bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiretroviral hepatotoxicity in human immunodeficiency virus‐infected patients
Authors: Hernandez L. V. , Gilson I. , Jacobson J. , Affi A. , Puetz T. R. , Dindzans V. J. 
Published: March 2003

Background:Drug hepatotoxicity is a potentially serious adverse reaction of antiretroviral therapy in human immunodeficiency virus‐infected patients. The impact of this problem in the routine treatment of patients with human immunodeficiency virus infection is poorly defined.Objectives:Our aim was to determine what clinical features are associated with hepatotoxicity in human immunodeficiency virus‐infected patients receiving antiretroviral therapy.Methods:Consecutive patients in a primary care‐based human immunodeficiency virus clinic were evaluated for hepatotoxicity. Clinic records were used to obtain patient characteristics, as well as independent variables including CD4+ count, coexisting hepatitis C and current alcohol use.Results:Sixty‐five patients taking antiretroviral therapy were evaluated. Twenty‐four were identified to have antiretroviral hepatotoxicity. An age over 40 years (P=0.019), an absolute CD4+ count of less than 310 cells/mL (P=0.002) and coexisting hepatitis C infection (P=0.035) were significantly associated with hepatotoxicity. Patients older than 40 years had a sevenfold increased risk (risk ratio, 6.9; 95% confidence interval, 1.7–27.3) and those with an absolute CD4+ count of less than 310 cells/mL had a tenfold increased risk (risk ratio, 10.2; 95% confidence interval, 2.5–41.9) for antiretroviral hepatotoxicity, in comparison with those who were younger or who had a greater absolute CD4+ count. Of the eight patients documented to have coexisting hepatitis C infection, six (75%) were in the antiretroviral hepatotoxicity group.Conclusions:An age older than 40 years and an absolute CD4+ count of less than 310 cells/mL were significantly associated with antiretroviral‐induced hepatotoxicity. The majority of our patients with chronic hepatitis C had hepatotoxicity from antiretroviral therapy.
Tegaserod, a 5‐HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation
Authors: Müller‐Lissner S. A. , Fumagalli I. , Bardhan K. D. , Pace F. , Pecher E. , Nault B. , Rüegg P. 
Published: March 2003

Aim:To investigate the efficacy and safety of tegaserod, a novel 5‐HT4 receptor partial agonist, in a randomized, double‐blind, placebo‐controlled, 12‐week treatment, multicentre study.Methods:Eight hundred and eighty‐one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks.Results:Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self‐administered questionnaire. At end‐point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12‐week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo.Conclusions:Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated.
A randomized comparison of four omeprazole‐based triple therapy regimens for the eradication of Helicobacter pylori in patients with non‐ulcer dyspepsia
Authors: Laurent J. , Mégraud F. , Fléjou J. F. , Caekaert A. , Barthélemy P. 
Published: March 2003

Background: Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens.Methods: Helicobacter pylori‐positive patients (n=323) with non‐ulcer dyspepsia were randomized to receive one of four 1‐week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2–5 (OAAz). Eradication was confirmed by urea breath test 4–6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure.Results:The eradication rate with OAAz was 38% (95% CI, 25.6–49.4) on intention‐to‐treat analysis, which was lower (P < 0.05) than with the other regimens [OCM, 61% (50.0–72.8); OBC, 65% (54.0–76.5); OAC, 72% (61.8–81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant.Conclusions:OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.
Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease
Authors: Marino G. , Rustgi V. K. , Salzberg G. , Johnson L. B. , Kuo P. C. , Plotkin J. S. , Flockhart D. A. 
Published: March 2003

