bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: non‐steroidal anti‐inflammatory drug‐induced gastrointestinal permeability
Authors: Davies  
Published: March 2003

Non‐steroidal anti‐inflammatory drugs induce damage throughout the entire gastrointestinal tract. Administration of site‐specific permeability probes is a non‐invasive technique for assessing the functional integrity of the gastrointestinal mucosa. A systematic search for NSAID‐induced permeability studies using MEDLINE and EMBASE, and an analysis of the literature on NSAID‐induced gastrointestinal permeability, were carried out. The advantages and disadvantages of the various probes and study protocols are discussed.Identification of the underlying mechanisms of regulatory control of the epithelial tight junction is still needed. A greater appreciation of the pharmacokinetics and distribution of NSAIDs, coupled with gastrointestinal permeability studies, may help delineate the pathogenesis of NSAID‐induced gastrointestinal toxicity. Non‐invasive tests of gastric, intestinal and colonic permeability have shown promise in both basic research and in clinical practice. While such tests could not replace endoscopy, they may represent clinically useful techniques for identifying patients who would benefit from endoscopy, to assess the response to treatment, and perhaps to predict the clinical course of disease.
Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid‐induced colitis in the rat
Authors: Miampamba  , Parr  , McCafferty  , Wallace  , Sharkey  
Published: March 2003

Background:We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)‐induced colitis in rats.Methods:TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immuno‐histochemistry.Results:When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post‐treated with BAC. In the groups examined 7 days after TNBS treatment, rats post‐treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre‐treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre‐treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS‐treated rats that had been pre‐treated with BAC.Conclusions:Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.
Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study
Authors: Stanley  , Forrest  , Dabos  , Gilchrist  , Hayes  
Published: March 2003

Background:It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low‐dose theophylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood flow and sodium excretion in cirrhotic patients.Methods:Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy.Results:After 7 days of spironolactone there were increases in urinary sodium excretion (43.5 ± 15.6 vs. 106.8 ± 34.7 mmol/day; P < 0.05) and urine volume (769.1 ± 206.5 vs. 1541.6 ± 342.6 mL/day; P < 0.05). No changes in the patients’ weight, creatinine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy.Conclusion:Adenosine antagonism in the form of low‐dose theophylline is less efficacious than spironolactone in the management of cirrhotic ascites.
Bone turnover during short‐term therapy with methylprednisolone or budesonide in Crohn’s disease
Authors: D’haens  , Verstraete  , Cheyns  , Aerden  , Bouillon  , Rutgeerts  
Published: March 2003

Background:Glucocorticosteroids are used frequently for the treatment of relapses of Crohn’s disease.Aim:To investigate the influence of the new topically active glucocorticosteroid budesonide in comparison with methylprednisolone on bone turnover in a randomized open trial.Methods:Twenty‐nine patients received either budesonide (controlled ileal release formulation) 9 mg for 10 weeks, or methylprednisolone 32 mg (equivalent to 40 mg prednisone) orally for 3 weeks with subsequent tapering.Results:Patients who completed the trial with methylprednisolone (n = 8) had suppression of serum osteocalcin (30.2 ± 2.6 to 20.4 ± 2.0 ng/mL, P < 0.01), whereas no changes in this parameter of bone synthesis were observed during budesonide treatment (n = 11) (34.8 ± 3.1 to 33.0 ± 3.5 ng/mL). Urinary pyridinolines and deoxypyridinolines, highly sensitive markers of bone degradation, did not change in either group.Conclusion:Short‐term methylprednisolone therapy impairs osteoblast activity in patients with Crohn’s disease whereas budesonide does not.
Prospective evaluation of a new anti‐ulcer agent, ecabet sodium, for the treatment of Helicobacter pylori infection
Authors: Ohkusa  , Takashimizu  , Fujiki  , Araki  , Ariake  , Shimoi  , Honda  , Enomoto  , Sakurazawa  , Horiuchi  , Suzuki  , Ishii  , Ishikura  
Published: March 2003

