bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized controlled trial of omeprazole or endoscopy in patients with persistent dyspepsia: a cost‐effectiveness analysis
Authors: Laheij  , Severens  , Lisdonk  , Verbeek  , Jansen  
Published: March 2003

BackgroundCost‐effectiveness analysis, Helicobacter pylori research and the development of proton pump inhibitors are having an increasing impact on the management of dyspepsia. However, clinical trials have not always included both H. pylori diagnosis and proton pump inhibitors in their protocols.MethodsPatients who were referred for upper gastrointestinal endoscopy by their general practitioner were randomized to either prompt endoscopy followed by directed medical treatment (conventional group, n = 38), or to empirical treatment with omeprazole and, in the case of symptom relapse, serological screening for H. pylori infection followed by eradication therapy in seropositive patients (empirical group, n = 42). The study lasted for up to 1 year.ResultsIn the empirical group, only 13 patients (31%) underwent endoscopy. The average number of days for which the patients kept records of their dyspeptic symptoms was 266 (95% CI: 226–307) in the empirical group, of which 166 (95% CI: 128–204) were symptom‐free. In the conventional group, 159 (95% CI: 119–198) out of 255 days (95% CI: 209–302) were recorded as symptom‐free. The average medical cost in the empirical group was 284 (95% CI: 218–350) and in the conventional group 491 (95% CI: 383–600). In the empirical group, two malignancies were found, whereas in the conventional group one malignancy was found.ConclusionsThe empirical drug treatment strategy in patients with persistent dyspeptic symptoms resulted in 69% fewer diagnostic endoscopies with lower medical costs and equal effectiveness in the first year, compared to prompt endoscopy followed by directed medical treatment.
Does eradication of Helicobacter pylori impair healing of nonsteroidal anti‐inflammatory drug associated bleeding peptic ulcers? A prospective randomized study
Authors: Chan  , Sung  , Suen  , Lee  , Wu  , Leung  , Chan  , Lai  , Lau  , Ng  , Chung  
Published: March 2003

Background:Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti‐inflammatory drug (NSAID)‐associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID‐associated bleeding peptic ulcers.Methods:Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1‐week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a 13C‐urea breath test that was performed at least 4 weeks after discontinuation of omeprazole.Results:195 H. pylori‐infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P = 0.31). On intention‐to‐treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P = 0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups.Conclusion:Eradication of H. pylori did not impair the healing of NSAID‐associated bleeding peptic ulcers.
Review article: efficacy of infliximab in Crohn’s disease — induction and maintenance of remission
Authors: Rutgeerts P.J. 
Published: March 2003

The primary goals of treating patients with Crohn’s disease are to induce a clinical remission, maintain the remission, and prevent associated complications. Various treatment regimens for patients with Crohn’s disease induce a response and remission; however, most prove ineffective for maintenance of the clinical effect. A therapeutic agent that can induce and maintain remission, while promoting the restoration of intestinal mucosa, would prove to be most beneficial in such a patient population.Several studies with infliximab have clinically demonstrated that the antitumour necrosis factor‐alpha therapy rapidly reduced the signs and symptoms in patients with moderate‐to‐severe Crohn’s disease. In acute studies with the chimeric monoclonal antibody, clinical benefit was associated with healing and reduction of inflammation in the bowel mucosal tissue. In a maintenance study, retreatment with infliximab maintained remission of the active disease. Additionally, treatment with the lowest infusion dose of infliximab (5 mg/kg) provided a high degree of clinical benefit with a long‐term outcome.
Novel therapies for Helicobacter pylori infection
Authors: OPEKUN  , EL‐ZAIMAITY  , OSATO  , GILGER  , MALATY  , TERRY  , HEADON  , GRAHAM  
Published: March 2003

Background:Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection.Aim:To evaluate orally administered novel therapies for the treatment of H. pylori infection.Methods:Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2‐3Galb1–4Glc‐(3′‐sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present.Results:None of the novel therapies appeared effective and no adverse events occurred.Conclusion:Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.
Effect of vitamin E in gastric mucosal injury induced by ischaemia‐reperfusion in nitric oxide‐depleted rats
Authors: NAITO  , YOSHIKAWA  , MATSUYAMA  , YAGI  , KASAI  , SUGIMOTO  , MASUI  , YOSHIDA  , KONDO  
Published: March 2003

