bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of enprostil on serum gastrin and pepsinogen A and C levels in patients on long‐term treatment with omeprazole
Authors: MEIJER J. L. , ANSEN J. B. M. J. J , BIEMOND I. , KUIJPERS I. J. , LAMERS C. B. H. W.
Published: July 2010

Background: Treatment of omeprazole induces profound inhibition of gastric acid secretion, resulting in hypergastrinaemia. In rats hypergastrinaemia induced by chronic administration of high doses of omeprazole resulted in ECL‐cell hyperplasia and subsequent carcinoid formation. This finding may limit long‐term therapy in man. The synthetic prostaglandin E2 analogue enprostil not only inhibits gastric acid secretion but also reduces serum gastrin in normal subjects and in peptic ulcer patients. The present study was undertaken to determine whether enprostil reduces serum gastrin in patients on long‐term treatment with omeprazole.

Methods: Eight patients with reflux oesophagitis treated with 40 mg omeprazole once daily for at least 3 months received 3 5 μg enprostil t.d.s. during a 5‐day treatment course. Basal and postprandial serum gastrin concentrations and pepsinogen A and C levels were measured on the day before, the first and the final day, and on the day after cessation of treatment.

Results: Enprostil significantly (P < 0.05) reduced basal serum gastrin from 65±15 pmol/L to 51 ± 13 pmol/L on the first treatment day, and to 41 ± 9 pmol/L on the final day. Enprostil also significantly (P < 0.05) reduced postprandial integrated serum gastrin from 6173 ± 849 pmol.h/L to 4516 ± 906 pmol.h/L and to 3532 ± 706 pmol.h/L on the first and final treatment days, respectively. On the day after cessation of treatment basal (57± 11 pmol/L) and postprandial integrated serum gastrin concentrations (5766 ± 864 pmol.h/L) were not significantly different when compared to pretreatment values. Enprostil had no significant influence on serum pepsinogens A and C. Conclusion: Short‐term co‐administration of enprostil lowers the serum gastrin levels in patients on long‐term treatment with omeprazole.
Short Report: omeprazole‐tetracycline combinations are inadequate as therapy for Helicobacter pylori infection
Authors: AL‐ASSI M. T. , GENTA R. M. , GRAHAM D. Y.
Published: July 2010

Background: Current triple antimicrobial therapies cure Helicobacter pylori infection in 60–90% of cases but are cumbersome. Addition of omeprazole to amoxycillin has been shown to enhance effectiveness when compared to amoxycillin alone

Method: We studied omeprazole 20 mg t.d.s. plus tetracycline 500 mg q.d.s. for 14 days (OMP/TCN) and omeprazole 40 mg in the morning plus tetracycline 500 mg q.d.s. along with bismuth subsalicylate tablets 2 q.d.s. (OMP/TCN/BSS) for 14 days. Forty‐four patients (19 OMP/TCN, 25 OMP/TCN/BSS) with H. pylori peptic ulcer disease were studied. H. pylori status was evaluated at least 4 weeks after ending antimicrobial therapy.

Results: In the OMP/TCN group cure of H. pylori infection was achieved in 5/19 (26%). Adding bismuth to the regimen improved the results; 4 weeks after ending therapy cure of H. pylori infection was achieved in 12/25 (48%).

Conclusions: Neither regimen can be recommended for routine cure of H. pylori infection. Although one cannot predict which antimicrobial therapies will be enhanced by the addition of omeprazole, these data suggest that future studies should evaluate drugs whose effectiveness is compromised by low pH.
Comparative bioavailability of 5‐aminosalicylic acid from a controlled release preparation and an azo‐bond preparation
Authors: CHRISTENSEN L. A. , FALLINGBORG J. , JACOBSEN B. A. , ABILDGAARD K. , RASMUSSEN H. H. , HANSEN S. H. , RASMUSSEN S. N.
Published: July 2010

Background: Knowledge of the bioavailability of 5‐aminosalicylic acid (5‐ASA, mesalazine) from the different 5‐ASA‐containing drugs is important for rational therapy of inflammatory bowel diseases.

Methods: The local and systemic bioavailability of 5‐ASA from a controlled release 5‐ASA preparation (Pentasa—2, 4 or 6 g/day) was investigated and compared with the azo‐bond 5‐ASA preparation olsalazine (Dipenturn—2 g/day) in 13 healthy volunteers during steady state conditions.

Results: The therapeutically relevant parameter of 5‐ASA at the rectal level, expressed as the mean concentration in faecal water, showed a significant trend towards higher concentrations with increasing Pentasa dose: 9.2 mmol/L, 19.0 mmol/L and 24.4 mmol/L, respectively. The concentration of olsalazine 2 g/day was 16.0 mmol/L. The concentration of the metabolite N‐acetyl‐5‐aminosalicylic acid (Ac‐5‐ASA) did not rise with increasing Pentasa dose, indicating saturable presystemic acetylating capacity of 5‐ASA. Total urinary excretion of 5‐ASA and Ac‐5‐ASA, as a percentage of the daily ingested 5‐ASA dose, remained constant on the three Pentasa doses, but there was a significant increase in the 5‐ASA fraction. Mean steady state plasma concentrations of 5‐ASA and Ac‐5‐ASA were significantly higher on Pentasa 4 g/day and 6 g/day than on 2 g/day. Values on Pentasa 2 g/day were comparable with those on olsalazine 2 g/day.

