerated, safe and preserve good eradication rates even when administered for a shorter than conventional duration.
Recurrent symptoms and gastro‐oesophageal reflux disease in patients with duodenal ulcer treated for Helicobacter pylori infection
Authors: Vakil  , Hahn  , McSorley
Published: March 2003

Background:

Eradication of Helicobacter pylori has been shown to prevent relapse of endoscopically detected duodenal ulcers. There is controversy regarding symptom improvement after therapy. Some studies have suggested that a substantial number of patients remain symptomatic after eradication therapy. Other studies suggest that gastro‐oesophageal reflux disease (GERD) may develop as a result of H. pylori eradication.

Aim:

To determine the relationship between symptoms and H. pylori eradication and to determine whether H. pylori eradication results in symptoms or endoscopic findings of GERD.

Methods:

Two hundred and forty‐two patients with endoscopically documented duodenal ulcer disease and evidence of H. pylori infection by rapid urease testing and histology were studied in four randomized, placebo‐controlled, double‐blind trials of H. pylori eradication therapy. All patients underwent symptom assessment and endoscopy with biopsy before therapy and 1 and 6 months after completing therapy. The rapid urease test and histology were used to determine H. pylori status. Interviewers were blinded to H. pylori status after eradication and were unaware of the endoscopic findings (interviews were performed prior to repeat endoscopy).

Results:

The presence of epigastric pain was significantly associated with persistent H. pylori infection 1 month after therapy (odds ratio 2.3, 95% CI: 1.02–5.2; P=0.041), as was nausea (OR 7.1, 95% CI: 0.93–55.6; P=0.029). The presence of epigastric pain was significantly associated with ulcer relapse at 6 months (OR 7.5, 95% CI: 3.6–15.7; P < 0.001) as was nausea (OR 5.1, 95% CI: 1.7–16.0; P=0.002). Heartburn was not associated with eradication of H. pylori or ulcer relapse. New onset reflux symptoms were reported by 17% (17 of 101 patients) at 6 months and were not significantly different in patients with (15%) and without (22%) persistent H. pylori infection (P=0.47). Erosive oesophagitis was present at endoscopy in one of the 17 cases that developed new heartburn.

Conclusions:

One month after completion of therapy, the presence of epigastric pain or nausea is associated with persistent infection and these symptoms at 6 months are suggestive of duodenal ulcer relapse. The incidence of GERD is not increased in patients who have eradication of H. pylori.
Personal review: is profound acid inhibition safe?
Authors: Waldum  , Brenna
Published: March 2003

Inhibitors of gastric acid secretion, particular proton pump inhibitors, are effective drugs in the treatment and prophylaxis of acid‐related diseases. Proton pump inhibitors are therefore prescribed widely, often for minor complaints.

Gastric acidity kills swallowed microorganisms, and acid secretion must be of biological importance because it is maintained in phylogenesis. Acid secretion is controlled by feedback mechanisms, mainly via gastrin. A decrease in acidity always causes an increase in plasma gastrin. The trophic effect of gastrin leads to hyperplasia and neoplasia of the enterochromaffin‐like (ECL) cell. ECL cell derived tumours in man were previously regarded as rare, and also as rather benign. It is now clear that the ECL cell gives rise to a significant proportion of gastric carcinomas. Moreover, ECL cell carcinoids secondary to hypergastrinaemia may develop into highly malignant tumours.

Treatment with a proton pump inhibitor is followed by rebound acid hypersecretion and decreased efficiency of H2‐blockers, thus such treatment may induce a type of physical dependence. It is therefore reasonable to be cautious and not to treat younger (< 50 years) patients for long periods of time with profound inhibitors of gastric acid secretion. Chromogranin A in the blood is a sensitive marker of the ECL cell mass, and it could be used to survey patients on long‐term proton pump inhibitors.
The osmotic laxative magnesium sulphate activates the ileal brake
Authors: Vu  , Nouwens  , Biemond  , Lamers  , Masclee
Published: March 2003

Background:

Alterations in gastrointestinal motility and hormone secretion, especially activation of the ileal brake, have been documented in malabsorption.

Aim:

To investigate whether artificially‐induced accelerated small intestinal transit activates the ileal brake mechanism.