Background: Neutrophil infiltration and lipid peroxide accumulation are involved in reperfusion‐induced gastric mucosal injury in nitric oxide‐depleted rats.Aim: To assess the effect of vitamin E on this injury.Methods: After ischaemia‐reperfusion, the total area of erosions, lipid peroxide contents in gastric mucosa, and gastric neutrophil accumulation were compared between nitric oxide‐depleted rats with deficient, normal, and increased vitamin E intake over 8 weeks. Thiobarbituric acid‐reactive substances and tissue‐associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration.Results: The total area of erosions was significantly increased in the vitamin E‐deficient group compared with the sufficient‐intake and vitamin‐supplemented groups. Both thiobarbituric acid‐reactive substances and myeloperoxidase activity also were significantly increased in the vitamin E‐deficient group compared with others. The total area of erosions closely paralleled the increases in both thiobarbituric acid‐reactive substances and myeloperoxidase activity.Conclusion: These results indicate that the inhibition of lipid peroxidation and interference with neutrophil infiltration by vitamin E may be responsible for its cytoprotective effect in ischaemia‐reperfusion.
A double‐blind, placebo‐controlled study of the efficacy and safety of non‐prescription ranitidine 75 mg in the prevention of meal‐induced heartburn
Authors: PAPPA  , WILLIAMS  , PAYNE  , BUARON  , MUSSARI  , CIOCIOLA  
Published: March 2003

Background: Ranitidine 75 mg (Zantac 75) has been shown to be effective for the treatment of pre‐existing heartburn symptoms.Aim: To compare the efficacy of dosing ranitidine 75 mg or placebo 30 min prior to a proven heartburn‐provoking meal in completely preventing or reducing subsequent heartburn symptoms.Methods: A randomized, double‐blind, parallel methodology was used at nine investigative centres. Following a screening visit, patients ate a standard test meal consisting of chilli, chips and a soft drink on two occasions. On the first occasion, patients received single‐blind placebo 30 min before the meal. This meal was used to qualify patients and to ensure the onset of a minimum level of heartburn. Patients who qualified were randomized (n = 284) to receive double‐blind ranitidine 75 mg or placebo 30 min before a second test meal administered 4–14 days later at the treatment visit. Patients recorded whether heartburn was present and rated heartburn severity by completing visual analogue scales at 15‐min intervals over the 4.5 h meal evaluation periods.Results: Statistically significant differences favouring ranitidine 75 mg were determined for complete prevention of heartburn (P < 0.006), heartburn severity area under the curve (P < 0.001), a clinical success end‐point (P < 0.001), and all other end‐points (P < 0.001).Conclusions: These data clearly demonstrate that ranitidine 75 mg is effective in completely preventing or decreasing heartburn when administered 30 min prior to a provocative meal.
Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans
Authors: HOND E. DEN , PEETERS  , HIELE  , BULTEEL  , GHOOS  , RUTGEERTS  
Published: March 2003

Background: Long‐term non‐steroidal anti‐inflammatory drug (NSAID) intake may induce increased intestinal permeability, eventually resulting in enteropathy. Because increased permeability might be related to cell damage resulting from energy depletion, it was hypothesized that glutamine—the major energy source of the intestinal mucosal cell—might prevent permeability changes.Methods: The 6‐h urinary excretion of 51Cr‐EDTA after an oral load of 51Cr‐EDTA was used in this study as a measure for intestinal permeability. Healthy volunteers underwent a series of permeability tests: (i) basal test; (ii) test following NSAID (indomethacin); (iii) test following NSAID in combination with glutamine and/or misoprostol.Results: The NSAID induced increased permeability in all volunteers. Pre‐treatment with glutamine (3 × 7 g daily, 1 week before NSAID‐dosing) did not prevent the NSAID‐induced increase in permeability. Multiple doses of glutamine close in time to NSAID‐dosing resulted in significantly lower permeability compared to the NSAID without glutamine. Co‐administration of misoprostol with the multiple‐dose scheme of glutamine resulted in a further reduction in the NSAID‐induced increase in permeability.Conclusions: Glutamine decreases the permeability changes caused by NSAID‐dosing when it is administered close in time, and misoprostol has a synergistic effect.
Changes in gastric mucosal ulcerogenic responses in rats with adjuvant arthritis: role of nitric oxide
Authors: Kato S. , Tanaka A. , Kunikata T. , Nishijima M. , Takeuchi K. 
Published: March 2003

