bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma hydroxy‐metronidazole/metronidazole ratio can detect early changes in hepatic function in ethanol‐induced liver injury
Authors: Da Silva  , David  , Muscará  , Sousa  , Ferraz  , De Nucci  , Polimeno  , Pedrazzoli  
Published: March 2003

Aims: To evaluate the usefulness of plasma hydroxy‐metronidazole/metronidazole (OH‐MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis.Methods: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol‐induced, non‐cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy‐metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion.Results: Patients with non‐cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child‐Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non‐cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH‐MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol‐abusing individuals, including patients with non‐cirrhotic alcoholic hepatopathy.Conclusions: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol‐induced liver disease.
Effect of basic fibroblast growth factor on gastric ulcer healing and its own mRNA expression
Authors: Pohle  , Shahin  , Domschke  , Konturek  
Published: March 2003

Background: The application of an acid‐stable mutein of basic fibroblast growth factor (bFGF) called CS23 results in acceleration of ulcer healing. The modes by which this cytokine exerts these effects are not yet completely understood.Aim: To describe the pattern of bFGF‐mRNA expression during ulcer healing and to examine the effects of exogenously applied CS23 on gastric ulcer healing in an animal model.Methods: The speed of healing of gastric ulcers, expression of extracellular matrix gene mRNAs such as pro α(I) collagen (by non‐radioactive in situ hybridization), cellular proliferation evidenced by the display of PCNA (by immunohistochemistry), angiogenesis, and the feedback of this growth factor on its own mRNA expression pattern were used to evaluate the effects of CS23 on rat gastric ulcer healing in an animal model.Results: CS23 accelerates gastric ulcer healing at 7, 14 and 21 days after ulcer induction. We found an increase in connective tissue beneath the ulcer bed in treated animals in comparison to controls. The expression of PCNA as well as pro α(I) collagen mRNA was markedly increased in ulcers, yet there was no distinct difference between treatment arms. In contrast, the density of microvessels was significantly increased in the submucosa of ulcers by CS23 application. bFGF‐mRNA expression is up‐regulated in the submucosa during early ulcer healing; this increase diminishes within days but can be restituted by the exogenous application of CS23.Conclusions: CS23 speeds gastric ulcer healing and significantly increases the density of microvessels in the ulcerated tissue without affecting the numbers of proliferating cells or the transcription of collagen mRNA. In addition, it augments the expression of bFGF‐mRNA during the later stages of healing, suggesting a positive feedback loop.
Oesophageal motility defects associated with nocturnal gastro‐oesophageal reflux on proton pump inhibitors
Authors: Fouad  , Katz  , Castell  
Published: March 2003

Background: Recent studies from our laboratory reveal that 70% of patients with gastro‐oesophageal reflux disease (GERD) on proton pump inhibitors twice daily (b.d.) have nocturnal gastric acid breakthrough (gastric pH < 4 > 1 h) which is often accompanied by oesophageal acid exposure. The pathogenesis of GER during gastric acid breakthrough is not clear.Aim: To determine the prevalence of oesophageal motility abnormalities in patients with nocturnal GER associated with nocturnal acid breakthrough on proton pump inhibitor b.d.Methods: We reviewed the pH‐metry and manometric studies of 100 consecutive patients with GERD who were on proton pump inhibitor b.d. pH tracings were analysed for the nocturnal period (10.00 hours until 06.00 hours). Nocturnal GER was defined as>  0.5% time distal oesophageal pH < 4. Manometric tracings were reviewed for lower oesophageal sphincter (LES) pressure and oesophageal body motility. Chi‐squared and Fischer’s test were used for statistical analysis.Results: Of the 100 patients, 74 (74%) had nocturnal gastric acid breakthrough. Thirty‐one (42%) had concurrent abnormal nocturnal GER (refluxers) and 43 out of 74 (58%) had no GER (non‐refluxers). The prevalence of ineffective oesophageal motility, and low LES pressure was significantly higher in refluxers than in non‐refluxers (P < 0.05, P < 0.001, respectively). Ineffective‐oesophageal motility has a high specificity (91%), but low sensitivity (45%) as a diagnostic predictor for patients who are more likely to develop nocturnal GER on proton pump inhibitor b.d.Conclusion: Ineffective oesophageal motility is a risk factor for proton pump inhibitor refractory GER.
Behaviour ofSaccharomyces boulardiiin recurrentClostridium difficiledisease patients
Authors: Elmer  , McFarland  , Surawicz  , Danko  , Greenberg  
Published: March 2003

Background:Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations ofSaccharomyces boulardiiin a patient population withClostridium difficiledisease (CDD) and correlates stool concentrations with efficacy.Methods:Patients with recurrent CDD all received a 10‐day standard antibiotic regimen together with 28 days ofS. boulardiior placebo. Stool samples were collected from patients at various time points and assayed forS. boulardii.Results:The mean concentration ofS. boulardiiof patients who recurred was 2.5 × 104CFU/g compared to 1 × 106CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%,P=0.007). Clearance ofS. boulardiiwas rapid; only 4% had positive stools 3 days after stopping dosing.Conclusions:After chronic dosing ofS. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentrations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not give a true reflection of the disturbed microecology in the disease state.
Characterization of M cell development during indomethacin‐induced ileitis in rats
Authors: Kucharzik  , Lügering  , Lügering  , Rautenberg  , Linnepe  , Cichon  , Reichelt  , Stoll  , Schmidt  , Domschke  
Published: March 2003

