bluuebunny/crossref_metadata_2025_split huggingface dataset:
Budesonide in the treatment of Crohn’s disease: a meta‐analysis
Authors: Papi C. , Luchetti R. , Gili L. , Montanti S. , Koch M. , Capurso L. 
Published: March 2003

Aim:To perform a meta‐analysis to assess the effectiveness and safety of oral budesonide for inducing remission in active Crohn’s disease and for preventing relapse in Crohn’s disease with medically‐ or surgically‐induced remission.Methods:All randomized, double‐blind controlled trials involving oral budesonide therapy in Crohn’s disease were retrieved from a Medline search, reviews articles or their bibliographies. Of 83 articles retrieved, 12 met the inclusion criteria. Data extraction was performed by three independent observers and scoring disagreements were resolved by consensus.Results:Six trials tested budesonide in active disease and six in quiescent disease. Budesonide was less effective than conventional corticosteroids for inducing remission of active Crohn’s disease (pooled rate difference, RD –8.5%; 95% CI: –16.4 to –0.7%; P=0.02), but corticosteroid‐related adverse events were reduced (RD –22.4%; 95% CI: –32 to –12.8%; P < 0.001). In quiescent Crohn’s disease, budesonide was as effective as placebo for preventing relapse in medically induced remission (RD –0.8%; 95% CI: –9.9 to 8.3%; P=0.42) and endoscopic recurrence in surgically induced remission (RD –3.5%; 95% CI: –16.9 to 9.8%; P=0.30). In the long term treatment, budesonide had an occurrence rate of corticosteroid‐related adverse effects similar to placebo (RD 5.3%; 95% CI: –3.9 to 14.5%; P=0.30).Conclusions:Budesonide is significantly less effective than conventional corticosteroids for inducing remission in active Crohn’s disease, but the risk of corticosteroid‐related adverse effects is significantly reduced. Budesonide is not effective in preventing relapse of Crohn’s disease after medically‐ or surgically‐induced remission.
Failure of a motilin receptor agonist (ABT‐229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double‐blind placebo‐controlled trial
Authors: Talley N. J. , Verlinden M. , Snape W. , Beker J. A. , Ducrotte P. , Dettmer A. , Brinkhoff H. , Eaker E. , Ohning G. , Miner P. B , Mathias J. R , Fumagalli I. , Staessen D. , Mack R. J. 
Published: March 2003

Introduction:Motilin‐receptor agonists are prokinetics; whether they relieve the symptoms of functional dyspepsia is unknown. We aimed to test the efficacy of the motilin agonist ABT‐229 in functional dyspepsia patients with and without delayed gastric emptying.Methods:Patients were randomized with postprandial symptoms and documented functional dyspepsia by endoscopy (n=589 in intention‐to‐treat analysis). Patients were assigned to either the delayed or normal gastric emptying strata, based on a validated 13C octanoic acid breath test. Patients were then further randomized within each strata, to receive one of four doses of ABT‐229 (1.25, 2.5, 5 or 10 mg b.d. before breakfast and dinner) or placebo for 4 weeks, following a 2‐week baseline. The primary outcome was the assessment of change in symptom severity over the 2 weeks from baseline to final visit, based on a self‐report questionnaire measuring severity on visual analogue scales.Results:Baseline characteristics across the treatment arms were very similar. No significant differences in the upper abdominal discomfort severity score (maximum 800 mm) were observed for any active treatment arm vs. placebo (mean change from baseline −139, −141, −145, −160 and −134 mm for placebo, 1.25, 2.5, 5, and 10 mg, respectively, at 4 weeks by intention‐to‐treat). More patients on placebo reported a good or excellent global response than patients on 1.25 or 5 mg of active therapy (both P < 0.05). The results were very similar in those with and without delayed gastric emptying. Helicobacter pylori status did not predict response. Excluding patients with any baseline heartburn (total remaining n=240), ABT‐229 10 mg was inferior to placebo in relief of upper abdominal discomfort.Conclusions:ABT‐229 was of no value for relief of symptoms in functional dyspepsia, compared with placebo.
Factors associated with consulting medical or non‐medical practitioners for dyspepsia: an Australian population‐based study
Authors: Westbrook J. I. , Mcintosh J. , Talley N. J. 
Published: March 2003

