bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional loss of TGF‐β signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice
Authors: Hahm K‐B. , Lee K. M. , Kim Y. B. , Hong W. S. , Lee W. H. , Han S. U. , Kim M. W. , Ahn B. O. , Oh T. Y. , Lee M. H. , Green J. , Kim S. J. 
Published: March 2003

Background:Downregulation of TGF‐β receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF‐β1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis.Methods:We generated transgenic mice, called pS2–dnRII or ITF–dnRII, of which the dominant negative mutant of the TGF‐β type II receptor was expressed under the control of tissue‐specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF‐β signalling in gastrointestinal carcinogenesis.Results:Gastric adenocarcinoma developed in pS2–dnRII mice, whereas only chronic active gastritis was noted in wild‐type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF‐β signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen‐labelling index when infected with H.pylori than wild‐type littermates (P < 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF–dnRII mice showed significantly higher incidences of ACF and colon cancers than wild‐type littermates.Conclusions:Maintaining normal TGF‐β signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.
The relationship between gastric cancer cells circulating in the blood and microsatellite instability positive gastric carcinomas
Authors: Czopek J. , Bialas M. , Rudzki Z. , Zazula M. , Pituch‐Noworolska A. , Zembala M. , Popiela T. , Kulig J. , Kolodziejczyk P. , Stachura J. 
Published: March 2003

Background:Cancers characterized by microsatellite instability may be biologically different from their counterparts with stable microsatellite sequences. Circulating cancers cell present in blood prior to surgery may constitute an adverse prognostic finding.Aim:To correlate these two phenomena with morphological features and survival in advanced gastric cancer.Methods:We examined 76 cases of resected sporadic, advanced gastric cancer by means of routine morphology and a panel of microsatellite markers. Sixty‐six cases were screened for presence of cancer cells circulating in blood prior to the surgery using combined morphological and immunocytochemical approach.Results:Twenty‐one (27.6%) cases demonstrated microsatellite instability in at least one locus. Among them 11 (14.5%) showed microsatellite instability in more than 30% (4/12) examined loci, and they were therefore designated as replication error positive (RER+). Circulating cancer cells were detected in 2/19 microsatellite instability and in 11/47 remaining cases (difference not significant). The survival of the microsatellite instability cases was significantly better. The presence of circulating cancer cells did not correlate with survival.Conclusion:It is possible that the microsatellite instability status, but not circulating cancer cells, constitutes a prognostic predictive factor in advanced gastric carcinoma. Confirmation of this hypothesis requires continuation of patient follow‐up.
Review article: albumin for circulatory support in patients with cirrhosis
Authors: Ginès P. , Guevara M. , De Las Heras D. , Arroyo V. 
Published: March 2003

SummaryRenal function abnormalities and ascites in cirrhosis are the final consequence of a circulatory dysfunction characterized by marked splanchnic arterial vasodilation. This causes a reduction in effective arterial blood volume and the homoeostatic activation of vasoconstrictor and sodium‐retaining systems. Albumin is very effective in preventing renal failure associated with large‐volume paracentesis and spontaneous bacterial peritonitis, conditions that are known to cause an impairment of circulatory function in patients with cirrhosis and ascites. Moreover, albumin administration improves survival in patients with spontaneous bacterial peritonitis. In patients with hepatorenal syndrome the administration of vasoconstrictor drugs in combination with albumin improves circulatory and renal function markedly and survival slightly. By contrast, the administration of albumin without vasoconstrictors has marginal or no effects on renal function in this setting.
Review article: the Molecular Adsorbents Recirculating System (MARS) in liver failure
Authors: Sen S. , Mookerjee R. P. , Davies N. A , Williams R. , Jalan R. 
Published: March 2003

SummaryIn recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. The molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialysed across an albumin‐impregnated membrane against a recirculated albumin‐containing solution, seems to be effective in removing albumin‐bound toxins, such as fatty acids, bile acids and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. Data regarding MARS experience in acute liver failure and in primary graft dysfunction are encouraging but limited. Its real usefulness in these settings is, at present, under evaluation in randomized controlled clinical trials.
Review article: initial therapy of reflux disease with esomeprazole
Authors: Dent J. 
Published: March 2003