Methods:

Eight healthy volunteers (four female, four male; age 21 ± 3 years) participated in four experiments: (a) meal with either oral magnesium sulphate (MgSO4) or placebo; and (b) fasting with either oral MgSO4 or placebo. Antroduodenal motility was recorded by perfusion manometry. Duodenocaecal transit time was determined by the lactulose H2 breath test. Gall‐bladder volume was measured by ultrasound at regular intervals, and blood samples were drawn for determination of cholecystokinin and peptide YY (RIA). Twenty‐four hour faecal weight and fat excretion were determined.

Results:

MgS04 significantly accelerated duodenocaecal transit time and increased faecal fat and weight in all subjects. MgSO4 significantly delayed the reoccurrence of phase III and affected antroduodenal motility during fasting but not after meal ingestion. Postprandial gall‐bladder relaxation and postprandial peptide YY release were significantly increased during the MgSO4 experiment compared to placebo.

Conclusions:

The osmotic laxative MgS04 accelerates intestinal transit both in the fasting and fed state. MgS04 activates the ileal brake mechanism only in the fed state, with peptide YY release and inhibition of gall‐bladder emptying.
Anti‐Helicobacter pylori activity of Chinese tea: in vitro study
Authors: Yee Yuk‐Kei , Koo Marcel Wing‐Leung
Published: March 2003

Background:

Chinese tea has an antibacterial activity against a wide range of bacteria. However, its activity against Helicobacter pylori has not been reported.

Method:

In this study the anti‐Helicobacter pylori effects of a Chinese tea (Lung Chen tea), and two tea catechins, epigallocatechin gallate and epicatechin and their minimum inhibitory concentrations (MICs) were examined. The effect of Lung Chen on metronidazole resistance was also studied using the E‐test.

Results:

Lung Chen, epigallocatechin gallate and epicatechin all inhibited the growth of H. pylori. The MIC90 for Lung Chen was 0.25–0.5% (w/w) and that of epigallocatechin gallate and epicatechin were 50–100 and 800–1600 μg/mL, respectively. Epigallocatechin gallate is probably the active ingredient responsible for most of the anti‐H. pylori activity of Chinese tea. Lung Chen did not reverse metronidazole resistance.

Conclusions:

Chinese tea has anti‐H. pylori activity in a daily consumed concentration, and epigallocatechin gallate is probably the active ingredient responsible for the action.
Failure of oesophageal acid control in candidates for Barrett's oesophagus reversal on a very high dose of proton pump inhibitor
Authors: Fass  , Sampliner  , Malagon  , Hayden  , Camargo  , Wendel  , Garewal
Published: March 2003

Background:

Normalization of oesophageal acid exposure using high dose proton pump inhibitors in patients who are candidates for ablation therapy has been suggested to be essential for successful Barrett's reversal. However, the success rate for achieving pH normalization has not been determined.

Methods:

Patients with Barrett's oesophagus (2–6 cm in length) who were found to be eligible for ablation therapy using multipolar electrocoagulation were included in this prospective study. Patients underwent an upper endoscopy to determine Barrett's length and other anatomic characteristics. Biopsies were obtained to rule out dysplasia. Subsequently, patients were treated with omeprazole 40 mg b.d. Twenty‐four hour oesophageal pH monitoring was performed after a mean period of 8.4 ± 0.6 days of therapy.

Results:

Twenty‐five patients were enrolled into the study. The pH test was abnormal in four (16%) of the study subjects. An additional two (8%) patients had abnormal supine percentage time with pH less than 4. There was no significant difference in oesophageal acid control between patients with long vs. short segment Barrett's oesophagus. Elderly (> 60 years) patients tended to have less acid control than younger (≤ 60 years) patients.

Conclusions:

Failure of oesophageal acid control in candidates for Barrett's oesophagus reversal on very high dose of proton pump inhibitor is not uncommon. Our study suggests that ambulatory 24‐h oesophageal pH monitoring should be considered in all candidates for Barrett's reversal who are treated with high dose proton pump inhibitor to ensure normalization of oesophageal acid exposure.
The effects of smoking and indomethacin on small intestinal permeability
Authors: Suenaert  , Bulteel  , Den Hond  , Hiele  , Peeters  , Monsuur  , Ghoos  , Rutgeerts
Published: March 2003

Background:

Smoking modulates inflammatory bowel disease, protecting from ulcerative colitis on the one hand and worsening the course of Crohn’s disease on the other. This influence might occur through changes in intestinal permeability, because permeability is increased in most patients with Crohn’s disease.

Aim:

To study the influence of smoking on small intestinal permeability and its increase induced by indomethacin.

