bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid suppression in peptic ulcer haemorrhage: a ‘meta‐analysis’
Authors: Selby  , Kubba  , Hawkey  
Published: March 2003

Background:The use of acid‐decreasing agents in the management of peptic ulcer haemorrhage continues to be controversial. Most clinical trials examining the efficacy of these drugs contain small numbers of patients, making it difficult to draw conclusions about their efficacy.Methods:We report a meta‐analysis that examined the effect of these drugs in the management of peptic ulcer haemorrhage. Included studies were located using a search of the Medline database between 1980 and 1999. Studies were published in English, randomized and controlled by a placebo group. Mantel–Haenszel and blinded random models were used in conducting the statistical processing of this meta‐analysis.Results:Twenty‐one randomized placebo‐controlled trials were included. The total number of patients was 3566 and the mean study size was 170 (range 20–1005). Seventeen of the papers assessed the efficacy of H2‐antagonists, three assessed proton pump inhibitors and one was concerned with antacid therapy. The meta‐analysis showed a significant reduction in re‐bleeding rates (odds ratio, OR 0.727, 0.618–0.855, P < 0.001) and surgery rates (OR 0.707, 0.582–0.859, P < 0.001) when acid decreasing agents are used for acute peptic ulcer haemorrhage. Mortality rates appear to be unaffected (OR 1.140, 0.818–1.588, P=0.49).Conclusions:This meta‐analysis demonstrates a significant beneficial effect of acid‐decreasing agents in lowering re‐bleeding and surgery rates, but demonstrated no effect upon mortality.
Inflammatory bowel disease: epidemiology and management in an English general practice population
Authors: Rubin G. P. , Hungin A. P. S. , Kelly P. J. , Ling J. 
Published: March 2003

Background:Inflammatory bowel diseases have significant long‐term morbidity and healthcare resource consequences. Studies based on secondary care records may have underestimated the contribution of general practitioners (GPs) to its management.Aims:To describe the epidemiology and management of inflammatory bowel disease using GP records as the primary data source.Methods:A systematic search of GP clinical records in northern England, identifying cases of inflammatory bowel disease, patient consultation behaviour, prescribing patterns, and extent of specialist care.Results:In a population of 135 723, the incidence of ulcerative colitis was 13.9/100 000 per year (CI: 7.5–20.3) and for Crohn’s disease 8.3/100 000 per year (CI: 3.4–13.2). The age–sex adjusted point prevalence for ulcerative colitis on 1st January 1995 was 243.4/100 000 (CI: 217.4–269.4) and for Crohn’s disease 144.8/100 000 (CI: 124.8–168.8). The mean number of consultations (s.d.) with specialists and GPs were similar, both in the first 12 months after referral (specialists 3.94 ± 3.15, GPs 3.34 ± 3.55) and in the most recent 12 months (1.02 ± 2.02, 1.04 ± 2.04). Only 29.9% of all patients were definitely under specialist care.Conclusions:Prevalence rates, but not incidence rates, for inflammatory bowel disease are substantially higher than previously described in UK populations. General practitioners make a significant contribution to meeting the healthcare needs of these patients.
Review article: gall‐bladder motor function in obesity
Authors: Petroni M. L. 
Published: March 2003

