bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐steroidal anti‐inflammatory drugs and Helicobacter pylori
Authors: Barr M. , Buckley M. , O'morain C. 
Published: March 2003

SummaryNon‐steroidal anti‐inflammatory drugs (NSAIDs) and Helicobacter pylori are well‐recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta‐ glandin metabolism. Clinical trials on the interrelation‐ ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda‐ tions should be implemented with regard to H. pylori eradication in patients on long‐term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.
The efficacy of a 40‐mg extended‐release formulation of cisapride in the treatment of patients with gastro‐oesophageal reflux
Authors: Katschinski  , Schirra  , Arnold  
Published: March 2003

Background:This study was conducted to assess the efficacy of a novel 40‐mg extended‐release formulation of cisapride in reducing gastro‐oesophageal reflux.Methods:According to a double‐blind, randomized, placebo‐controlled design, 19 patients with pathological gastro‐oesophageal reflux were treated with extended (40 mg o.d.) or immediate (10 mg q.d.s.) release formulations for two periods of 4 days each (pH‐monitoring on day four). Patients received identical treatments in both periods to allow limits of agreement defining equivalent potency of both formulations to be derived from intra‐individual variability of treatment effects.Results:The extended‐release formulation decreased total and upright reflux times by 5.5 ± 1.3% and 8.1 ± 2.1% (P < 0.001), respectively. It did not change the percentage supine reflux time but diminished the mean duration of reflux episodes by 1.0 ± 0.4 min (P=0.005). The total number of reflux episodes remained unaltered with both formulations. Immediately‐released cisapride decreased total, upright, and supine acid exposures by 5.8 ± 1.3%, 6.8 ± 1.6% (P < 0.002) and 3.6 ± 1.8%, respectively, and mean duration of episodes by 0.9 ± 0.2 min (P ≤ 0.05). Equivalent potency for both formulations was accepted in terms of percentage total and upright acid exposure and mean duration of episodes.Conclusions:The 40‐mg extended‐release formulation of cisapride decreases total acid exposure and in this study is equivalent to the conventional immediate‐release 10 mg q.d.s. regimen. Cisapride primarily interferes with reflux by improving oesophageal acid clearance.
Lack of a pharmacokinetic interaction between lansoprazole or pantoprazole and theophylline
Authors: Pan  , Goldwater  , Zhang  , Pilmer  , Hunt  
Published: March 2003

Aim:To study the potential pharmacokinetic interaction between lansoprazole or pantoprazole and theophylline at steady state.Methods:Theophylline 200 mg extended‐release formulation was administered twice daily on days 1–11 to 30 healthy, non‐smoking males. On days 5–11, 15 subjects received concomitant lansoprazole 30 mg once daily (o.d.) and 15 subjects received concomitant pantoprazole 40 mg o.d.Results:No significant changes in the steady‐state theophylline maximum plasma concentration (Cmax), time to Cmax (Tmax), minimum plasma concentration (Cmin), area under the plasma concentration–time curve over the 12‐h dosing interval (AUC0–12), or apparent total oral clearance (CL/F) were observed within the two treatment groups when theophylline was administered alone or in combination with lansoprazole or pantoprazole. In addition, no significant differences in the changes of steady‐state theophylline pharmacokinetics from day 4 to day 11 were noted between the two treatment groups. Treatment with theophylline in combination with either lansoprazole or pantoprazole was well tolerated. All adverse events were transient and rated mild to moderate in severity.Conclusion:Co‐administration of either lansoprazole or pantoprazole in healthy subjects does not significantly affect the steady‐state pharmacokinetics of theophylline at the therapeutic doses tested.
An evaluation of whole blood testing for Helicobacter pylori infection in the Chinese population
Authors: Wong  , Wong  , Tang  , Lai  , Yuen  , Hu  , Chan  , Lau  , Lai  , Lam  
Published: March 2003