SummaryLarge clinical trials in patients with reflux oesophagitis have shown esomeprazole, 40 mg once daily, to be convincingly superior in the healing of oesophagitis when compared with both omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily. The greatest advantage for esomeprazole is with healing of the more severe grades of oesophagitis. Esomeprazole, 40 mg once daily, has also been shown to be significantly superior in the treatment of heartburn. Studies in endoscopy‐negative patients, or in both oesophagitis and endoscopy‐negative patients, have demonstrated good efficacy for esomeprazole, with high levels of symptom control achieved in the first 7 days of therapy.
Clinical economics review: functional (non‐ulcer) dyspepsia
Authors: Tebaldi  , Heading  
Published: March 2003

Dyspepsia is common within the general population and it imposes a significant burden on health‐care resources. Calculation of the economic implications of functional dyspepsia is constrained by the fact that it is only possible to make this diagnosis in a minority of individuals with the disorder, because many do not seek medical attention and investigation is not appropriate for all who do. Studies which attempt to assess the effectiveness or cost‐effectiveness of therapy may be further constrained by the fact that there is now good evidence that many patients with dyspepsia seek medical attention not so much because of the severity of symptoms, but because they fear that the symptoms signal the presence of some serious underlying disease. In this situation, effective well‐founded reassurance that no serious disease is present is an important outcome of medical intervention and one which should be included in an economic appraisal of dyspepsia management.For obvious reasons, it is sensible to compare the cost‐effectiveness of various clinical management strategies applicable in dyspepsia. Decision‐tree analyses are currently fashionable but suffer from the major defect that there is no theoretical basis from which patient satisfaction with treatment options can be assessed. It is suggested that for disorders such as functional dyspepsia, which are non‐lethal and non‐progressive, recommendations about acceptable clinical manage‐ ment strategies require that account be taken of patient satisfaction with the strategies being reviewed. Cost‐effectiveness calculations which take no account of this aspect of outcome are of limited relevance to clinical practice.
The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro‐oesophageal reflux disease
Authors: Ruth  , Hamelin  , Röhss  , Lundell  
Published: March 2003

Background:Mosapride is a novel prokinetic agent facilitating acetylcholine release from the enteric cholinergic neurones through a selective 5‐HT4 receptor agonistic action. It is also active through its main metabolite M1, which is a 5‐HT3 antagonist. The importance of motor dysfunction in the pathogenesis of gastro‐oesophageal reflux disease (GERD) makes it interesting to examine the effect of mosapride on oesophageal acid exposure.Methods:The effect of mosapride on oesophageal 24‐h acid reflux variables was studied in 21 patients with GERD symptoms and a pre‐entry total acid exposure time (pH < 4) of more than 5%. Ambulatory pH monitoring was performed after treatment with 40 mg mosapride citrate or placebo q.d.s. for 2 days in random order, using a double‐blind crossover technique, with a washout period of at least 5 days.Results:Mosapride was significantly more effective than placebo in decreasing the total number of reflux episodes, the total number of reflux episodes lasting more than 5 min and the total time, as well as the amount of day time, of intra‐oesophageal pH below 4. Consequently, mosapride also significantly improved total acid clearance time.Conclusion:Mosapride 40 mg q.d.s. is effective in decreasing acid reflux in the oesophagus in patients with GERD and therefore has the potential to be effective in the treatment of this disease.
Ranitidine bismuth citrate versus omeprazole triple therapy for the eradication of Helicobacter pylori and healing of duodenal ulcer
Authors: Catalano  , Catanzaro  , Bentivegna  , Brogna  , Condorelli  , Cipolla  
Published: March 2003

Aim:To compare the efficacy and safety of triple therapy with omeprazole plus amoxycillin and clarithromycin vs. ranitidine bismuth citrate plus amoxycillin and clarithromycin in the treatment of Helicobacter pylori‐associated duodenal ulcers.Methods:Eighty‐one patients with duodenal ulcers were randomized to the following treatments: 39 cases with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week plus omeprazole 20 mg b.d. for 2 weeks (omeprazole + amoxycillin + clarithromycin (OAC)), and 42 cases to the same regimen of amoxycillin and clarithromycin for 7 days plus ranitidine bismuth citrate 400 mg b.d. for 2 weeks (ranitidine bismuth citrate + amoxycillin + clarithromycin (RbAC)). Upper gastrointestinal endoscopy was performed together with a rapid urease test and histological examination of antral and corpus biopsy samples prior to treatment and 4 weeks after the end of therapy.Results:Thirty‐four patients in the OAC group and 38 in the RbAC group completed the treatment and 4‐week follow‐up. H. pylori was eradicated in 30 of 34 patients (88%) in the OAC group and in 32 of 38 patients (84%) in the RbAC group according to a per‐protocol analysis (P = N.S.). Thirty‐three (97%) patients treated with OAC and 36 (95%) treated with RbAC presented healed duodenal ulcers at 4 weeks (P = N.S.). On an intention‐to‐treat basis there was no difference in H. pylori eradication between the OAC (77%) and RbAC groups (76%); duodenal ulcer healing was achieved in 85 and 86% of patients in the OAC and RbAC groups, re‐ spectively (P = N.S.).Conclusion:The OAC and RbAC triple therapy regimens proved equally effective in both H. pylori eradication and in duodenal ulcer healing.
Pantoprazole‐based 10‐day triple therapy is effective in Helicobacter pylori eradication
Authors: Bardhan  , Morton  , Slater  , Perry  , Cherian  , Jones  , Brookes  , Thompson  , Morris  , McCaldin  
Published: March 2003

