bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of Helicobacter pylori on cell proliferation and apoptosis in gastric epithelial cell lines
Authors: Takagi A. , Watanabe S. , Igarashi M. , Koike J. , Hasumi K. , Deguchi R. , Koga Y. , Miwa T. 
Published: March 2003

Summary Background: Helicobacter pylori has been implicated in the pathogenesis of gastric cancer and malignant lymphoma. It is not known whether the bacterium stimulates cell proliferation directly or if apoptosis induced by H. pylori leads to a hyperproliferative response. Aim: To clarify the precise mechanism of H. pylori action on gastric epithelial cell growth, we compared the response of two cell lines, Kato III (p53 deletion) and MKN 45 (p53 wild type), to the organism. To determine the role of Helicobacter vacuolating cytotoxin in gastric mucosal injury, we examined the relation between vacuolating activity and apoptosis under several conditions. Methods: Five cytotoxic and four noncytotoxic strains of H. pylori were used, each with an inoculum of 107 cfu/mL. The effect on the growth in MKN 45 and Kato III cells was studied by MTT assay. Vacuolating cytotoxin activity was determined using RK‐13 cells. Results: Neither cytotoxic nor noncytotoxic strains induced apoptosis, but death of MKN 45 cells was induced by pre‐treatment with interferon‐γ and culture with TNF‐α. In contrast, some strains of H. pylori increased proliferation of Kato III cells. Furthermore, cell death induced by cytotoxic strains, but not noncytotoxic strains, was significantly augmented by amoxycillin 5–50 g/mL (P = 0.0016). On the other hand, acid‐treated supernatant fluids from cultures of H. pylori showed enhanced vacuolating activity but did not induce cell death, suggesting that death is attributable to some factor other than the cytotoxin. Conclusion: These findings suggest that H. pylori induces apoptosis by a means independent of vacuolating cytotoxin.
Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial
Authors:   THE BRITISH–ITALIAN GALLSTONE STUDY GROUP, Petroni M. L. , Jazrawi R. P. , Pazzi P. , Lanzini A. , Zuin M. , Pigozzi M. G. , Fracchia M. , Galatola G. , Alvisi V. , Heaton K. W. , Podda M. , Northfield T. C. 
Published: March 2003

Background:Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization.Aim:To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy.Patients and methods:A total of 154 symptomatic patients with radiolucent stones (≤ 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6‐monthly oral cholecystography and ultrasonography for up to 24 months.Results:Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side‐effects or dropout rate. Complete gallstone dissolution on an intention‐to‐treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively.Conclusion:There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.
Up‐regulation of cyclooxygenase‐1 and ‐2 in human gastric ulcer
Authors: To K. F. , Chan F. K. L. , Cheng A. S. L. , Lee T. L. , Ng Y. P. , Sung J. J. Y. 
Published: March 2003

Background:The expression of cyclooxygenase (COX) in human gastric ulcers is unknown.Aim:To study the expression and cellular localization of cyclooxygenase in human gastric ulcers.Methods:A total of 38 surgical gastric ulcer specimens were studied; 20 were Helicobacter pylori‐positive and 18 were associated with NSAID use. Twenty non‐ulcerated, histologically normal gastric specimens were used as controls. The cellular localization of COX‐1 and COX‐2 were determined by immunohistochemistry and double immunofluorescence. Cyclooxygenase messenger RNA (mRNA) was measured by reverse transcription‐polymerase chain reaction and localized by in situ hybridization.Results:In control specimens, COX‐1 was detected in stromal cells in the lamina propria. There was focal and weak immunostaining for COX‐2 in the foveolar epithelium. At the ulcer edge, COX‐1 was significantly increased in lamina propria cells whereas COX‐2 was strongly expressed in the hyperplastic foveolar epithelium in H. pylori‐ and non‐steroidal anti‐inflammatory drugs (NSAID)‐associated ulcers. At the ulcer base, there was strong expression of COX‐1 and COX‐2 in myofibroblasts, macrophages and endothelial cells in the granulation tissue, irrespective of H. pylori status or NSAID use. Messenger RNA of COX‐1 and COX‐2 were demonstrated by reverse transcription‐polymerase chain reaction. Double immunofluorescence and in situ hybridization confirmed the cellular localization of cyclooxygenase at protein and mRNA levels, respectively.Conclusion:Both COX‐1 and COX‐2 are up‐regulated in human gastric ulcers.
Once versus divided daily dosing with delayed‐release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters
Authors: Hussain F. N. , Ajjan R. A. , Kapur K. , Moustafa M. , Riley S. A. 
Published: March 2003