Background:Near patient tests for Helicobacter pylori were developed to assist in the management of dyspepsia patients in general practice. Most studies were performed in western populations.Aim:To evaluate the rapid whole blood test (Flexpack HP) for H. pylori in the Chinese population.Methods:Consecutive dyspeptic patients referred for upper endoscopy were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus for rapid urease test (CLO test) and histological examination. After endoscopy, the whole blood test (FlexPack HP) was performed according to the manufacturer’s instruction. Patients then received a 13C‐urea breath test. Results of the whole blood test were compared with the gold standard (CLO test, histology and 13C‐urea breath test).Results:A total of 294 consecutive patients gave a valid Flexpack HP result for interpretation. The mean age of patients was 47.7 (range 15–85) years. Analysis showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 58%, 92%, 91%, 63% and 73% respectively.Conclusion:The FlexPack HP whole blood test showed good specificity but lacked sensitivity. It is not sensitive enough to be used in a general practice setting for the test‐and‐treat approach in the Chinese population.
Dose‐dependent effects of ketoprofen on the human gastric mucosa in comparison with ibuprofen
Authors: Donnelly  , Richardson  , Hawkey  , Courtauld  , Stack  
Published: March 2003

Background:As non‐steroidal anti‐inflammatory drugs (NSAIDs) become available for over‐the‐counter use, it is important to define doses that would not cause undue gastroduodenal damage during the short periods for which self‐medication with NSAIDs is licensed.Aim:To establish what dose of ketoprofen most closely resembles the maximum dose of ibuprofen (400 mg t.d.s.) licensed for self‐medication.Methods:We studied healthy volunteers in a double‐blind double‐dummy randomized crossover study. Each subject took, over four separate 10‐day dosing periods, ibuprofen 400 mg t.d.s., ketoprofen 12.5 mg t.d.s., ketoprofen 25 mg t.d.s. or ketoprofen 50 mg t.d.s. Mucosal injury was assessed by endoscopy at baseline and on the 3rd and 10th day of each dosing period. Ex vivo gastric mucosal prostaglandin (PG) E2 evoked by vortex mixing was measured by radioimmunoassay. Serum thromboxane was also measured by radioimmunoassay.Results:Ketoprofen 50 mg t.d.s. suppressed prostaglandin synthesis to a significantly greater extent than ibuprofen and caused significantly more gastroduodenal injury. The profile of prostaglandin synthesis and injury on ketoprofen 12.5 mg t.d.s. most closely resembled that of ibuprofen 400 mg t.d.s.Conclusions:Ketoprofen 12.5 mg t.d.s. is an appropriate dose for self‐medication, which is likely to be similar to ibuprofen 400 mg t.d.s. in its effects on the stomach and duodenum.
Influence of age on the steady state disposition of drugs commonly used for the eradication of Helicobacter pylori
Authors: Ammon  , Treiber  , Kees  , Klotz  
Published: March 2003

Background:The success of eradication therapy for Helicobacter pylori might be affected by the age of patients.Aim:To investigate whether disposition of drugs commonly used for H. pylori eradication is age‐dependent.Methods:Trough steady state serum levels of lansoprazole or ranitidine, amoxycillin, clarithromycin and metronidazole were monitored in 232 patients during the last dosing interval of a 5‐day quadruple H. pylori eradication regimen. Detailed pharmacokinetic analysis was performed in 28 patients.Results:Linear correlations between age and trough serum levels were observed with lansoprazole (r=0.25; P=0.002), ranitidine (r=0.38; P=0.001) and clarithromycin (r=0.36; P < 0.0001). These associations were also inversely dependent of creatinine clearance for ranitidine (r=0.36; P=0.001) and clarithromycin (r=0.30; P < 0.0001). Multiple linear regression revealed age as an important factor influencing trough serum levels of lansoprazole, clarithromycin and ranitidine. There were significant inverse relationships between creatinine clearance and area under curve of ranitidine (r=0.88; P < 0.0001) and amoxycillin (r=0.56; P=0.002). Multiple linear regression revealed serum creatinine as the most important factor influencing the area under curve of ranitidine, clarithromycin and amoxycillin.Conclusions:Age per se has little influence on pharmacokinetics of amoxycillin and ranitidine, which depend more on age‐dependent decline in renal function. The influence of age, but not renal function was established for lansoprazole. Age and renal function have independent impacts on clarithromycin disposition.
Cerebral near infrared spectroscopy for the measurement of indocyanine green elimination in cirrhosis
Authors: Therapondos  , Plevris  , Stanley  , Peters  , Teig  , Hayes  
Published: March 2003

