bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin‐dependent) diabetes mellitus
Authors: Annese V. , Lombardi G. , Frusciante V. , Germani U. , Andriulli A. , Bassotti G. 
Published: November 2003

Background:Erythromycin, a macrolide antibiotic, has been shown to have gastric prokinetic effects and has been proposed as an alternative therapeutic option for diabetic gastroparesis. However, its efficacy has not yet been compared with that of other prokinetic drugs.Aims:The purpose of the present study was to compare the effects of erythromycin (250 mg 60 min before meals) and cisapride (10 mg 30 min before meals) on gastric emptying of healthy subjects and insulin‐dependent diabetics.Patients and methods:Six type 1 diabetic patients with a previous scintigraphic demonstration of gastroparesis and five healthy subjects were recruited for the study. Gastric emptying was scintigraphically studied by labelling the solid component of a standard test meal. Three scintigraphic studies, spaced at least 3 days apart, were carried out on each subject, basally and after erythromycin or cisapride.Results:Cisapride significantly accelerated gastric emptying in both the healthy subjects and the diabetic patients without any significant effect on the lag‐time, whereas erythromycin in addition to a significant improvement of the overall gastric emptying also showed a pronounced effect on the lag‐time in both groups (controls 25 ± 5 vs. 37 ± 8 min, P≤0.04; diabetics 65 ± 11 vs. 112 ± 16 min, P<0.03).Conclusions:Erythromycin may represent an effective therapeutic alternative to more established forms of treatment in patients with diabetic gastroparesis, especially when other drugs have failed.
The long‐term management of patients with bleeding duodenal ulcers
Authors: McAlindon M. E. , Taylor J. S. W. , Ryder S. D. 
Published: November 2003

Background:Gastrointestinal haemorrhage is a common complication of duodenal ulcers. Patients who bleed are at substantial risk of recurrent bleeding.Aim:To determine whether appropriate therapeutic steps were taken to reduce the risk of recurrent haemorrhage in patients with a bleeding duodenal ulcer.Methods:The management of patients surviving a duodenal ulcer bleed in the University Hospital, Nottingham, was assessed by case‐note review before (1993) and after (1995–1996) institution of clinical guidelines. The following measures aimed at reducing the risk of recurrent haemorrhage were considered appropriate: stopping non‐steroidal anti‐inflammatory drugs (NSAIDs) when these were implicated in bleeding; successful eradication of Helicobacter pylori if present; and long‐term maintenance acid‐suppression therapy.Results:In 1993, appropriate steps were taken to reduce the risk of recurrent haemorrhage in only 48% of cases. Following the institution of guidelines, management improved significantly in 1995–1996 (appropriate in 83% of cases, P<0.001), was associated with increased referral to gastroenterologists (P<0.001), improved patient compliance with follow‐up (P<0.05), and more rigorous attempts to identify (P<0.001) and ensure clearance (P<0.001) of H.␣pylori.Conclusion:In this study, inadequate long‐term management of patients with a bleeding duodenal ulcer was common. This was due to a failure to adopt strategies aimed at reducing the risk of ulcer relapse and rebleeding. The quality of care improved significantly following the institution of guidelines and encouragement to refer to gastroenterologists.
Comparison of two dosing regimens of cisapride in the treatment of reflux oesophagitis
Authors: Schütze K. , Bigard M. A. , Waes L. van , Hinojosa J. , Bedogni G. , Hentschel E. 
Published: November 2003

Aim:In an international, multicentre, double‐blind trial, to document the therapeutic equivalence of two dosing regimens of cisapride on endoscopic healing and symptom improvement in patients with proven reflux oesophagitis grade I or II (Savary–Miller).Methods:Four hundred and seven patients were randomly allocated to treatment with either cisapride 10 mg q.d.s or cisapride 20 mg b.d. for 8–12 weeks depending on whether complete healing was found at endoscopy. The primary parameters of efficacy were cure of oesophagitis and improvement of the reflux symptom score.Results:The healing rates at endpoint were 73% in both treatment groups. The mean total reflux symptom score decreased from baseline to endpoint from 7.9–2.1 (cisapride 10 mg q.d.s.) and 7.9–2.5 (cisapride 20 mg b.d.). Each of the two treatment regimens was well tolerated. The most frequently (6.9%) reported adverse event (diarrhoea) was mild or moderate in most cases and can be explained by the pharmacological action of cisapride.Conclusions:The results of the study demonstrate that cisapride 10 mg q.d.s. and 20 mg b.d. are equivalent in terms of efficacy and safety in the treatment of reflux oesophagitis.
current practice and future perspectives in the management of gastro‐oesophageal reflux disease
Authors: LAMBERT R. 
Published: November 2003

