bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection
Authors: Miyake K. , Tsukui T. , Futagami S. , Tatsuguchi A. , Shinoki K. , Hiratsuka T. , Iizumi T. , Nagata K. , Shinji Y. , Wada K. , Yamada N. , Kobayashi M. , Sakamoto C. 
Published: March 2003

Background: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury.Aim:To investigate whether acid suppression treatment after eradication influences the development of gastric erosions.Methods:Eighty‐one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2‐blocker for 6 months (H2‐blocker‐positive) and 41 received no treatment (H2‐blocker‐negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication.Results:Cumulative prevalence of gastric erosions in the H2‐blocker‐positive group was significantly lower than in the H2‐blocker‐negative group, 25% vs. 42%, respectively. In the H2‐blocker‐negative group but not the H2‐blocker‐positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis.Conclusions:Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.
No difference in the level of gastric mucosal cell apoptosis and proliferation in Helicobacter pylori‐colonized p53 heterozygous knockout mice
Authors: Suzuki H. , Miyazawa M. , Kai A. , Suzuki M. , Suematsu M. , Miura S. , Ishii H. 
Published: March 2003

Background:We previously reported that attenuated epithelial apoptosis and enhanced proliferation in comparison with mice might link to the specific carcinogenesis in Mongolian gerbils and suggested that the difference in both strains might be due to a difference in genetic background. p53 is a well‐known tumour suppressor gene, mutation of which is also known to be involved in gastric cancer formation.Aim:The present study was designed to examine the level of gastric epithelial apoptosis and proliferation in p53 heterozygous knockout mice (p53+/−) colonized with Helicobacter pylori(Sydney strain: SS1).Methods:Female p53+/− mice and wild‐type controls were orally inoculated with SS1 and the stomachs were examined 24 weeks later. DNA fragmentation was measured by levels of cytoplasmic mono‐ & oligo‐nucleosomes as well as by the TUNEL method. Gastric mucosal proliferative activity was morphometrically evaluated from the PCNA‐stained tissue specimens. Gastric mucosal myeloperoxidase (MPO) activity was measured to evaluate mucosal inflammation.Results:DNA fragmentation and the number of TUNEL‐positive cells, as well as PCNA‐positive cell number increased significantly in both groups of H. pylori‐infected mice, suggesting that levels of apoptosis and proliferation may be independent of a deficiency of one p53 allele. MPO activity in p53+/− mice and wild‐type controls increased to the same level.Conclusion:Although H. pylori inoculation per se induces an increase in cell turnover in mice, heterozygous mutation of p53 did not significantly modify the balance in cell apoptosis and proliferation.
Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders
Authors: Camilleri  , Ford  
Published: March 2003

Aim:To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea.Source:Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these.Results:In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea‐predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT3 antagonists.Conclusion:Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.
Comparison of the effect of the antacid Rennie versus low‐dose H2‐receptor antagonists (ranitidine, famotidine) on intragastric acidity
Authors: Netzer  , Brabetz‐Höfliger  , BrÜndler  , Flogerzi  , Hüsler  , Halter  
Published: March 2003

Background:Symptoms of functional dyspepsia are common and patients often self‐medicate with antacids, or with low‐dose H2‐antagonists which are available as over‐the‐counter medications. To date, there has been limited information available comparing the effects on intragastric acidity of these two types of over‐the‐counter medication. Therefore we studied the effect of the antacid Rennie and two H2‐antagonists on the intragastric pH of fasting volunteers.Methods:Sixteen healthy, fasting volunteers were randomized into a double‐blind, placebo‐controlled, four‐way crossover study comparing Rennie (calcium‐magnesium carbonate) 1360 mg, ranitidine 75 mg, famotidine 10 mg and placebo. Their effect on gastric pH was monitored by a 4‐h gastric pH‐metry. The primary efficacy parameter was the time lag before an intragastric pH > 3.0 was reached after drug administration.Results:The median time lag before pH > 3.0 was reached after drug administration was 5.8 min for Rennie, 64.9 min for ranitidine, 70.1 min for famotidine and 240.0 min for placebo. The percentage of time with values of pH > 3.0 was 10.4% for Rennie, 61.4% for ranitidine, 56.6% for famotidine and 1.4% for placebo.Conclusion:The onset of action in fasting volunteers was significantly faster with the antacid than with the two H2‐antagonists. The duration of action was significantly longer with an H2‐antagonist than with the antacid. This suggests that the two products should be used for different indications: antacids are superior for rapid pain relief, whereas H2‐antagonists might be better for symptom prophylaxis—for example for nocturnal dyspepsia.
Low rate of emergence of clarithromycin‐resistant Helicobacter pylori with amoxycillin co‐therapy
Authors: Laine L. , Suchower L. , Frantz J. , Connors A. , Neil G. 
Published: March 2003