Conclusions: The study confirmed that 5‐ASA is released from Pentasa in a predictable manner, the amount released increasing with dose. Olsalazine is an excellent generator of 5‐ASA in the colon.
Protective action of diosmectite treatment on digestive disturbances induced by intestinal anaphylaxis in the guinea‐pig
Authors: THEODOROU V. , FIORAMONTI J. , DROY‐LEFAIX M. T. , PLIQUE O. , BUÉNO L.
Published: July 2010

Methods: Colonic transit time, faecal moisture and intestinal permeability were assessed in guinea‐pigs sensitized intraperitoneally with cow's milk and challenged with an oral administration of β‐lactoglobulin. One group of animals was treated for 1 week with diosmectite (500 mg.kg/day) and another with placebo. A control group was not sensitized but treated with diosmectite.

Results: In sensitized animals receiving placebo, challenge with β‐lactoglobulin induced a significant (P < 0.05) decrease in colonic transit time, and increases in faecal moisture and intestinal permeability. These changes were not observed in animals treated with diosmectite.

Conclusion: Diosmectite pre‐treatment protects against allergic digestive disturbances induced by antigen administration in guinea‐pigs sensitized to cow's milk.
Flumecinol for the treatment of pruritus associated with primary biliarg cirrhosis
Authors: TURNER I. B. , RAWLINS M. D. , WOOD P. , JAMES O. F. W.
Published: July 2010

Objective: To determine whether flumecinol (3‐trifluoromethyl‐α‐ethylbenzhydrol, Zixoryn) is effective in ameliorating pruritus of cholestasis, particularly in primary bilary cirrhosis.

Methods and Results: 50 patients (46 with primary biliary cirrhosis, PBC) took oral flumecinol 600 mg or identical placebo once weekly for 3 weeks. Patients assessed pruritus by scoring a daily 100 mm visual analogue scale (VAS; 0 = no itch, 100 = severe, continuous, day and night intolerable itch). Quality of life was similarly measured. Patients scored the VAS daily for a 7–day baseline and for a further 21 days. Subjectively, pruritus improved in 13 of 24 on flumecinol and 10 of 26 on placebo (X2= 1.24, P= 0.2 7). Median difference in fall in VAS pruritus score between baseline week (mean score for each individual used) and the last week was 8.0 [95 % confidence interval (CI) –2.1 to 20.81 and for VAS quality of life was 5.0 (95% C1 0.4 to 13.0) both in favour of flumecinol over placebo. Later, 19 patients (all PBC) were randomised to flumecinol 300 mg or placebo daily for 3 weeks. Subjectively, pruritus improved in 7 of 10 on flumecinol and 1 of 9 on placebo (Fisher's exact test, P= 0.02). Median difference in fall in VAS pruritus score was 19.8 mm (95 % CI 3.3 to 40.7 mm) in favour of flumecinol over placebo and for quality of life was 3.5 mm (95 % C1 – 5.9 to 24.9 mm). Flumecinol did not significantly affect liver function tests, antipyrine clearance or serum total bile acids, and was not associated with any significant side‐effects.

Conclusion: Flumecinol was safe at the above doses and short term treatment with 300 mg daily, significantly ameliorated pruritus in primary biliary cirrhosis.
Short report: time course of clinical response with fluconazole for Candida oesophagitis in patients with AIDS
Authors: WILCOX C. M.
Published: July 2010

Background: Although fluconazole is increasingly utilized for the therapy of Candida oesophagitis in patients with AIDS, the time course of response has not been adequately defined.

Methods: Over a 48‐month period, all HIV‐infected patients undergoing upper endoscopy at a large city‐county hospital were identified prospectively. Symptomatic patients with endoscopic and histopathologically confirmed Candida oesophagitis in whom oral antifungal therapy had not been received within the past three months were treated in an open‐label fashion with fluconazole 200 mg on the first day followed by 100 mg daily for two weeks. All patients were followed clinically to determine the rapidity of response.

Results: Eighteen patients were identified; all but two were male. Candida oesophagitis was graded as severe in 13 patients (72 %). A complete symptomatic response was seen by five days in seven patients (39 %) and by seven days in nine additional patients (cumulative response, 89 %). The two other patients had improved by at least 50% at one week, with a complete symptomatic response seen at two weeks.

Conclusions: Our study confirms anecdotal experience suggesting that fluconazole results in a rapid clinical response for Candida oesophagitis in patients with AIDS. Given this rapidity, a one‐week course of empiric treatment with fluconazole for HIV‐infected patients with newly developed esophageal symptoms could be used as an appropriate time period to assess a response prior to further diagnostic evaluation with endoscopy.
Review article: Helicobacter pylori eradication–understandable caution but no excuse for inertia
Authors: PENSTON J. G.
Published: July 2010

The long‐term management of patients with peptic ulcer disease is unsatisfactory, as judged by the persistently high levels of haemorrhage, perforation and death from this condition in Western countries. Although ulcer recurrence and complications can be prevented, many patients with peptic ulcer disease fail to receive the benefits of modern therapeutic regimens.