Background:Indocyanine green (ICG) clearance is a useful indicator of hepatic function but most measurement methods are invasive.Aim:To validate a less invasive technique using cerebral near infrared spectrophotometry (NIRS) to measure ICG elimination, and to compare it with the established methods for the determination of ICG clearance in a group of normal controls and patients with cirrhosis.Method:NIRS was used to measure ICG elimination in 41 cirrhotic patients and nine healthy volunteers. The first 13 of the cirrhotic patients also had their ICG clearance measured by the conventional spectrophotometric technique.Results:NIRS ICG elimination rate (ICG‐k) and spectrophotometry ICG‐k values correlated strongly (r= 0.828, P < 0.001, n=13). There was a significant reduction in the mean NIRS‐k in cirrhotic patients and within Child–Pugh classes A, B, and C (P < 0.001).Conclusion:Measurement of ICG elimination by the NIRS method is at least as reliable as the conventional spectrophotometric technique in normals and in patients with cirrhosis. This technique merits further development for use as a bedside, less invasive liver function test.
Efficacy of sucralfate for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole‐based regimen
Authors: Adachi  , Ishihara  , Hashimoto  , Hirakawa  , Niigaki  , Takashima  , Kaji  , Kawamura  , Sato  , Okuyama  , Watanabe  , Kinoshita  
Published: March 2003

Background:Sucralfate has an inhibitory action against Helicobacter pylori and enhances the anti‐H. pylori activity of antimicrobials.Aim:To evaluate the efficacy and safety of sucralfate‐based eradication therapy for H. pylori infection, compared with that based on lansoprazole, in a randomized multicentre study.Subjects and methods:The subjects were 150 H. pylori‐positive patients. They were randomly assigned to one of two regimens for 2 weeks: sucralfate 1 g t.d.s., amoxycillin 500 mg t.d.s., and clarithromycin 400 mg b.d. (SAC regimen: 75 patients); or lansoprazole 30 mg o.m. with the same antimicrobial medications (LAC regimen: 75 patients). Cure of infection was assessed by a 13C urea breath test 1 month after completion of treatment.Results:Eight patients (four in the SAC group and four in LAC group) could not continue therapy because of severe diarrhoea, and three did not take the 13C urea breath test after therapy. Cure rates for intention‐to‐treat, all‐patients‐treated, and per protocol analysis in the SAC group were 80%, 83%, and 88%, respectively, and those in the LAC group were 87%, 87%, and 92%, respectively. There were no significant differences in cure rate or adverse effects between the two regimens.Conclusion:Sucralfate in combination with amoxycillin and clarithromycin is as effective as lansoprazole‐based eradication therapy for H. pylori.
Rabeprazole, amoxycillin and low‐ or high‐dose clarithromycin for cure of Helicobacter pylori infection
Authors: Kihira K. , Satoh K. , Saifuku K. , Kawakami S. , Fukazawa K. , Ishino Y. , Kimura K. , Sugano K. 
Published: March 2003