Background:Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance.Aim:To assess pre‐ and post‐treatment antibiotic resistance in three double‐blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin.Methods:Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4–6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and ≥ 2 negative tests. Susceptibility testing was performed using the Etest.Results:In the 91 patients with pre‐treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin‐susceptible H. pylori isolates. In the 10 patients with pre‐treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates.Conclusions:Use of amoxycillin co‐therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin‐containing regimen.
Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro
Authors: Hiraishi  , Sasai  , Oinuma  , Shimada  , Sugaya  , Terano  
Published: March 2003

Background:Polaprezinc has been shown to exert an anti‐oxidant property in a tube experiment, protect gastric mucosa from experimental ulcerations in vivo, and accelerate the healing of gastric ulcer in humans.Aim:To examine a possible protective effect of polaprezinc on oxidant‐mediated injury in primary monolayer cultures of rat gastric fundic mucosa.Methods:Cytotoxicity was quantified by measuring 51Cr release. Whether or not polaprezinc exerts an antioxidant property was investigated by determining the effect of this agent on hydrogen peroxide (H2O2)‐induced injury. The effects of polaprezinc on superoxide (O2–·) generation as well as on ethanol (EtOH)‐induced injury were also examined. Generation of O2–· was assessed by the reduction in cytochrome c.Results:H2O2 caused a time‐ and dose‐dependent increase in 51Cr release. The dose‐response curve of 51Cr release by H2O2 shifted to the right in the presence of polaprezinc. Polaprezinc, at submillimolar concentrations, prevented H2O2‐induced 51Cr release. EtOH also caused a dose‐dependent increase in 51Cr release, which was prevented by the addition of polaprezinc. The incubation of cells with EtOH caused an increase in cytochrome c reduction, as the concentrations of EtOH increased. Polaprezinc inhibited EtOH‐induced cytochrome c reduction. Protection by polaprezinc was microscopically associated with the prevention of monolayer disruption.Conclusions:Polaprezinc is antioxidative and directly protects gastric mucosal cells from noxious agents through its antioxidant properties in vitro. This finding may provide the theoretical basis for the usage of an antiulcer drug with antioxidant properties for the treatment of gastric inflammation, such as that induced by ethanol.
Effect of CYP2C19 polymorphism on serum levels of vitamin B12 in patients on long‐term omeprazole treatment
Authors: SAGAR  , JANCZEWSKA  , LJUNGDAHL  , BERTILSSON  , SEENSALU  
Published: March 2003

Background:The S‐mephenytoin hydroxylase is a polymorphic cytochrome P450 (CYP) enzyme, identified as CYP2C19, which catalyses the metabolism of omeprazole and some other drugs.Aim:To determine whether long‐term treatment with omeprazole affects serum vitamin B12 levels, and if so to what extent it depends on CYP2C19 activity.Methods:Serum vitamin B12 levels (pmol/L) were assessed in 179 patients. Genotyping for wild‐type (wt) and mutated (mut) CYP2C19 alleles was performed by allele‐specific PCR amplification.Results:One‐hundred and eleven of the patients received one dose of 20 mg omeprazole. No difference in B12 levels were found between heterozygous (wt/mut) (n = 23) and homozygous (wt/wt) (n = 85) patients (mean ± s.d., 350 ± 82 vs. 315 ± 87 pmol/L, respectively). Three patients were mut/mut, with serum vitamin B12 levels of 303 ± 50 pmol/L. In the 68 patients on long‐term (>1 year) therapy with 20 mg omeprazole daily, serum vitamin B12 levels were lower in the heterozygous (wt/mut) (n = 19) compared to homozygous wt/wt (n = 49) (246 ± 71 vs. 305 ± 98 pmol/L, P = 0.01, respectively). In one patient (mut/mut) who was studied both after a single dose and after long‐term (15 months) treatment with omeprazole, serum vitamin B12 decreased from 360 to 178 pmol/L. In the wt/mut, but not in the wt/wt group, serum vitamin B12 levels were significantly lower in patients on long‐term therapy compared with those receiving one dose (246 ± 71 vs. 350 ± 82 pmol/L, P < 0.0001, respectively).Conclusions:CYP2C19 polymorphism significantly affected serum vitamin B12 levels in patients on long‐term therapy with omeprazole. In the future, genotyping of CYP2C19 may be useful for patients in need of long‐term treatment with omeprazole or other proton pump inhibitors.
Citric acid or orange juice for the 13C‐urea breath test: the impact of pH and gastric emptying
Authors: Leodolter  , Domínguez‐Muñoz J. Enrique , Von Arnim  , Malfertheiner  
Published: March 2003