In recent years, eradication of Helicobactor pylori has been promoted as a‘cure’for peptic ulcer disease and, while such claims are premature, there can be little doubt that this treatment–when successful– dramatically improves the medium‐term prognosis of ulcer patients. However, in general, clinicians have given this promising therapeutic advance a lukewarm welcome. The aim of this detailed review of the literature is to remove the uncertainty and confusion surrounding many aspects of eradication therapy.

Estimates are provided of the eradication rates after either triple therapy or the combination of omeprazole plus amoxycillin, and the sources of variation in published studies are discussed. Problems associated with eradication therapy, including side effects, compliance and re‐infection, are addressed in order to ascertain the extent and clinical significance of each factor. In addition, studies reporting the outcome of patients with peptic ulcer disease after eradication are assessed with reference to both ulcer recurrence and complications. The result of the review is to dissipate much of the scepticism concerning eradication therapy. However, whilst acknowledging the efficacy of eradication therapy, its limitations have also to be recognized. By itself, it does not provide the complete answer to peptic ulcer disease. For some ulcer patients, eradication therapy is the preferred option; for others, prophylactic therapy with H2‐receptor antagonists is more suitable. Guidelines are proposed for the selection of patients for each alternative therapy. The crucial point is that patients with peptic ulcer–excluding the small proportion with a mild form of the disease—require positive, long‐term management consisting of either continuous prophylaxis with H2‐receptor antagonists or the eradication of Helicobacter pylori.
Antidepressant therapy in 138 patients with irritable bowel syndrome: a five‐year clinical experience
Authors: CLOUSE R. E. , LUSTMAN P. J. , GEISMAN R. A. , ALPERS D. H.
Published: July 2010

Background: Antidepressant agents may have a therapeutic role in functional gastroenterologic disorders, but controlled investigations in irritable bowel syndrome (IBS) have not provided satisfactory practice recommendations. To help with future study design, we reviewed a five‐year clinical experience with antidepressant agents in out‐patients with IBS. Methods: Presenting features, treatment course, and clinical outcome were determined from a chart review of 138 patients attending a university‐based gastroenterology practice.

Results: Patients were treated with up to five antidepressants in separate, consecutive trials if a satisfactory end‐point had not been reached. Tricyclic antidepressants were utilized 130 times, newer antidepressants 39 times, and anxiolytic‐antidepressants 47 times. Improvement and complete remission in bowel symptoms occurred in 89% and 61% of patients, respectively, during antidepressant therapy. Median dosages being prescribed when remission occurred were less than those conventionally used in clinical psychiatry (50 mg/day for several tricyclic antidepressants). Age, gender, symptom duration, and presence of psychological symptoms did not discriminate those who remitted from those who did not, whereas a pain predominant symptom pattern was more commonly associated with symptom remission (P < 0.05 comparing symptom patterns). Symptom remission was more likely during the first antidepressant treatment than with subsequent trials in the group with continued symptoms (P = 0.01), but nearly half of the patients with side effects or no benefit from the first agent who went on to subsequent trials remitted during treatment with an alternative antidepressant.

Conclusions: The design of this retrospective review is not capable of determining the efficacy of antidepressants for IBS. Our observations in conjunction with other available data suggest that future trials should employ low daily dosages, carefully assess pain response, include patients with and without active psychiatric symptoms, and utilize a second agent for subjects intolerant or unresponsive to the first.
The effect of tripotassium dicitrato bismuthate on the rat stomach
Authors: WALDUM H. L. , QVIGSTAD G. , MÅVIK R. , BRENNA E. , SYVERSEN U. , SANDVIK A. K.
Published: July 2010

Background: Bismuth has been used as symptomatic treatment of dyspepsia for many years. It promotes healing of peptic ulcers and reduces their recurrence. The beneficial effect of bismuth on duodenal ulcer disease is thought to be due to an effect on Helicobacter pylori, although it has a rather weak bactericidal effect on H. pylori in vitro. Eradication of H. pylori in duodenal ulcer patients by a combination of bismuth, tetracycline and metronidazole has been reported to increase the density of somatostatin‐producing D cells in the antrum. A reduced D cell density in the antral mucosa of duodenal ulcer patients could explain their exaggerated gastrin release.

Aims/methods: To test the possibility that bismuth could affect the neuroendocrine cells independently of the presence of H. pylori or not. we gave rats a diluted tripotassium dicitrato bismuthate solution by gastric gavage for 14 days.

Results: Tripotassium dicitrato bismuthate treatment did not affect maximal pentagastrin‐stimulated acid secretion or histamine release in isolated rat stomachs or the density of argyrophil cells in the oxyntic and antral mucosa. However, it significantly reduced the duodenal concentration of gastrin and calcitonin gene‐related peptide, and the density of G cells in the antrum and duodenum.

Conclusion: The effect of tripotassium dicitrato bismuthate on the G cell may be of significance for its beneficial effect on duodenal ulcer disease.
Topical anticolitic efficacy and selectivity of the glucocorticoid budesonide in a new model of acetic acid‐induced acute colitis in the rat
Authors: FABIA R. , ArRAJAB A. , WILLÉN R. , BRATTSAND R. , ERLANSSON M. , SVENSJÖ E.
Published: July 2010

Aims: To study the effect of local or parenteral administration of the glucocorticoid budesonide in the acetic acid‐induced colitis model in the rat.