Background:Delayed‐release mesalazine is traditionally taken as three divided doses. However, it is well‐recognized that dosing frequency has a significant impact on compliance and that once daily dosing is preferable.Methods:We measured serum, urinary, faecal and rectal tissue concentrations of 5‐aminosalicylic acid and N‐acetyl 5‐aminosalicylic acid in 24 healthy volunteers following dosing with delayed‐release mesalazine, 1.2 g or 2.4 g daily, given as either a single daily dose at 08:00 hours or in three divided doses at 08:00, 13:00 and 18:00 hours.Results:Urinary and faecal excretion and rectal tissue concentrations of 5‐aminosalicylic acid and N‐acetyl 5‐aminosalicylic acid were similar following single or divided daily dosing, at both doses studied. Peak serum concentrations were found at 06:00–09:00 following divided dosing and at 17:00–20:00 following once daily dosing. However, peak and trough serum levels and serum area under curve values (AUC) were similar with both regimens and at both doses.Conclusions:Urinary, faecal and rectal tissue concentrations are similar following single or divided daily dosing. Minor differences in serum levels were apparent but maximum, minimum and AUC values were similar. Clinical trials should examine the efficacy and toxicity of once daily dosing in patients with ulcerative colitis.
Quality of life in functional dyspepsia: responsiveness of the Nepean Dyspepsia Index and development of a new 10‐item short form
Authors: Talley N. J. , Verlinden M. , Jones M. 
Published: March 2003

Background:The Nepean Dyspepsia Index is a reliable and valid measure of quality of life in functional dyspepsia, but responsiveness has been little studied. The Nepean Dyspepsia Index originally contained 42 items designed to measure impairment of a subject’s ability to engage in relevant aspects of their life because of dyspepsia, and their enjoyment of these aspects; in addition, the individual importance of areas was assessed. It was subsequently shortened to 25 items, yielding five sub‐scales.Aim:To test the Nepean Dyspepsia Index’s responsiveness and develop a responsive, very short form.Methods:A randomized, double‐blind controlled trial was performed in 589 patients with documented functional dyspepsia. Symptoms and quality of life were measured at baseline, 2 and 4 weeks. Responsiveness of the Nepean Dyspepsia Index quality‐of‐life section was evaluated by correlation with symptom scores and calculation of standardized changes in scores. Two items from each sub‐scale which best represented the area of life (by factor loadings) were selected to create the 10‐item short form (SF; short form‐Nepean Dyspepsia Index). Internal consistency was assessed by Cronbach’s alpha and responsiveness was assessed as above.Results:The Nepean Dyspepsia Index quality‐of‐life scales demonstrated excellent responsiveness to change in both the active and placebo arms (standardized response means all > 1.0). The Nepean Dyspepsia Index accounted for only 8% of the variance in percentage change in symptoms (by visual analogue scales), indicating that it was evaluating areas of life not covered by symptoms. The 10‐item short form had adequate internal consistency (all scales ≥ 0.70) and all strongly (and significantly) correlated with the long form sub‐scales; it was also highly responsive.Conclusion:The Nepean Dyspepsia Index is a responsive disease‐specific quality‐of‐life measure; the 10‐item short form can be applied in clinical trials of functional dyspepsia.
Meta‐analysis of randomized controlled trials comparing standard clinical doses of omeprazole and lansoprazole in erosive oesophagitis
Authors: Sharma V. K. , Leontiadis G. I. , Howden C. W. 
Published: March 2003

Background:Omeprazole and lansoprazole are used to treat erosive oesophagitis in the respective daily doses of 20 and 30 mg.Aim:To investigate, by meta‐analysis, whether treatment with lansoprazole 30 mg increases erosive oesophagitis healing rates over omeprazole 20 mg.Methods:We searched for randomized, double‐blind trials comparing omeprazole 20 mg and lansoprazole 30 mg in endoscopically diagnosed erosive oesophagitis. After assessing for homogeneity, non‐heterogeneous trials were combined and pooled healing rates derived. We calculated the relative benefit increase, absolute benefit increase and number needed to treat.Results:Six trials without significant heterogeneity met predetermined inclusion criteria. By per protocol analysis, pooled healing rates for omeprazole 20 mg and lansoprazole 30 mg were, respectively, 74.7% and 77.7% after 4 weeks and 87.0% and 88.7% after 8 weeks. The corresponding figures by intention‐to‐treat analysis were 70.8% and 72.7% after 4 weeks and 81.8% and 83.3% after 8 weeks. In each analysis the absolute benefit increase for lansoprazole was small and its 95% confidence interval encompassed zero.Conclusion:Lansoprazole 30 mg produces healing rates in erosive oesophagitis that are not statistically significantly different to those of omeprazole 20 mg.
Efficacy of parenteral methotrexate in refractory Crohn’s disease
Authors: Chong R. Y. , Hanauer S. B. , Cohen R. D. 
Published: March 2003

