bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrophic gastritis during long‐term omeprazole therapy affects serum vitamin B12 levels
Authors: Schenk  , Kuipers  , Klinkenberg‐Knol  , Bloemena  , Sandell  , Nelis  , Snel  , Festen  , Meuwissen  
Published: March 2003

Background: Omeprazole maintenance therapy for gastro‐oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori‐infected patients and with a decreased absorption of protein‐bound, but not of unbound cobalamin.Aim: To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy.Methods: Forty‐nine H. pylori‐positive GERD patients were treated with omeprazole for a mean (± s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow‐up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow‐up for histopathological scoring according to the updated Sydney classification.Results: At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow‐up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow‐up. During follow‐up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136–716) vs. (T1) 341 (136–839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156–716) at latest follow‐up (P < 0.01).Conclusions: The development of atrophic gastritis during omeprazole treatment in H. pylori‐positive GERD patients is associated with a decrease of serum vitamin B12 levels.
Propranolol stereoisomer plasma concentrations and portal haemodynamic response in patients with liver cirrhosis
Authors: Schepke  , Raab  , Hoppe  , Brensing  , Paar  , Potyka  , Sauerbruch  
Published: March 2003

Background: The haemodynamic effect of propranolol on portal pressure in patients with portal hypertension is highly variable and does not correlate with propranolol racemate plasma concentrations.Aim: To investigate the stereoselective metabolism of the propranolol enantiomers and its impact on portal haemodynamics in patients with liver cirrhosis since only S‐propranolol is haemodynamically active.Methods: Twenty patients with liver cirrhosis and portal hypertension received 40 mg propranolol orally. Portal blood velocity (PBV) and propranolol stereoisomer plasma concentrations were determined.Results: During the 4 h examination period we observed a significant reduction in PBV (18.3 ± 2.2%, P < 0.0001) vs. baseline. The area under the curve (AUC) during the study period was significantly different for the two isomers (S‐propranolol 1217.0 ± 118.5 nmol.h/L; R‐propranolol 728.8 ± 103.8 nmol.h/L, P < 0.0001). Seven patients (35%) were portal haemodynamic non‐responders to propranolol. Propranolol stereoisomer AUC values were no different between responders (S‐propranolol 1133.3 ± 132.0 nmol.h/L; R‐propranolol 718.0 ± 129.7 nmol.h/L) and non‐responders (S‐propranolol 1371.8 ± 250.5 nmol.h/L; R‐propranolol 746.9 ± 200.3 nmol.h/L); neither was there a correlation between propranolol enantiomer plasma concentrations and the portal haemodynamic effect.Conclusions: Our data demonstrate a stereoselective metabolism of propranolol enantiomers in liver cirrhosis. However, following oral propranolol administration, stereoisomer plasma concentrations do not predict the portal haemodynamic effect.
Mesalazine‐induced apoptosis of colorectal cancer: on the verge of a new chemopreventive era?
Authors: Bus  , Nagtegaal  , Verspaget  , Lamers  , Geldof  , Van Krieken  , Griffioen  
Published: March 2003

Background: It is an accepted fact that non‐steroidal anti‐inflammatory drugs (NSAIDs) are potent inhibitors of colorectal carcinogenesis. However, the major disadvantages of NSAIDs are gastrointestinal and renal toxicity. We conducted a prospective pilot study on the effects of the safe salicylic acid derivative, mesalazine, on apoptosis and proliferation of tumour cells and on normal tissue in colorectal cancer patients.Methods: Patients with colorectal cancer were asked to take mesalazine enemas for 14 days. Biopsies from malignant and normal tissue were taken prior to and after this treatment. Apoptosis was scored on haematoxylin/eosin‐stained tissue sections, and cell proliferation was assessed by the proliferation marker Ki‐67.Results: Ten out of 14 patients completed the study. The apoptotic score increased significantly in the tumour samples (pre‐treatment 14.6 ± 1.3 vs. post‐treatment 19.4 ± 0.8; P < 0.03). The apoptotic index in the normal mucosa was unchanged (pre‐treatment 3.1 ± 0.4 vs. post‐treatment 2.9 ± 0.3; N.S.). The cell proliferation in malignant tissue, according to the Ki‐67 score, was hardly affected by mesalazine (pre‐treatment 522 ± 38 vs. post‐treatment 493 ± 39; N.S.). There was no effect on the Ki‐67 index of normal mucosa (pre‐treatment 24.2 ± 2.0 vs. post‐treatment 28.3 ± 2.0; N.S.).Conclusions: This pilot study conducted in patients with colorectal cancer clearly shows that mesalazine selectively induces apoptosis of tumour cells. On the basis of these findings, which need to be confirmed in larger studies, it may be speculated that 5‐ASA could be useful in the chemoprevention of colorectal cancer.
A randomized dose–response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn’s disease and ulcerative colitis
Authors: Egan  , Sandborn  , Tremaine  , Leighton  , Mays  , Pike  , Zinsmeister  , Lipsky  
Published: March 2003