BackgroundA new anti‐ulcer agent, ecabet sodium, is active against Helicobacter pylori.AimTo assess the efficacy of ecabet sodium for the eradication of H. pylori in patients with gastroduodenal diseases.MethodsIn a prospective, randomized and controlled study, patients infected with H. pylori were assigned to one of the following two groups: group LA, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. after meals for 2 weeks, and group LAE, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. + ecabet sodium 1000 mg b.d. after meals for 2 weeks. H. pylori status was determined before and at least 4 weeks after the therapy by rapid urease test, histology and a urea breath test.ResultsOf 101 patients (mean age 53 years, range 17–77 years, M/F: 68/33) enrolled in the study, 97 patients completed the protocol. Four patients were withdrawn because of diarrhoea (three from group LA) and skin rash (one from group LAE). The eradication of H. pylori was achieved in 28/48 (58%) patients in group LA and 38/49 (78%) patients in group LAE. The rate of eradication of H. pylori produced by the LAE treatment was significantly higher than that produced by the LA treatment. Side‐effects appeared in two patients (malaise 1, skin rash 1) in group LAE and in seven patients (diarrhoea 6, dizziness 1) in group LA. These side effects disappeared spontaneously with cessation of the treatment.ConclusionsEcabet sodium in combination with lansoprazole and amoxycillin increased the rate of eradication of H. pylori. Ecabet sodium appeared to reduce the incidence of diarrhoea as a side‐effect of the dual LA therapy.
Factors affecting solubility and penetration of clarithromycin through gastric mucus
Authors: Grübel  , Cave  
Published: March 2003

Background:Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined.Aim:To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti‐ulcer agents affect clarithromycin penetration through gastric mucus.Methods:Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti‐ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay.Results:Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2–7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre‐treatment of PGM with aluminium‐magnesium‐containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin.Conclusions:The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre‐treatment of mucus with anti‐ulcer medications does not increase the penetration of clarithromycin through mucus.
Omeprazole, azithromycin and either amoxycillin or metronidazole in eradication of Helicobacter pylori in duodenal ulcer patients
Authors: Včev  , Včeva  , Štimac  , Takač  , Dmitrović  , Kovač  
Published: March 2003

BackgroundAzithromycin is a new generation, acid stable, macrolide antibiotic that achieves remarkably high concentrations in gastric tissue (above the minimal inhibitory concentration for Helicobacter pylori) after oral administration.AimTo establish whether azithromycin plus omeprazole in association with either amoxycillin or metronidazole are useful in curing H. pylori infection in patients with a duodenal ulcer.MethodsOne hundred patients with active duodenal ulcers and H. pylori infection were treated with omeprazole (days 1–10, 40 mg b.d.; days 11–24, 40 mg o.m.; days 25–42, 20 mg o.m.) plus azithromycin 500 mg o.m. for the first 6 days. Patients were randomly assigned to receive either amoxycillin 1 g b.d. (OAzA group; n = 50) or metronidazole 400 mg t.d.s. (OAzM group; n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before the treatment and 6 weeks after completion of therapy.ResultsNinety‐seven patients completed the study. H. pylori infection was eradicated in 85% (41/48) of patients in the OAzA group (intention‐to‐treat analysis 82%) vs. 74% (36/49) of patients in the OAzM group (intention‐to‐treat analysis: 72%) (N.S.). All ulcers had healed after 6 weeks of omeprazole treatment. Side‐effects, usually minor, were recorded in 13% (OAzA group) and 47% (OAzM group) of patients (P < 0.001), but therapy was discontinued for only one patient in the OAzA group (N.S.).ConclusionTen days of treatment with omeprazole plus (for the first 6 days) azithromycin and either amoxycillin or metronidazole provides effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.
Duplex‐Doppler evaluation of the effects of propranolol and isosorbide‐5‐mononitrate on portal flow and splanchnic arterial circulation in cirrhosis
Authors: Piscaglia  , Gaiani  , Siringo  , Gramantieri  , Serra  , Bolondi  
Published: March 2003