Background: There is an ongoing debate about the optimal test drink to be used in the 13C‐urea breath test (13C‐UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C‐UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C‐UBT.Aim: To compare the diagnostic accuracy of the 13C‐UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined.Methods: H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C‐UBT was performed on two consecutive days by giving 75 mg of 13C‐urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C‐sodium acetate breath test; 50 mg of 13C‐sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink.Results: Twenty‐six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7 ± 5.2‰ vs. 23.2 ± 3.4‰, P < 0.001) and higher area under the curve (1507 ± 198 vs. 927 ± 128, P < 0.001) were observed in H. pylori‐positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C‐UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2= 60.9 ± 3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7 ± 3.1 min, P < 0.001).Conclusion: 13C‐UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C‐UBT.
On demand therapy of reflux oesophagitis — a prospective study of symptoms, patient satisfaction and quality of life
Authors: Wilhelmsen  , Hatlebakk  , Olafsson  , Berstad  
Published: March 2003

Background: In patients with low‐grade reflux oesophagitis adequate symptom control is the aim of treatment. Effervescent tablets alleviate heartburn more rapidly than ordinary tablets.Aim: To investigate symptom control, patient satisfaction, health‐related quality of life and disease progress when ranitidine 150 mg effervescent tablets were offered as on demand treatment. We also wanted to investigate whether any biological or psycho‐social factor could predict patient satisfaction.Method: Consecutive patients with endoscopically verified reflux oesophagitis grade I–II were followed up for 12 months. 24 h pH‐metry, disease history, symptoms and several psycho‐social factors were registered at baseline and 12 months follow‐up.Results: Eighty‐one patients were included. Mean age was 50.7 years (range 21–82), 63% were men. Mean tablet consumption was 1.21 per day (range 7–1016 tablets/year). At the 1‐year follow‐up discomfort resulting from reflux symptoms was significantly reduced (P < 0.001), and the patients’ social and vocational life improved. Eighty‐four percentage of the patients were satisfied with the treatment. 24 h pH‐metry or number of reflux episodes did not change. We did not find any factors able to predict patient satisfaction.Conclusions: On demand therapy with ranitidine effervescent tablets was well accepted by the majority of patients with reflux oesophagitis grade I. Even though the number of reflux episodes did not change, the patients experienced less discomfort due to reflux symptoms, and their social and vocational life was better. There was no significant progression of the disorder during the 1‐year follow‐up. No predictive factor for patient satisfaction was found.
Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions
Authors: Dammann  , Burkhardt  , Wolf  
Published: March 2003