Background:Methotrexate is steroid‐sparing in short‐term trials for refractory Crohn’s disease. This study assesses the impact of dosing and administration on the long‐term utility of methotrexate in Crohn’s disease.Methods:The efficacy and tolerability of methotrexate were assessed in all refractory Crohn’s disease patients treated at the University of Chicago from 1 September 1989 to 6 June 1997.Results:Seventy‐six patients were identified: 43% male, mean age 35 years, mean Crohn’s disease duration 9.5 years. Mean methotrexate duration was 55 weeks; mean dose was 20 mg/week. Drug administration was parenteral (78%), oral (13%), or combination (8%). Improvement occurred in 63% after a mean of 9 weeks, for a mean duration of 65 weeks. Remission occurred in 37% after a mean of 22 weeks, for a mean duration of 59 weeks. Improvement and remission were highest with parenteral therapy, but dose‐independent. Parenteral therapy maintained remission in 46%. Improvement (P=0.05) and remission (P=0.01) were more likely for patients under 40. Improvement rates were higher with concurrent steroids (P=0.02) or antibiotics (P=0.01). Side‐effects occurred in 46%, resulting in discontinuation in 18%. Prednisone was decreased in 78%, and stopped in 40%.Conclusions:Long‐term therapy with methotrexate in Crohn’s disease is safe, effective, steroid‐sparing, and most efficacious in younger patients and when given parenterally.
Usefulness of Helicobacter pylori stool antigen test to monitor response to eradication treatment in children
Authors: Oderda G. , Rapa A. , Marinello D. , Ronchi B. , Zavallone A. 
Published: March 2003

Background:The monitoring of the results of eradication treatment is a crucial step for patients with Helicobacter pylori gastritis. A non‐invasive test for H. pylori antigens in stools (HpSA) was recently validated for children.Aim:To evaluate the accuracy of HpSA in monitoring eradication treatment in children.Methods:In 60 children, H. pylori gastritis was diagnosed by endoscopy and the 13C‐urea breath test. The children were treated and returned for a follow‐up 13C‐urea breath test 6 weeks after the end of treatment. Children were considered cured when the 13C‐urea breath test was negative. Stool were collected at baseline, and at 2 and 6 weeks. Stool antigens were measured by HpSA.Results:According to 13C‐urea breath test, 6 weeks after the end of treatment 49 children were cured and 11 were still H. pylori‐positive. The sensitivity and specificity of HpSA on stools collected 2 weeks after therapy were 100%. At 6 weeks specificity was 93.9 and sensitivity 100%. Results by visual reading were concordant with the plate‐reader in all but two cases at baseline.Conclusions:HpSA is accurate for monitoring treatment in children as early as 2 weeks after therapy, when information is most useful and unachievable with other tests. Results by visual reading are accurate, and this can make the test cheaper and more practical.
A drug therapy for the prevention of variceal haemorrhage
Authors: Tripathi D. , Hayes P. C. 
Published: March 2003

The development of varices is a major complication of cirrhosis, and variceal haemorrhage has a high mortality. There have been major advances in the primary and secondary prevention of variceal haemorrhage over the last 20 years involving endoscopic, radiological and pharmacological approaches. This review concentrates principally on drug therapy, particularly on the numerous haemodynamic studies. Many of these drugs have not been studied in clinical trials, but provide data about the underlying pathogenesis of portal hypertension.Also covered in this review are the randomized controlled trials and meta‐analyses that involve a large number of patients. These trials involve relatively few drugs such as non‐selective beta‐blockers and nitrates. Correlations between haemodynamic and clinical parameters are discussed.Despite the recent increase in the use of alternative endoscopic therapies, an effective and well tolerated drug remains a clinically important research goal.
The potential role for photodynamic therapy in the management of upper gastrointestinal disease
Authors: Barr H. , Dix A. J. , Kendall C. , Stone N. 
Published: March 2003

Photodynamic therapy involves the activation of an exogeneously administered, or an endogenously gen‐erated, photosensitizer with light to produce localized tissue destruction. It is an attractive, predominantly endosopic technique for the palliation of advanced upper gastrointestinal cancer and the eradication of early neoplastic and pre‐neoplastic lesions. The nature of the biological response allowing safe healing and the exploitation of tissue threshold effects mean that adjacent tissue damage can be minimized.This review used a database of 368 papers. The nature of the photosensitizer is critical to the depth of tissue damage and the risk of adjacent tissue damage and stricture formation. The generation of protoporphyrin IX following administration of 5‐aminolaevulinic acid has proved useful for the treatment of high‐grade dysplasia in Barrett’s oesophagus. A double‐blind randomized placebo controlled trial has confirmed that it is a safe and effective method for the ablation of low‐grade dysplasia. The treatment of more advanced lesions requires exogeneously administered photo‐sensitizers. However, recent data indicate that the neoplastic potential remains in some patients and continued follow‐up is necessary.Photodynamic therapy can be used to eradicate early neoplasia and palliate advanced cancer, but caution is required before a definitive cure can be claimed.
Oral tacrolimus long‐term therapy in patients with Crohn’s disease and steroid resistance
Authors: Ierardi E. , Principi M. , Francavilla R. , Pisani A. , Rendina M. , Ingrosso M. , Guglielmi F. W. , Panella C. , Francavilla A. 
Published: March 2003

