bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population‐based case control study of the safety of sulfasalazine use during pregnancy
Authors: Nørgård B. , Czeizel A. E. , Rockenbauer M. , Olsen J. , Sørensen H. T. 
Published: March 2003

Background:We studied the human teratogenic risk of sulfasalazine because this drug interferes with folate metabolism.Methods:Case control study within the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980–1996; based on 22 865 new‐born infants or foetuses with congenital abnormalities, and 38 151 babies without any detected congenital abnormalities (control group).Results:Seventeen pregnant women (0.07%) were treated with sulfasalazine in the case group, and 26 (0.07%) in the control group. The overall adjusted adds ratio of congenital abnormalities after sulfasalazine treatment was odds ratio=1.2 (95% confidence interval: 0.6–2.1). None of the analyses indicated any significant increased prevalence of selected congenital abnormalities among the exposed compared with the not exposed.Conclusions:We found no significant increased prevalence of selected congenital abnormalities in the children of women treated with sulfasalazine during pregnancy. However, the amount of information is limited and additional data are needed to rule out a teratogenic effect.
Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and the beneficial effect of acid suppression
Authors: Vreeburg E. M. , Levi M. , Rauws E. A. J. , Deventer S. J. H. V. , Snel P. , Bartelsman J. W. F. M. , Ten Cate J. W. , Tytgat G. N. J. 
Published: March 2003

Background:The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re‐bleeding. The haemostatic mechanisms that may influence the re‐bleeding of ulcers are largely unknown.Aim:We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity.Methods:Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D‐Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes.Results:Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24‐h ranitidine infusion.Conclusions:Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.
Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes
Authors: Horai Y. , Kimura M. , Furuie H. , Matsuguma K. , Irie S. , Koga Y. , Nagahama T. , Murakami M. , Matsui T. , Yao T. , Urae A. , Ishizaki T. 
Published: March 2003

Background:S‐mephenytoin 4’‐hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19‐related genetic polymorphism.Aim:To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status.Methods:Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post‐dose.Results:Five homo EM, six hetero EM and four PM subjects were H. pylori‐negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC0–24 and plasma levels of rabeprazole were observed among the three different genotype groups.Conclusion:The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.
Modified seven‐day, quadruple therapy as a first line Helicobacter pylori treatment
Authors: Calvet X. , Garcia N. , Gené E. , Campo R. , Brullet E. , Sanfeliu I. 
Published: March 2003

Background:Cure rates of 7‐day triple therapy seem to be decreasing. Quadruple therapies may be an alternative, although their complex administration makes patient acceptance difficult.Objective:To test the usefulness of a thrice a day, quadruple therapy to cure Helicobacter pylori infection.Patients and methods:A total of 122 consecutive patients with peptic ulcer and Helicobacter pylori infection were treated with omeprazole 20 mg b.d., tetracycline chlorhydrate 500 mg t.d.s., metronidazole 500 mg t.d.s., and bismuth subcitrate 120 mg t.d.s. administered with meals for 7 days. Cure was tested by either endoscopy or breath test after 2 months, and by urea breath test 6 months after therapy.Results:Seven patients were lost to follow‐up. Of the remaining 115, 110 were cured at the first control, giving an intention‐to‐treat cure rate of 90.2% (95% CI: 83–95%) and a per protocol cure rate of 95.7% (95% CI: 90–98%). One hundred three patients returned for a 6‐month breath test; all but one were cured. Side‐effects were minimal or minor in 47 patients (40.8%) and moderate in four (3.4%). Compliance was good, 95% of patients taking more than 90% of the pills. Six (5%) patients stopped treatment after 1, 2, 4 (two patients) and 6 (two patients) days.Conclusion:Thrice a day quadruple therapy shows excellent cure rates, far above 90%, is well‐tolerated and compliance is easy. Head‐to‐head comparison with triple therapies as first line Helicobacter pylori treatment seems warranted.
Acid suppression in the management of gastro‐oesophageal reflux disease—an appraisal of treatment options in primary care
Authors: Jones R. , Bytzer P. 
Published: March 2003

