bluuebunny/crossref_metadata_2025_split huggingface dataset:
The systemic load and efficient delivery of active 5‐aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine
Authors: STØA‐BIRKETVEDT  , FLORHOLMEN  
Published: March 2003

Background:There have been reports of nephrotoxic reactions in patients with ulcerative colitis treated with 5‐aminosalicylic acid (5‐ASA) preparations.Aim:To compare the efficacy in delivery of active 5‐ASA to the colon and the systemic load as the basis for potential long‐term toxicity during treatment with olsalazine or mesalazine in patients with ulcerative colitis in remission.Patients and Methods:Fifteen patients with ulcerative colitis were treated with olsalazine or mesalazine, each for 7 days in an open, randomized, crossover design study. 5‐ASA and acetyl‐5‐ASA (Ac‐5‐ASA) in plasma and urine were measured by high performance liquid chromatography.Results:The plasma concentration of 5‐ASA was 1.2 ± 0.1 μmol/L (mean ± S.E.M.) for olsalazine and 8.0 ± 1.9 μmol/L for mesalazine, while the plasma concentration of Ac‐5‐ASA was 2.8 ± 0.2 μmol/L for olsalazine and 10.8 ± 1.6 μmol/L for mesalazine. The amount of 5‐ASA excreted in the urine was 68 ± 30 μmol/24 h for olsalazine and 593 ± 164 μmol/24 h for mesalazine. The amount of Ac‐5‐ASA in the urine was 1260 ± 102 μmol/24 h for olsalazine and 3223 ± 229 μmol/24 h for mesalazine. The urinary recovery of total 5‐ASA plus Ac‐5‐ASA (as a percentage of the given dose) was 23 ± 2.1% for olsalazine and 39 ± 3.6% for mesalazine. The ratio between the plasma concentrations of mesalazine and olsalazine differed significantly both for 5‐ASA (5.1) and Ac‐5‐ASA (3.6); for 5‐ASA (9.9) and Ac‐5‐ASA (2.6) in urine, and for the urinary recovery of total 5‐ASA plus Ac‐5‐ASA (1.7). Moreover, in the mesalazine group there was a large variation in the individual plasma concentrations of 5‐ASA and Ac‐5‐ASA, with maximal values 5–6‐fold higher than that in the olsalazine group.Conclusion:The systemic load of active 5‐ASA is significantly higher for mesalazine than for olsalazine, when based on the dosages given and when calculated on an equimolar basis. Some of the patients in the mesalazine group showed unexpected high levels of plasma and urinary 5‐ASA concentrations, a finding which may have long‐term safety implications.
Anti‐ulcerogenic properties of endothelin receptor antagonists in the rat
Authors: PADOL  , HUANG  , HUNT  
Published: March 2003

Background: Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET‐1 and ET‐3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin‐1 levels in patients suffering from peptic ulcers.Aim: To study the possibility that endothelin receptor antagonists may have beneficial effects and prevent the development of gastric ulcers. We have tested in rats the orally‐active endothelin antagonist bosentan (Ro 47‐0203) and Ro 48‐5695, which is 10–30 times more potent than bosentan on endothelin receptors.Methods: Water immersion restrained stress (WIRS) and indomethacin were used to provoke gastric mucosal damage. Endothelin receptor antagonists were administered orally prior to the induction of gastric damage. The gastric lesion index (mm), assessed macroscopically, and myeloperoxidase (MPO) activity were used as markers of the extent of mucosal injury.Results: Bosentan at 100 and 30 mg/kg administered orally caused attenuation of gastric damage in the WIRS model by 58% and 42%, respectively. Bosentan also caused complete reduction of MPO activity. In indomethacin‐induced gastric damage, 100 mg/kg bosentan attenuated gastric damage by 45% and 61% as measured by the gastric lesion index and MPO activity respectively. Ro 48‐5695 was at least 30 times more potent than bosentan in reducing indomethacin‐induced mucosal damage and at 3 mg/kg, caused a decrease of 49% in the gastric lesion index and a reduction in MPO activity of 41%. Bosentan and Ro 48‐5695 possess weak antisecretory properties as tested in the mouse gastric gland assay, than cannot, alone, account for their anti‐ulcer properties.Conclusions: Both endothelin receptor antagonists prevented the development of gastric mucosal injury in the rat. Disturbances in the gastric microcirculation are responsible for the development of experimental gastric ulcers. The anti‐ulcer properties of these two endothelin antagonists suggest possible new therapeutic approaches to controlling gastric inflammation.
Patterns of consultation and treatment for heartburn: findings from a Singaporean community survey
Authors: Ho  , Kang  , Seow  
Published: March 2003