Methods:

50 smokers and 50 nonsmokers underwent a 51Cr‐EDTA basal permeability test and the same test after challenge with indomethacin 125 mg p.o.

Results:

Small intestinal permeability was the same in smokers (median 1.22%; IQR 1.00–1.58) and nonsmokers (1.24%; 0.94–1.66). Basal small intestinal permeability was lower in females (1.09%; 0.87–1.33) than in males (1.48%; 1.18–1.88). Indomethacin challenge increased permeability by 110% (71–141) in smokers, vs. 156% (78–220) in the nonsmokers (P=0.04).

Conclusion:

Smoking reduces the effect of NSAID on small intestinal permeability. It is therefore unlikely that the adverse effect of smoking on Crohn’s disease is related to its influence on intestinal permeability.
Gastric acidity and acid breakthrough with twice‐daily omeprazole or lansoprazole
Authors: Katz  , Hatlebakk  , Castell
Published: March 2003

Background:

In patients with severe gastro‐oesophageal reflux disease (GERD), proton pump inhibitors are being used increasingly in twice‐daily regimens to improve control of gastric acidity. Few data exist to compare the ability of the most‐often used proton pump inhibitors, omeprazole and lansoprazole, to control gastric acid at twice‐daily dosage regimens. Nocturnal acid breakthrough, defined as gastric pH < 4.0 continuously for > 60 min, may compromise treatment goals in patients with GERD.

Aim:

To compare the effects of omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. on gastric acidity and the relative ability of each dosage regimen to prevent acid breakthrough.

Methods:

In a crossover pharmacodynamic study, 20 healthy volunteers (10 male, 10 female, mean age 38 years) were given omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. for 7 days each, in a randomized manner. Each dosage regimen was separated by a minimum 7‐day period where no medication was administered. On day 7 of each regimen, 24‐h intragastric pH‐metry was performed. The percentage of time for which gastric pH was below 4.0 and 3.0, the occurrence of daytime and nocturnal acid breakthrough, and the duration of action of each regimen were compared. Non‐parametric statistics for paired data were used.

Results:

The percentage time for which gastric pH was below 4.0 was significantly lower with omeprazole 20 mg b.d. (median 14.8%) than with lansoprazole 30 mg b.d. (median 24.2; P=0.0372). Fourteen subjects showed more effective acid control when taking omeprazole; these were significantly more often H. pylori‐negative patients compared with those for whom acid control was better on lansoprazole (P < 0.001). Nocturnal acid breakthrough occurred in seven patients (35%) on omeprazole and in 10 (50%) on lansoprazole (N.S.).

Conclusion:

In healthy volunteers, twice‐daily dosing of omeprazole 20 mg b.d. appears to be significantly more effective than lansoprazole 30 mg b.d. in controlling gastric acidity. The clinical importance of such a difference remains to be defined in GERD patients.
Review article: the clinical role of anti‐TNFα antibody treatment in Crohn's disease
Authors: Bell  , Kamm
Published: March 2003

The recent licensing of anti‐TNFα antibody treatment offers the potential to radically alter the course of severe Crohn's disease using genetically‐engineered drugs directed against a specific inflammatory mediator. Controlled randomized trials have demonstrated clinical benefit associated with tissue healing in patients with active intestinal disease and fistulae, often when conventional therapies were unsuccessful. This therapy is expensive, however, and long‐term efficacy and safety data are still awaited. This review considers the nature of this therapy and the current evidence for its clinical benefit and adverse effects. The treatment is also considered in the context of available immunosuppressive agents, with suggestions about its practical application.
Bioavailability of four ursodeoxycholic acid preparations
Authors: Williams  , Al‐Knawy  , Blanchard
Published: March 2003

Background:

Ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones.

Objectives:

The objective of this study was to compare the bioavailability of four commercially available ursodeoxycholic acid formulations in standardized doses.

Methods:

Twenty‐four healthy subjects were studied in groups of four, and received each of the different UDCA preparations in random order, with a 1‐week washout or more in‐between. Serum UDCA levels were determined for a 6‐h period. The mean area under the curve (AUC), Cmax and Tmax were determined for each drug formulation, and the results compared. Dose proportionality was determined using the Canadian Ursofalk tablet using either 250 mg, 500 mg or 750 mg dosing. The intraparticipant variability was assessed by asking each participant to repeat the last drug that they took the second time, 1 week later.