Background: Low‐dose aspirin (acetylsalicylic acid, ASA) increases the risk of developing peptic ulceration.Aim: To investigate the gastroduodenal mucosal tolerability of enteric‐coated ASA (EC‐ASA) 100 mg/day compared to either placebo (study 1) or plain ASA 100 mg/day (study 2) in healthy volunteers.Methods: Study 1: In this double‐blind study 18 volunteers received randomized dosing with either EC‐ASA 100 mg or placebo for 15 days. Study 2: 41 volunteers underwent randomized 7‐day dosing of either EC‐ASA 100 mg or plain ASA 100 mg in this double‐blind, parallel‐group, comparison study. In both studies acute gastroduodenal mucosal lesions were assessed endoscopically before treatment, on the morning of day 1 after the first dose (only in study 2), and on the morning after the last dose of the test medication.Results: Study 1 did not reveal any significant differences between the lesion scores of EC‐ASA and placebo. In contrast, in study 2 significantly higher total gastroduodenal mucosal lesion scores were observed on day 1 after the first dose and after 7 days of dosing with plain ASA (mean sum of the lesion scores in the gastric fundus, body, antrum and in the duodenal bulb: day 1: plain ASA 3.95 ± 3.38 vs. EC‐ASA 1.43 ± 1.91, P=0.03; day 7: plain ASA 6.35 ± 4.10 vs. EC‐ASA 2.00 ± 2.02, P=0.0004). Tolerance of the test drugs was good, and no other adverse events were observed.Conclusions: Enteric‐coated aspirin 100 mg/day causes significantly less gastroduodenal damage over 7 days than the same dose of plain aspirin, when given to healthy subjects. There was little gastric injury and no significant differences between EC‐ASA and placebo in this respect.
Effects of current and former cigarette smoking on the clinical course of Crohn’s disease
Authors: Cosnes  , Carbonnel  , Carrat  , Beaugerie  , Cattan  , Gendre  
Published: March 2003

Background: Cigarette smoking is associated with a more severe course of Crohn’s disease, but individual factors determining this effect are poorly known and it is not clear whether smoking cessation is associated with an improvement in the disease activity.Aim: To assess the factors determining the harmful effect of smoking in individuals with Crohn’s disease.Methods: A total of 622 consecutive patients with Crohn’s disease and Crohn’s disease activity index <200 were enrolled in a prospective 12–18 month cohort study. Patients were classified as current smokers, former smokers, or non‐smokers. Alcohol consumption, oral contraceptive use, body mass index, and blood lipid levels were also recorded. The main outcome measure was the rate of flare‐up.Results: A total of 139 current smokers (46%) developed a flare‐up, vs. 79 non‐smokers (30%) and 13 former smokers (23%). The relative risk of flare‐up adjusted for confounding factors was 1.35 (1.03–1.76) in current smokers. This risk was increased in patients with previously inactive disease and in those who had no colonic lesions. It became significant above a threshold of 15 cigarettes per day. Former smokers behaved like non‐smokers. Obesity, dyslipidaemia, and alcohol consumption had no significant effect.Conclusions: Current smoking, particularly heavy smoking, markedly increases the risk of flare‐up in Crohn’s disease. Former smokers have a risk similar to that of non‐smokers.
The effect of an inhibitor of matrix metalloproteinases on colonic inflammation in a trinitrobenzenesulphonic acid rat model of inflammatory bowel disease
Authors: Sykes  , Bhogal  , Brampton  , Chander  , Whelan  , Parsons  , Bird  
Published: March 2003

Background: Recent publications have reported that matrix metalloproteinases (MMPs) are expressed in colonic tissue taken from ulcerative colitis and Crohn’s disease patients.Aim: To evaluate the effects of a matrix metalloproteinase inhibitor, marimastat, on colonic inflammation in experimental colitis induced by trinitrobenzenesulphonic acid (TNBS)‐ethanol in the rat.Methods: Rats were dosed (by mouth) for 7 days (b.d.) with either sulphasalazine (50 mg/kg), marimastat (40 mg/kg) or vehicle. TNBS‐ethanol was administered rectally on the 4th day of dosing. On the last day of dosing, colons were removed and assessed for inflammation using myeloperoxidase activity, production of soluble TNFα (tumour necrosis factor α), clinical score and histological assessment. In addition, the bioavailability and effect of marimastat on a range of MMPs were assessed in‐vitro.Results: In this study we have confirmed that marimastat is a broad spectrum MMPI with a bioavailability of 5%. TNBS rats dosed with sulphasalazine had a significantly lower (P < 0.05) myeloperoxidase activity, TNFα production and a markedly lower clinical score. Similarly, rats dosed with marimastat had a significantly lower (P < 0.05) myeloperoxidase activity and clinical score, but the TNFα production was not significantly reduced.Conclusions: Dosing rats with TNBS‐induced colitis using sulphasalazine or marimastat produced a significant reduction in tissue injury and inflammation.