Background: The prevalence of reflux‐type symptoms among community individuals in Singapore is low.Aim: To describe the healthcare‐seeking behaviour of those subjects with heartburn.Methods: A cross‐sectional survey, using a reliable and valid questionnaire, was carried out on a race‐stratified random sample of residents, aged 21–95 years, in a Singaporean town; 93% responded (n=696).Results: The ethnic‐adjusted prevalence of heartburn for the past 1‐year was 4.6%. Sixteen (30%) of the 53 heartburn sufferers had sought consultation for their symptoms. They were more likely to have severe heartburn (P < 0.001), and to have complained of nocturnal awakening due to heartburn (P < 0.05) than those who did not present to medical attention. Ethnic origin did not influence the consultation pattern. Only 18 (34%) of the 53 heartburn sufferers received pharmacological therapy for their symptoms. The most commonly used medication was antacid. Medication use was associated with symptom severity (P < 0.05), but not ethnicity.Conclusions: Heartburn is uncommon in the general population of Singapore. Few heartburn sufferers seek medical attention, and most do not receive medications for symptomatic control. The decision to seek medical advice and/or to medicate was generally linked to symptom severity, but not to ethnicity.
The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non‐ulcer dyspepsia
Authors: Miyaji  , Azuma  , Ito  , Abe  , Ono  , Suto  , Ito  , Yamazaki  , Kohli  , Kuriyama  
Published: March 2003

Background: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non‐ulcer dyspepsia. In addition, it has been reported that Helicobacter pylori induced inflammation of the gastric mucosa may affect gastric motility.Aim: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in non‐ulcer dyspepsia patients.Methods: A total of 46 non‐ulcer dyspepsia patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori‐positive non‐ulcer dyspepsia patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after being cured of H. pylori infection.Results: A total of 67.4% of the non‐ulcer dyspepsia patients were H. pylori‐positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in non‐ulcer dyspepsia patients. H. pylori‐positive non‐ulcer dyspepsia patients were divided into three groups according to their gastric emptying: the delayed gastric emptying group, the normal gastric emptying group, and the rapid gastric emptying group. In the delayed and rapid gastric emptying groups, the gastric emptying and symptom scores were improved significantly by the eradication therapy. However, there was no improvement in symptom scores in the normal gastric emptying non‐ulcer dyspepsia group by the eradication therapy.Conclusions: Disturbed gastric emptying and antral myoelectrical activity play roles in non‐ulcer dyspepsia. Helicobacter pylori infection, inducing disturbed gastric emptying, may cause some non‐ulcer dyspepsia symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in non‐ulcer dyspepsia patients with disturbed gastric emptying. H. pylori eradication therapy is effective in H. pylori‐positive non‐ulcer dyspepsia patients with disturbed gastric emptying.
Salvage therapies after failure of Helicobacter pylori eradication with ranitidine bismuth citrate‐based therapies
Authors: Chan  , Sung  , Suen  , Wu  , Ling  , Chung  
Published: March 2003