SummaryA number of epidemiological studies has established obesity as a risk factor for gallstone disease. More recently, studies have suggested a relationship between gallstone disease and the metabolic syndrome linked to central adiposity, whose cardinal feature is represented by hyperinsulinaemia. Studies on fasting gall‐bladder volume in obese subjects show that this parameter correlates with weight, body mass index (BMI) and body surface area; however, this is also true for large‐sized non‐obese subjects. Gall‐bladder volume also correlates with abdominal fat and with impaired glucose tolerance. In contrast to the well‐established role of bile supersaturation in the pathogenesis of gallstones in obesity, data are controversial on whether gall‐bladder motor function is defective in obese subjects. However, studies were heterogeneous for subjects' BMI, emptying stimulus, technique used and parameters assessed to evaluate gall‐bladder motor function. Also, differences in baseline gall‐bladder volume may lead to wide differences in bile ‘washout' effect despite apparently similar percentage changes in volume or content. Although post‐prandial plasma levels of cholecysto‐ kinin (CCK) are normal in obese subjects, there is some evidence that a sub‐group of obese subjects could have decreased sensitivity to CCK, possibly mediated by hyperinsulinaemia. Further studies using standard physiological stimuli and controlling for glucose tolerance, fasting insulin levels and baseline gall‐bladder volume are needed to establish the role of gall‐bladder motor function in the pathogenesis of gallstone disease in obesity.
Review article: gall‐bladder motor function in diabetes mellitus
Authors: Pazzi P. , Scagliarini R. , Gamberini S. , Pezzoli A. 
Published: March 2003

SummaryAlthough some controversy exists, diabetic patients generally are thought to have a two‐ to threefold increased risk of cholesterol gallstones. From previous studies there is no convincing evidence for a supersaturated bile in diabetics, whereas several reports indicate that impaired gall‐bladder emptying could be one of the important factors in the increased incidence of gallstones in diabetics. However, studies of gall‐bladder motility in diabetics have yielded conflicting results, probably because of substantial heterogeneity in the patients studied, emptying stimulus and technique used to assess gall‐bladder motor function. The mechanism of the gall‐bladder emptying abnormality in diabetics is not completely understood, although it has been proposed that it could represent a manifestation of denervation caused by visceral neuropathy. Based on normal post‐prandial cholecystokinin release, it can be ruled out that impaired cholecystokinin release is the mechanism responsible for reduced gall‐bladder emptying in diabetics. Other possible explanations for impaired gall‐bladder contraction in diabetics include a decreased sensitivity of the smooth muscle of the gall‐bladder to plasma cholecystokinin, and/or decreased cholecysto‐ kinin receptors on the gall‐bladder wall.
A systematic review of Helicobacter pylori eradication treatment schedules in children
Authors: Oderda G. , Rapa A. , Bona G. 
Published: March 2003

SUMMARYMethods  We systematically reviewed all available data in the paediatric literature on treatment for Helicobacter pylori infection to determine overall efficacy of different schedules. A comprehensive search of all published articles and letters from 1987, and of abstracts presented at three main meetings on this topic between 1997 and 1999, was carried out. Results from all English and French papers, letters and abstracts were extracted and analysed.Results  Only 30 full articles and 16 abstracts were found, with results on eradication of H. pylori in 870 and 1552 children, respectively. Monotherapy or dual therapy with an antisecretory drug plus one antibiotic showed a very low efficacy. Dual therapies with bismuth plus one antibiotic (either amoxycillin or a nitro‐ imidazole) or two antibiotics when administered for 2 or more weeks were as effective as either bismuth‐based or proton pump inhibitor‐based triple therapies. Triple therapies were less effective than in adults, and while bismuth‐based triple therapies were more effective when given for 2 weeks than for one week, proton pump inhibitor‐based triple therapies have a similar efficacy irrespective of the duration.Conclusion  In children dual therapies seemed as effective as triple therapies, and longer courses of proton pump inhibitor‐base triple therapies are not better than shorter ones.
Tegaserod
Authors: Camilleri M. 
Published: March 2003