Background and aims:The optimum initial dose of methotrexate for steroid‐requiring inflammatory bowel disease is not known.Aim:To compare directly the efficacy and toxicity of methotrexate 15 and 25 mg/week, and to explore the value of methotrexate blood levels as predictors of outcome.Methods:A 16‐week randomized single‐blind comparison of subcutaneous methotrexate 15 or 25 mg/week was performed in 32 patients with steroid‐requiring Crohn’s disease or ulcerative colitis. Patients who did not respond to methotrexate 15 mg/week were further studied for an additional 16 weeks on methotrexate 25 mg/week. Blood was drawn every 2 weeks for methotrexate levels.Results:After 16 weeks, 17% of patients in each group achieved remission; 39% of patients randomized to 15 mg/week and 33% of patients randomized to 25 mg/week improved (P=N.S.). Clinical status improved in four out of 11 patients after methotrexate dose escalation from 15 to 25 mg/week. Toxicity was not different between the treatment groups. Methotrexate blood levels did not predict efficacy or toxicity.Conclusions:For induction of remission in steroid‐requiring inflammatory bowel disease, subcutaneous methotrexate at initial doses of 15 and 25 mg/week are equally efficacious. At these doses, response is not associated with blood methotrexate concentrations.
Complete resolution of heartburn symptoms and health‐related quality of life in patients with gastro‐oesophageal reflux disease
Authors: Revicki  , Crawley  , Zodet  , Levine  , Joelsson  
Published: March 2003

Background:Medical treatments for gastro‐oesophageal reflux disease (GERD) vary in their ability to completely resolve heartburn and other symptoms. Although GERD reduces health‐related quality of life (HRQL) little is known about the relationship between resolution of heartburn symptoms with medical therapy and HRQL. We evaluated the association between complete resolution of heartburn symptoms and functioning and well‐being in three samples of patients with GERD.Methods:We analysed baseline and follow‐up assessments of heartburn symptoms and HRQL scores from three clinical trials (total n=1351) comparing omeprazole and ranitidine for acute symptomatic treatment of GERD. Heartburn symptoms were measured using patient diaries and/or patient self‐report. HRQL was assessed using the Psychological General Well‐Being Index (PGWB) in all three clinical trials and the SF‐36 Health Survey in two clinical trials. Resolution of heartburn symptoms was defined as no heartburn reported during the assessment period.Results:We observed statistically significant differences favouring patients with no heartburn symptoms on the PGWB total score (P=0.018 to P < 0.0001) and anxiety (P=0.002 to P < 0.0001), general health (P=0.05 to P < 0.0001), positive well‐being (P=0.028 to P < 0.0001) and vitality (P=0.05 to P < 0.0001) sub‐scale scores at 4–14 weeks. Patients with no heartburn reported better SF‐36 pain (P=0.005 to P < 0.0001) and general health perceptions (P=0.032 to P < 0.0001) compared with patients still experiencing heartburn symptoms at 4–24 weeks. SF‐36 physical component summary scores were significantly better in patients with no heartburn symptoms compared with patients with heartburn symptoms at 4–24 weeks (P=0.013 to P=0.009), while mental component summary scores were only significantly different at 24 weeks (P=0.0005) in one of the two studies where the SF‐36 was utilized.Conclusions:Complete resolution of heartburn symptoms was consistently associated with improvement in HRQL; the greatest impact was observed on measures of psychological well‐being and physical functioning and well‐being. Effective treatment of GERD that completely resolves heartburn results in clinically significant improvement in patient HRQL.
Have we found the source of Helicobacter pylori?
Authors: Mégraud F. , Broutet N. 
Published: March 2003

SummaryBesides the well established Helicobacter pylori reservoir, i.e. the human stomach, numerous other sources have been hypothesized. However, none has been definitely proven. In some instances (pig, sheep), Helicobacter species closely related but different from H. pylori were detected but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (cat) but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies which theoretically can be a vehicle, but practically speaking are not because of too few viable bacteria present in faeces. Molecular epidemiology studies demonstrating the route of transmission (faecal–oral, oral–oral or gastro–oral) are still lacking but recent studies have confirmed the presence of viable H. pylori in vomitus and in faeces in the event of diarrhoea.
Helicobacter pylori and gastric cancer − the clinicians' point of view
Authors: Huang J‐Q. , Hunt R. H. 
Published: March 2003