Background:Hepapoietin is a naturally occurring cytokine that promotes hepatocyte growth. Animal studies have suggested that hepapoietin and hepatocyte growth factor have a potential role in the prevention and management of liver diseases. However, human studies have been lacking.Aim:To evaluate the safety and pharmacokinetics of single escalating doses of hepapoietin in patients with chronic liver disease.Methods:An open‐label, single escalating dose trial with five different doses of hepapoietin (1, 3, 10, 30 and 100 mg) was performed. Adults with chronic, compensated, non‐viral liver disease were included. Liver function tests were obtained before dosing, 24 h after hepapoietin administration and on days 4, 7, 30 and 45. All patients were followed for 45 days.Results:Twenty‐five subjects received hepapoietin, with five subjects each at 1, 3, 10, 30 and 100 mg of hepapoietin. Significant decreases occurred in total bilirubin, ammonia, partial thromboplastin time and cholesterol levels overall, and both high‐density and low‐density lipoprotein cholesterol showed a downward trend. An increase in albumin was observed at the 30 mg dose level. Slight decreases in haemoglobin and red blood cell levels were observed at day 4, but returned to normal levels immediately thereafter. Child–Pugh scores from day 0 to day 7 were improved in 24%, stable in 64% and worse in 12% of patients. Hepatic encephalopathy displayed changes from day 0 to day 45 with improvement in 16%, no change in 80% and worsening in 4%.Conclusions:Hepapoietin in doses up to 100 mg is safe for use in humans. Potential benefits are suggested by significant decreases in bilirubin, ammonia, partial thromboplastin time and cholesterol levels and an increase in albumin. Further studies with multiple dosing regimens are needed to identify the clinical utility of hepapoietin in the management of chronic liver disease.
Dose‐related effects of motilin on proximal gastrointestinal motility
Authors: Kamerling I. M. C. , Van Haarst A. D. , Burggraaf J. , Schoemaker H. C. , Biemond I. , Jones R. , Cohen A. F. , Masclee A. A. M. 
Published: March 2003

Aim:To assess non‐invasively the dose–response relations for the effects of exogenous motilin on antrum contraction frequency, gall‐bladder volume and gastric myoelectrical activity.Methods:In a double‐blind, randomized, placebo‐controlled, five‐way crossover study, 10 fasted healthy volunteers were infused intravenously with synthetic human motilin (0.5, 1, 2 and 4 pmol.min/kg) or placebo for 60 min. Gall‐bladder volume and antrum contractions were assessed by ultrasonography and gastric myoelectrical activity by electrogastrography. Motilin concentrations were measured using a radioimmunoassay.Results:Baseline plasma motilin levels (60 pmol/L) were similar for all treatments. Motilin levels increased upon the start of infusion and rapidly returned to baseline after cessation of the infusion. At motilin doses of 2 and 4 pmol.min/kg, the antrum contraction frequency was significantly augmented, with maximum differences of two contractions per 2‐min interval compared to placebo, while no changes in gastric myoelectrical activity were observed. Changes in gall‐bladder volume were not significantly different for any of the motilin doses compared to placebo.Conclusions:Motilin increased antrum contraction frequency, whereas no effect on gastric myoelectrical activity was observed. Antrum contraction frequency appears to be a useful biomarker for motilin efficacy, and motilin doses of 2 and 4 pmol.min/kg were equally effective.
Treatment with a proton pump inhibitor promotes corpus gastritis in patients with Helicobacter pylori‐infected antrum‐predominant gastritis
Authors: Suzuki M. , Suzuki H. , Kitahora T. , Miyazawa M. , Nagahashi S. , Suzuki K. , Ishii H. 
Published: March 2003