Gastro‐oesophageal reflux disease (GERD) is primarily due to incompetence of the lower oesophageal sphincter (LOS) and crural diaphragm, with transient LOS relaxation frequently accounting for daytime reflux. In the absence of drugs that adequately correct the motility defects of GERD, treatment is directed towards decreasing gastric acidity. Oesophageal healing is related to control of 24‐h intragastric acidity, the degree of acid suppression and duration of treatment.H2‐receptor antagonists are generally less effective in GERD than in peptic ulcer disease. While providing symptomatic relief in non‐erosive GERD, they are often ineffective in healing erosive oesophagitis. Proton pump inhibitors provide more rapid and complete healing and symptom resolution. They are superior to H2‐receptor antagonists in the long‐term management of erosive oesophagitis and in reducing recurrence of oesophageal stricture following mechanical dilatation. In Barrett's oesophagus, high‐dose proton pump inhibitors in combination with laser/photodynamic ablation therapy can produce metaplastic regression, although this does not preclude future emergence of adenocarcinoma.Surgical morbidity and mortality rates in GERD generally remain higher than those associated with long‐term pharmacotherapy. However, direct comparisons between laparascopic anti‐reflux surgery and proton pump inhibitor maintenance therapy remain to be performed.Although there is no evidence that H. pylori infection worsens the severity of oesophagitis or that H. pylori is carcinogenic in the metaplastic oesophageal mucosa, it has been suggested that H. pylori‐positive patients requiring long‐term proton pump inhibitor therapy receive bacterial eradication therapy to reduce the risk of developing atrophic gastritis.
Twenty‐four‐hour intragastric acidity and plasma gastrin during 3‐month treatment with omeprazole in healthy subjects
Authors: DELCHIER J.‐C. , BENAMOUZIG R. , STANESCU L. , ROPERT A. , VALLOT T. , WIRQUIN V. , ROUDOT F. , LAMARQUE D. , HAMELIN B. 
Published: November 2003

Background: Prolonged treatment with omeprazole 20 or 40 mg/day is sometimes required, especially for severe oesophagitis. However, information about long‐term effects on intragastric acidity and plasma gastrin response with such drug regimens is scarce. Methods: Sixteen healthy subjects (11 men, 5 women, mean age 29 years) randomly received either 20 or 40 mg of omeprazole once daily (at 08.00 h) for 3 months. Gastric pH was recorded every 6 s for 24 h from noon to noon under standardized conditions, and blood samples were collected hourly in order to determine the 24‐h plasma gastrin response on day 0 (pre‐entry), day 7, day 28 and day 90. Results: From day 0 to day 7, 24‐h median pH increased from 1.7 to 4.6 and mean percentage of time at pH < 4 decreased from 89% to 35% with omeprazole 20 mg. Respective values with omeprazole 40 mg were 1.9 to 4.3, and 89% to 34%. Inhibition of gastric acidity remained unchanged during the 3 months of treatment. Despite similar effects on the basis of 24‐h analysis, the decrease in daytime acidity was slightly higher with omeprazole 40 mg than with omeprazole 20 mg. Twenty‐four‐hour integrated plasma gastrin significantly increased with both drug regimens between day 0 and day 7 (P < 0.01), and between day 7 and day 28 (P < 0.01) with omeprazole 40 mg; there was no significant increase between day 28 and day 90 with either of the drug regimens. Conclusion: Omeprazole 20 and 40 mg/day provides long‐term stable acid suppression with a progressive increase in gastrin response, stabilizing after 2 months of treatment.
Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis
Authors: GIONCHETTI P. , VENTURI A. , RIZZELLO F. , CORBELLI C. , FANTI S. , FERRETTI M. , BOSCHI S. , MIGLIOLI M. , CAMPIERI M. 
Published: November 2003

Background: Rectal treatment with mesalazine enemas is the first‐line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5‐ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. Methods: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc‐SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5‐ASA and Ac‐5‐ASA were measured for 6 h. Results: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac‐5‐ASA was low. Conclusions: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.
Comparison of ranitidine and lansoprazole in short‐term low‐dose triple therapy for Helicobacter pylori infection
Authors: Kihira K. , Satoh K. , Saifuku K. , Taniguchi Y. , Takimoto T. , Yamamoto H. , Ido K. , Yoshida Y. , Kimura K. 
Published: November 2003

Aim:To evaluate the efficacy and safety of two 1‐week low‐dose triple‐therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection, 99␣patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole.Methods:The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended.Results:The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79–97%) and 92% in the RCM group (45 of 49; 95% CI = 84–99%). The incidence of adverse events was 16% and 18% for the two groups, respectively.Conclusions:No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2‐blocker is sufficient to achieve optimal H. pylori eradication.
Zamifenacin (UK‐76, 654), a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome
Authors: Houghton L. A. , Rogers J. , Whorwell P. J. , Campbell F. C. , Williams N. S. , Goka J. 
Published: November 2003