Aim:To investigate the efficacy of a short course of pantoprazole‐based triple therapy in Helicobater pylori eradication in a single‐centre pilot study.Methods:Patients with active or healed duodenal ulcer or with gastric erosions or gastritis, all of whom were H. pylori‐positive, received 10 days of twice‐daily open treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and tinidazole 500 mg. H. pylori was assessed at entry and 28–35 days after the end of treatment by rapid urease test (at entry only), culture and antimicrobial sensitivity, histology and 13C urea breath test. The criterion for eradication was a negative result in all three tests.Results:Seventy patients were treated, of whom four were excluded from analysis due to major deviations from the study protocol. Eradication of H. pylori was achieved in 57/66 patients (per protocol analysis 86% (95% CI: 78–95%)) and was higher in patients with organisms sensitive to nitroimidazole before treatment (sensitive: 47/53 (89%), insensitive: 10/13 (77%)). There was marked reduction in acute gastritis throughout the stomach while chronic gastritis decreased only in the corpus. Healing was achieved in all 24 patients with active duodenal ulcer. Treatment was complied with; only one patient missed one of the 20 doses. Adverse events were of mild or moderate intensity and did not require withdrawal from treatment.Conclusion:A short course of pantoprazole‐based triple therapy is well tolerated and effective in eradicating H. pylori.
Dose–response relationship of lansoprazole to gastric acid antisecretory effects
Authors: Blum  , Hunt  , Kidd  , Shi  , Jennings  , Greski‐Rose  
Published: March 2003

Background:Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and gastro‐oesophogeal reflux disorders. Optimal healing rates of antisecretory therapy for peptic acid disease is dependent upon the degree and duration of acid suppression and the length of treatment.Objective:To evaluate the extent and duration of gastric acid suppression of several lansoprazole regimens, administered for 5 consecutive days in 32 healthy adult male subjects.Methods:Intragastric 24‐h pH monitoring was performed in 32 healthy subjects in a randomized, double‐blind, four‐way crossover study. Sixteen subjects (Group 1) received lansoprazole 30 mg o.d. (once daily), 15 mg b.d. (twice daily), 30 mg b.d. and 30 mg t.d.s. (three times a day) for 5 days; and 16 subjects (Group 2) received lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. for 5 days.Results:Mean 24‐h intragastric pH values for lansoprazole 30 mg o.d., 15 mg b.d., 30 mg b.d. and 30 mg t.d.s. were 4.47, 4.57, 5.07 and 5.63, respectively. Multiple‐dose regimens of lansoprazole 30 mg b.d. and t.d.s. produced greater acid suppression compared to lansoprazole 30 mg o.d. and 15 mg b.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 15 mg b.d. Mean 24‐h intragastric pH values for lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. were 4.13, 4.45, 5.19 and 5.13, respectively. Multiple‐dose regimens of lansoprazole 60 mg b.d. and t.d.s. produced significantly greater acid suppression compared to lansoprazole 30 mg o.d. and 60 mg o.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 60 mg o.d. Lansoprazole 30 mg t.d.s., 60 mg b.d. and 60 mg t.d.s. produced significantly greater percentage time above pH 3, 4, 5 and 6 than did lansoprazole 30 mg o.d. Post‐regimen serum gastrin values increased by 50–130% from pre‐study mean values but remained within normal range and returned to pre‐study values 7–14 days post‐dosing.Conclusions:Multiple‐dose regimens of lansoprazole (≥30 mg b.d. for 5 days) produce significantly increased intragastric pH and significantly longer duration of increased intragastric pH than does lansoprazole 30 mg administered once daily.
Screening for Helicobacter pylori in young dyspeptic patients referred for investigation—endoscopy for those who test negative
Authors: Breslin  , Lee  , Buckley  , O’morain  
Published: March 2003