Methods: Colitis was induced in an exteriorized colonic segment by administration of 4% acetic acid for 15 s. Four days later, this colonic segment with colitis was examined using a morphological scoring system, and measurements of myeloperoxidase activity and of plasma exudation into the colonic segment. The experimental colitis showed morphological similarities to human ulcerative colitis, with 3‐fold increase in myeloperoxidase activity and 6‐fold increase in the plasma exudation. Budesonide in different doses administered for 3 days, starting one day after acetic acid instillation, prevented the development of colitis in a dose‐dependent manner. The best effect of budesonide on the morphological score was achieved after local treatment at a dose of 10″5 M twice daily (76% reduction compared with a control colitis group) and parenteral treatment with 0.75 mg/kg (80% reduction). These doses also normalized myeloperoxidase activity and significantly reduced the plasma exudation. The systemic effects of the drug were most pronounced in the group treated with parenteral budesonide. This group showed the greatest reduction in body weight and a significant reduction of the weight of adrenal glands and spleen (as compared to controls). Thymus weight in animals treated systemically was significantly lower than in locally treated animals. In the group treated with local budesonide the weight of adrenals was reduced. However, the weights of spleen and thymus were not reduced and the reduction of the body weight was even less than in the control group.

Conclusion: Local treatment with budesonide at a dose of 10−5 M (0.17 mg/kg if completely absorbed, but only 0.03 mg/kg with 15% bioavailability on colonic application) was as effective as parenteral treatment at a dose of 0.75 mg/kg in the attenuation of acetic acid‐induced colitis in the rat, but resulted in minor systemic side‐effects.
Clarithromycin‐amoxycillin therapy for Helicobacter pylori infection
Authors: AL‐ASSI M. T. , GENTA R. M. , KARTTUNEN T. J. , GRAHAM D. Y.
Published: July 2010

Background: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin‐metronidazole combination therapy led us to evaluate clarithromycin‐amoxycillin dual therapy for H. pylori infection.

Methods: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology.

Results: H. pylori infection was cured in 86% (95% CI = 78–99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects.

Conclusion: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.
The outcome of peptic ulcer haemorrhage in relation to consumption of nonsteroidal anti‐inflammatory drugs or aspirin
Authors: CHOUDARI C. P. , ELTON R. A. , PALMER K. R.
Published: July 2010

Aim: To compare the outcome of 76 patients who presented with severe peptic ulcer haemorrhage whilst taking nonsteroidal anti‐inflammatory drugs (NSAIDs) or aspirin with that of 112 patients who were not taking these drugs and who developed peptic ulcer haemorrhage over the same time period.

Methods: The two groups of patients were managed identically and endoscopic therapy was attempted in all cases.

Results: The group taking NSAIDs or aspirin tended to be older and had a higher prevalence of cardio‐respiratory disease. The severity of bleeding (as assessed by the presence of shock, anaemia and endoscopic stigmata) was similar in the two groups. Outcome in terms of uncontrolled haemorrhage, rebleeding and blood transfusion requirements did not differ significantly in the two groups. The NSAID group had a significantly longer duration of admission, almost certainly attributable to a higher prevalence of co‐morbid diseases.

Conclusions: Despite the deleterious effects of NSAIDs and aspirin upon renal and platelet function, the prognosis of peptic ulcer bleeding is not adversely affected by NSAID or aspirin therapy.
Inhibition of 5‐hydroxytryptamine re‐uptake impairs human gall‐bladder emptying
Authors: GORARD D. A. , HEALY J. C. , O'DONNELL L. J. D. , FARTHING M. J. G.
Published: July 2010

Background: 5‐Hydroxytryptamine (5‐HT) is an important neurotransmitter in the enteric nervous system. The intrinsic neural plexus of the gall‐bladder resembles the enteric nervous system and similarly contains 5‐HT neurones. The action of 5‐HT on gallbladder motility has been investigated in animals but its effect on the human gall‐bladder in vivo is unknown.

Methods: The effect of indirect 5‐HT agonism using paroxetine, a specific inhibitor of neuronal 5‐HT reuptake, on gall‐bladder motility was investigated in 12 healthy volunteers. In a randomized double‐blind crossover design, gall‐bladder motility was assessed after administration of 30 mg paroxetine daily for two days and after placebo. Ultrasonography was used to determine gall‐bladder volumes while fasting and at 5 min intervals following a 250 kcal mixed liquid meal.

Results: Fasting gall‐bladder volumes of 21.8 ± 3.2 ml on placebo and 28.0± 3.5 ml on paroxetine were similar. Paroxetine impaired postprandial gall‐bladder emptying. Residual gall‐bladder volume was 10.2 ±2.7 ml with placebo and 17.1±2.7 ml with paroxetine (P < 0.05). Ejection fraction was 57.3 ±7.7% on placebo and 40.9 ± 4.7% on paroxetine (P < 0.05).

Conclusion: 5‐HT pathways may participate in the regulation of biliary motility, and this study demonstrates an inhibitory role of 5‐HT in the control of human gall‐bladder emptying.
Meta‐analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome
Authors: POYNARD T. , NAVEAU S. , MORY B. , CHAPUT J. C.
Published: July 2010

Aim: To assess the efficacy of smooth muscle relaxants in the treatment of patients with irritable bowel syndrome, a meta‐analysis of 26 selected double‐blind randomized trials vs. placebo was performed.