SummaryAlthough the incidence of gastric cancer has declined dramatically in Western countries, the most recent data from the International Agency for Research on Cancer show that it remains the second most common cancer worldwide and caused 628 000 deaths in 1990. The incidence and prevalence of gastric cancer are projected to increase over the next few decades in less developed countries as a result of the increased longevity of H. pylori‐infected populations and improved therapies. Gastric carcinogenesis is a multistep and multifactorial process beginning with H. pylori‐associated gastritis in most cases. H. pylori infection, together with other environmental factors and individual susceptibility, determine the final risk for the development of gastric cancer. The magnitude of H. pylori infection as a risk factor for gastric cancer in the published H. pylori and gastric cancer epidemiology studies may have been underestimated due to the inclusion of improperly selected controls. Eradication of the infection has been shown to prevent the occurrence of metachronous gastric cancer following endoscopic resection of early gastric cancer in a Japanese study. However, the generalization of this study to other populations is difficult because of the vast differences in the definition of gastric atrophy and early gastric cancer between Japanese and Western pathologists. Until an international consensus on the pathological diagnosis of gastric atrophy and early gastric cancer is reached, interpretation of studies performed in different countries remains difficult. Clinicians rely on the correct pathological diagnosis to guide the management of H. pylori infection‐associated gastrointestinal diseases.
Does eradication of Helicobacter pylori alone heal duodenal ulcers?
Authors: Ge  , Zhang  , Xiao  , Chen  , Hu  
Published: March 2003

Bakcground:Eradication of Helicobacter pylori infection prevents duodenal ulcer (DU) relapse, but it remains uncertain whether eradication of H. pylori alone heals duodenal ulceration.Aim:To test the hypothesis that eradication of H. pylori infection is accompanied by healing of duodenal ulcer.Methods:A total of 115 consecutive patients with endoscopically confirmed H. pylori‐infected duodenal ulcer were randomly assigned to one of two groups. Group BTC patients received a 1‐week course of colloidal bismuth subcitrate 220 mg b.d., tinidazole 500 mg b.d., clarithromycin 250 mg b.d. Group OBTC patients received omeprazole 20 mg daily for 4 weeks with the BTC regimen during the first week. Endoscopy with antral biopsies and 13C‐urea breath test (UBT) were performed before and 4 weeks after completion of the 7‐day triple or quadruple therapy.Results:Eight patients dropped out (four in BTC and four in OBTC). Duodenal ulcer healing rates on an intention‐to‐treat basis in BTC and OBTC were 86% (95% CI: 77–95%) and 90% (95% CI: 82–98%), respectively. The eradication rates of H. pylori on an intention‐to‐treat basis in BTC and OBTC were 88% (95% CI: 79–96%) and 91% (95% CI: 84–99%), respectively. There were no statistically significant differences in ulcer healing rates and eradication rates between these two groups (P > 0.05). Epigastric pain resolved more rapidly in patients assigned to OBTC compared with those assigned to BTC. Both of the two regimens were well tolerated with only minor side‐effects (3% of the 115 patients) and the compliance was good.Conclusions:BTC is a very effective H. pylori eradication regimen. Almost all duodenal ulcers heal spontaneously after cure of H. pylori infection using a 1‐week low‐dose bismuth‐based triple therapy. Treating duodenal ulcer with simultaneous administration of omeprazole achieves ulcer pain relief more rapidly.
Review article: nitroimidazole resistance in Helicobacter pylori
Authors: Van Der Wouden  , Thijs  , Van Zwet  , Kleibeuker  
Published: March 2003

The efficacy of a nitroimidazole‐containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are meta‐ bolized by H. pylori by several nitro‐reductases of which an oxygen‐insensitive NADPH nitroreductase encoded by the rdxA gene is the most important. Null mutations in this gene are associated with resistance.Susceptibility testing to nitroimidazoles may give variable results. This is not only related to the slow growth under specific conditions, but also to variability in the activity of the other nitroreductases and the ability to deactivate toxic metabolites of an NI and to repair DNA damage. Moreover, co‐infections with resistant and susceptible bacteria are frequently found. The presence of nitroimidazole resistance is related to the previous use of this drug. The prevalence of resistance is rising and nowadays 10–50% of the isolates are resistant.Resistance reduces the efficacy of a treatment regimen to a variable degree. This is related to efficacy of the other components of the regimen and the treatment duration. Whether a nitroimidazole is still effective in resistant strains remains unresolved.When nitroimidazole resistance is present, a nitro‐imidazole‐containing regimen should be avoided or a regimen with other highly effective components should be used.
Similarities between ileal Crohn’s disease and indomethacin experimental jejunal ulcers in the rat
Authors: Anthony  , Pounder  , Dhillon  , Wakefield  ,   THE INFLAMMATORY BOWEL DISEASE STUDY GROUP
Published: March 2003