Background:Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis.Aim:To quantitatively investigate the effect of a proton pump inhibitor on the mucosal neutrophil reaction.Methods:Forty‐six H. pylori‐infected patients (17 duodenal ulcer, 29 gastric ulcer) were enrolled. During endoscopic examination, biopsy samples were obtained from the antrum and the corpus. The tissue content of neutrophil myeloperoxidase was measured by enzyme‐linked immunoabsorbent assay, and H. pylori infection was histologically assessed. A proton pump inhibitor was administered orally for 8 weeks.Results:In the patients as a whole, antral myeloperoxidase decreased significantly after proton pump inhibitor treatment, but corpus myeloperoxidase remained largely unchanged. In duodenal ulcer patients, myeloperoxidase significantly decreased in the antrum, but increased in the corpus. In gastric ulcer patients, a significant reduction was observed in antral myeloperoxidase, but corpus myeloperoxidase remained unchanged. In the antral myeloperoxidase > corpus myeloperoxidase subgroup (n=24), antral myeloperoxidase significantly decreased, whereas corpus myeloperoxidase increased. No changes were observed at either site in the corpus myeloperoxidase > antral myeloperoxidase subgroup. Histology showed that the antral bacterial load of H. pylori decreased in all subgroups, but that it was mostly unchanged in the corpus.Conclusions:Proton pump inhibitor treatment stimulated the neutrophil reaction in the corpus mucosa of duodenal ulcer patients and of patients in whom antral neutrophil accumulation was more predominant than that of the corpus. This phenomenon may not be caused by increased bacterial density.
Expression of cyclooxygenase‐2 in chronic hepatitis B and the effects of anti‐viral therapy
Authors: Cheng A. S. L. , Chan H. L. Y. , Leung N. W. Y. , Liew C. T. , To K. F. , Lai P. B. S. , Sung J. J. Y. 
Published: March 2003

Backgound:Cyclooxygenase‐2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase‐2 and chronic hepatitis B is unknown.Aim:To investigate the expression and cellular localization of cyclooxygenase‐2 in chronic hepatitis B patients and the effects of anti‐viral therapy.Methods:Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase‐2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non‐viral‐infected livers were used as controls. The cyclooxygenase‐2 immunoreactivities of paired liver biopsies from 12 patients receiving anti‐viral therapy were compared.Results:Immunohistochemistry and in situ hybridization revealed that cyclooxygenase‐2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase‐2 expression compared with controls. The cyclooxygenase‐2 expression of hepatitis B e antigen‐positive and ‐negative chronic hepatitis B patients was not significantly different, although the necro‐inflammatory activity of the latter group was significantly lower. Over‐expression of cyclooxygenase‐2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen‐positive chronic hepatitis B patients received anti‐viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro‐inflammatory activity in all 12 patients, no significant change in cyclooxygenase‐2 expression was found.Conclusions:Chronic hepatitis B is associated with elevated cyclooxygenase‐2 levels in hepatocytes, and the over‐expression of this enzyme does not reflect inflammatory activity. Up‐regulation of cyclooxygenase‐2 persists after successful anti‐viral therapy.
Single subject trials as a research instrument in gastrointestinal pharmacology
Authors: Madsen L. G. , Bytzer P. 
Published: March 2003

The single subject trial is a randomized controlled trial carried out in the individual patient, and the result obtained is specific to the individual patient and the drug being investigated. This type of trial offers a supplement to traditional parallel group trials, especially in patients with heterogeneous disorders, often characterized by varying treatment responses and/or high placebo response rates. Pooled results from several individual single subject trials could extend the conclusions beyond the individual patient, and help to characterize a subset of responders to a specific treatment or clarify the heterogeneity of the disease.The basic principles of the different single subject trial designs are described. Advantages and limitations are reviewed with a special focus on published trials in functional gastrointestinal disorders.The single subject trial may be a valuable supplement to traditional drug treatment trials, either used as isolated trials in individual patients to determine optimal therapy, or in groups of patients to identify those with a uniform response to treatment. However, the lack of validation and reliability studies limits the value of the single subject trials presented so far.
Effect of Helicobacter pylori eradication on duodenal ulcer scar in patients with no clinical history of duodenal ulcer
Authors: Kim J. S. , Kim S. G. , Choi I. J. , Park M. J. , Kim B. G. , Jung H. C. , Song I. S. 
Published: March 2003