Aim: To examine gastric mucosal ulcerogenic responses to indomethacin and HCl/ethanol in adjuvant arthritic (AA) rats.Methods and Results: Arthritis was induced in male Dark Agouti (DA) rats by injection of Freund's complete adjuvant (FCA) into the right hind paw. The gastric ulcerogenic response to indomethacin was markedly worsened in AA rats, depending on the degree of arthritic change. This aggravation of indomethacin‐induced gastric lesions in AA rats was significantly prevented by NG‐nitro‐L‐arginine methyl ester (L‐NAME) and amino‐guanidine as well as dexamethasone. In contrast, the mucosal ulcerogenic response to HCl/ethanol was inhibited in AA rats. The suppression of HCl/ethanol‐induced gastric lesions in AA rats was reversed almost totally by L‐NAME and aminoguanidine as well as dexamethasone and partly by indomethacin. The expression of inducible nitric oxide synthase (iNOS) mRNA was observed in the stomach of AA rats but not of normal rats. Moreover, the luminal releases of nitric oxide (NO) metabolites as well as prostaglandin (PG) E2 were significantly increased in AA rats.Conclusions: The gastric mucosal ulcerogenic responses were modified in AA rats, in different manners depending on the irritants; an increase in response to indomethacin and a decrease in response to HCl/ethanol. These changes may both be accounted for by increased production of NO by iNOS, and the latter is also partly related to increased production of PGs.
The influence of Helicobacter pylori on oesophageal acid exposure in GERD during acid suppressive therapy
Authors: Peters  , Kuipers  , Ganesh  , Sluiter  , Klinkenberg‐Knol  , Lamers  , Kleibeuker  
Published: March 2003

Background: Helicobacter pylori exaggerates the effect of acid suppressive drugs on intragastric pH. It is unknown whether this is relevant for the treatment of GERD.Aim: To compare oesophageal acid exposure and symptoms in H. pylori‐negative and H. pylori‐positive GERD patients during low and profound acid suppression.Methods: Barrett’s oesophagus patients with gastro‐ oesophageal acid reflux were studied by 24‐h oesophageal pH‐metry at baseline and during randomized treatment with omeprazole 40 mg b.d. or ranitidine 150 mg b.d. H. pylori status was determined by a serum IgG ELISA. Symptoms were scored on a four‐graded scale.Results: Of 58 patients, 26 (14 H. pylori‐negative, 12 H. pylori‐positive) were randomized to omeprazole, 32 (16 H. pylori‐negative, 16 H. pylori‐positive) to ranitidine. At baseline, oesophageal acid exposure and symptoms did not differ between H. pylori‐negative and H. pylori‐positive: mean time proportion pH < 4 per 24 h was 16.1% (95% CI 11.5–23.2) in H. pylori‐negative, and 15.8% (11.3–21.4) in H. pylori‐positive patients. Omeprazole treatment resulted in a decrease of acid reflux per 24 h from 23.4% (7.9–39.3) to 0.0% (0.0–2.9) in H. pylori‐negative, and from 17.3% (8.9–38.8) to 0.1% (0.0–1.7) in H. pylori‐positive patients; ranitidine resulted in a decrease from 14.4% (10.5–18.5) to 9.3% (5.6–12.8) in H. pylori‐negative, and from 15.1% (9.8–21.0) to 9.0% (3.1–20.1) in H. pylori‐positive patients, the difference between H. pylori‐negative and H. pylori‐positive patients being N.S. There was no significant difference between H. pylori‐negative and H. pylori‐positive patients with respect to erect and supine acid reflux, or symptom scores in both treatment groups.Conclusions: H. pylori infection does not influence oesophageal acid reflux and symptoms in patients with Barrett’s oesophagus, either at baseline or during low as well as profound acid suppressive therapy. We conclude that the dose of acid suppression does not have to be titrated upon H. pylori status in GERD.
Low‐dose intravenous azathioprine may be effective in the management of acute fulminant colitis complicating inflammatory bowel disease
Authors: Casson  , Davies  , Thomson  , Lewis  , Walker‐Smith  , Murch  
Published: March 2003