Aim:To report the results of a prospective, open‐label, uncontrolled study in 13 patients affected by Crohn’s disease with resistance to steroids.Methods:The patients were treated long‐term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1–0.2 mg.day/kg and adjusted in order to achieve levels of 5–10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate.Results:Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn’s disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life‐quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low‐dose steroids was required in five patients. Two patients underwent surgery.Conclusions:Tacrolimus therapy appears to be associated with both short‐ and long‐term benefits, and may represent a therapeutic option in Crohn’s disease when conventional therapies fail. This study encourages its use in controlled trials.
Food hypersensitivity and irritable bowel syndrome
Authors: Zar S. , Kumar D. , Benson M. J. 
Published: March 2003

Irritable bowel syndrome is a common condition but its pathophysiology remains poorly understood. Many irritable bowel syndrome patients give a history of food intolerance, but data from dietary elimination and re‐challenge studies are inconclusive. Multiple aetio‐pathological mechanisms have been postulated.The gut has an extensive immune system but current understanding of processing of food antigens in health and disease is limited. There is no clinically useful marker available to test for food hypersensitivity in irritable bowel syndrome. Researchers have employed both skin tests and serum immunoglobulins (IgG and IgE) as markers of food hypersensitivity in various disorders including irritable bowel syndrome, but published data are equivocal.In this article, the evidence for the role of food hypersensitivity in irritable bowel syndrome is reviewed and, based on the available data, a possible pathophysiological hypothesis has been formulated.
Infliximab induces potent anti‐inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn’s disease
Authors: Cornillie F. , Shealy D. , D'Haens G. , Geboes K. , Van Assche G. , Ceuppens J. , Wagner C. , Schaible T. , Plevy S. E. , Targan S. R. , Rutgeerts P. 
Published: March 2003

Background:Anti‐TNFα therapy with infliximab is effective for Crohn’s disease. Infliximab neutralizes the biological activities of TNFα, a cytokine involved in host‐defence against certain infections.Aim:To evaluate the effects of infliximab on the gut and peripheral immune system functions.Methods:Biopsies and blood samples from three clinical trials of infliximab in Crohn’s disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed.Results:Infliximab has a serum half‐life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNγ and TNFα did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy.Conclusion:The clinical efficacy of infliximab is based on local anti‐inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn’s disease patients.
Role of reactive oxygen metabolites in aspirin‐induced gastric damage in humans: gastroprotection by vitamin C
Authors: Pohle T. , Brzozowski T. , Becker J. C. , Van Der Voort I. R. , Markmann A. , Konturek S. J. , Moniczewski A. , Domschke W. , Konturek J. W. 
Published: March 2003

Background:The roles of active oxygen metabolites and anti‐oxidative defenses in aspirin (ASA)‐induced gastric damage have been little studied.Aim:We determined the effects of aspirin (400 mg b.d.) with or without vitamin C (480 mg b.d.) for 3 days on gastric mucosa in human volunteers.Methods:Gastric injury was assessed endoscopically; gastric blood flow, reactive oxygen release (quantified by chemiluminescence), lipid peroxidation, myeloperoxidase, superoxide dismutase and glutathione peroxidase activity and intragastric vitamin C content were measured. Expression of superoxide dismutase and glutathione peroxidase mRNAs was assayed semi‐quantitatively.Results:ASA produced erosions, a marked increase in chemiluminescence, lipid peroxidation, and myeloperoxidase activity. It also resulted in a suppression of gastric blood flow, intragastric vitamin C levels, superoxide dismutase and glutathione peroxidase activities. The addition of vitamin C significantly attenuated gastric damage and reversed the effects of ASA on these parameters. Superoxide dismutase and glutathione peroxidase mRNAs were decreased in ASA‐treated subjects; the addition of vitamin C restored their regular levels.Conclusions:(i) free radical‐induced lipid peroxidation and suppression of antioxidizing enzymes play an important role in gastric damage induced by aspirin; (ii) increased myeloperoxidase activity suggests activated neutrophils to be the major source of these radicals; (iii) vitamin C protects against ASA‐induced damage due to its anti‐oxidizing activity.