bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of genes for spasmolytic peptide, transforming growth factor alpha and for cyclooxygenase (COX)‐1 and COX‐2 during gastric adaptation to aspirin damage in rats
Authors: Konturek  , Brzozowski  , Pierzchalski  , Kwiecien  , Pajdo  , Hahn  , Konturek  
Published: March 2003

Background:NSAIDs, such as aspirin (ASA), cause widespread mucosal damage, but repeated ASA insults appear to induce mucosal tolerance (adaptation) to this␣injury. The mechanism of the gastric adaptation to the damage induced by ASA has not been fully explained.Aim:To determine the role of the mucosal gene expression for spasmolitic peptide (SP) (a member of trefoil peptides) and transforming growth factor alpha (TGFα) as well as for cyclooxygenase (COX)‐1 and COX‐2 during gastric adaptation to ASA in rats.Methods:Gastric lesions were produced by ASA (100 mg/kg in 1.5 mL of 0.2 M HCl) applied intragastrically (i.g.) as a single dose, every day for 5 days. Control rats were given 1.5 mL of vehicle (0.2 M HCl i.g.) as a single dose, during 5 consecutive days. Gastric blood flow (GBF) was measured by H2‐gas clearance technique and gastric mucosal specimens were taken for the assessment of cell␣proliferation rate in gastric mucosa by bromodeoxyuridine (BrdU) uptake, mucosal generation of prostaglandin E2 measured by radioimmunoassay, and for expression of SP, TGFα COX‐1 and COX‐2 mRNA as determined by RT‐PCR. To quantify the relative amounts of mRNA for SP and TGFα, southern blotting analysis of the PCR products was performed and the intensity of PCR products was compared with that of β‐actin used as a standard.Results:ASA applied once produced numerous gastric erosions, but with repeated ASA doses the adaptation to this NSAID developed, the area of gastric lesions being reduced by 86% after six consecutive ASA insults. This adaptation to ASA was accompanied by approximately a 90% reduction in prostaglandin E2 biosynthesis, by a significant rise in BrdU uptake by glandular cells predominantly in the neck region of gastric glands and by expression of SP (SP/β‐actin ratio; 0.96 ± 0.08 in ASA‐adapted mucosa vs. 0.38 ± 0.05 in the control mucosa) and TGFα (TGFα/β‐actin ratio: 0.97 ± 0.07 in ASA‐adapted mucosa vs. 0.77 ± 0.06 in the control mucosa). COX‐1 expression was detected in vehicle‐control gastric mucosa and after single exposure to ASA or after six consecutive ASA insults, while COX‐2 mRNA was not detected in vehicle‐control gastric mucosa, but appeared after single ASA insult and was sustained after subsequent ASA doses.Conclusions:(i) Gastric adaptation to aspirin injury involves enhanced cell proliferation which appears to be mediated by increased expression of SP and TGFα, and (ii) rapid upregulation of COX‐2 expression following single and repeated ASA insults may represent a compensatory response to suppression of prostaglandin generation by this NSAID.
The Leeds Dyspepsia Questionnaire: a valid tool for measuring the presence and severity of dyspepsia
Authors: Moayyedi  , Duffett  , Braunholtz  , Mason  , Richards  , Dowell  , Axon  
Published: March 2003

BackgroundThere is currently no validated questionnaire that assesses both the presence and severity of dyspepsia.AimTo develop the Leeds Dyspepsia Questionnaire (LDQ) as a measure of the presence and severity of dyspepsia, and to assess the validity, reliability and responsiveness of this instrument.MethodsUnselected patients attending either a hospital dyspepsia clinic or a general practice surgery were interviewed by a trained gastroenterologist or a general practitioner on the presence and severity of dyspepsia. This opinion was compared with the results of the nurse‐administered LDQ. Test–retest reliability was assessed by the same research nurse re‐administering the LDQ 4–7 days after the initial visit in a subgroup of hospital patients. In a further subgroup of patients one researcher interviewed the patients and a second researcher re‐administered the LDQ within 30 min to evaluate inter‐rater reliability. The responsiveness of the LDQ was measured by repeating it in patients with endoscopically proven peptic ulcer or oesophagitis 1 month after receiving appropriate therapy.ResultsThe LDQ was administered to 99 general practice and 215 hospital patients. In the GP population 41/98 (42%) had dyspepsia according to the GP and the LDQ had a sensitivity of 80% (95% CI: 65–91%) and a specificity of 79% (95% CI: 66–89%). The weighted kappa statistic for the agreement between the LDQ and the clinician for the severity of dyspepsia was 0.58 in the GP population and 0.49 in hospital patients. The kappa statistic for test–retest reliability was 0.83 in 107 patients. The LDQ had excellent inter‐rater reliability with a kappa statistic of 0.90 in 42 patients. The median LDQ score fell from 22.5 (range 9–36) to 4.5 (range 0–27) in 12 patients 1 month after receiving appropriate therapy (Wilcoxon signed rank test, P < 0.0001).ConclusionThe LDQ is a valid, reliable and responsive instrument for measuring the presence and severity of dyspepsia.
Protective effects of zinc in indomethacin‐induced gastric mucosal injury: evidence for a dual mechanism involving lipid peroxidation and nitric oxide
Authors: Joseph  , Varela  , Kanji  , Subramony  , Mihas  
Published: March 2003