Background:A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding.Aim:To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide‐5‐mononitrate, on splanchnic circulation.Methods:Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide‐5‐mononitrate.Results:The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide‐5‐mononitrate (≥ 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide‐5‐mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney.Conclusions:Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of ≥ 20% after the acute addition of isosorbide‐5‐mononitrate to chronic propranolol treatment.
Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country
Authors: Ahuja  , Dhar  , Bal  , Sharma  
Published: March 2003

Background:A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined.Aim:To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer.Methods:Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C‐urea breath test) were randomized into three treatments groups: (1) LAS (n = 21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n = 18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n = 21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication.Results:Intention‐to‐treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks.Conclusions:High H. pylori eradication rates were achieved using the amoxycillin‐ and clarithromycin‐based therapies. Fewer side‐effects, better compliance and low cost favoured the amoxycillin‐based therapy.
An ascending single‐dose safety and tolerance study of an oral formulation of rabeprazole (E3810)
Authors: Lew  , Barbuti  , Kovacs  , Sytnic  , Humphries  , Walsh  
Published: March 2003

Background:Proton pump inhibitors such as omeprazole produce a long‐lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin. Rabeprazole (E3810) is a new substituted benzimidazole H+,K+ ATPase inhibitor. It acts as an irreversible, non‐competitive inhibitor of the H+,K+ ATPase and preliminary studies demonstrate that rabeprazole produces a potent and long‐lasting inhibition of gastric acid secretion and a low level of hypergastrinaemia.Aim:This randomized, double‐blind, placebo‐controlled study was performed to further examine the effects of different single doses of rabeprazole on gastric acid secretion and serum gastrin.Methods:In this study, four groups of 10 healthy, non‐smoking Helicobacter pylori‐negative men (mean age 22.5 ± 3.9 years) received single oral doses of 10, 20, 30 and 40 mg of rabeprazole. Two of the 10 volunteers in each group received placebo as part of the double‐blind study design. All volunteers who entered into the study had a normal gastric acid secretory capacity as evaluated by pentagastrin challenge. Prior to administration of the first dose of test drug, volunteers underwent an inpatient 24‐h measurement of baseline intragastric pH. One week later, volunteers received the test drug and again underwent an inpatient 24‐h measurement of intragastric pH. During both periods, plasma samples were collected at specified intervals over 48 h and were sent for analysis of rabeprazole and gastrin levels.Results:Administration of rabeprazole resulted in a dose‐dependent increase in the duration and extent of intragastric pH elevation. The response among all volunteers receiving drug was significantly different from placebo, with greater acid inhibition occurring in the 30 and 40 mg groups. In addition, there was also a dose‐related increase in plasma gastrin. The pharmacokinetics of rabeprazole were similar to those of other proton pump inhibitors with a t1/2 of between 0.7 and 1.0 h. There were no clinically significant effects on patient laboratory tests or serious adverse events.Conclusions:The results of this study suggest that rabeprazole is as potent as omeprazole and lansoprazole in inhibiting gastric acid secretion.
The influence of cisapride on gastric tone and the perception of gastric distension
Authors: Tack  , Broeckaert  , Coulie  , Janssens  
Published: March 2003