Background:Studies in young dyspeptic patients have suggested that screening strategies based on non‐invasive H. pylori testing can reduce endoscopy workload by 25–40%. Such strategies usually propose that only H. pylori‐positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease.Aim:To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori‐negative dyspeptics.Methods:Seventy‐two consecutive patients under 45 years of age undergoing investigation for ‘ulcer‐like’ dyspepsia had invasive and non‐invasive determination of H. pylori status. Individuals found to be H. pylori‐positive at endoscopy received 1 week of proton pump inhibitor‐based triple therapy. H. pylori‐negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically‐positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy.Results:According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow‐up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically‐positive patients would ultimately have required an endoscopy and the other 25 serologically‐positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically‐negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population.Conclusion:A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.
Influence of clarithromycin dosage on pantoprazole combined triple therapy for eradication of Helicobacter pylori
Authors: Ellenrieder  , Fensterer  , Waurick  , Adler  , Glasbrenner  
Published: March 2003

Background:Low‐dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known.Aim:To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole.Methods:One hundred and sixty‐three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.), metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the 13C‐urea breath test.Results:One‐hundred and thirty‐nine patients completed the study. Based on a per protocol analysis, successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention‐to‐treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%).Conclusions:Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.
One‐week use of ranitidine bismuth citrate, amoxycillin and clarithromycin for the treatment of Helicobacter pylori‐related duodenal ulcer
Authors: Sung  , Leung  , Ling  , Yung  , Chan  , Lee  , Cheng  , Chung  
Published: March 2003

Background:Proton pump inhibitors have been widely used in combination with amoxycillin, clarithromycin or metronidazole for the treatment of Helicobacter pylori infection.Aim:To study the effects of 1‐week ranitidine bismuth citrate (RBC)‐based triple therapy in the treatment of H. pylori‐related duodenal ulcers.Method:Patients with duodenal ulcers and H. pylori infection were prospectively randomized to receive either RBC with amoxycillin and clarithromycin for 1 week (RAC), or omeprazole with amoxycillin and clarithromycin for 1 week (OAC). No additional ulcer healing drug was used after the 1‐week medication. Patients were assessed for H. pylori eradication, ulcer healing and side‐effects after receiving the therapies.Results:One hundred consecutive patients were recruited to this study, with 50 patients randomized to each treatment group. In the intention‐to‐treat analysis, duodenal ulcers were completely healed in 45 (90%) patients in the RAC group and 43 (89.6%) in the OAC group (P = 1.0). H. pylori eradication was confirmed in 47 (94%) in the RAC group and 42 (87.5%) in the OAC group (P = 0.31). There was no significant difference in the severity of side‐effects experienced by the two treatment groups.Conclusion:One‐week RBC‐based triple therapy is an effective treatment for H. pylori‐related duodenal ulcers. The therapeutic effects are comparable to a 1‐week course of proton pump inhibitor‐based triple therapy.
The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non‐ulcer dyspepsia
Authors: Besherdas  , Leahy  , Mason  , Harbord  , Epstein  
Published: March 2003

Background:The electrogastrogram (EGG), which records gastric myoelectrical activity, is abnormal in one‐third of adult patients with non‐ulcer dyspepsia (NUD).Aim:To observe the effects of cisapride on EGG in adults with NUD.Methods:Twenty‐seven NUD patients who had undergone a pre‐ and post‐prandial EGG were entered into an open study. All patients completed a dyspepsia symptom questionnaire and were then treated with cisapride 10 mg t.d.s. The dyspepsia questionnaire was repeated in all those completing 4 weeks of treatment. Those with an initial abnormal EGG (< 70% of slow wave activity at 2–4 cycles per minute) had a repeat EGG at the end of the study.Results:Treatment with cisapride was associated with a significant improvement in the post‐prandial EGG (P = 0.007). After 4 weeks of treatment, 7 of 13 abnormal EGGs normalized. Symptom scores improved significantly in the 13 patients with an abnormal EGG who completed treatment (P < 0.0003), but not in NUD patients with a normal EGG (P = 0.48).Conclusion:In this open study, treatment of NUD with cisapride was associated with significant symptom improvement in patients with an abnormal pre‐treatment EGG, but not those with a normal EGG, with a significant improvement of the post‐prandial EGG.