Background: The management of acute fulminant colitis unresponsive to intravenous steroids is usually surgical. However, recent evidence suggests that intravenous administration of azathioprine at very high doses may allow more rapid onset of clinical efficacy, although its use has not previously been reported in the emergency situation.Aim: To report the successful use of intravenous azathioprine in the management of acute fulminant colitis complicating both Crohn’s disease and ulcerative colitis.Method: We initially used intravenous azathioprine because of the refusal of the family of the first patient to accept surgery following failure of conventional medical management. Importantly the azathioprine was successful at the low dose of 3 mg/kg.day, equivalent to standard oral doses. Two subsequent patients demonstrated a similar resolution. All were weaned successfully to oral azathioprine and have remained in long‐term endoscopic and histological remission.Conclusion: These preliminary data suggest that low‐dose intravenous azathioprine may be helpful adjunct therapy in selected cases of severe fulminant colitis. However, the need for close monitoring and daily surgical assessment remains paramount, and a formal trial of low‐dose intravenous azathioprine is required before it may be more widely recommended.
Effect of ranitidine bismuth citrate on the phospholipase A2 activity of Naja naja venom and Helicobacter pylori: a biochemical analysis
Authors: Ottlecz  , Romero  , Lichtenberger  
Published: March 2003

Background: Helicobacter pylori has become recognized as a fundamental pathogen in the development of gastritis and peptic ulcer disease. Bismuth compounds in combination with antibiotics are widely used to treat H. pylori associated peptic ulcer disease.Methods: In this study we measured and analysed the inhibitory effect of ranitidine bismuth citrate (RBC, Pylorid, Tritec) on the activity and kinetics of phospholipase A2 (PLA2) (E.C.3.1.1.4) of commercial cobra (Naja naja) venom and H. pylori (French press lysates) using
L‐α‐dipalmitoyl‐(2[1–14C]palmitoyl)‐phosphatidylcholine as substrate.Results: Our data suggest that RBC might exert a dose‐dependent uncompetitive inhibition on PLA2 activity of both H. pylori and Naja naja venom. the inhibitory effect of RBC on the PLA2 activity cannot be abolished by the optimal concentration of calcium (10 m
M), indicating its mechanism to be unrelated to the displacement of calcium from the activation site of the enzyme.Conclusion: Our results suggest that one of the mechanisms by which bismuth compounds are therapeutically effective in the treatment of H. pylori associated gastritis is by inhibiting the activity of the degradative PLA2 enzyme secreted by H. pylori. As a consequence of the inhibitory action of RBC on PLA2 of the bacteria, the extracellular and/or intracellular phospholipid components of the gastric mucosal barrier are preserved.
Review article: liver support systems in acute hepatic failure
Authors: Rahman  , Hodgson  
Published: March 2003

The treatment of acute hepatic failure has developed rapidly over the last 40 years, reducing morbidity and mortality from this syndrome. Whilst this has been partly attributed to significant improvements in the specialist medical management of these patients, advances in surgical techniques and pharmaceutical developments have led to the establishment of successful liver transplantation programmes, which have improved mortality significantly.This review will examine the clinical impact of alternative methods that have been used to provide extra‐corporeal hepatic support. Non‐biological, bio‐ logical and hybrid hepatic extra‐corporeal support will be explored, offering a comprehensive historical overview and an appraisal of present and future advances.
Helicobacter pylori treatment instead of maintenance therapy for peptic ulcer disease: the effectiveness of case‐finding in general practice
Authors: De Wit  , Quartero A. O. Puartero , Numans  
Published: March 2003