Background:Little is known about how many dyspeptics in the population consult medical and non‐medical practitioners, or the factors associated with various consulting patterns.Methods:A cross‐sectional survey of 748 Australians with dyspepsia investigated their age, sex, dyspepsia symptoms, medical and non‐medical consultations, and health status on the SF‐12.Results:Overall, 56% had ever consulted a medical practitioner for dyspepsia. Of these, 54% consulted within 6 months of first symptoms. Non‐medical practitioners were consulted by 29%. Compared to dyspeptics in all, or most, other consulting groups, subjects who did not consult (37%, group NO) were characterized by fewer symptoms, better physical health, and younger age. Those who only consulted doctors (34%, group M) were older and had better mental, but poorer physical health. Those who only consulted non‐medical practitioners (7%, group N) were younger and had better physical, but poorer mental health. Dyspeptics consulting both medical and non‐medical practitioners (22%, group M + N), were older, more dissatisfied with medical care, had more symptoms and poorer physical and mental health. Timing of medical consultations was similar in groups M and M + N. Group M + N dyspeptics consulted similar types, but more non‐medical practitioners than group N. No sex differences were found in consulting behaviour.Conclusions:Many dyspeptics do not consult; they have fewer symptoms than consulters. Consultation with non‐medical practitioners is common and is associated with poor mental health. Dyspeptics seeking advice from both medical and non‐medical practitioners are less satisfied with their medical management than those who only consult doctors for their dyspepsia.
Review article: transcription factors and growth factors in ulcer healing
Authors: Szabo S. , Khomenko T. , Gombos Z. , Deng X. M. , Jadus M. R. , Yoshida M. 
Published: March 2003

SummaryThis review is focused on recent investigations demonstrating a pharmacological and patho‐physiologic role in gastroduodenal ulceration for growth factors such as basic fibroblast growth factor (bFGF), platelet‐derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), as well as for transcription factors. Our experiments revealed accelerated healing, without decreased gastric acid secretion, of chronic cysteamine‐induced duodenal ulcers in rats treated daily for 3 weeks with intragastric administration of bFGF, PDGF or VEGF. Our recent studies also indicate a pathophysiological role of endogenous growth factors in the natural history of experimental duodenal ulcer development and healing.More recently, we investigated the genetic regulation of these growth factors in experimental duodenal ulceration. Since gene expression is most effectively controlled by transcription factors, proteins that bind tocis‐acting elements of DNA and guide the binding of polymerase II to start the transcription of specific mRNA, we tested the hypothesis that the expression of IEGs and their transcription factor products, such as Egr‐1 and Sp1, might precede the increased synthesis of bFGF, PDGF and VEGF in duodenal ulcer healing. Indeed, the duodenal ulcerogen cysteamine, but not its nonulcerogen and toxic analogue ethanolamine, rapidly increased duodenal (but not gastric) mucosal levels of ET‐1, which was followed by enhanced expression of Egr‐1 and a decrease in Sp1 in the preulcerogenic stage of duodenal ulceration. These changes in levels of ET‐1 and expression of transcription factors were also accompanied by increased expression of the CDK inhibitor p21. Thus, not only growth factors such as bFGF, PDGF and VEGF, but also transcription factors such as Egr‐1 and Sp1 and the cell cycle regulator p21, may play a role in the natural history of experimental duodenal ulceration.
Gastric epithelial cell proliferation and apoptosis in Helicobacter pylori‐infected mice
Authors: Yamaguchi T. , Nakajima N. , Kuwayama H. , Ito Y. , Iwasaki A. , Arakawa Y. 
Published: March 2003

Summary Background: Helicobacter pylori causes gastritis and is strongly associated with gastroduodenal ulcer and gastric cancer. The bacterium is associated with an increased rate of epithelial proliferation, which can be reversed by eradication of the organism. The mechanism of this response is not known, but this epithelial proliferation is one of the risk factors for developing gastric carcinoma. Recently, apoptosis also was found to be increased in the gastric mucosa of persons carrying H. pylori. Methods: cagA‐positive H. pylori isolated from a human gastric ulcer was inoculated into BALB/C mice. At 4, 6, 12, 18 and 24 weeks, mice were injected with bromodeoxyuridine 5 mg/kg and killed 1 h later. Proliferation was analysed by histochemical staining for BrdU; apoptosis was examined by the TUNEL assay. Results: The number of BrdU‐labelled cells in the antrum was significantly increased by H. pylori infection beginning 12 weeks after infection. The number of apoptotic cells in this tissue was increased significantly by 6 weeks after inoculation. Conclusion: The proliferation observed in H. pylori infection may be a response to increased apoptosis.
Interactive roles of endogenous prostaglandin and nitric oxide in regulation of acid secretion by damaged rat stomachs
Authors: Takeuchi K. , Sugamoto S. , Yamamoto H. , Kawauchi S. , Tashima K. 
Published: March 2003