Methods: Five end‐points were assessed: global assessment, abdominal pain, constipation, abdominal distension and the absence of adverse reactions. Analyses were performed according to the intention‐to‐treat method. For each end‐point, the drug efficacy was assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to the type of drug, the treatment duration, the prevalence of constipated patients, the trial design and the methodological quality.

Results: All myorelaxants analysed were significantly better than placebo for the improvement of global assessment (62% improvement rate vs. 35% on placebo, that is 27% improvement rate, P < 0.01) and for pain improvement (64% improvement rate vs. 45% on placebo, that is 19% improvement rate, P < 0.01). No significant differences were observed for constipation and abdominal distension. The percentage of patients with adverse reactions was significantly higher in patients receiving myorelaxants than placebo (6% mean difference, P < 0.01).

Conclusion: According to this overview five drugs have proved their clinical efficacy in patients with irritable bowel syndrome, without significant adverse reactions: cimetropium bromide, pinaverium bromide, trimebutine. octilium bromide and mebeverine.
Basal serum gastrin concentrations before and after eradication elicobacter pylori infection measured by sequence specific radioimmunoassays
Authors: WITTEMAN E. M. , VERHULST M. L. , KONING R. W. de , HOPMAN W. P. M. , JANSEN J. B. M. J.
Published: July 2010

Background: Helicobacter pylori infection of the antral mucosa is responsible for an increase in basal and stimulated serum gastrin. In the present study we have investigated whether gastritis induced by H. pylori is responsible for abnormalities in the processing of gastrin in dyspeptic patients.

Methods: Basal serum gastrin was measured by radioimmunoassay before, 5 weeks, and 1 year after anti‐H. pylori therapy in 73 H. pylori positive functional dyspeptic patients. Three region‐specific antisera were used, specific for the biologically active carboxy‐terminal part, the biologically inactive aminoterminal part of gastrin 1–17, and for the nonsulphated tyrosyl residue in gastrin 1–17.

Results: Basal serum gastrin levels were markedly (P < 0.01) decreased 5 weeks and 1 year after successful eradication of H. pylori (n= 39) but not in the patients in whom treatment failed (n= 34). A decline of gastrin was observed for each of the three radioimmunoassays. Conclusion: The decrease of serum gastrin levels in all three radioimmunoassays after a successful eradication of H. pylori does not point to major changes in the processing of gastrin. These results suggest that G‐cells in the antral mucosa are not functionally affected by the inflammation.
A selective NK‐2 antagonist blocks the increase of canine colonic tone and ileal contractions induced by the NK‐2 selective receptor agonist, [βAla8] neurokinin A‐(4–10)
Authors: BASILISCO G. , PHILLIPS S. F.
Published: July 2010

Background: The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non‐peptide NK‐2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK‐2 receptor agonist [βAla8] neurokinin A‐(4–10)

Methods: Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum, 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK‐2 antagonist SR48968, 10, 100, 1000 μg/kg, followed after 30 min by 2 μg/kg of the agonist [βAla8] neurokinin A‐(4–10). Experiments were replicated twice in each dog.

Results: The NK‐2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose‐dependent fashion (Spearman's rank, r= 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [βAla8] neurokinin A‐(4–10) increased ileal contractions: pre‐treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [βAla8] neurokinin A‐(4–10) interrupted the motility front; this effect was not antagonized by SR48968.

Conclusions: SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK‐2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract.
Bioavailability of single and multiple doses of a new oral formulation of 5‐ASA in patients with inflammatory bowel disease and healthy volunteers
Authors: GIONCHETTI P. , CAMPIERI M. , BELLUZZI A. , BOSCHI S. , BRIGNOLA C. , MIGLIOLI M. , BARBARA L.
Published: July 2010

Aims: An oral multiparticulate coated formulation of 5‐aminosalicylic acid (5‐ASA; mesalazine) has been developed to provide a controlled release of the drug, in a pH‐dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl‐5‐ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration.

Methods: Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5‐ASA and Ac‐5‐ASA were measured for 48 h.

Results: In the single oral dose regimen, systemic absorption of 5‐ASA and Ac‐5‐ASA were low and did not differ between the three groups. Only about 20% of the 5‐ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5‐ASA and Ac‐5‐ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5‐ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges.

Conclusions: The new oral 5‐ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum‐colon therapeutic activity.
Budesonide versus prednisolone retention enemas in active distal ulcerative colitis
Authors: LÖFBERG R. , THOMSEN O. ØSTERGAARD , LANGHOLZ E. , SCHIÖLER R. , DANIELSSON Å. , SUHR O. , GRAFFNER H. , PÅHLMAN L. , MATZEN P. , MØLLER‐PETERSEN J. F. , HALVORSEN L. , HOVDENAK N. , WILLEN R. , PERSSON T. , SEIDEGÅRD C.
Published: July 2010

Methods: Efficacy and safety of the topically acting glucocorticosteroid budesonide retention enema (2.3 mg/ 11 5 mL) were compared with prednisolone disodium phosphate enema (31.25 mg/125 mL) in patients with active distal ulcerative colitis. The study was a randomized, multicentre trial, with two parallel groups and single‐blind to the investigator. One hundred patients with active ulcerative colitis, not reaching beyond the splenic flexure as determined by endoscopy, were treated for up to 8 weeks. Results: Forty‐five patients were randomized to receive budesonide and 5 5 to prednisolone. Both treatment groups improved significantly in terms of endoscopic and histological scoring during the study, but there were no statistically significant differences between the two groups. Clinical remission, defined as no more than three daily bowel movements without blood and endoscopically non‐inflamed mucosa, was achieved in 16% of the patients in the budesonide group after four weeks and in 24% in the prednisolone group (N.S.).