Background: Both Crohn’s disease ileal ulcers and indomethacin‐induced jejunal ulcers in the rat have a predilection for the mesenteric margin of the bowel wall. Unlike the anti‐mesenteric margin, the mesenteric margin is supplied by small end‐arteries that might render it more sensitive to ischaemic injury.Aim: To examine, in both situations, the histological relationship between the precise localization of small bowel ulcers and the mesenteric margin.Methods: Ileal Crohn’s disease ulcers identified in surgical resection specimens (n=5) and indomethacin‐induced lesions in the rat jejunum (n=6) were examined macroscopically and histologically.Results: In both the human ileum and the rat jejunum, ulcers occurred consistently along the mesenteric margin, with the most extensive mucosal injury occurring at two adjacent sites on either side of the midline of this margin. At these two sites, feeding arteries entered the muscularis propria.Conclusions: For anatomical reasons apparently related to the vasculature of the human and rodent small bowel, specific sites along the mesenteric margin are susceptible to Crohn’s disease ulceration and NSAID damage, respectively.
Helicobacter pylori infection is associated with milder gastro‐oesophageal reflux disease
Authors: Wu  , Sung  , Chan  , Ching  , Ng  , Go  , Wong  , Ng  , Chung  
Published: March 2003

Background:We have previously demonstrated a negative relationship between the prevalence of Helicobacter pylori and gastro‐oesophageal reflux disease (GERD).Aim:To study the effects of H. pylori infection on the severity of GERD.Methods:Ethnic Chinese patients with frequent heartburn and/or endoscopic oesophagitis were studied. Endoscopic examination was performed to assess the severity of oesophagitis (modified Savary–Miller grading) and the presence of hiatus hernia. Biopsies were taken for rapid urease testing and confirmation of Barrett’s oesophagus. Risk factors which may affect the severity of oesophagitis (age, sex, smoking, drinking, diabetes mellitus, hiatus hernia, H. pylori status and body mass index) were evaluated by a multiple regression model. The cagA status of H. pylori infected GERD and age‐and‐sex matched controls were determined by Western blot. Age‐and‐sex matched non‐reflux patients were recruited as controls for comparison.Results:Two hundred and twenty‐five patients with GERD were studied, of whom 77 (34%) were infected with H. pylori. Oesophagitis and Barrett’s oesophagus were found in 140 patients (62%) and six patients (3%), respectively. H. pylori infected patients had significantly less severe oesophagitis compared to the uninfected group (P=0.022). All patients with Barrett’s oesophagus were uninfected. Factors that predicted severe oesophagitis included age over 60 years (P < 0.001) and hiatus hernia (P < 0.001). H. pylori infection was the only factor that showed a negative correlation with severe oesophagitis (P=0.011). The prevalence of the cagA positive strain in endoscopy‐negative GERD, erosive oesophagitis and control subjects was 70, 76 and 78%, respectively (P=0.75).Conclusions: H. pylori infection is associated with milder GERD.
Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers
Authors: Kees  , Holstege  , Ittner  , Zimmermann  , Lock  , Schölmerich  , Grobecker  
Published: March 2003

Background:Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease. The interaction of antimicrobial therapy and acid suppression is not yet well elucidated.Aims:To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady‐state conditions in volunteers.Methods:In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days. Blood plasma levels of the drugs were measured. In addition, roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy.Results:The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other. When compared to roxithromycin administered alone, its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice (3.0–5.0 μg/mL vs. 0.3–0.4 μg/mL) and gastric tissue (antrum: 3.8–4.0 vs. 2.8 μg/g, fundus: 5.9–7.4 vs. 4.2–4.4 μg/g).Conclusions:Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other. However, proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori.
Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR
Authors: Tomassetti  , Migliori  , Corinaldesi  , Gullo  
Published: March 2003

Background:Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days.Aim:To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours.Methods:A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non‐functioning pancreatic tumours, two with Zollinger–Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6–15 months).Results:In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5‐hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger–Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side‐effects were observed.Conclusions:Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.