Background:Delayed gastric emptying, impaired gastric accommodation to a meal and hypersensitivity to gastric distension have been implied in the pathophysiology of functional dyspepsia. Dyspeptic patients are often treated with the prokinetic drug cisapride.Aim:To assess the effects of cisapride on perception of gastric distension and gastric accommodation to a meal.Methods:Eighteen healthy volunteers underwent a gastric barostat study on two occasions, after pre‐treatment with placebo or cisapride 10 mg q.d.s. Graded isobaric and isovolumetric distensions were performed until the subjects reported discomfort. Volume and pressure changes were recorded and perception was scored by a questionnaire. In 10 volunteers, the amplitude of the gastric accommodation to a mixed liquid meal was also measured.Results:Pre‐treatment with cisapride significantly lowered thresholds for perception and for discomfort, both during isobaric (4.3 ± 0.7 vs. 3.2 ± 0.7 and 12.2 ± 1.2 vs. 9.2 ± 0.9 mmHg above minimal distending pressure (MDP), respectively, P < 0.05) and isovolumetric (256 ± 46 vs. 200 ± 35 and 644 ± 36 vs. 511 ± 40 mL, respectively, P < 0.05) distensions. Cisapride significantly enhanced the size of the meal‐induced fundus relaxation (143 ± 37 vs. 270 ± 50 mL, P < 0.05).Conclusions:Cisapride enhances both the perception of gastric distension and the gastric accommodation to a meal. These data suggest that cisapride may provide benefit to patients with impaired postprandial relaxation of the fundus.
Short‐term low‐dose pantoprazole‐based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients
Authors: Pazzi  , Scagliarini  , Gamberini  , Matarese  , Rizzo  , Gullini  
Published: March 2003

Background:The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton‐pump inhibitor pantoprazole as part of these regimens has not yet been widely tested.Aim:To evaluate the efficacy and tolerability of a 1‐week low‐dose pantoprazole‐based triple therapy in patients with H. pylori‐positive duodenal ulcer.Methods:In an open single‐centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithomycin 250 mg b.d. H.␣pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4–6 weeks after the end of treatment, confirmed 4 weeks later by 13C‐urea breath test.Results:Sixty‐six patients (93%) completed the trial and five patients were lost to follow‐up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per‐protocol analysis: 92.4%, 95% CI: 83.2–97.5%; intention‐to‐treat analysis: 85.9%, 95% CI: 75.7–93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).Conclusions:One‐week low‐dose pantoprazole‐based triple therapy is a simple, effective and well‐tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.
Triple regimens using lansoprazole or ranitidine bismuth citrate for Helicobacter pylori eradication
Authors: Spadaccini  , Fanis  , Sciampa  , Russo  , Silla  , Pantaleone  , Virgilio  , Pizzicanella  
Published: March 2003

Background:A combination of an antisecretory agent with two antibiotics is considered the ‘gold standard’ for Helicobacter pylori eradication.Objectives:To compare the eradication rates and the safety profile of two short‐term triple therapies containing lansoprazole (L) or ranitidine bismuth citrate (RBC) as antisecretory agents.Methods:One hundred and twelve H. pylori‐positive patients either with peptic ulcer (56 duodenal ulcers: 25 active and 31 with a history of ulcer; 13 gastric ulcers: nine active and four with a history of ulcer) or gastritis (43) were included in an open, randomized, controlled trial. H. pylori infection was initially detected by CLO‐test and histology on antral and corpus biopsies. H.␣pylori‐positive patients were randomized to receive L plus clarithromycin (C) 250 mg b.d. plus tinidazole (T) 500 mg b.d. (LCT) or RBC plus C 250 mg b.d. and T 500 mg b.d. for 7 days (RbcCT). L or RBC were administered for a further 3 weeks in patients with active peptic ulcers. A second endoscopy was performed at least 6 weeks after the end of therapy for the assessment of H. pylori infection by CLO‐test and histology. Eradication was assumed if all the tests were negative for H. pylori.Results:Forty‐eight patients in the LCT group and 45 in the RbcCT group were assessed for H. pylori eradication. The eradication rates, according to intention‐to‐treat (ITT) and per protocol (PP) analyses were, respectively, 76.8% and 89.5% for the LCT group, and 73.2% and 91.1% for the RbcCT group. No statistically significant difference in eradication rates was found between the two groups by Mantel–Haenszel test. All peptic ulcers were healed. In patients in whom H. pylori had been eradicated, the severity of gastritis was significantly reduced. Side‐effects were rare. One patient in the LCT group and two in the RbcCT group were withdrawn because of adverse events.Conclusion:Short‐term triple therapy with either lansoprazole or RBC is equally effective and well tolerated.