After 8 weeks treatment the clinical remission rate in the groups had increased to 36 % for budesonide and 47% for prednisolone (N.S.).

Mean morning plasma cortisol levels were unchanged in the budesonide group, whereas they were significantly suppressed in the prednisolone group after 2, 4 and 8 weeks (P < 0.0001). Side effects were mild and rare in both groups.

Conclusions: Treatment with budesonide enema in active distal ulcerative colitis was comparable, regarding efficacy, to treatment with conventional prednisolone enema. A prolongation of the treatment time from 4 to 8 weeks doubled the clinical remission rate in both groups. However, budesonide may be preferable to prednisolone since it causes less systemic effects as reflected by a lack of plasma cortisol suppression.
Efficacy of rifaximin in the treatment of symptomatic diverticular disease of the colon. A multicentre double‐blind placebo‐controlled trial
Authors: PAPI C. , CIACO A. , KOCH M. , CAPURSO L.
Published: July 2010

Background and aims: In a recent open trial we have shown the efficacy of long term intermittent administration of a poorly absorbable antibiotic (rifaximin) in obtaining symptomatic relief in uncomplicated diverticular disease of the colon. The aim of this double‐blind placebo‐controlled trial was to test our previous observations.

Methods: One hundred and sixty‐eight outpatients with symptomatic uncomplicated diverticular disease were treated with fibre supplementation (glucomannan 2 g/day) plus rifaximin 400 mg b.d. for 7 days every month (84 patients), or with glucomannan 2 g/day plus placebo two tablets b.d. for 7 days every month (84 patients). Clinical evaluation was performed at admission and at three‐month intervals for 12 months.

Results: After 12 months, 68.9 % of the patients treated with rifaximin were symptom‐free or mildly symptomatic, compared to 39.5% in the placebo group (P= 0.001). Symptoms such as bloating and abdominal pain or discomfort were primarily affected by antibiotic treatment when compared with placebo (P < 0.001).

Conclusion: Rifaximin appears to be of some advantage in obtaining symptomatic relief in diverticular disease of the colon when compared with fibre supplementation alone.
The effect of oral vancomycin on chronic idiopathic constipation
Authors: CELIK A. F. , TOMLIN J. , READ N. W.
Published: July 2010

Background: A case study reporting the efficacy of oral vancomycin in a patient with chronic idiopathic constipation prompted this prospective trial of oral vancomycin in eight female patients (aged 21–61 years) with severe constipation resistant to the action of dietary fibre.

Methods: The trial was divided into two consecutive 14‐day periods. During the first period, each patient was given ispaghula, 3.5 g twice a day, and during the subsequent period they took 250 mg vancomycin t.d.s. per os, as well as the fibre supplement. During both periods they collected stools and recorded daily bowel symptoms (stool frequency, straining, stool consistency, subjective stool volume) in a diary. At the end of each period whole gut transit time and the breath hydrogen response to a standard meal, giving oro‐caecal transit time, were measured along with gastrointestinal symptoms which were assessed on visual analogue scales.

Results: Vancomycin caused a significant improvement in stool frequency, consistency, ease of defecation and the amount of stool patients felt they produced (all P < 0.05), but objective measures of daily stool weight and whole gut or oro‐caecal transit time were not significantly different. Basal breath hydrogen levels were higher after vancomycin treatment in seven out of eight patients. One patient experienced a complete remission of symptoms when she took vancomycin and remains in remission after 14 months. This patient showed no elevation in basal breath hydrogen level.

Conclusion: Although this study does not support the use of vancomycin for most patients with constipation, the results suggest that modification of the intraluminal flora may be of value in the treatment of the occasional case of idiopathic constipation.
Prescribing of antacids and ulcer‐healing drugs in primary care in the north of England
Authors: ROBERTS S. J. , BATEMAN D. N.
Published: July 2010

Background: This study describes the pharmaco‐epidemiology of ulcer‐healing therapies in primary care in the north of England.

Methods: Anonymous patient‐specific prescribing data were extracted from computerized general practice records for 41 practices. Prescribing prevalences were determined according to patient age, gender and recorded prescription indication, for both antacids and H2‐receptor antagonists or omeprazole.

Results: During the year of the study, antacids were prescribed for 3.9% of the study population, and H2‐receptor antagonists or omeprazole for 3.7%. Rates increased with age, peaking at 99 (antacids) and 87 (H2‐receptor antagonists) per 1000 population aged 65–84 years. Antacid prescribing rates for women were over twice those for men amongst those aged 15–34 years. For H2‐receptor antagonists, rates were higher in men than women, with the excess attributable to prescribing for ulcer indications, although at all ages prescribing for oesophagitis was more prevalent among women. Of the patients prescribed H2‐receptor antagonists or omeprazole, 45 % (accounting for 51% of prescription items) had indications which included peptic ulcer or oesophagitis, 42 % had gastritis or dyspepsia only (35% items), and in 13 % no peptic indication was recorded. For each of antacids and H2‐receptor antagonists, the practices had similar prescribing profiles according to patient age and gender, but their absolute levels differed up to two‐fold.