Summary Background: The acid inhibitory mechanism in the damaged stomach is known to involve endogenous nitric oxide (NO) as well as prostaglandin (PG). Aim: To investigate the interaction between PG and NO in regulation of acid secretion in the stomach following damage. Methods: Under urethane anaesthesia, a rat stomach was mounted in an ex vivo chamber and perfused with saline. Acid secretion, luminal PGE2, NO metabolites (NOx) and histamine output were measured before and after application of 20 m
m taurocholate Na (TC) for 30 min, with or without pre‐treatment with indomethacin and/or NG‐nitro‐
l‐arginine methyl ester (L‐NAME). Results: Exposure of the stomach to TC caused a decrease in acid secretion, with concomitant increase of both luminal NOx and PGE2. Either L‐NAME or indomethacin reduced the decrease in acid secretion in response to TC, but only L‐NAME allowed acid secretion to increase over basal values. L‐NAME prevented the increase of luminal NOx after TC treatment, while indomethacin inhibited PGE2 release during and after exposure to TC. The increase in acid secretion in the presence of L‐NAME was prevented when indomethacin was given concomitantly. TC treatment increased histamine output in the lumen, a process that was enhanced by L‐NAME but reduced by indomethacin. Conclusions: Damage to the stomach increases both NO and PG in the lumen, and decreases acid secretion. Inhibiting NO production increases acid secretion in the damaged stomach, but only when PG biosynthesis is intact. It is assumed that endogenous PG has a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect probably through enhancing the release of mucosal histamine.
Helicobacter pylori screening for individuals requiring chronic NSAID therapy: a decision analysis
Authors: Scheiman J. M. , Bandekar R. R. , Chernew M. E. , Fendrick A. M. 
Published: March 2003

Introduction:Although it is incontrovertible that Helicobacter pylori causes peptic ulcer disease, controversy persists regarding the impact of H. pylori infection on the incidence of NSAID‐related complications and whether H. pylori eradication reduces the rate of adverse events.Methods:A symptom‐driven decision analytic model was developed to compare the clinical and economic impact of H. pylori screening compared to a strategy of no H. pylori testing for individuals requiring chronic NSAID therapy. In the principal analysis, it was assumed that untreated H. pylori infection increased the ulcer risk by 50% and that successful eradication reduced the risk of adverse events to that of uninfected patients. Patients’ ulcer risk and the protective effect of H. pylori eradication were evaluated using sensitivity analysis.Results:When compared to no H. pylori testing, H. pylori screening led to fewer symptomatic ulcers (no test, 5.4; H. pylori test, 4.6 per 100 patient years) and ulcer complications (no test, 2.6; H. pylori test, 2.3 per 100 patient years) and a higher cost per patient (no test, $435; H. pylori test, $556). The incremental cost attributable to the H. pylori screening strategy to prevent a symptomatic and complicated ulcer was $16 805 and $31 842, respectively. The clinical and cost‐effectiveness advantage of H. pylori screening improved as patients’ ulcer risk increased or the protective effect of H. pylori eradication was enhanced.Conclusions:Based upon the available evidence, H. pylori screening has the potential to reduce NSAID‐related adverse events for average‐risk patients at an incremental cost. Until controlled investigations definitively quantify the effect of H. pylori eradication on clinically significant NSAID‐related adverse events, a compelling argument can be made for H. pylori testing for chronic NSAID users at increased risk of ulcer disease.
Randomized trial of low‐dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non‐steroidal anti‐inflammatory drugs
Authors: Chan F. K. L. , Sung J. J. Y. , Ching J. Y. L. , Wu J. C. Y. , Lee Y. T. , Leung W. K. , Hui Y. , Chan L. Y. , Lai A. C. W. , Chung S. C. S. 
Published: March 2003

Background:Prophylactic misoprostol or non‐steroidal anti‐inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury.Aim:To compare nabumetone vs. co‐therapy of naproxen with low‐dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users.Methods:NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long‐term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500–1000 mg/day) and misoprostol (200 μg b.d.), or nabumetone (1000–1500 mg/day) and placebo misoprostol for 24 weeks. The primary end‐point was recurrent upper gastrointestinal bleeding. The secondary end‐point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia.Results:A total of 90 patients were included in the intention‐to‐treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98–11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group.Conclusions:Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low‐dose misoprostol nor nabumetone is adequate for high‐risk NSAID users.
Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus
Authors: Bytzer P. , Talley N. J. , Jones M. P. , Horowitz M. 
Published: March 2003