Background:Indomethacin causes gastric mucosal injury, although the pathogenesis is not fully understood. Zinc, is known to have gastroprotective effects in both humans and experimental animals. Aim: To determine (i) the protective effects of zinc in indomethacin‐induced gastric mucosal injury in rats, and (ii) whether these cytoprotective effects are mediated by changes in gastric lipid peroxidation and/or nitric oxide synthase activity.Methods:Gastric lesions were induced in rats by the intragastric administration of indomethacin. Morphological changes, lipid peroxidation (malondialdehyde levels) and nitric oxide synthase activity were determined in animals pre‐treated with zinc sulphate and in controls.Results:Indomethacin significantly increased malondialdehyde levels and decreased NOS activity. These effects were attenuated by pre‐treatment with zinc (P < 0.005 and 0.0001, respectively). The protective effects of zinc were readily abolished in animals pre‐treated with N‐nitro‐L‐arginine methyl ester (L‐NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre‐treatment.Conclusions:Zinc provides protection against indomethacin‐induced gastric mucosal injury. These protective effects result from the inhibition of lipid peroxidation and the preservation of mucosal nitric oxide synthase.
Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus—evaluation of 24‐h pH monitoring
Authors: Haruma  , Mihara  , Okamoto  , Kusunoki  , Hananoki  , Tanaka  , Yoshihara  , Sumii  , Kajiyama  
Published: March 2003

Background:Recent studies have shown that the eradication of Helicobacter pylori results in a gastric acid secretion which decreases to normal levels in patients with duodenal ulcer disease. The aim of this study was to evaluate the effect of eradication of H. pylori in a 24‐h study of gastric acidity in patients with atrophic gastritis of the corpus.Methods:Intragastric acidity was measured by continuous 24‐h pH monitoring, and the histology of the gastric antrum and corpus were evaluated in 14 H. pylori‐positive patients with histologically proven atrophic gastritis of the corpus (10 men, 4 women; mean age, 57 years) before and 1 year after anti‐H. pylori therapy.Results:H. pylori was absent in 13 of 14 patients 1 year after treatment. Both gastritis and atrophy scores were significantly lower after eradication therapy (P < 0.01). The 24‐h median pH and the percentage of 24‐h pH readings above 4.0 units were significantly decreased after eradication therapy (from 5.12 ± 0.36 to 2.69 ± 0.21, and from 65.5 ± 6.6% to 28.2 ± 6.1%, P < 0.01, respectively.)Conclusion:Eradication of H. pylori increases 24‐h gastric acidity in patients with atrophic gastritis of the corpus. Improvement of the histology of the gastric antrum and corpus may lead to the normalization of gastric acidity.
Glucose metabolism and insulin sensitivity in inactive inflammatory bowel disease
Authors: Capristo  , Mingrone  , Addolorato  , Greco  , Gasbarrini  
Published: March 2003

Background:Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin‐resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance.Aim:To measure body composition, whole body glucose uptake and oxidation in Crohn’s disease and ulcerative colitis patients with inactive disease.Methods:All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn’s disease (five males, aged 31.1 ± 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 ± 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group.Results:Crohn’s disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (μmol/kg/min) was found between groups (respectively 42.5 ± 6.78 in Crohn’s disease, 40.2 ± 8.00 in ulcerative colitis and 41.4 ± 10.8 in control subjects). Glucose storage and oxidation did not differ between groups.Conclusion:Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat‐free mass preservation and low blood and tissue cytokine concentration.
Triple therapy for Helicobacter pylori eradication is more effective than long‐term maintenance antisecretory treatment in the prevention of recurrence of duodenal ulcer: a prospective long‐term follow‐up study
Authors: WONG  , LAM  , LAI  , HU  , CHING  , HO  , YUEN  , CHAN  , LAU  , LAI  
Published: March 2003