Gastro‐oesophageal reflux disease (GERD) is one of the most common conditions presenting to the primary care physician. Despite progress in understanding and treatment of the disease, strategies for capitalizing on these advances are less well developed. In many practices, H2‐receptor antagonists still remain the most widely prescribed treatment for GERD, despite the availability of the more effective acid‐suppressant proton pump inhibitors.This review examines the relative efficacies of acid‐suppressant drugs in minimizing oesophageal acid exposure and outlines the evidence for the superiority of proton pump inhibitors over standard‐dose H2‐antagonists in symptom relief, erosion healing and prevention of relapse in GERD. Current prescribing patterns and considerations for the general practitioner are also examined. The availability and impact of over‐the‐counter H2‐antagonists on the treatment of GERD and their relative cost‐effectiveness vs. proton pump inhibitors are also addressed.A hierarchy of drug efficacy (full‐dose proton pump inhibitor > half‐dose proton pump inhibitor > high‐dose H2‐antagonist > standard‐dose H2‐antagonist or prokinetic) applies in principle to all GERD patients, (with or without oesophagitis). The most effective initial therapy for GERD is also likely to be the most cost‐effective one, if treatment failure leads to higher utilization of medical resources.The application of these recommendations to the management of non‐endoscoped GERD, endoscopy‐negative GERD and low‐grade oesophagitis as well as higher grade oesophagitis is also reviewed.
Anti‐inflammatory and tissue‐protectant drug effects: results from a randomized placebo‐controlled trial of gastritis patients at high risk for gastric cancer
Authors: Fischbach L. A. , Correa P. , Ramirez H. , Realpe J. L. , Collazos T. , Ruiz B. , Bravo L. E. , Bravo J. C. , Casabon A. L. , Schmidt B. A. 
Published: March 2003

Background:The inflammatory process involvingHelicobacter pylori‐associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal andin vitrostudies suggesting that tetracyclines have both anti‐inflammatory and tissue‐protectant effects unrelated to their antimicrobial activity. We attempted to modulate components ofH. pylori’sinflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host’s reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt.Methods:We conducted a 16‐week placebo‐controlled clinical trial with 374H. pylori‐associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo.Results:Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change inH. pyloridensity and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent ofH. pyloridensity or inflammation.Conclusion:The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent ofH. pyloridensity and inflammation.
Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six‐month follow‐up study
Authors: Hurenkamp G. J. B. , Grundmeijer H. G. L. M. , Van Der Ende A. , Tytgat G. N. J. , Assendelft W. J. J. , Van Der Hulst R. W. M. 
Published: March 2003

Background:It remains controversial whether successful H. pylori eradication leads to relief of dyspepsia and the subsequent arrest or tapering of acid‐suppressant drug therapy, or to an aggravation of acid‐related dyspepsia requiring more acid‐suppressant drug intake.Aim:To evaluate prospectively the effect of H. pylori eradication on the requirement of acid‐suppressant drug or antacids and the evolution of dyspeptic symptoms in chronic acid‐suppressant drug users with peptic ulcer disease.Materials and methods:The use of acid‐suppressant drugs, rescue antacids and predominant symptoms were recorded prospectively during 24 weeks after H. pylori eradication therapy in 75 peptic ulcer disease patients.Results:In 71 patients with complete follow‐up, ulcers were healed at follow‐up endoscopy and H. pylori was successfully eradicated. After 6 months, 93% (66 out of 71) of chronic acid‐suppressant drug users had stopped acid‐suppressant drug intake. The mean daily acid‐suppressant drug dosage per patient decreased from 1.72 at entry to 0.03 units acid‐suppressant drug (98%; P < 0.0001) during follow‐up. The mean number of antacid tablets/day/patient was 0.26 during follow‐up for the relief of mild inter‐current dyspeptic symptoms. Medication use was not different in peptic ulcer disease patients with or without gastro‐oesophageal reflux disease at baseline. The prevalence of gastro‐oesophageal reflux disease decreased from 42% before to 35% after H. pylori eradication (N.S.).Conclusion:Successful H. pylori eradication in peptic ulcer disease patients almost completely eliminates the need for acid‐suppressant drug regardless of the presence or absence of gastro‐oesophageal reflux disease at entry.
Comparison of the effects of concanavalin‐A and epidermal growth factor on epithelial cell proliferation in the rat intestine
Authors: Fitzgerald A. J. , Jordinson M. , Rhodes J. M. , Singh R. , Calam J. , Goodlad R. A. 
Published: March 2003

