bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of water extracts of CagA positive or negative Helicobacter pylori on proliferation, apoptosis and connexin formation in acetic acid‐induced gastric ulcer of rats
Authors: Mine T. , Endo C. , Kushima R. , Kushima W. , Kobayashi I. , Muraoka H. , Taki R. , Fujita T. 
Published: March 2003

Summary Aim: To investigate the influence of water extracts of CagA‐positive or ‐negative Helicobacter pylori on healing of chronic gastric ulcers and on connexin formation, proliferation and apoptosis, in acetic acid‐induced chronic gastric ulcers in rats. Methods: Acetic acid was used to induce chronic gastric ulcers in rats, and a water extract of H. pylori was given by mouth every day. Connexin 32 formation was assessed using Western blotting as previously described. The frequencies of proliferating cell nuclear antigen staining and of TdT‐mediated dUTP‐biotin nick end labelling were examined. Results: In untreated rats, acetic acid‐induced gastric ulcers healed after 14 days and the electrophoretic band corresponding to connexin 32 appeared 4 days after ulcer induction. Treatment with a water extract of H. pylori delayed ulcer healing, with the ulcers remaining unhealed even on the 14th day; healing was delayed more when treatment was with an extract of CagA‐positive rather than CagA‐negative H. pylori. Connexin 32 appeared earlier when treatment was with a CagA‐negative rather than a CagA‐positive extract, but in both cases later than in the untreated control group. Proliferating cell nuclear antigen labelling on the fourth day was seen in 14.5% ± 1.6% of mucosal cells of control group, but in 35.9% ± 1.4% and 36.5% ± 1.4% of mucosal cells treated with either VacA(+)CagA(–) and VacA(+)CagA(+) H. pylori extract, respectively. Furthermore, extracts of both H. pylori strains, especially VacA(+)Cag(+) H. pylori promoted apoptosis. Conclusions: A water extract of H. pylori increased both proliferation and apoptosis, which are related to excerbation and healing of ulcer as well as appearance of connexin 32.
Review article: control of gall‐bladder motor function
Authors: Shaffer E. A. 
Published: March 2003

SummaryMuscular contraction of the gall‐bladder is the primary determinant of bile delivery into the duodenum. Where bile goes following its secretion by the liver depends upon a co‐ordinated series of pressure interrelations between the hepatic secretory pressure at the entrance to the biliary system, a low pressure conduit, and the pressure differences between the gall‐bladder, cystic duct and sphincter of Oddi. During fasting, the relatively higher tone in the sphincter of Oddi fosters the entry of bile into the gall‐bladder. The gall‐bladder accommodates this influx without an increase in intravesicular pressure through its compliance or distensibility, which consists of active muscle relaxation and passive fibroelastic components. The concentrating function of the gall‐bladder keeps the volume small. Once about every 120 min during the interdigestive period, gall‐bladder emptying occurs coincident with intense duodenal contractions, all part of the migratory myoelectric complex. This helps maintain the enterohepatic circulation of bile salts. Motilin, which mediates these events during fasting, acts by stimulating intrinsic cholinergic nerves. Cholecystokinin is the major determinant of gall‐bladder emptying with eating. Cholecystokinin acts through pre‐ganglionic cholinergic nerves, to initiate gall‐bladder contraction. Agonists like cholecystokinin and acetylcholine cause contraction of gall‐bladder smooth muscle through signal transduction, which increases intracellular calcium levels and so initiates the contractile machinery. Cholecystokinin also acts on the sphincter of Oddi via pre‐ganglionic cholinergic nerves to release vasoactive intestinal polypeptide and nitric oxide, and so lower tone. These events are co‐ordinated with motility and secretory events in the upper gastrointestinal tract, delivering bile at appropriate times into the duodenum.
Helicobacter pylori, mucosal inflammation and symptom perception – new insights into an old hypothesis
Authors: Stanghellini V. , Barbara G. , De Giorgio R. , Tosetti C. , Cogliandro R. , Cogliandro L. , Salvioli B. , Corinaldesi R. 
Published: March 2003