Results:

The mean AUC was 68.99 μmol/1.6 h−1 for the USA UDCA tablet, 59.34 μmol/1.6 h−1 for the Canadian UDCA tablet, 55.55 μmol/1.6 h−1 for Ursolvan capsules, and 46.66 μmol/1.6 h−1 for Actigall capsules. The mean Cmax values were 24.29, 17.85, 16.63 and 413.32 nmol/mL, respectively. The mean Tmax was 1.82, 2.3, 2.79 and 3.39 h, respectively. Linear aggression analysis assessing the direct proportionality of AUC on the dose for the Canadian UDCA tablet gave an estimate of 0.063 + 0.0164 (standard error, P‐value=0.0117), e.g. if the dose increases from 250 mg to 500 mg, the serum ursodeoxycholic acid increases by 250 × 0.063=15.75. There was excellent reproducibility for the AUC for the North American tablets (0.97, 0.88) compared to the two capsules (0.32, 0.15).

Conclusions:

The significantly higher AUC and Cmax and shorter Tmax for the Canadian Ursofalk tablets compared to the UDCA capsule preparations supports better bioavailability.
The effect of unfiltered coffee on potential biomarkers for colonic cancer risk in healthy volunteers: a randomized trial
Authors: Grubben  , Van Den Braak  , Broekhuizen  , De Jong  , Van Rijt  , De Ruijter  , Peters  , Katan  , Nagengast
Published: March 2003

Background:

Epidemiologic studies suggest that coffee use might protect against colorectal cancer. Inconsistencies as to the effect of coffee use and colorectal cancer between epidemiologic studies might be related to the type of coffee brew.

Objective:

We studied the effect of unfiltered coffee consumption on putative biomarkers for colonic cancer risk.

Design:

A total of 64 healthy volunteers (31 men and 33 women), with a mean age of 43 ± 11 years were randomly assigned to two groups in a crossover design, with two intervention periods of 2 weeks separated by a washout period of 8 weeks. Treatments were 1 L of cafetière (French press) coffee daily or no coffee. At the end of each intervention period, fasting blood samples, colorectal biopsies and 48 h faeces were collected.

Results:

No effect of coffee on colorectal cell proliferation, assayed by estimating the Proliferating Cell Nuclear Antigen labelling index, was seen. Additionally, no effects were seen on the concentrations of faecal soluble bile acids and colorectal mucosal glutathione S‐transferase activity. However, unfiltered coffee significantly increased the glutathione content in the colorectal mucosa by 8% and in plasma by 15%. Other aminothiols in plasma also increased on coffee.

Conclusion:

Unfiltered coffee does not influence the colorectal mucosal proliferation rate, but might increase the detoxification capacity and anti‐mutagenic properties in the colorectal mucosa through an increase in glutathione concentration. Whether this effect indeed contributes to a lower colon cancer risk remains to be established.
Drug‐induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions
Authors: Bytzer P. , Hallas J.
Published: March 2003

Background:

A large variety of drugs have been implicated in causing dyspepsia. Due to the high background incidence of dyspepsia it is impossible to distinguish between spontaneous and truly drug‐related symptoms. Most patients with dyspeptic symptoms are treated empirically. Drug‐induced dyspepsia might therefore be reflected in the sequencing of prokinetics relative to other medications.

Aim:

To screen a large prescription database for signs of drug‐induced functional dyspepsia, applying a symmetry principle.

Methods:

Prescription data on all incident users of cisapride and metoclopramide were used to identify individuals who had started their first therapies with a prokinetic drug and an index drug within a 100‐day span. A dyspepsia‐provoking effect of the index drug would manifest as an excess of persons with the prokinetic drug prescribed last in this selected population. Relative to conventional analyses based on case–control or cohort design, this principle is robust to confounders that are stable over time.

Results:

In the cisapride analysis (1825 persons) no single drug had adjusted rate ratios significantly above unity. An inverse signal for antidepressants (rate ratio 0.57; 95% CI: 0.39–0.84) suggests that these drugs may have a therapeutic effect against functional dyspepsia. In the metoclopramide analysis (6126 persons) positive signals were found for 14 drugs, all well‐known for causing nausea as a side‐effect, with the exception of insulin (rate ratio 2.91, 95% CI: 1.40–8.11).

Conclusions:

Drug‐induced symptoms of functional dyspepsia are rare and do not contribute to the use of cisapride. The start of insulin treatment may induce nausea.