Conclusions: Prescribing of antacids and ulcer‐healing drugs varies systematically with patient age and gender. Consequently, evaluation of crude prescribing rates, without reference to patient demography, is unreliable as a guide to levels of usage. In general practice, H2‐receptor antagonists and omeprazole appear to be over‐prescribed for minor indications.
Role of pepsin in the development of indomethacin‐induced antral ulceration in the rat
Authors: GAW A. J. , WILLIAMS L. V. , SPRAGGS C. F. , JORDAN C. C.
Published: July 2010

Aims: To examine the effects of a pepsin inhibitor, pepstatin‐A, a long acting H2‐receptor blocker, loxtidine, exogenous pepsin and exogenous acid against indomethacin‐induced antral ulceration in the rat.

Results: Indomethacin (60 mg/kg s.c.) caused antral ulceration in fasted/re‐fed rats over a period of 4 h. Ulceration was prevented in a dose‐dependent manner by treatment with pepstatin‐A (0.1–1 mg.kg hourly) or loxtidine (3 mg/kg) given orally. Acidified methylcellulose (1 mL hourly per os) enhanced damage and also prevented protection by loxtidine (3 mg/kg per os). The protection by pepstatin‐A was not altered by treatment with acidified methylcellulose but was reversed by treatment with a 10‐fold excess of pepsin.

Conclusion: These studies suggest that mucosal degradation by pepsin, rather than direct damage by luminal acid, was the major factor in the development of indomethacin‐induced antral ulceration in the rat.
Maintenance of gastric pH above 6 with intravenous famotidine in patients with a bleeding duodenal ulcer
Authors: DELCHIER J.‐C. , AMINE I. EL , ROUDOT‐THORAVAL F. , ELOUAER‐BLANC L. , LAMARQUE D. , STANESCU L.
Published: July 2010

Background: The secondary prevention of bleeding from ulcers may be improved if antisecretory drugs are able to maintain a 24‐h gastric pH close to neutral.

Aim: To evaluate the effect of intravenous famotidine at a conventional dose of 40 mg/day on 24‐h intragastric pH in patients with a bleeding duodenal ulcer, and to determine the dose required to maintain gastric pH > 6 by use of a Gastrojet (MIC, Switzerland) device (a pH meter‐controlled programmable pump).

Methods: Twelve patients (nine men, three women), aged 24–78 years, admitted for a bleeding duodenal ulcer, were studied after active bleeding had stopped for at least 6 h. Gastric pH was recorded for two consecutive 24‐h periods, each starting at 16.00 hours. The patients were fasted during these periods and received an infusion of 2.5 L of isotonic glucose. They were given famotidine, as a continuous i.v. infusion of 40 mg during one period, and at a rate determined by the Gastrojet during the other period (in a random sequence), with the aim of maintaining the gastric pH above 6.

Results: The 24‐h median (interquartile range) pH and the mean (± S.E.M.) percentage of the 24‐h period with a gastric pH > 6 were both significantly higher during the Gastrojet period than during the continuous infusion: 6.4 (6.3–6.5) vs. 5.7 (2.7–6.4) (P < 0.01) and 74±5% vs. 44 ± 7% (P < 0.002), respectively. The mean dose of famotidine delivered by the Gastrojet was 172 mg (range: 101–200 mg). The entire available amount of famotidine (200 mg) was delivered in four of the 12 patients. The percentage of time at pH > 6 (mean ± S.E.M.) was significantly higher at night (22.00 to 07.00 hours) than during the rest of the day (88 ± 2 vs. 70 ± 6%; P < 0.005) and the mean quantity of famotidine delivered per hour was significantly lower during the night (6.3 ± 0.8 mg/h vs. 8.4 ± 0.5 mg/h; P < 0.02).

Conclusion: We conclude that 40 mg of famotidine delivered as a continuous i.v. infusion is not sufficient to maintain gastric pH > 6 for 24 h in duodenal ulcer patients. Our study with the Gastrojet device shows that it may be possible to achieve this goal by using a much larger dose, preferably delivered during the day.
Eradication of Helicobacter pylori with lansoprazole and clarithromycin
Authors: HARRIS A. W. , GUMMETT P. A. , LOGAN R. P. H. , ASHWORTH H. M. , BARON J. H. , MISIEWICZ J. J.
Published: July 2010

Background: Helicobacter pylori eradication with omeprazole and clarithromycin varies between 40 and 80%. The dose, frequency and duration of treatment may account for these differences. Lansoprazole, a recently introduced proton pump inhibitor, is a more potent H. pylori bacteriostat in vitro than omeprazole. The aim of this open, comparative, randomized study was to investigate the efficacy and safety of lansoprazole 30 mg once or twice a day (and for 2 vs. 4 weeks) plus clarithromycin 500 mg t.d.s. for 2 weeks, in the eradication of H. pylori.

Methods: Sixty‐six patients with H. pylori infection received clarithromycin 500 mg t.d.s. for 2 weeks and one of four lansoprazole regimens: 30 mg once a day for 2 (Group 1, n= 16) or 4 (Group 2, n= 16) weeks, or 30 mg b.d. for 2 (Group 3, n= 18) or 4 (Group 4, n= 16) weeks. H. pylori eradication was determined by the 13C‐urea breath test 4 weeks after finishing treatment.