Background:Concanavalin‐A, the lectin present in Jack beans, binds to mannose‐ and glucose‐containing residues and can interact with the epidermal growth factor receptor and moderate cell proliferation in vitro.Aim:To compare the actions of concanavalin‐A and epidermal growth factor on the gastrointestinal tract in vivo.Methods:Rats maintained on total parenteral nutrition were given intragastric concanavalin‐A, intravenous epidermal growth factor or concanavalin‐A and epidermal growth factor. Cell proliferation and crypt fission were assayed in ‘micro‐dissected’ crypts.Results:Concanavalin‐A and epidermal growth factor both significantly elevated proliferation in the small intestine and colon. No significant interaction between the effects of these two agents was seen, except in the mid small intestine where there was a synergistic interaction. Concanavalin‐A had no effect on crypt branching. Epidermal growth factor significantly reduced branching in the distal small intestine and mid colon.Conclusion:The effects of the two agents appeared to be separate, except in the mid small intestine where they were additive. This is in marked contrast with the actions reported in vitro, where concanavalin‐A is a powerful inhibitor of epidermal growth factor‐induced cell proliferation. Concanavalin‐A thus has potential for enhancing the functions of the small intestine.
Ranitidine bismuth citrate with clarithromycin alone or with metronidazole for the eradication of Helicobacter pylori
Authors: Bardhan K. D. , Morton D. , Perry M. J. , Sanders D. S. , Morris P. , Rowland A. , Thompson M. , Mitchell T. R. , Roberts P. M. 
Published: March 2003

Background: Both triple therapy with ranitidine bismuth citrate (RBC) plus two antibiotics for 7 days and dual therapy of RBC with clarithromycin for 14 days have been extensively studied; both regimens effectively eradicate Helicobacter pylori. However, few studies have assessed the efficacy of dual therapy given for 7 days.Aim: To compare the efficacy and safety of RBC 400 mg with clarithromycin 500 mg, alone or with metronidazole 400 mg, given twice daily for 7 days for the eradication of H. pylori.Methods: This single centre, randomized, double‐blind study involved 118 patients with dyspepsia or a history of peptic ulcer disease. H. pylori infection was detected initially by CLO test, and confirmed in 109 patients by urea breath test and/or microbiology culture. H. pylori eradication was assessed 4 and 12 weeks after the end of treatment by urea breath test. H. pylori antibiotic susceptibility was assessed pre‐study in all patients, and post‐treatment in patients with a positive post‐treatment urea breath test. Adverse events were recorded throughout the study.Results: H. pylori was eradicated in 93% of patients who received RBC with clarithromycin and metronidazole and in 84% of patients who received RBC with clarithromycin (intention‐to‐treat rates). Per protocol eradication rates were 98% and 90% for triple therapy and dual therapy, respectively. The eradication of metronidazole‐resistant H. pylori was achieved in 100% and 88% of patients following dual therapy and triple therapy, respectively, and acquired resistance to clarithromycin occurred in only one patient following treatment failure. Both treatments were well‐tolerated; only one patient (2%) was withdrawn from each treatment group due to adverse events.Conclusions: RBC with clarithromycin and metronidazole is a highly effective and well‐tolerated triple therapy regimen for the eradication of H. pylori. RBC with clarithromycin dual therapy has a similar efficacy, and offers an alternative to triple therapy when there are concerns about treatment with metronidazole or the use of multiple antibiotics. Both regimens are effective against antibiotic‐resistant strains of H. pylori.
H2‐receptor antagonists in the treatment of functional (nonulcer) dyspepsia: a meta‐analysis of randomized controlled clinical trials
Authors: Redstone H. A. , Barrowman N. , Veldhuyzen Van Zanten S. J. O. 
Published: March 2003

Aim:To perform a meta‐analysis evaluating the efficacy of H2‐receptor antagonists in functional (nonulcer) dyspepsia.Selection of studies:A Medline search was used to identify placebo controlled randomized clinical trials, using the subject headings dyspepsia and H2‐receptor antagonist.Outcome measures:Global assessment by the patient of dyspepsia symptoms, improvement of epigastric pain and complete relief of epigastric pain.Results:Twenty‐two studies met the inclusion criteria, 15 of which reported the active drug to be superior to placebo. Many studies suffered from suboptimal study design. The odds ratio in favour of active drug was 1.48 (95% confidence interval: 0.9–2.3) for global assessment of dyspepsia symptoms, 2.3 (95% CI: 1.6–3.3) for improvement of epigastric pain, and 1.8 (95% CI: 1.2–2.8) for complete relief of epigastric pain.Conclusion:There is some evidence that H2‐receptor antagonists are superior to placebo in functional dyspepsia, but larger studies evaluating higher doses of H2‐receptor antagonists and of longer duration are necessary to determine the exact effect size.
Helicobacter pylori testing in the primary care setting: which diagnostic test should be used?
Authors: Weijnen C. F. , De Wit N. J. , Numans M. E. , Kuipers E. J. , Hoes A. W. , Verheij T. J. M. 
Published: March 2003