Background:Salvage therapies after initial Helicobacter pylori eradication failure of ranitidine bismuth citrate (RBC)‐based regimens remain undefined.Aim:To test the efficacy of 1‐week omeprazole, amoxycillin and clarithromycin as a second‐line treatment and 1‐week quadruple therapy after repeated failures of RBC‐ and proton pump inhibitor‐based regimens.Method:Patients were recruited from a recently published prospective randomized study if confirmed to have failed H. pylori eradication with RBC‐based regimens. They were given omeprazole 20 mg, amoxycillin 1 g and clarithromycin 500 mg (OAC) b.d. for 1 week. 13C‐urea breath test was performed 4 weeks after the conclusion of medication. Those who failed to respond to OAC were given 1‐week quadruple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg and metronidazole 400 mg q.d.s. plus omeprazole 20 mg b.d.).Results:Among 398 patients receiving RBC‐based therapies, 40 (10%) had failed eradication (RAC=7, RC‐2=12, RMC=7, and RMT=14). OAC was prescribed to 31 patients (RAC=4, RC‐2=9, RMC=6, and RMT=12) and 68% had successful eradication. Nine out of 10 patients with failed second treatment received quadruple therapy; successful eradication occurred in 83% (5 out of 6) after repeated failures of clarithromycin‐based regimens.Conclusion:One‐week OAC is not an optimal second‐line therapy when RBC‐clarithromycin combinations fail. Quadruple therapy appears to be effective despite repeated failures of clarithromycin‐based RBC or proton pump inhibitor therapies.
The effects of omeprazole on healing and appearance of small gastric and duodenal lesions during dosing with diclofenac in healthy subjects
Authors: Dorta  , Nicolet  , Vouillamoz  , Margalith  , Saraga  , Bouzourene  , Häcki  , Stolte  , Blum  , Armstrong  
Published: March 2003

Background:Non‐steroidal anti‐inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage. Omeprazole prevents the formation, and accelerates the healing, of NSAID‐induced ulcers.Aim:To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac.Methods:In a double‐blind, double‐dummy, placebo‐controlled, crossover study, 12 healthy volunteers received consecutive, 2‐week courses of omeprazole (40 mg o.d.) and placebo, in random order, with an intervening, 4‐week washout period; diclofenac (50 mg t.d.s.), was given for the second week of each course. Five endoscopies were performed, one at the outset and the others before and after each course of diclofenac. Biopsies were taken from the endoscopically normal mucosa of the corpus, antrum and duodenum and also from any new mucosal lesion that developed after diclofenac. The sites of biopsies taken before each course of diclofenac were evaluated endoscopically after each course to assess the extent of healing according to a predetermined healing score scale.Results:The healing scores observed after administration of placebo/diclofenac (median=0; range 0–6) and after omeprazole/diclofenac (median=0; range 0–6; P=0.17) did not differ. Small gastroduodenal lesions developed de novo in six subjects during placebo/diclofenac and in seven during omeprazole/diclofenac. Focal chemical gastropathy was observed only in close proximity to macroscopic lesions.Conclusions:In healthy subjects, omeprazole does not accelerate the healing of pre‐existing mucosal lesions or prevent the development of small diclofenac‐induced mucosal lesions.
Towards identifying optimal doses for alpha‐2 adrenergic modulation of colonic and rectal motor and sensory function
Authors: Malcolm  , Camilleri  , Kost  , Burton  , Fett  , Zinsmeister Alan R. 
Published: March 2003

Rationale:Visceral sensation and motility are important in functional gut disorders and are partly controlled by adrenergic innervation.Objectives:To characterize the α2‐adrenergic control of motor and sensory function of descending colon and rectum.Methods:In 32 healthy volunteers, we assessed compliance, fasting and postprandial tone, and sensations of gas, urgency and pain during phasic distentions. Each subject received one agent at clinically approved doses: clonidine (0.05, 0.1, 0.2 or 0.3 mg p.o.); or the α2 antagonist yohimbine (0.0125 mg, 0.05 mg, 0.125 mg or 0.2 mg intravenously and infusion over 2.5 h).Results:Clonidine increased colonic and rectal compliance, and reduced tone, pain, gas sensation and rectal urgency. Clonidine showed large pairwise differences in sensation and motility between 0.05 and 0.1 mg doses, which did not interfere with the colon’s motor response to feeding. Conversely, yohimbine dose‐dependently altered the compliance curve, increased tone and sensations of gas, pain and urgency. Drug effects in the colon were more marked at low distensions; α2 modulation of rectal sensation was observed at all levels of distension.Conclusions:α2‐adrenergic mechanisms modulate colorectal sensations and motility; at doses as low as 0.05 mg, clonidine reduced colorectal sensation while the tone response to feeding was preserved. These studies provide insight into the potential use of α2 agents in disease states.
Ulcer‐healing drugs are required after eradication of Helicobacter pylori in patients with gastric ulcer but not duodenal ulcer haemorrhage
Authors: Lai K. C. , Hui W. M. , Wong B. C. Y. , Hu W. H. C. , Lam S. K. 
Published: March 2003