The role of Helicobacter pylori and the accompanying mucosal inflammatory response in functional dyspepsia is still undefined. Human and animal studies have clearly demonstrated a link between intestinal mucosal inflammation and changes in sensory‐motor function. Growing clinical and basic evidence supports the concept that a similar paradigm may occur in H. pylori‐related dyspepsia. The infection may both induce gastric dysmotility and trigger neuroplastic changes in the afferent neural pathways leading to visceral hyperalgesia. A reduction of central antinociceptive control systems may also play a pathophysiological role. H. pylori eradication has provided disappointing results in terms of improvement of symptoms. This may reflect the long‐term recovery of neuroplastic changes occurring in the afferent nervous system or, alternatively, the incomplete resolution of gastritis and the persistent production of inflammatory mediators by resident cells in the muscularis externa.The identification of these mechanisms may provide a better understanding of the pathophysiology of H. pylori‐related dyspepsia and prompt innovative therapeutic approaches.
The gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase‐2, in humans
Authors: Hawkey C. J. , Jackson L. , Harper S. E. , Simon T. J. , Mortensen E. , Lines C. R. 
Published: March 2003

Highly selective inhibitors of cyclooxygenase‐2, such as rofecoxib, are hypothesized to have an improved gastrointestinal tolerability and safety profile compared with non‐selective NSAIDs, which inhibit cyclooxygenase‐1 and cyclooxygenase‐2 non‐selectively. This paper reviews data from randomized, double‐blind, placebo‐controlled studies which investigated the effects of rofecoxib and NSAIDs on the human gastrointestinal tract.In healthy subjects, rofecoxib 25 mg and 50 mg daily had no effect on gastric mucosal prostaglandin synthesis, whilst naproxen 1000 mg daily caused a 70% reduction. Therapeutic doses of rofecoxib 25 mg and 50 mg daily did not increase intestinal permeability or faecal blood loss in healthy subjects, whereas increases in both measures were seen with indometacin 150 mg or ibuprofen 2400 mg. A supra‐therapeutic dose of rofecoxib (250 mg) given daily for 7 days did not induce an increase in gastroduodenal erosions in healthy subjects, whilst increased numbers of erosions were found in subjects given ibuprofen 2400 mg or aspirin 2600 mg.The endoscopic findings in healthy subjects were confirmed in two 6‐month clinical studies involving 1516 patients with osteoarthritis; the incidences of ulcers following rofecoxib 25 mg or 50 mg daily were similar to placebo and less than ibuprofen 2400 mg. The advantage of rofecoxib over NSAIDs in these studies appears to translate into clinically relevant benefits; an analysis of 5435 patients with osteoarthritis found a significantly lower incidence of gastrointestinal perforations, ulcers and bleeds in patients taking rofecoxib compared with patients taking NSAIDs.Overall, the findings from these studies suggest that, as a result of cyclooxygenase‐1 sparing, rofecoxib is significantly less gastrotoxic than non‐selective NSAIDs, and may not differ from placebo.
Maximal acid reflux control for Barrett’s oesophagus: feasible and effective
Authors: Srinivasan R. , Katz P. O. , Ramakrishnan A. , Katzka D. A. , Vela M. F. , Castell D. O. 
Published: March 2003