Tegaserod (Zelmac), an aminoguanidine indole derivative of serotonin, is a selective partial agonist highly selective for 5‐HT4 receptor with an affinity constant in the nanomolar range. Tegaserod does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and distributes widely into tissues. Pharmacokinetics of oral tegaserod are linear in the 2–12 mg dose range. After oral administration tegaserod is metabolized mainly pre‐systemically; when absorbed, intact tegaserod is excreted as N‐glucuronides mainly via the bile. No clinically relevant drug–drug interactions were identified. Tegaserod has proven safe in toxicity studies.In pharmacodynamic studies, tegaserod stimulated the peristaltic reflex in vitro, increased canine intestinal and colonic motility and transit, reduced visceral afferent firing or sensation in response to distension in animals, and accelerated gastric, small bowel and colonic transit in healthy patients, and small bowel transit in patients with constipation‐predominant irritable bowel syndrome.Three large phase III randomized, double‐blinded, and placebo‐controlled trials were performed predominantly in females (≈ 85%) with constipation‐predominant irritable bowel syndrome. Overall, phase III results support efficacy as assessed by the subject’s global assessment of relief with significant improvement in secondary endpoints such as abdominal pain, bowel frequency and consistency. Tegaserod was well‐tolerated; the most frequent adverse event was transient diarrhoea.
Three‐day lansoprazole quadruple therapy for Helicobacter pylori‐positive duodenal ulcers: a randomized controlled study
Authors: Wong B. C. Y. , Wang W. H. , Wong W. M. , Lau G. K. K. , Fung F. M. Y. , Kung N. N. S. , Chu K. M. , Lai K. C. , Hu W. H. C. , Hu F. L. , Liu X. G. , Chan C. K. , Yuen M. F. , Hui W. M. , Lam S. K. 
Published: March 2003

Aim:To compare the efficacy and tolerability of a 3‐day quadruple therapy with a standard 7‐day triple therapy in eradicating Helicobacter pylori infection and healing duodenal ulcers.Methods:Patients with H. pylori‐positive duodenal ulcers were randomized to receive either lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 400 mg twice daily for 7 days (LCM‐7) or lansoprazole 30 mg, clarithromycin 500 mg, metronidazole 400 mg, and bismuth subcitrate 240 mg twice daily for 3 days (LCMB‐3). No pre‐ or post‐treatment acid suppression was used. Follow‐up endoscopy was performed at week 6.Results:A total of 118 patients were recruited. Sixty patients in the LCM‐7 group and 53 patients in the LCMB‐3 group returned for endoscopy. Intention‐to‐treat eradication rates were 87% and 86% (P=0.94) and per protocol eradication rates were 87% and 94% (P=0.29) in the LCM‐7 and LCMB‐3 groups, respectively. Per protocol and intention‐to‐treat ulcer healing rates were 98% and 98% in LCM‐7 and 100% and 91% in LCMB‐3, respectively. There were no significant differences in efficacy in relation to the initial metronidazole and clarithromycin susceptibility. Significant reduction in the duration of side‐effects was found in the LCMB‐3 group.Conclusion:The 3‐day quadruple therapy is highly effective, better tolerated and can be considered as a first‐line therapy in duodenal ulcer management.
Ambulatory gastric pH monitoring: proper probe placement and normal values
Authors: Fackler W. K. , Vaezi M. F. , Richter J. E. 
Published: March 2003

Background: Gastric acid production may persist while patients are treated with proton pump inhibitors. Twenty‐four‐hour intragastric pH monitoring is being used to identify gastric acid in the stomach while on medical therapy.Aim: To identify the optimal region of the stomach to demonstrate the presence of gastric acid.Method: Probe locations confirmed with fluoroscopy after placement and prior to removal. In experiment 1, five volunteers underwent simultaneous, 24‐h gastro‐oesophageal pH monitoring with the pH sensors located in the gastric antrum, body, fundus and distal oesophagus. In experiment 2, five volunteers underwent simultaneous 24‐h pH monitoring with sensors located side by side in the gastric fundus assessing the reproducibility of gastric pH in this region. In experiment 3, 35 volunteers underwent 24‐h pH monitoring with pH sensors located in the distal oesophagus and gastric fundus. The mean percentage time for which pH < 4 was calculated for total, upright, and supine time periods. Results: pH profiles for the gastric fundus and body are similar—the mean percentage total time for which pH < 4 was 92.2% and 90.1%, respectively (P=N.S.). These values are significantly different from the antrum; pH < 4=54.6% (P < 0.01). pH values from the gastric fundus are highly reproducible (linear regression P= 0.004, r2=0.96). The normal values (mean ± 95th percentile) for percentage time gastric pH < 4 in the fundus were: total 95.6 ± 1.5%, upright 94.8 ± 1.8%, and supine 96.5 ± 2.3%.Conclusion: The fundus is the optimal location to evaluate the presence of gastric acid; pH values are highly reproducible in this area. Normal values for percentage time gastric pH < 4 for a healthy population are now defined.
Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function
Authors: Nogi K. , Haruma K. , Taniguchi H. , Yomota E. , Okajima M. , Hananoki M. , Hata J. , Kusunoki H. , Onoda Y. 
Published: March 2003