Results: Per protocol analysis (53 patients) shows that H. pylori was eradicated in 6/13 (46%) in Group 1, 7/13 (54%) in Group 2, 9/14 (64%) in Group 3 and 9/13 (69%) in Group 4. Thirty‐one of 68 patients experienced side effects. Analysis on an intention‐totreat basis gave similar results.

Conclusion: The dose of lansoprazole appears to be more important than the duration of therapy. Dual therapy with lansoprazole and clarithromycin should be investigated further as a possible treatment regimen for H. pylori infection.
Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection
Authors: YOUSFI M. M. , EL‐ZIMAITY H. M. T. , AL‐ASSI M. T. , COLE R. A. , GENTA R. M. , GRAHAM D. Y.
Published: July 2010

Background: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multidrug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole.

Methods: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks.

Results: Thirty‐three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole‐based triple therapy and eight with macrolide‐based therapy (five with clarithromycinbased therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%–96%) including 90% of those who had failed previous anti‐H. pylori therapies. Mild side effects were reported by 18%. Conclusion: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.
Treatment and prevention of relapse of mild oesophagitis with omeprazole and cisapride: comparison of two strategies
Authors: KIMMIG J. M.
Published: July 2010

Background: Oesophagitis is usually a chronic condition. Healing with omeprazole is often followed by early relapse. Combination treatment and subsequent maintenance treatment with the prokinetic cisapride may be of benefit in relapse prevention.

Methods: Patients with endoscopically proven oesophagitis, grade I (n= 120) or grade II (n= 105), were randomized in an open fashion to receive 8 weeks of healing treatment with omeprazole 20 mg daily (OM) followed by 12 months of follow‐up without maintenance treatment, or 8 weeks of combined treatment of omeprazole 20 mg daily plus cisapride 5 mg t.d.s. (OMCIS) followed by 12 months of maintenance treatment with cisapride 5 mg t.d.s. (CIS). Only the patients healed after acute treatment were included in the 12‐month follow‐up study for evaluation of endoscopic relapse.

Results: In the group of patients with oesophagitis grade I (n= 58 receiving OM, n= 62 receiving OMCIS), healing rates were comparable for both acute treatment regimens. In the group of patients with grade II (n= 54 receiving OM, n= 51 receiving OMCIS), the healing rates were slightly but not significantly in favour of OMCIS after 4 and 8 weeks of treatment. During the 12 months of follow‐up, CIS maintenance treatment was associated with a significant reduction of relapse. In the group of patients with initial grade I oesophagitis, the relapse rates after 3 months were 20% in the OMCIS group receiving CIS maintenance treatment, compared to 48 % in the group healed on OM without further maintenance treatment (P= 0.04). After 6 months, these relapse rates were 31% and 85% respectively (P < 0.001), and after 12 months 40% and 96% (P < 0.001). In the group of patients with initial grade II oesophagitis, they were, respectively, 20% vs. 39% after 3 months (P= 0.056), 41% vs. 78% after 6 months (P < 0.001) and 52% vs. 95 % after 12 months (P < 0.001).

Conclusions: The results of this open study indicate that continued treatment with cisapride 5 mg t.d.s. (after initial healing with omeprazole 20 mg daily plus cisapride 5 mg t.d.s.) is beneficial in the long‐term management of grade I and II oesophagitis : this treatment approach significantly reduces the high relapse rate observed after stopping healing treatment with omeprazole.
Treatment of Helicobacter pylori infection with a combination of itraconazole and omeprazole
Authors: KELLER J. J. , van der HULST R. W. M. , TYTGAT G. N. J.
Published: July 2010

Aim : To determine the in vivo anti‐microbial activity of a high‐dose itraconazole and omeprazole regimen against Helicobacter pylori.

Methods: In an open pilot study, 10 H. pylori positive dyspeptic patients were treated with itraconazole 200 mg b.d. and omeprazole 200 mg b.d. for 7 days. Follow‐up upper gastrointestinal endoscopy was performed 4–5 weeks after completion of therapy. Eradication of H. pylori infection was determined by histopathological examination and culture of biopsies from the antrum and corpus.

Results: Eradication was not observed in any patient.

Conclusion: This combination of itraconazole with omeprazole does not eradicate H. pylori infection.
The development of atrophic gastritis—Helicobacter pylori and the effects of acid suppressive therapy
Authors: KUIPERS E. J. , LEE A. , KLINKENBERG‐KNOL E. C. , MEUWISSEN S. G. M.
Published: July 2010

Helicobacter pylori is uniquely adapted to survival in the strongly acidic gastric lumen. In vitro, both acid and certain acid suppressors affect bacterial growth. In vivo, there is little evidence that acid suppressors have any effect on bacterial survival. In contrast, decrease of acid secretion quickly leads to a spreading of the bacterial infection throughout the body and fundus of the stomach, which is accompanied by an increase of the associated gastritis.

Helicobacter pylori gastritis may, in a substantial number of infected subjects, ultimately lead to atrophy and intestinal metaplasia, conditions with an increased risk for gastric cancer. This review summarizes the data on the interrelation between Helicobacter pylori, gastric acid secretion and development of atrophic gastritis.