Introduction:The treatment of patients with Barrett’s oesophagus is controversial. Debate exists regarding the use and value of high dose acid suppression as the standard of practice. Despite prolonged use of high dose proton pump inhibitors (40 mg omeprazole, 60 mg lansoprazole), most studies have shown no convincing evidence of significant regression of Barrett’s length. These studies, however, have used fixed doses of proton pump inhibitors and did not regularly document control of oesophageal acid exposure.Aim:To determine whether regression of Barrett’s epithelium can be achieved with documented maximal acid suppression.Methods:We have prospectively followed nine patients with Barrett’s oesophagus (eight male; mean age 60 years) for more than 1 year. They were all treated using medical therapy with pH monitoring documenting oesophageal acid exposure over 24 h < 1.6% of the time, and with two or more esophagogastroduodenoscopies performed by the same endoscopist.Results:Acid control was individually tailored and achieved with proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) and ranitidine at bedtime (HS) (Ran) if necessary. All nine patients (100%) showed some evidence of regression. All nine patients (100%) showed a decrease in Barrett’s length (mean 2 cm, range 1–3 cm). Six out of nine (66.67%) patients showed evidence of squamous islands on the last oesophagogastroduodenoscopy. The mean total distal oesophageal acid exposure was 0.38% (range: 0–1.5%). The mean follow‐up of patients was 54 months (range: 13–118 months).Conclusions:Consistent and individually tailored maximal acid suppression documented by pH‐metry is achievable and may result in decreased length and development of squamous islands in patients with Barrett’s epithelium. This approach should be further evaluated as potentially the preferred medical treatment for these patients.
Review article: the risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment
Authors: Aithal G. P. , Mansfield J. C. 
Published: March 2003

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is incre‐ ased by immunosuppressive treatment with azathiop‐ rine, 6‐mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments.The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow‐up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population‐based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2–3‐fold, may be compatible with both sets of data.Studies of the risks associated with immuno‐ suppression are less satisfactory, with smaller numbers of patients and relatively short follow‐up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant‐related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long‐term safety, but post‐marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6‐mercaptopurine.Population‐wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.
Outcomes of Helicobacter pylori treatment in community practice and impact of therapeutic effectiveness information on physician behaviour
Authors: Fennerty M. B. , Magaret N. , Dalros L. , Faigel D. , Lieberman D. , Shaw M. 
Published: March 2003

Background:The effect of knowledge of Helicobacter pylori eradication rates on physician choice of treatment regimen is unknown. As practice variation results in differences in outcome, it is important to determine whether physician behaviour can be altered by such knowledge.Aims:(i) To determine whether dissemination of practice variation and effectiveness data regarding H. pylori changes subsequent prescribing behaviour and (ii) whether this change results in an improvement in the effectiveness of therapy.Methods:Community gastroenterologists in the Portland metropolitan area enrolled patients being treated for H. pylori. The regimen used, diagnostic method, indication and success in eradication was measured. Patient‐centred factors were also measured, including symptoms, interest in post‐treatment diagnostic testing and willingness to pay.Results:Significantly more physicians participating in both studies used proton pump inhibitor–triple therapy based regimens in this trial (46% vs. 85%, P=0.01), although the overall difference between the two trials was not significant (62% vs. 83%, P=0.11). There was no change in overall eradication rates by per protocol analysis between trials (84% vs. 85%, P=0.78), but a significant decrease in effectiveness by intention‐to‐treat analysis observed in this study (80% vs. 71%, P=0.03). Significantly more patients were treated for reasons other than peptic ulcer disease in this study (P=0.0003).Conclusions:The overall effectiveness of H. pylori therapy in practice remains good. There has been a shift in the choice of treatment regimen and indication for therapy between the time periods of the two studies. Dissemination of treatment data appears to effect prescribing behaviour, but whether it has a beneficial effect on treatment outcome remains unproven.
The role of age and salivation in acid clearance in symptomatic patients with gastro‐oesophageal reflux disease
Authors: Orr W. C. , Chen C.‐L. , Sloan S. 
Published: March 2003