Background: Maintenance therapy with acid‐inhibiting medication is common in general practice. Since the eradication of Helicobacter pylori has become the treatment of choice for peptic ulcer disease, H. pylori treatment could replace maintenance therapy in patients with an ulcer history.Aim: To determine the effectiveness of a full peptic ulcer disease history case‐finding strategy, together with subsequent H. pylori testing and treatment, in discontinuing maintenance therapy.Method: Patients were included from seven general practices, who had been using acid‐inhibiting medication for more than 3 months in the period May 1996–May 1997. Patients with a history of proven peptic ulcer disease were tested, and treated with proton pump inhibitor‐triple therapy if positive. Maintenance therapy was discontinued and restart within 12 months was monitored.Results: Long‐term acid suppression was used by 2.8% of the practice‐populations. A peptic ulcer disease history was found in 18% of the patients, 73% of whom were offered the ‘H. pylori test and treat’ alternative. The majority responded: 92% of the H. pylori‐infected patients were treated, 78% of whom successfully discontinued long‐term medication.Conclusion: Implementing an ‘H. pylori test and treat’ strategy enabled one‐third of the patients with a peptic ulcer disease history to stop maintenance therapy successfully. The strategy contributes to reduction of long‐term drug use, but compliance needs improvement.
Nα‐methyl histamine and histamine stimulate gastrin release from rabbit G‐cells via histamine H2‐receptors
Authors: Bliss  , Healey  , Arebi  , Calam  
Published: March 2003

Background:Gastrin release by Helicobacter pylori may be an important step in the pathway leading to duodenal ulceration. A histamine H3‐receptor agonist was found to release gastrin from antral mucosal fragments; this was interpreted as being due to suppression of somatostatin release. H. pylori is reported to produce Nα‐methyl histamine (NαMH), which is an agonist of H3 as well as other histamine receptors. H. pylori infection also recruits mast cells, which release histamine.Aim:To determine the direct effects of histamine receptor agonists on isolated gastrin cells.Methods:Rabbit G‐cells were prepared by countercurrent elutriation and cultured on 24‐well plates.Results:NαMH (10–6–10–4 M) caused a dose‐dependent increase in gastrin release from a basal level of 2.3 ± 0.2% total cell content (TCC; mean ± S.E.M.) to a maximum of 5.1 ± 0.7%, an increase of 117% (P < 0.005) above basal. This was abolished by the H2‐antagonist ranitidine (10–5 M), but not by immunoblockade with anti‐somatostatin antibody, the H1‐antagonist chlorpheniramine (10–5 M) or the H3‐antagonist thioperamide (10–4 M). The histamine H2‐receptor agonist dimaprit (10–6–10–4 M) increased gastrin release from 2.4 ± 0.2% to 3.6 ± 0.2% TCC (P < 0.001). Gastrin release was also stimulated by histamine (10–7–10–4 M) from a basal value of 3.0 ± 0.3% to 5.4 ± 0.5% TCC (P < 0.001). This also was inhibited by ranitidine (10–5 M) (P < 0.01).Conclusion:NαMH and histamine release gastrin from G‐cells via H2‐receptors; this might contribute to H. pylori‐associated hypergastrinaemia.
N‐bisphosphonates cause gastric epithelial injury independent of effects on the microcirculation
Authors: Wallace  , Dicay  , Mcknight  , Bastaki  , Blank  
Published: March 2003

Background:Nitrogen‐containing bisphosphonates have been shown to be effective for the treatment of osteoporosis and Paget’s disease of bone. Unfortunately, these drugs also have the capacity to irritate the upper gastrointestinal mucosa. In this study we investigated the ability of alendronate and pamidronate to directly damage the gastric epithelium and attempted to determine whether these drugs caused injury through gastric microcirculatory alterations.Methods:An ex vivo gastric chamber model was used. Effects of topically applied alendronate and pamidronate on transmucosal potential difference and epithelial integrity (histology) were determined. Also, the effects of agents capable of preventing microvascular injury in the stomach (PGE2 and two nitric oxide donors) were examined for their ability to prevent gastric injury induced by the two N‐bisphosphonates.Results:Alendronate and pamidronate caused a concentration‐dependent decrease in transmucosal potential difference, widespread epithelial injury and infiltration of neutrophils into the mucosa. PGE2 and the two nitric oxide donors did not prevent the changes in potential difference or the epithelial injury, but did reduce neutrophil infiltration. Significant release of PGE2 into the lumen was observed following application of the two bisphosphonates, but neither drug altered mucosal blood flow.Conclusions:These results suggest that these N‐bis‐ phosphonates directly damage the gastric epithelium independent of actions on the microvasculature.