Aim:To study the efficacy of a 2‐week anti‐Helicobacter therapy in the healing of H. pylori‐associated bleeding peptic ulcers.Methods:Omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g, twice daily, were given for 2 weeks to 180 patients with H. pylori‐associated bleeding peptic ulcers. Endoscopy was repeated 4 weeks after the eradication therapy to assess healing of the peptic ulcers.Results:Repeat endoscopies were performed in 168 patients (42 gastric ulcer and 126 duodenal ulcer) who followed the protocol. Thirty‐eight patients with bleeding gastric ulcers and 124 patients with bleeding duodenal ulcers healed 4 weeks after treatment (per protocol analysis; gastric ulcer: 91% vs. duodenal ulcer: 98%; P=0.035). No patients who were compliant to the study medications suffered from re‐bleeding. Stepwise discriminant analysis demonstrated that small ulcers (< 15 mm) and the presence of duodenal ulcers best predicted healing of the peptic ulcers.Conclusions:Ulcer‐healing drugs should be continued after a 2‐week course of omeprazole‐containing anti‐Helicobacter therapy for gastric ulcers and large peptic ulcers that have bled, but can be omitted in most patients with a bleeding duodenal ulcer.
Cetraxate, a mucosal protective agent, combined with omeprazole, amoxycillin, and clarithromycin increases the eradication rate of Helicobacter pylori in smokers
Authors: Kamada T. , Haruma K. , Miyoshi E. , Mihara M. , Kitadai Y. , Yoshihara M. , Sumii K. , Kajiyama G. , Tahara K. , Mukai T. , Kawamura Y. , Hattori N. 
Published: March 2003

Background:Our previous study demonstrated that Helicobacter pylori eradication was less effective in smokers than in non‐smokers. Cetraxate is an anti‐ulcer drug that increases gastric mucosal blood flow.Aim:To evaluate the effect of cetraxate combined with new triple therapy for the eradication of H. pylori in smokers.Methods:This study had a single‐centre, double‐blind, randomized non‐placebo design. A total of 106 consecutive H. pylori‐positive smoking patients were randomly allocated to one of two regimens: one group received omeprazole (20 mg), amoxycillin (1500 mg), and clarithromycin (600 mg) for 7 days (OAC, n=55). The other group recieved OAC plus cetraxate (600 mg) for 7 days (OAC + CET, n=51). The success of H. pylori eradication was evaluated by histology and the 13C‐urea breath test at 4 weeks after completion of treatment.Results:By intention‐to‐treat analysis, the H. pylori eradication rate was 55% in the OAC group and 92% in the OAC + CET group (P < 0.01). By per protocol analysis, the H. pylori eradication rate was 58% in the OAC group and 94% in the OAC + CET group (P < 0.01).Conclusion:Cetraxate combined with new triple therapy increases the eradication of H. pylori in smokers.
High‐dose ecabet sodium improves the eradication rate of Helicobacter pylori in dual therapy with lansoprazole and amoxicillin
Authors: Kagaya H. , Kato M. , Komatsu Y. , Mizushima T. , Sukegawa M. , Nishikawa K. , Hokari K. , Takeda H. , Sugiyama T. , Asaka M. 
Published: March 2003

Aim:The additive effect of ecabet sodium in combination with dual therapy on Helicobacter pylori eradication was evaluated.Methods: H. pylori‐positive chronic gastritis patients were randomly assigned to one of the following three groups and medicated for 2 weeks. Group LA: dual therapy (lansoprazole 30 mg o.d. plus amoxicillin 750 mg b.d.). Group LA1E: dual therapy plus ecabet sodium (1 g b.d.). Group LA2E: dual therapy plus ecabet sodium (2 g b.d.). Patients were evaluated 4 weeks after the cessation of treatment by culture and 13C‐urea breath test.Results:Seventy‐one patients (mean age, 56.6 years; range, 26–79 years; 40 males, 31 females) were enrolled in this prospective, single‐blind study, and 68 completed the protocol. The eradication rates per protocol patient were 43% in group LA, 62% in group LA1E, and 79% in group LA2E, and those on the intention‐to‐treat basis were 42% in group LA, 57% in group LA1E and 79% in group LA2E. The eradication rate in group LA2E was significantly higher than group LA (P=0.032 in per protocol, P=0.022 in intention‐to‐treat). Adverse effects were observed in 10 patients in this study. There were no severe adverse effects caused by ecabet sodium.Conclusion:High‐dose ecabet sodium increases eradication rates of H. pylori in dual therapy with lansoprazole and amoxicillin.
Hypochlorhydria induced by a proton pump inhibitor leads to intragastric microbial production of acetaldehyde from ethanol
Authors: Väkeväinen S. , Tillonen J. , Salaspuro M. , Jousimies‐Somer H. , Nuutinen H. , Färkkilä M. 
Published: March 2003