Background:Rabeprazole sodium is a proton pump inhibitor.Aim:To evaluate the efficacy and safety of 1‐week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori.Methods:A total of 100 subjects with H. pylori were randomly divided into two groups of 1‐week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b.d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E‐test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment.Results:There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention‐to‐treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76–95%) and 89% (95% CI: 80–97%); RAC800: 94% (95% CI: 87–100%) and 97% (95% CI: 94–100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin‐resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group.Conclusion:One‐week triple therapy with rabeprazole, amoxycillin and low‐dose clarithromycin is effective for the eradication of H. pylori infection.
Enhanced bioavailability of azathioprine compared to 6‐mercaptopurine therapy in inflammatory bowel disease: correlation with treatment efficacy
Authors: Cuffari C. , Hunt S. , Bayless T. M. 
Published: March 2003

Background:Azathioprine and 6‐mercaptopurine have proven efficacy in the treatment of Crohn’s disease. Immunosuppression is mediated by their intracellular metabolism into active 6‐thioguanine metabolites, and clinical responsiveness to therapy in patients with inflammatory bowel disease has been correlated with the measure of erythrocyte 6‐thioguanine levels.Aims and methods:To perform a dosing equivalency analysis and comparison of clinical efficacy in 82 patients with inflammatory bowel disease on long‐term (> 2 months) therapy with either branded azathioprine (Imuran) (n=26), generic azathioprine (n=38), or 6‐mercaptopurine (n=18), based on the measurement of erythrocyte 6‐thioguanine metabolite levels.Results:Disease remission was achieved in 51% (42 out of 82) of patients treated with either azathioprine or 6‐mercaptopurine therapy, and correlated well with high erythrocyte 6‐thioguanine levels (> 250 pmoles/8 × 108 RBCs). Patients treated with either branded azathioprine or 6‐mercaptopurine achieved significantly higher erythrocyte 6‐thioguanine levels than patients treated with generic azathioprine, thereby suggesting that branded azathioprine has improved oral bioavailability compared to generic azathioprine. These data are consistent with the putative immunosuppressive role of 6‐thioguanine metabolites in the treatment of inflammatory bowel disease, and provides a basis for developing a therapeutic index of clinical efficacy based on the measurement of erythrocyte 6‐thioguanine metabolite levels.Conclusions:Our results suggest that differences in bioavailability may have clinical relevance when considering the need to optimize erythrocyte 6‐thioguanine metabolite levels in patients deemed unresponsive to treatment on conventional drug dosages.
Helicobacter pylori–gastrin link in MALT lymphoma
Authors: Konturek P. C. , Konturek S. J. , Starzyska T. , Marlicz K. , Bielanski W. , Pierzchalski P. , Karczewska E. , Hartwich A. , Rembiasz K. , Lawniczak M. , Ziemniak W. , Hahn E. C. 
Published: March 2003

Background:There is accumulating evidence for the role of Helicobacter pylori in the development of gastric cancer as well as of lymphomas that arise in mucosa‐associated lymphoid tissue (MALT). We reported recently that gastric cancer patients show high prevalence of cagA‐positive H. pylori and express gastrin and gastrin receptors enabling them to stimulate tumour growth in autocrine fashion.Aims:Since the H. pylori infection is considered to be more strongly associated with MALT lymphoma than with gastric cancer, we decided to determine the gastrin and its receptors’ mRNA expression and gastrin content in this tumour as well as the release of this hormone both into plasma and gastric lumen. Twenty MALT lymphoma patients were compared with 100 age‐ and gender‐matched controls with similar dyspeptic symptoms.Results:The overall H. pylori seropositivity in MALT lymphoma was about 90% and CagA positivity was 70%, compared to 56% and 33%, respectively, in controls. The serum gastrin in MALT lymphoma was about sixfold higher than in controls while gastric luminal gastrin in these patients was over 70 times higher than in controls. Gastrin content in tumour was about 10‐fold higher than in antral mucosa. Gastrin and gastrin‐receptor (CCKB‐receptor) mRNA were detected by reverse transcriptase–polymerase chain reaction in cancer tissue whilst in the fundic and antral mucosa, only enhanced expression of CCKB‐receptor mRNA and gastrin mRNA was detected, respectively. Histamine stimulation in MALT lymphoma induced acid secretion that was only about 30% of control value due to atrophic gastritis. This study confirms an important role of CagA‐positive H. pylori in the pathogenesis of MALT lymphoma and shows that this lymphoma is capable of synthesizing and releasing potent growth promoting gastrin, possibly due to the action on G‐cells of H. pylori‐originated Nα‐methyl histamine and cytokines (tumour necrosis factor alpha and interleukin‐8).Conclusions:Gastric MALT lymphoma is closely linked to CagA‐positive H. pylori infection. Gastrin and its receptors may be implicated in the pathogenesis of gastric lymphoma.
Omeprazole and CYP2C19 polymorphism: effects of long‐term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders
Authors: Sagar M. , Bertilsson L. , Stridsberg M. , Kjellin A. , Mårdh S. , Seensalu R. 
Published: March 2003