Background: Helicobacter pylori eradication has become the standard treatment for duodenal ulcer. However, there is no relevant evidence for antibacterial treatment of the white scar stage of duodenal ulcer (duodenal ulcer scar) in patients with no past history of duodenal ulcer.Aim:To investigate whether H. pylori eradication could decrease duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.Patients and methods:We prospectively enrolled 66 patients with duodenal ulcer scar: 53 were H. pylori‐positive and 13 were H. pylori‐negative. H. pylori‐positive patients were randomly assigned into two groups (two‐to‐one allocation): 36 patients were assigned to the treatment group and 17 to the follow‐up group. Thirteen H. pylori‐negative patients were followed up according to the study protocol. Follow‐up endoscopy was performed to evaluate ulcer scar changes and H. pylori status 6 weeks after anti‐H. pylori treatment and then every 6 months for up to 30 months.Results:Active duodenal ulcer recurrence was identified in seven of 23 H. pylori‐positive/non‐cured patients (30%). There was no duodenal ulcer recurrence in 43 H. pylori‐negative/cured patients (0%), which was significantly different in terms of duodenal ulcer recurrence (P=0.001).Conclusions: H. pylori eradication is effective at preventing active duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.
Influence of Helicobacter pylori infection and eradication on blood lipids and fibrinogen
Authors: Elizalde J. I. , Piqué J. M. , Moreno V. , Morillas J. D. , Elizalde I. , Bujanda L. , De Argila C. M. , Cosme A. , Castiella A. , Ros E. ,   (FOR THE GROUP OF STUDY OF OESOPHAGEAL GASTRIC DISEASES FROM THE SPANISH GASTROENTEROLOGICAL ASSOCIATION)
Published: March 2003

Background:An association between Helicobacter pylori infection and heart disease has been suggested. A potential mechanism may be inflammation‐induced atherogenic changes of lipoproteins, but epidemiological studies have provided conflicting results.Methods:In a prospective multicentre study, 830 patients submitted for endoscopy and H. pylori testing were evaluated. Of the 686 H. pylori‐positive patients, 487 received and 199 did not receive eradication treatment. Serum lipids and plasma fibrinogen were measured at baseline in all patients and 3 months later in those initially positive for H. pylori.Results: H. pylori had no influence on baseline lipid or fibrinogen levels. Increases in high‐density lipoprotein cholesterol were observed in 368 patients who received eradication treatment and in 193 untreated patients: 0.06 mmol/L (P=0.000) and 0.07 mmol/L (P=0.009), respectively. Similar minor increases in total cholesterol and triglycerides occurred in both groups. Lipid changes were related to symptom relief and a reduction in smoking. Eradication therapy was associated with a minor decrease in plasma fibrinogen irrespective of the resolution of infection.Conclusions: H. pylori has no influence on blood lipids or fibrinogen. Both the eradication of infection and symptomatic treatment without eradication are associated with minor lipid changes related to symptom relief and lifestyle modifications. Thus, the inflammatory changes associated with H. pylori are unlikely to affect lipoprotein or fibrinogen metabolism.
A randomized, double‐blind, comparative study of standard‐dose rabeprazole and high‐dose omeprazole in gastro‐oesophageal reflux disease
Authors: Holtmann G. , Bytzer P. , Metz M. , Loeffler V. , Blum A. L. 
Published: March 2003