Background:Acetaldehyde, produced locally in the digestive tract, has recently been shown to be carcinogenic in humans.Aim:To examine the effect of iatrogenic hypochlorhydria on intragastric acetaldehyde production from ethanol after a moderate dose of alcohol, and to relate the findings to the changes in gastric flora.Methods:Eight male volunteers ingested ethanol 0.6 g/kg b.w. The pH, acetaldehyde level and microbial counts of the gastric juice were then determined. The experiment was repeated after 7 days of lansoprazole 30 mg b.d.Results:The mean (± S.E.M.) pH of the gastric juice was 1.3 ± 0.06 and 6.1 ± 0.5 (P < 0.001) before and after lansoprazole, respectively. This was associated with a marked overgrowth of gastric aerobic and anaerobic bacteria (P < 0.001), by a 2.5‐fold (P=0.003) increase in gastric juice acetaldehyde level after ethanol ingestion, and with a positive correlation (r=0.90, P < 0.001) between gastric juice acetaldehyde concentration and the count of aerobic bacteria.Conclusions:Treatment with proton pump inhibitors leads to hypochlorhydria, which associates with intragastric overgrowth of aerobic bacteria and microbially‐mediated acetaldehyde production from ethanol. Since acetaldehyde is a local carcinogen in the concentrations found in this study, long‐term use of gastric acid secretory inhibitors is a potential risk‐factor for gastric and cardiac cancers.
Review article: the ‘mechanical pumps' and the enterohepatic circulation of bile acids – defects in coeliac disease
Authors: Lanzini A. , Lanzarotto F. 
Published: March 2003

SummaryBile acid pool size is maintained relatively constant at about 3–5 g in healthy subjects by two mechanisms, enterohepatic circulation and de novo synthesis of bile acids. This latter mechanism compensates for the daily faecal loss (about 0.2–0.6 g) of bile acids, whereas the bulk of the pool is conserved by the former mechanism. The driving forces of the enterohepatic circulation are constituted by chemical pumps, including intestinal absorption and hepatic uptake, and by mechanical pumps, including gall‐bladder and intestinal motility. The latter provide the main propulsive forces for bile acids to reach the site of intestinal absorption, and by contrast with the very rapid chemical pumps, mechanical pumps have storage capacity for the bile acid pool and therefore comprise the slow limb of the enterohepatic circulation.
1In coeliac disease, a disease classically described as a malabsorption syndrome associated with mucosal atrophy of the small intestine, both gall‐bladder and small intestinal motor functions are impaired, and in this article we review the mechanisms involved in these defects, how they influence the enterohepatic circulation of bile acids, and the evidence supporting the concept that both the gall‐bladder and the small intestinal motor functions represent the main factors affecting the kinetics of the enterohepatic circulation.
Esomeprazole 20 mg maintains symptom control in endoscopy‐negative gastro‐oesophageal reflux disease: a controlled trial of ‘on‐demand’ therapy for 6 months
Authors: Talley N. J. , Lauritsen K. , Tunturi‐Hihnala H. , Lind T. , Moum B. , Bang C. , Schulz T. , Omland T. M. , Delle M. , Junghard O. 
Published: March 2003

Background:Most patients with gastro‐oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy.Aim:To assess the efficacy of ‘on‐demand’ treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer.Methods:In this multicentre, double‐blind study, 342 endoscopy‐negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4‐week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted.Results:All 342 patients (191 males), aged 19–79 (mean 49) years, were evaluable in the intention‐to‐treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on‐demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1–3 consecutive days (esomeprazole) or 4–13 consecutive days (placebo). Use of antacids was > 2‐fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles.Conclusions:On‐demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy‐negative GERD.