Background:Cisapride has been shown to have not only prokinetic effects, but also salivary stimulating effects. Both of these mechanisms play an important role in the acid clearance of the oesophagus.Aim:To access the efficacy of cisapride in facilitating acid clearance in patients with symptomatic gastro‐oesophageal reflux disease.Methods:Fifteen older adults and 15 younger adults with symptomatic gastro‐oesophageal reflux disease completed the study. The acid clearance test was accomplished by infusing 15 mL of 0.1 NHCl into the distal oesophagus, and the number of swallows was determined to achieve an oesophageal pH of 4.0. This was accomplished under baseline conditions and salivary stimulation with a peppermint lozenge. After 1 week of treatment with cisapride (10 mg, q.d.s.), the acid clearance test was repeated.Results:The lozenge produced a significant decrease in the number of swallows compared to baseline in both groups (P < 0.01). There was a significant decrease in the number of swallows after the treatment with cisapride compared to baseline in both groups (P < 0.01). No significant difference was found in the number of swallows when comparing cisapride with lozenge.Conclusions:Cholinergic stimulation of salivation is an effective means of facilitating oesophageal acid clearance. Drugs, such as 5 hydroxytriptamine (5‐HT)4‐receptor agonists, should be considered as potentially important compounds in the treatment of gastro‐oesophageal reflux disease.
Plasma transforming growth factor‐β1 level and efficacy of α‐tocopherol in patients with non‐alcoholic steatohepatitis: a pilot study
Authors: Hasegawa T. , Yoneda M. , Nakamura K. , Makino I. , Terano A. 
Published: March 2003

Background:Non‐alcoholic steatohepatitis is a distinct entity, characterized by fatty change, lobular inflammation and fibrosis of the liver. Some cases of non‐alcoholic steatohepatitis progress to cirrhosis, but it is not easy to distinguish this disease from non‐alcoholic fatty liver by non‐invasive examinations. No proven therapy for non‐alcoholic steatohepatitis exists. Transforming growth factor‐β1 is implicated in the development of liver fibrosis, and is inhibited by α‐tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor‐β1 and the effect of α‐tocopherol on the clinical course of non‐alcoholic steatohepatitis were investigated.Methods:Twelve patients with non‐alcoholic steatohepatitis and 10 patients with non‐alcoholic fatty liver, with a diagnosis confirmed by liver biopsy, were studied. None of the patients had a history of alcohol abuse, habitual medicine or malignant or inflammatory diseases. All patients were negative for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then α‐tocopherol (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor‐β1 level and liver biopsies were undertaken before and after the 1‐year α‐tocopherol treatment.Results:The serum alanine transaminase level decreased in non‐alcoholic fatty liver patients, but not in non‐alcoholic steatohepatitis patients, after 6 months of dietary therapy. Although the serum alanine transaminase level in non‐alcoholic steatohepatitis patients was reduced during the 1‐year α‐tocopherol treatment, α‐tocopherol had no effect on the serum alanine transaminase level in non‐alcoholic fatty liver patients. The histological findings, such as steatosis, inflammation and fibrosis, of the non‐alcoholic steatohepatitis patients were improved after α‐tocopherol treatment. The plasma transforming growth factor‐β1 level in non‐alcoholic steatohepatitis patients was significantly elevated compared with that in non‐alcoholic fatty liver patients and healthy controls, and decreased, accompanied by an improvement in serum alanine transaminase level, with α‐tocopherol treatment.Conclusions:lOur data suggest that the measurement of the level of plasma transforming growth factor‐β1 represents a possible method of distinguishing between non‐alcoholic steatohepatitis and non‐alcoholic fatty liver. Long‐term α‐tocopherol treatment may be safe and effective for non‐alcoholic steatohepatitis. A randomized, controlled, double‐blind trial is needed to confirm the full potential of α‐tocopherol in the management of non‐alcoholic steatohepatitis.
Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn’s disease
Authors: Goodgame R. W. , Kimball K. , Akram S. , Ike E. , Ou C.‐N. , Sutton F. , Graham D. 
Published: March 2003