Background: The effectiveness of Helicobacter pylori eradication treatment and long term acid suppression maintenance in the natural course of duodenal ulcer has not been directly compared.Aim: To compare in a prospective randomized study the effectiveness of H. pylori eradication on the prevention of recurrence of duodenal ulcer with long‐term maintenance acid suppression therapy.Methods: One hundred and fourteen duodenal ulcer patients were randomized to the treatment over a 12‐month period. Fifty‐seven of them received triple therapy consisting of 1 g sucralfate q.d.s. for 28 days, 300 mg metronidazole q.d.s. for 14 days and 250 mg clarithromycin q.d.s. for 14 days. Another 57 received 20 mg omeprazole q.d.s. for 12 months. An upper endoscopy was performed before treatment, at 6 weeks, and 2, 6 and 12 months after the first endoscopy. Side‐effects were self‐recorded and clinical follow‐ups were arranged for up to 4.25 years.Results: The ulcer healing rate was 90.2% (95% confidence interval (95% CI): 79–97%) in the omeprazole group at 6 weeks as compared to 83.3% (95% CI: 70–93%) in the triple therapy group (P = 0.38). There was a higher success rate of pain control in the omeprazole group. Side‐effects were more frequently reported and compliance was poorer in the triple therapy group during the first 4 weeks. During follow‐up, more relapses were seen in the omeprazole group (9.8%, 95% CI: 3–21%) than the triple therapy group (4.2%, 95% CI: 1–13%) at 1 year (P = 0.44). All relapses were due to the persistence of H. pylori infection. At the 1 year follow‐up, none of the patients who were H. pylori negative had an endoscopic relapse compared to 7 out of 56 patients who remained H. pylori positive (12.5%, 95% CI: 5–24%, P = 0.018). After a mean follow‐up of 4.07 years, none of those who remained H. pylori negative had an ulcer relapse while the 11 out of 41 who remained H. pylori positive had an ulcer relapse (26.8%, 95% CI 14–43, P = 0.0005).Conclusions: Both regimens were highly effective in healing ulcers. The eradication of H. pylori infection was associated with more side‐effects and poor compliance but was more effective than the maintenance therapy in reducing the recurrence of duodenal ulcers. For the prevention of ulcer recurrence, testing of H. pylori status after triple therapy is more important than maintenance therapy.
Lack of effect of spearmint on lower oesophageal sphincter function and acid reflux in healthy volunteers
Authors: Bulat R. , Fachnie E. , Chauhan U. , Chen Ying , Tougas G. 
Published: March 2003

Background: Spearmint is commonly used as an antispasmodic and as a flavouring in several medications including antacids. It can produce heartburn, presumably by lowering lower oesophageal sphincter (LES) tone, but the mechanism has not previously been objectively examined.Aim: To study the effect of spearmint on LES function, acid reflux and symptoms.Methods: In healthy volunteers, a Dent Sleeve and a pH electrode were placed in the distal oesophagus. They were then given spearmint either in a flavouring (0.5 mg), or a high (500 mg) dose, or a placebo, using a double‐blind randomized crossover design. LES pressure, oesophageal pH and symptoms were recorded for 30 min before and after administration.Results: LES pressure was not affected by spearmint, either high dose (19.6 vs. 16.0 mmHg), flavouring dose (20.2 vs. 19.8 mmHg) or placebo (20.5 vs. 19.2 mmHg, all N.S.). There were no differences in reflux occurrence following high dose (mean = 0.65 vs. 0.85 episodes), low dose (0.4 vs. 0.5 episodes) or placebo (0.7 vs. 1.10 episodes, all N.S.). There was a significant increase in mean symptom scores following high‐dose spearmint (0 vs. 0.35, P = 0.03), but not low dose (0 vs. 0.2) or placebo (0 vs. 0.5, both N.S.). One subject reported symptoms with placebo, one with low dose, and six with high dose; all without increased reflux episodes or decreased sphincter pressure.Conclusion: Spearmint has no effect on LES pressure or acid reflux. Flavouring doses of spearmint do not produce more symptoms than placebo while high doses can be associated with symptoms, presumably from direct mucosal irritation but not reflux.
Antibiotic combination therapy in patients with chronic, treatment‐resistant pouchitis
Authors: Gionchetti P. , Rizzello F. , Venturi A. , Ugolini F. , Rossi M. , Brigidi P. , Johansson R. , Ferrieri A. , Poggioli G. , Campieri M. 
Published: March 2003