Background: Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post‐cholecystectomy syndrome.Aim: To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs.Methods: Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter‐digestive state in dogs with or without cholecystectomy.Results: Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non‐cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog.Conclusion: Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy.
Anal sphincter biofeedback and pelvic floor exercises for faecal incontinence in adults—a systematic review
Authors: Norton C. , Kamm M. A. 
Published: March 2003

Background: Faecal incontinence is a common health care problem. Biofeedback is extensively used in clinical practice to treat faecal incontinence.Aim: To systematically review and evaluate the evidence from clinical studies on the effectiveness of biofeedback as a treatment for faecal incontinence in adults.Methods: A systematic literature search was undertaken using electronic databases, with review of the retrieved references.Results: The search identified 46 studies published in English using biofeedback to treat adults complaining of faecal incontinence. Those studies included a total of 1364 patients. Of those studies with adequate data, 275 out of 566 patients (49%) were said to be cured of symptoms of faecal incontinence following biofeedback therapy and 617 out of 861 (72%) patients were reported to be cured or improved. Studies varied in the method of biofeedback used, criteria for success and the outcome measures used. Only eight of the 46 studies employed any form of control group.Conclusions: The data suggest that biofeedback and exercises help a majority of patients with faecal incontinence. However, methodological variation, lack of controls and a lack of validated outcome measures are problems in evaluating these results.
Randomized controlled trial comparing botulinum toxin injection to pneumatic dilatation for the treatment of achalasia
Authors: Mikaeli J. , Fazel A. , Montazeri G. , Yaghoobi M. , Malekzadeh R. 
Published: March 2003

Background:Therapeutic options for achalasia include pharmacological therapy, surgical myotomy, pneumatic dilatation and intrasphincteric botulinum toxin injection.Aim:To compare botulinum toxin injection with pneumatic dilatation in a randomized trial.Patients/methods:Forty adults with newly diagnosed achalasia were randomized to receive botulinum toxin (n=20) or pneumatic dilatation (n=20). Symptom scores were evaluated at 1, 6 and 12 months. Clinical relapse was defined as a symptom score greater than 50% of baseline. Relapsers received a second botulinum toxin injection or pneumatic dilatation.Results:The cumulative 12‐month remission rate was significantly higher after a single pneumatic dilatation (53%) compared to a single botulinum toxin injection (15%)(P < 0.01). The 12‐month estimated adjusted hazard for relapse and need for retreatment for the botulinum toxin group was 2.69 times that of the pneumatic dilatation group (95% confidence interval; 1.18–6.14). When a second treatment was administered to the relapsers in each group, the cumulative remission rate 1 year after initial treatment was significantly higher in the pneumatic dilatation group (100%) compared to the botulinum toxin group (60%) (P < 0.01). There were no major complications in either group.Conclusions:Pneumatic dilatation is more efficacious than botulinum toxin in providing sustained symptomatic relief in patients with achalasia. The efficacy of a single pneumatic dilatation is similar to that of two botulinum toxin injections.
Inhibition of human colon cancer cell growth by antisense oligodeoxynucleotides targeted at basic fibroblast growth factor
Authors: Netzer P. , Domek M. , Pai R. , Halter F. , Tarnawski A. 
Published: March 2003