Background:A mycobacterial infection may be the cause of Crohn’s disease in some patients. Measurement of intestinal permeability may identify Crohn’s disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury.Aim:To assess the effect of 3 months of clarithromycin and ethambutol on the disease activity and intestinal permeability in patients with Crohn’s disease at high risk of relapse.Methods:Patients with Crohn’s disease, with a lactulose–mannitol permeability test above 0.03, were randomly assigned to receive either clarithromycin, 500 mg twice daily, and ethambutol, 15 mg/kg daily, or identically appearing placebo for 3 months in addition to their regular therapy. The Harvey–Bradshaw index and the lactulose–mannitol test were assessed in a blind fashion every 3 months for 12 months.Results:Thirty‐one patients were randomized to receive either drugs (n=15) or placebo (n=16). The groups were similar in age, sex, duration of disease, location of disease, past complications and disease severity. Specifically, there was no difference between the drug or placebo groups in the mean Harvey–Bradshaw index (4.8 vs. 4.4), number with active disease (33% vs. 44%) and mean lactulose–mannitol test (0.06 vs. 0.10). During the 12‐month follow‐up period, there were no consistent, statistically significant differences in the mean Harvey–Bradshaw index or lactulose–mannitol test between treatment and placebo groups. Individual patients showed either improvement or worsening of these indices, but these were not related to study medication. Specifically, no ‘cures’ were noted with anti‐mycobacterial treatment.Conclusions:Three months of treatment with clarithromycin and ethambutol does not benefit Crohn’s disease patients who are receiving standard medical therapy.
Rabeprazole‐based 3‐day and 7‐day triple therapy vs. omeprazole‐based 7‐day triple therapy for the treatment of Helicobacter pylori infection
Authors: Wong B. C. Y. , Wong W. M. , Yee Y. K. , Hung W. K. , Yip A. W. C. , Szeto M. L. , Li K. F. , Lau P. , Fung F. M. Y. , Tong T. S. M. , Lai K. C. , Hu W. H. C. , Yuen M. F. , Hui C. K. , Lam S. K. 
Published: March 2003

Background:Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti‐Helicobacter effects.Aim:To compare two different regimens of rabeprazole‐based triple therapy vs. 7‐day omeprazole‐based triple therapy for the eradication of Helicobacter pylori infection.Method:Patients with proven H. pylori infection were randomized to receive: (i) 7‐day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3‐day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7‐day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment.Results:One hundred and seventy‐three patients were randomized. H. pylori eradication rates (intention‐to‐treat, n=173/per protocol, n=167) were 88%/91% for 7‐day rabeprazole‐based therapy, 72%/72% for 3‐day rabeprazole‐based therapy and 82%/89% for 7‐day omeprazole‐based therapy, respectively. The per protocol eradication rate was significantly better in the 7‐day rabeprazole‐based therapy and 7‐day omeprazole‐based therapy groups when compared to the 3‐day rabeprazole‐based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated.Conclusions:The efficacy of seven‐day rabeprazole‐based triple therapy is similar to 7‐day omeprazole‐based triple therapy for the eradication of H. pylori infection.
The efficacy of thymosin in the treatment of chronic hepatitis B virus infection: a meta‐analysis
Authors: Chan H. L.‐Y. , Tang J.‐L. , Tam W. , Sung J. J.‐Y. 
Published: March 2003

Background:Trials of thymosin treatment in chronic hepatitis B virus infection have been small and the results have been inconsistent.Aim:To conduct a meta‐analysis to evaluate the efficacy of thymosin treatment in chronic hepatitis B virus infection.Methods:Randomized controlled trials comparing thymosin for over 24 weeks vs. placebo (or usual care) in the treatment of chronic hepatitis B virus infection were identified through MEDLINE, EMBASE and the Cochrane Register of Clinical Trials. Biochemical (normalization of transaminases) and virological (loss of hepatitis B virus DNA and hepatitis B e antigen) responses were analysed using the intention‐to‐treat method. The odds ratio was used to measure the magnitude of the efficacy.Results:Five trials (353 patients) were identified. The odds ratio (95% confidence interval) of the virological response of thymosin over placebo at the end of treatment, 6 months post‐treatment and 12 months post‐treatment were 0.56 (0.2–1.52), 1.67 (0.83–3.37) and 2.67 (1.25–5.68), respectively. There was an increasing trend of the virological response with time since the cessation of thymosin treatment (P=0.02). There was no difference in the biochemical response between the thymosin and placebo groups at the end of treatment, 6 months post‐treatment and 12 months post‐treatment.Conclusions:Thymosin is effective in suppressing viral replication in chronic hepatitis B virus infection, but the effect is delayed until 12 months after the cessation of treatment.