Background:The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short‐term treatment.Aim:To investigate the relationship between CYP2C19 genotype and the effects of long‐term omeprazole treatment.Material and methods:A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele‐specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods.Results:In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long‐term treatment (> 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean ± s.e.) were both about threefold higher in the wild type/mutated (52.1 ± 7.6 p
M and 7.3 ± 1.3 n
M (n=19), respectively) compared to wild type/wild type (14.7 ± 0.9 p
M and 2.5 ± 0.1 n
M (n=52), respectively; both comparisons P=0.0001). In a single mutated/mutated patient on long‐term treatment, both gastrin and chromogranin A were high (88 p
M and 13.7 n
M, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long‐term treatment, compared with the corresponding wild type/wild type (n=49) group (147 ± 19 μg/L vs. 193 ± 12 μg/L, P=0.04).Conclusion:Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long‐term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual’s capacity to metabolize omeprazole.
Management of Helicobacter pylori in duodenal ulcer: a cost‐effectiveness analysis
Authors: García‐Altés A. , Jovell A. J. , Serra‐Prat M. , Aymerich M. 
Published: March 2003

Background:Empirical eradication therapy of H. pylori has been proposed as a therapeutic alternative for duodenal ulcer.Aim:To identify the cost‐effectiveness of empirical eradication therapy vs. test‐and‐treatment for the management of patients already diagnosed with a duodenal ulcer.Methods:A decision analysis was performed to compare the cost‐effectiveness of empirical eradication therapy of H. pylori diagnosed duodenal ulcer vs. eradication therapy after confirmatory diagnosis of Helicobacter pylori infection by means of several diagnostic tests.Results:The empirical eradication therapy of duodenal ulcer was found to be the most effective and cost‐effective strategy of all the alternatives. Amongst the alternatives, which included the previous performance of confirmatory diagnostic tests, the best cost‐effectiveness ratio used a serology test. The model was robust in the face of changes in the values of therapeutic effectiveness, sensitivity and specificity of the diagnostic tests, prevalence of H. pylori infection in duodenal ulcer, duration of the antisecretory therapy, and number of medical visits.Conclusions:Based on our cost‐effectiveness analysis, a treat approach is more effective and cost‐effective than a test‐and‐treat approach in the clinical management of already diagnosed duodenal ulcer.
5‐day vs. 7‐day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication
Authors: Isomoto H. , Furusu H. , Morikawa T. , Mizuta Y. , Nishiyama T. , Omagari K. , Murase K. , Inoue K. , Murata I. , Kohno S. 
Published: March 2003

Aim:To determine whether a 5‐day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7‐day regimen.Methods:A total of 139 H. pylori‐infected patients were randomized to receive either a 5‐day or 7‐day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C‐urea breath test.Results:On the intention‐to‐treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5‐ and 7‐day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5‐ and 7‐day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance.Conclusions:Our 5‐day regimen of RCA yielded inferior results, whereas the 7‐day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor–clarithromycin–amoxicillin therapies cannot be recommended.