Background: Pouchitis is the major long‐term complication after ileal pouch‐anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment‐resistant disease.Aims: To evaluate the efficacy of an antibiotic combination for chronic active, treatment‐resistant pouchitis.Patients and Methods: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture.Results: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9–17) and 4 (range 0–16), respectively (P < 0.002). No side‐effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance.Conclusions: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment‐resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.
A systematic review of Helicobacter pylori eradication therapy—the impact of antimicrobial resistance on eradication rates
Authors: Houben  , Beek D. Van De , Hensen  , Craen A. J. M. De , Rauws  , Tytgat  
Published: March 2003

Background: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates.Methods: A comprehensive search of all published trials on H. pylori eradication therapy was carried out via an electronic database search, hand‐searching and checking reference lists of pharmaceutical companies and other reviews. Full papers and abstracts in the English language which study currently advised eradication regimes were included.Results: 770 study‐arms were analysed. Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92%. In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth‐based triple and proton pump inhibitor‐based triple therapies. For quadruple therapy, a significant difference in efficacy was found in the equal‐effects analysis; however, this could not be confirmed in the random‐effects analysis. In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one‐ and two‐week clarithromycin containing proton pump inhibitor‐triple therapies and of 58% for two‐week ranitidine bismuth citrate combined with clarithromycin therapies. For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce.Conclusions: The cure rate with most regimens dropped significantly, in case of nitroimidazole‐resistant strains, compared to nitroimidazole‐susceptible strains. In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce. These data should allow physicians to make a better choice of an appropriate therapy for their patients.
Sustained response to interferon‐α or to interferon‐α plus ribavirin in hepatitis C virus‐associated symptomatic mixed cryoglobulinaemia
Authors: Calleja  , Albillos  , Moreno‐Otero  , Rossi  , Cacho  , Domper  , Yebra  , Escartín  
Published: March 2003

Background: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia.Aim: To investigate the efficacy of anti‐viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV‐associated symptomatic mixed cryoglobulinaemia.Patients and methods: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12‐month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12‐months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV‐RNA and cryoglobulins were performed.Results: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow‐up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or dissapearance of the MC‐associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%).Conclusions: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV‐associated MC. The presence of cryoglobulins does not affect the response to anti‐viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or dissapearance of MC‐associated clinical manifestations.
Lansoprazole pharmacokinetics differ in patients with oesophagitis compared to healthy volunteers
Authors: Barclay  , Begg  , Robson  , Peters  , Ketelbey  
Published: March 2003

Aim: To compare the pharmacokinetics of lansoprazole in patients with reflux oesophagitis and in healthy volunteers, after a single dose and at steady‐state.Patients and methods: A 30 mg dose of lansoprazole was administered orally daily for 7 days in eight healthy male volunteers aged 21–24 years, and in 16 patients aged 29–65 years with grade 2 or 3 reflux oesophagitis. The pharmacokinetics were assessed over the 24 h dose interval following the first dose and again after the 7th dose.Results: Within both the patient and volunteers groups, there were no significant differences between day 1 and day 7 in any of the pharmacokinetic parameters including maximum concentration (Cmax), area under the concentration–time curve (AUC), and terminal half‐life of elimination (t½). However, on both days 1 and 7, values were significantly higher in the patients than in the healthy volunteers. On day 7, Cmax was 1343 ng/mL in patients compared with 765 ng/mL in healthy volunteers, AUC was 3458 ng.h/mL vs. 1350 ng.h/mL and t½ was 1.62 h vs. 0.90 h.Conclusion: The differences in results for the pharmacokinetics reflect reduced lansoprazole clearance in the patient group. Other research has not found a difference in pharmacokinetics when comparing healthy volunteers with patients with acid‐related disorders. The difference in lansoprazole clearance in this study may be related to a variety of factors that are different in patients compared with young normal volunteers, such as age, gender, other drugs, and reduced general well‐being.