Background:Gastrointestinal symptoms are commonly reported as side‐effects of oral hypoglycaemic drugs. It may be very difficult to distinguish between spontaneous and truly drug‐related symptoms due to the high background incidence of gastrointestinal symptoms. Gastrointestinal symptoms in diabetic patients have also been linked to factors associated with long‐standing disease and suboptimal control.Aim:To explore the association between gastrointestinal symptoms and treatment with oral hypoglycaemic drugs in a large cohort of subjects with type 2 diabetes.Patients and methods:956 subjects with type 2 diabetes participated in the study. All subjects completed a validated, self‐administered questionnaire on gastrointestinal symptoms, diabetes, drug use and various potential risk factors for gastrointestinal symptoms. The association between oral hypoglycaemics and nine gastrointestinal symptom groups was assessed based on logistic regression.Results:405 of the 956 patients used oral hypoglycaemic drugs. Metformin use was independently associated with chronic diarrhoea (odds ratio 3.08, 95% CI: 1.29–7.36, P < 0.02) and with faecal incontinence (odds ratio 1.95, 95% CI: 1.10–3.47, P < 0.05). Use of sulphonylureas was associated with less abdominal pain, but not with any other gastrointestinal symptom.Conclusions:Troublesome gastrointestinal symptoms do not appear to be caused by oral hypoglycaemics, except for diarrhoea and faecal incontinence, which are strongly and independently associated with metformin use.
The effect of oral administration of Lactobacillus GG on antibiotic‐associated gastrointestinal side‐effects during Helicobacter pylori eradication therapy
Authors: Armuzzi A. , Cremonini F. , Bartolozzi F. , Canducci F. , Candelli M. , Ojetti V. , Cammarota G. , Anti M. , De Lorenzo A. , Pola P. , Gasbarrini G. , Gasbarrini A. 
Published: March 2003

Background:One‐week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side‐effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug‐related manifestations.Aim:To determine whether adding the probiotic Lactobacillus GG to an anti‐H. pylori regimen could help to prevent or minimize the gastrointestinal side‐effects burden.Methods:Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side‐effects and an overall judgement of tolerability.Results:Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1–0.9; relative risk=0.3, 95% CI: 0.1–0.9; relative risk=0.5, 95% CI: 0.2–0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04).Conclusions: Lactobacillus GG supplementation showed a positive impact on H. pylori therapy‐related side‐effects and on overall treatment tolerability.
Cure of Helicobacter pylori infection in elderly patients: comparison of low versus high doses of clarithromycin in combination with amoxicillin and pantoprazole
Authors: Pilotto A. , Franceschi M. , Leandro G. , Bozzola L. , Rassu M. , Soffiati G. , Di Mario F. , Valerio G. 
Published: March 2003

Background:Advancing age may influence clarithromycin’s pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor and amoxicillin in elderly patients.Aim:To compare the efficacy and tolerability of clarithromycin 250 mg vs. clarithromycin 500 mg twice daily (b.d.) in combination with pantoprazole and amoxicillin in elderly patients.Methods:One hundred and fifty‐four elderly patients with H. pylori‐associated ulcer disease or chronic gastritis were consecutively randomized to receive pantoprazole 40 mg daily plus amoxicillin 1 g, and either clarithromycin 250 mg b.d. (PAC 250) or clarithromycin 500 mg b.d. (PAC 500). Two months after therapy, endoscopy and gastric biopsies were repeated.Results:The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively, 83% and 79% (ITT analysis) and 94% and 88% (PP analysis) (P=N.S.). Significant decreases in chronic gastritis activity both in the body (P < 0.00001) and the antrum (P < 0.0001) of the stomach were found in H. pylori‐cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5%) and seven in PAC 500 (9%) reported adverse events (P=N.S.). One patient in PAC 250 (25%) and three in PAC 500 (43%) discontinued the study because of these drug‐related side‐effects (P=N.S.).Conclusions:In elderly patients, 1‐week triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin is a highly effective and well tolerated anti‐H. pylori treatment. With this combination, clarithromycin at the lower dose of 250 mg b.d. achieved excel‐ lent cure rates and minimized adverse events and costs.
The limitations of corticosteroid therapy in Crohn’s disease
Authors: Rutgeerts P. J. 
Published: March 2003

Corticosteroids are highly effective in inducing clinical remission in patients with active Crohn’s disease. However, the role of corticosteroids in the treatment of this disease is primarily ameliorative because they are ineffective in maintaining remission or healing mucosal lesions. Nearly half of the patients who initially respond to corticosteroid therapy develop a dependency on corticosteroids or have a relapse within 1 year. In addition, use of these agents is often limited by a relatively high risk of serious adverse effects that can involve nearly every major body system. These effects include: bone loss, which can develop with even short‐term and low‐dose corticosteroid therapy; metabolic complications such as glucose intolerance and diabetes mellitus; increased intraocular pressure and glaucoma; and potentially lethal infections.To minimize the risk of toxicity, corticosteroids are increasingly recommended for short‐term use only at the lowest effective dose to induce remission in patients with moderately to severely active Crohn’s disease. Corticosteroid formulations with low systemic bioavailability, such as controlled‐release budesonide, may be associated with a lower rate of dermatologic adverse effects but appear to be somewhat less effective than conventional corticosteroids in inducing remission in patients with active Crohn’s disease.Immunosuppressive agents such as azathioprine, 6‐mercaptopurine, and methotrexate have demon‐ strated corticosteroid‐sparing effects, facilitating the withdrawal of corticosteroids when initiated as maintenance therapy. Infliximab can be used as an alternative to corticosteroids.