bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SUMMARYBackground: 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

SUMMARYAims: 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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.