Background:Zamifenacin is a new potent gut M3 selective muscarinic antagonist developed for possible use in irritable bowel syndrome.Methods:In this multicentre, double‐blind, parallel group, placebo‐controlled study, the effect of a single dose of zamifenacin 10 mg or 40 mg on both fasting (30 min) and fed (60 min) colonic motor activity was assessed in 36 patients with irritable bowel syndrome (aged 25–68 years; 19 male). Colonic motility was recorded using a five‐channel solid‐state catheter introduced by colonoscopy to a depth of 35 cm in an unprepared colon.Results:Zamifenacin 40 mg profoundly reduced colonic motility, particularly after the meal (P < 0.05). This was reflected by a significant reduction in the mean amplitude of contractions, number of contractions, percentage duration of contractions, activity index and the motility index (P < 0.05). A smaller reduction in all the motility parameters was obtained with 10 mg zamifenacin, but these changes were not statistically significant. Three patients each on placebo and zamifenacin reported side‐effects, but these were mild and transient.Conclusion:A single 40 mg dose of zamifenacin significantly reduces colonic motility in irritable bowel syndrome patients without significant antimuscarinic effects. The results of this study confirm that the concept of developing selective antimuscarinic agents may be a promising approach to the treatment of irritable bowel syndrome. Not only would such compounds benefit from not having the usual side‐effects of anticho‐linergics but they might also offer much more in the way of dose flexibility.
Pharmacokinetics of N‐acetylcysteine are altered in patients with chronic liver disease
Authors: JONES A. L. , JARVIE D. R. , SIMPSON D. , HAYES P. C. , PRESCOTT L. F. 
Published: November 2003

Background: The threshold plasma paracetamol concentration at which N‐acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patients with cirrhosis. Aim: The aim was to determine if the pharmacokinetics of NAC are altered by chronic liver disease. Subjects and methods: NAC was given intravenously in a dose of 600 mg over 3 min to nine patients with biopsy‐proven cirrhosis (Child's grade; 1 A, 4 B, 4 C; aetiology: 7 alcohol‐related, 1 primary biliary cirrhosis, 1 secondary biliary stenosis) and six healthy matched controls. Venous blood was taken at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC administration. Serum NAC was estimated by HPLC. The data were normalized to a standard body weight of 70 kg. Results: The area under the serum concentration–time curve was increased (152.34 mg/L.h ± 50.38 s.d.) in cirrhotics compared with normal controls; (93.86 mg/L.h ± 9.60 s.d.) (P < 0.05). The clearance of NAC was reduced in patients with chronic liver disease (4.52 L/h ± 1.87 s.d.) compared with controls (6.47 L/h ± 0.78; P < 0.01). Conclusions: Increased vigilance for untoward anaphylactoid reactions is necessary in cirrhotics as they may have higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.
Seven‐day treatment for Helicobacter pylori infection: ranitidine bismuth citrate plus clarithromycin and tetracycline hydrochloride
Authors: WILLIAMS M. P. , HAMILTON M. R. , SERCOMBE J. C. , POUNDER R. E. 
Published: November 2003

Background: Dual therapy with ranitidine bismuth citrate plus clarithromycin twice daily for 14 days is an effective regimen for eradicating Helicobacter pylori infection. Aim: To determine whether this regimen can be improved by the addition of a second antibiotic, tetracycline hydrochloride, whilst reducing the duration of treatment to 7 days. Methods: Sixty‐one out‐patients were enrolled to this open treatment study. All had H. pylori infection, as determined by 13C‐urea breath test and, for those undergoing endoscopy, by rapid urease test. Patients were treated with ranitidine bismuth citrate 400 mg, clarithromycin 500 mg and tetracycline hydrochloride 500 mg all twice daily for 7 days. Eradication of H.␣pylori was assessed by two separate 13C‐urea breath tests, the first 28–68 days after the completion of treatment, the second 28–162 days later. H. pylori infection was considered cured if both tests were negative. Results: All 61 patients were included in the intention‐to‐treat efficacy analysis. Successful eradication of H.␣pylori was achieved in 55/61 patients (90 %; 95% CI: 82–98%). Fifty‐nine out of sixty‐one patients reported 100% compliance; one patient missed a single dose of medication and the other withdrew at 48 h due to nausea and vomiting. Minor adverse events were reported by 30/61 patients. Conclusion: One‐week triple therapy with ranitidine bismuth citrate, clarithromycin and tetracycline, all twice daily, is a safe and well‐tolerated regimen which eradicates H. pylori in 90% of infected patients.
Influence of tegaserod on proximal gastric tone and on the perception of gastric distension
Authors: Tack J. , Vos R. , Janssens J. , Salter J. , Jauffret S. , Vandeplassche G. 
Published: November 2003