Background:Basic fibroblast growth factor has been shown to be mitogenic in colon cancer cell lines. In human malignant melanoma cells, antisense oligodeoxynucleotides targeted against basic fibroblast growth factor messenger RNA significantly inhibit cell growth. However, the efficacy of such an antisense oligodeoxynucleotide strategy has not been evaluated for colon cancer cells.Aim:To investigate whether basic fibroblast growth factor can stimulate the growth of HT‐29 human colon cancer cells and whether antisense oligodeoxynucleotides can inhibit growth of these cells at baseline.Methods:Western blotting analyses were used to confirm the presence of basic fibroblast growth factor protein in this cell line. Cell growth was assessed after 2, 4 and 6 days of treatment by cell counting using the trypan blue exclusion method. Phosphorothioate‐ modified oligodeoxynucleotides (10 μM) were used, complementary to codon 60 of the basic fibroblast growth factor messenger RNA. Cationic liposomes (DOTAP) were used to enhance the cellular uptake of the oligodeoxynucleotides.Results:Western blotting demonstrated the presence of basic fibroblast growth factor protein in this cell line. Basic fibroblast growth factor (1–40 ng/mL) dose‐dependently stimulated cell growth and peak values were obtained at a dose of 20 ng/mL. By contrast, antisense oligodeoxynucleotide treatment significantly inhibited cell growth compared with the sense oligodeoxynucleotide‐treated cells (P=0.007). This inhibition was reversed by the addition of basic fibroblast growth factor, 20 ng/mL.Conclusion:Treatment targeted against basic fibroblast growth factor messenger RNA inhibits growth of HT‐29 human colon cancer cells. This finding may provide a rationale for the therapeutic use of antisense oligodeoxynucleotides targeted at basic fibroblast growth factor for the treatment of colon cancer.
Pharmacokinetics and pharmacodynamics of esomeprazole, the S‐isomer of omeprazole
Authors: Andersson T. , RÖhss K. , Bredberg E. , Hassan‐Alin M. 
Published: March 2003

Background:Esomeprazole, the S‐isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid‐related diseases.Aim:To examine the pharmacokinetics and pharmacodynamics of esomeprazole.Methods:In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin‐stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5.Results:The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin‐stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin‐stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5).Conclusions:The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.
The treatment of inflammatory bowel disease with 6‐mercaptopurine or azathioprine
Authors: Nielsen O. H. , Vainer B. , Rask‐Madsen J. 
Published: March 2003

The thioguanine derivative, azathioprine, is a prodrug of 6‐mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6‐mercaptopurine have been used in the treatment of inflammatory bowel disease, i.e. ulcerative colitis and Crohn’s disease, for more than 30 years. However, widespread use of azathioprine or 6‐mercaptopurine in inflammatory bowel disease is of more recent origin, the primary reason being a long‐standing debate on the efficacy of these agents in inflammatory bowel disease. Both drugs are slow acting, which is why clinical efficacy cannot be expected until several weeks or even months of treatment have elapsed. Consequently, azathioprine and 6‐mercaptopurine have no place as monotherapy in the treatment of acute relapsing inflammatory bowel disease.Today, azathioprine and 6‐mercaptopurine are the most commonly used immunomodulatory drugs in the treatment of inflammatory bowel disease. Their clinical effects are probably identical, although their exact mode of action is still unknown. The mode of action of azathioprine is thought to be multifactorial, including conversion to 6‐mercaptopurine (which acts as a purine antimetabolite), possible blockade of thiol groups by alkylation, inhibition of several pathways in nucleic acid biosynthesis (preventing proliferation of cells involved in the determination and amplification of the immune response) and damage to DNA through the incorporation of thiopurine analogues. However, 6‐thioguanine nucleotides may accumulate in toxic doses in myeloid precursor cells, resulting in life‐threatening myelosuppression. Azathioprine and 6‐mercaptopurine are further known to alter lymphocyte function, reduce the number of lamina propria plasma cells and affect natural killer cell function.The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6‐mercaptopurine in the treatment of inflammatory bowel disease.