Background:Rabeprazole has a faster onset of antisecretory action than omeprazole, and it is of interest to determine whether this translates into faster symptom relief in patients with gastro‐oesophageal reflux disease.Aims:To assess the relief from heartburn after 3 days of treatment with standard‐dose rabeprazole or high‐dose omeprazole (primary end‐point). Secondary end‐points included the decrease in score for other symptoms of gastro‐oesophageal reflux disease, healing rates and quantification of antacid use.Methods:Patients with endoscopically confirmed erosive oesophagitis were randomized to receive 4 weeks of double‐blind treatment with rabeprazole (20 mg) or omeprazole (40 mg). Patients who were not healed after 4 weeks received a further 4 weeks of treatment.Results:Two hundred and seventy‐four patients were screened, 251 patients were randomized and 230 patients completed the trial. The numbers of patients with relief from heartburn on day 4 were similar in the two groups (84% for rabeprazole; 95% confidence interval, 76–90%; 83% for omeprazole; 95% confidence interval, 75–89%). There were no significant differences between the treatments in the relief from other gastro‐oesophageal reflux disease symptoms or in healing rates. The number of reports of severe heartburn during the first 3 days was higher in the omeprazole group (daytime heartburn: 4.7% for rabeprazole vs. 10.3% for omeprazole, P=0.005; night‐time heartburn: 4.7% for rabeprazole vs. 9.8% for omeprazole, P=0.01; statistical comparisons defined post hoc).Conclusions:Standard‐dose rabeprazole was as effective as high‐dose omeprazole in relieving symptoms by day 4 of treatment and in healing oesophageal lesions, but had a faster onset of action in patients with severe heartburn. This suggests that the improved pharmacological properties of rabeprazole translate into a clinically relevant advantage.
Effectiveness of two quadruple, tetracycline‐ or clarithromycin‐containing, second‐line, Helicobacter pylori eradication therapies
Authors: Georgopoulos S. D. , Ladas S. D. , Karatapanis S. , Triantafyllou K. , Spiliadi C. , Mentis A. , Artikis V. , Raptis S. A. 
Published: March 2003

Background:There are no guidelines on second‐line therapies for Helicobacter pylori eradication failures of omeprazole–clarithromycin–amoxicillin triple therapy.Aim:To compare the efficacy of two second‐line therapies for persistent H. pylori infection.Methods:Over a 6‐year period, patients with persistent H. pylori infection following omeprazole–clarithromycin–amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology.Results:Of the 95 randomized patients, 88 (93%) completed the study. Age, sex, smoking, ulcer/non‐ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention‐to‐treat analysis, eradication was achieved in 41 of the 49 patients (84%; 95% confidence interval, 70.4–92.7%) and 27 of the 46 patients (59%; 95% confidence interval, 43.3–73.0%) of the tetracycline‐ and clarithromycin‐containing groups, respectively (P=0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P=0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P=0.036).Conclusions:Tetracycline‐containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole–amoxicillin–clarithromycin regimen.
The efficacy of methotrexate for maintaining remission in inflammatory bowel disease
Authors: Fraser A. G. , Morton D. , McGovern D. , Travis S. , Jewell D. P. 
Published: March 2003

Background:The management of patients with inflammatory bowel disease who are resistant to or intolerant of azathioprine remains a challenge. Low‐dose methotrexate has been shown to be effective in inducing remission in Crohn's disease.Aim:This review was conducted because there are limited long‐term follow‐up data during and after stopping treatment. There are also limited data on the use of methotrexate in ulcerative colitis.Methods:The study was a retrospective review of clinical notes. Remission was defined as minimal bowel symptoms without the need for oral steroids for 3 months. Relapse was defined as bowel symptoms that required steroid treatment or surgery.Results:Seventy patients were reviewed; 48 had Crohn's disease and 22 had ulcerative colitis. The mean duration of treatment was 17.1 months; the mean maintenance dose was 20 mg weekly. Remission was achieved in 34 of 55 patients who completed more than 3 months of treatment (62%). Life‐table analysis showed that the chances of remaining in remission at 12, 24 and 36 months (if treatment was continued) were 90%, 73% and 51%, respectively. The chances of remaining in remission after stopping treatment at 6, 12 and 18 months were 42%, 21% and 16%, respectively. The dose of methotrexate (mg/kg) was associated with the induction of remission (P=0.02). Treatment was equally effective for Crohn's disease and ulcerative colitis.Conclusions:Maintenance methotrexate treatment gives acceptable remission rates for treatment periods up to 3 years. After stopping treatment, relapse is frequent and occurs early (usually within 1 year).