SummaryBackground: Tegaserod, a 5‐hydroxytryptamine‐4 receptor agonist, enhances gastric emptying, but its effects on proximal stomach function have not been studied.Aim: To study the effect of tegaserod on gastric compliance, accommodation and perception of distension in humans.Methods: Nineteen healthy volunteers (10 females; mean age, 23.9 years) were studied on three separate occasions after 7 days of treatment with placebo, tegaserod 2 mg b.d. or tegaserod 6 mg b.d. in a double‐blind, randomized, three‐way cross‐over design. After the introduction of a barostat bag, stepwise distensions were performed to determine gastric compliance and sensitivity, and a mixed liquid meal was administered in isobaric mode to assess accommodation.Results: Tegaserod had no effect on the pressures or volumes inducing first perception or discomfort. Tegaserod 6 mg b.d. enhanced fasting gastric compliance compared with placebo. Pre‐prandial and post‐prandial intra‐balloon volumes were significantly higher after 6 mg b.d. than after placebo. Both tegaserod 2 and 6 mg b.d. shortened the time to maximum post‐prandial intra‐balloon volume. The amplitude of meal‐induced gastric relaxation (post‐prandial minus pre‐prandial volumes) did not differ between the treatment arms.Conclusion: In humans, tegaserod allows for larger intra‐balloon volumes both before and after a meal. These findings warrant the investigation of the therapeutic potential of tegaserod in dyspeptic patients with impaired accommodation.
Ursodeoxycholic acid — adverse effects and drug interactions
Authors: Hempfling W. , Dilger K. , Beuers U. 
Published: November 2003

SummaryBackground : Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking.Aim : As experimental data suggest a role of bile acids in the regulation of hepatic drug metabolism at both the transcriptional and post‐transcriptional level, the literature was screened for adverse drug reactions and drug interactions related to ursodeoxycholic acid.Methods : A systematic review of the literature was performed using a refined search strategy to evaluate the adverse effects of ursodeoxycholic acid and its interactions with other drugs.Results : Ursodeoxycholic acid caused diarrhoea in a small proportion of patients. Rare skin reactions were due to drug adjuvants rather than the active substance. Decompensation of liver cirrhosis was reported after the administration of ursodeoxycholic acid in single cases of end‐stage primary biliary cirrhosis. Recurrent right upper quadrant abdominal pain was incidentally observed. The absorption of ursodeoxycholic acid was impaired by colestyramine, colestimide, colestipol, aluminium hydroxide and smectite. Metabolic drug interactions were reported for the cytochrome P4503A substrates, ciclosporin, nitrendipine and dapsone.Conclusions : Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected.
Is there any association between myocardial infarction, gastro‐oesophageal reflux disease and acid‐suppressing drugs?
Authors: Johansson S. , Wallander M.‐A. , Ruigómez A. , García Rodríguez L. A. 
Published: November 2003

SummaryBackground : A link between gastro‐oesophageal reflux disease and coronary heart disease has been suggested.Aim : To estimate the incidence of myocardial infarction in patients with newly diagnosed gastro‐oesophageal reflux disease in comparison with that in the general population.Methods : A population‐based cohort study was performed in the UK. Patients aged 18–79 years with a first diagnosis of gastro‐oesophageal reflux disease (n = 7084) were identified and a group of 10 000 patients free of gastro‐oesophageal reflux disease were sampled. A nested case–control analysis was performed to assess the risk factors for myocardial infarction.Results : The incidence of myocardial infarction in the general population was 4.0 per 1000 person‐years [95% confidence interval (CI), 3.2–4.9] and 5.1 per 1000 person‐years (95% CI, 4.1–6.4) in patients with gastro‐oesophageal reflux disease. The relative risk of myocardial infarction in patients with gastro‐oesophageal reflux disease was 1.4 (95% CI, 1.0–1.9). The increased risk of myocardial infarction was limited to the immediate days after the diagnosis of gastro‐oesophageal reflux disease. Previous chest pain was an important predictor of myocardial infarction in patients free of gastro‐oesophageal reflux disease. No association was found between the use of acid‐suppressing drugs and the risk of myocardial infarction.Conclusion : Our results suggest that gastro‐oesophageal reflux disease is not an independent predictor of myocardial infarction. Rather, the increased risk of myocardial infarction in patients with gastro‐oesophageal reflux disease in the immediate days after diagnosis indicates that prodromal ischaemic symptoms were misinterpreted as reflux symptoms.