Aim: To identify the most accurate and efficient test for diagnosing Helicobacter pylori infection in primary care patients.Study design: A whole blood test, an ELISA, and carbon13 urea breath test (CUBT) were evaluated in a primary care setting and validated against two different gold standards that used gastric biopsies.Population: Primary care patients who had dyspeptic complaints lasting at least 2 weeks and were referred for endoscopy.Outcomes measured: Positive and negative predictive values, sensitivity and specificity were determined for all three noninvasive H. pylori tests.Results: Data from the three non‐invasive H. pylori tests were available for 136 primary care dyspeptic patients referred for endoscopy. They were compared with data from the gold standards. The positive predictive value of the whole blood test was in the range 71–75%, the ELISA 83–86%, and the CUBT 88–92%, while the negative predictive values were in the ranges 72–77%, 96–100%, and 95–98%, respectively. The sensitivity of the whole blood test was in the range 36–42%, the ELISA 93–100%, and the CUBT 92–97%, while the specificities were in the ranges 92–93%, 90–91% and 93–95%, respectively. The positive predictive value of the ELISA dropped significantly at lower H. pylori infection rates.Discussion: Both the ELISA and CUBT are effective in the primary care setting, while the whole blood tests produces inferior results. ELISA might, however, be less suitable for detecting H. pylori infection in a population with a low rate of infection.
Synergy between low‐dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal‐induced heartburn
Authors: Robinson M. , Rodriguez‐Stanley S. , Ciociola A. A. , Filinto J. , Zubaidi S. , Miner P. B. , Gardner J. D. 
Published: March 2003

Background:The pathophysiology of recurrent postprandial heartburn and the basis for the effectiveness of antacids or low doses of histamine H2‐receptor antagonists have not been well studied.Methods:The selected subjects (n=26) had heartburn more than four times a week for at least 2 months, which was responsive to antacids. Gastric pH and oesophageal pH were measured for 1 h before, during, and 4.5 h after ingestion of a meal over 0.5 h. Heartburn severity was assessed at 15‐min intervals beginning at the end of the meal. Each subject randomly received placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time‐weighted means of the acid concentrations for every second of the postprandial recording period.Results:There was a close temporal relationship between heartburn and oesophageal acidity. Most oesophageal acid exposure occurred over a 90‐min period that began approximately 45 min after the end of the meal. During this period the gastric acid concentration was less than 5% of maximal. Ranitidine significantly decreased gastric but not oesophageal acidity, whilst antacid significantly decreased oesophageal but not gastric acidity. Ranitidine plus antacid significantly decreased both gastric and oesophageal acidity. Antacid alone and ranitidine plus antacid significantly decreased heartburn severity.Conclusions:Determining integrated gastric and oesophageal acidity provides novel information regarding the pathophysiology of meal‐induced heartburn as well as the actions of low‐dose ranitidine and antacid. For subjects with meal‐induced heartburn, treatment with low‐dose ranitidine plus antacid is particularly effective in decreasing gastric and oesophageal acidity as well as heartburn severity.
Glicentin, an active enteroglucagon, has a significant trophic role on the small intestine but not on the colon in the rat
Authors: Sasaki M. , Fitzgerald A. J. , Mandir N. , Sasaki K. , Wright N. A. , Goodlad R. A. 
Published: March 2003

Background:Many experiments have indicated that the gut glucagons (enteroglucagons) are associated with cell proliferation in the small intestine. However, recent studies have failed to show trophic effects of glicentin (enteroglucagon) on the intestine.Aims:To examine the effects of glicentin on intestinal proliferation in vivo in the rat.Methods:Rats were established on total parenteral nutrition for 6 days. Four experimental groups were given daily doses of 1, 4, 20 and 80 μg/rat of glicentin via the jugular vein. Rats fed by total parenteral nutrition and rats fed chow ad libitum were used as controls. Tissues taken from the duodenum, jejunum, ileum and colon were fixed in Carnoy’s fluid and microdissected to determine the metaphase arrest scores and crypt fission ratios.Results:The mean metaphase arrest scores per crypt of the small intestine were significantly increased in the rats given 4, 20 and 80 μg of glicentin. These responses were dose‐dependent, and were most prominent in the ileum. Crypt fission of the ileum was significantly decreased in the 20 and 80 μg glicentin groups. Glicentin had no effects on proliferation or fission in the colon.Conclusions:Glicentin is trophic to the rat small intestine, but not the colon.