Background: M cells play an important role in the intestinal immune system as they have a high capacity for transcytosis of a wide range of microorganisms and macromolecules. However, little is known about the role of M cells during intestinal inflammation.Aim: We studied M cell development during indomethacin‐induced intestinal inflammation in rats.Methods: Ileitis in rats was induced by two subcutaneous injections with indomethacin (7.5 mg/kg) given 24 h apart. Rats were sacrificed after 14 days and tissue was analysed by fluorescence microscopy and electron microscopy. M cells could be visualized by using the FITC‐labelled mAb anti‐cytokeratin (CK)‐8 (clone 4.1.18), which was recently identified as specific M cell marker in rats. The number of cytokeratin‐8 positive M cells was related to the surface of the follicle associated epithelium. For morphological studies, we used both transmission electron microscopy (T.E.M.) and scanning electron microscopy (S.E.M.).Results: In non‐inflamed ileum M cells were scarce. Only 4% of the follicle associated epithelium were M cells, whereas an increase of M cells up to 11% was found in inflamed follicle associated epithelium (P < 0.001). The rate of M cell induction depended on the macroscopic degree of inflammation. T.E.M./S.E.M. studies showed that in inflamed tissue most M cells underwent apoptosis with typical morphological signs. In contrast to apoptotic M cells, the neighbouring enterocytes usually appeared intact. The number of mononuclear cells below the follicle associated epithelium was significantly increased. S.E.M. studies revealed that during induced ileitis mononuclear cells migrated from the lamina propria into the gut lumen by passing through apoptotic M cells.Conclusions: During indomethacin‐induced ileitis in rats the increase in M cell number in association with apoptosis of M cells may alter the intestinal barrier function. These observations may play a pivotal role in the pathogenesis of chronic intestinal inflammation, e.g. in inflammatory bowel disease.
Ibuprofen versus other non‐steroidal anti‐inflammatory drugs: use in general practice and patient perception
Authors: Hawkey  , Cullen  , Pearson  , Holmes  , Doherty  , Wilson  , Garrud  , Garner  , Maynard  , Logan  
Published: March 2003

Objective:To investigate whether ibuprofen was as well‐regarded by patients as other non‐steroidal anti‐inflammatory drugs (NSAIDs).Design:Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records.Setting:General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate.Subjects:Unselected patients receiving NSAIDs prescribed for all indications for use.Main outcome measures:Effectiveness of ibuprofen and other NSAIDs, possible drug related adverse events, patients’ overall satisfaction with ibuprofen and other NSAIDs, factors associated with choice of ibuprofen, drug costs of ibuprofen and other NSAIDs.Results:The main NSAIDs used were ibuprofen, diclofenac and naproxen. Ibuprofen use ranged from 1.0% of prescriptions in one practice to 69.1% in another. Although ibuprofen was generally prescribed in low doses, it was perceived by patients as being as effective as the other NSAIDs used, even after allowing for severity of the pre‐treatment condition. Overall, 50.5% of patients rated their NSAID the best treatment they had received for their condition with no differences between individual drugs.Conclusions:Ibuprofen is as highly regarded as other NSAIDs when used in similar circumstances. Switching patients to ibuprofen may be a realistic way of reducing financial and medical costs associated with NSAIDs.
Cure of Helicobacter pylori infection does not improve symptoms in non‐ulcer dyspepsia patients—a double‐blind placebo‐controlled study
Authors: Miwa  , Hirai  , Nagahara  , Murai  , Nishira  , Kikuchi  , Takei  , Watanabe  , Sato  
Published: March 2003

Background:It remains controversial whether the cure of H. pylori infection improves NUD symptoms.Aim:To conduct a double‐blind placebo‐controlled single centre study with concealed allocation to investigate this question.Patients and methods:Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated.Results:The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group.Conclusion:Although histological parameters were significantly improved in the treatment group, there was no significant improvement in symptoms of NUD in the treatment group compared to placebo.
Fasting induces impairment of gastric mucosal integrity in non‐insulin‐dependent diabetic (db/db) mice
Authors: Kinoshita  , Igarashi  , Kume  , Saito  , Arakawa  
Published: March 2003

Background:Although diabetic patients often have gastrointestinal complications, the gastric mucosal function in diabetes has not been well documented.Aim:To investigate the effect of fasting on the gastric mucosa in C57BL/KsJ–db +/+ db (db/db) mice, genetically non‐insulin‐dependent diabetic animals.Methods:Blood glucose levels, gastric mucosal morphology, and the amount of gastric mucin were examined before and after 18 h of fasting with free access to water in db/db mice and their non‐diabetic littermates (db/m).Results:Although 18 h of fasting reduced the blood glucose levels of both db/db and db/m mice, fasting decreased the amount of gastric adherent mucin and caused haemorrhagic gastric lesions only in db/db mice. After fasting, oral administration of ethanol induced much more severe gastric damage in db/db than in db/m mice. The above fasting‐induced gastric damage such as haemorrhagic lesions, loss of the mucin, and the increased sensitivity to ethanol worsened as the duration of diabetes became longer. Glucose ingestion in drinking water during the fasting counteracted the fall in blood glucose and prevented the decrease in the amount of gastric mucin and the formation of gastric mucosal lesions in db/db mice.Conclusion:These findings indicate that fasting‐induced glucose deficit causes gastric mucosal lesions and increases the susceptibility of gastric mucosa to noxious agents owing to the loss of mucus glycoprotein in db/db mice. Prolonged diabetes is likely to augment the severity of fasting‐induced impairment of the gastric mucosal function.
Gastric myoelectric activity in older adults treated with cisapride for gastro‐oesophageal reflux disease
Authors: Orr  , Zhang  , Mcclanahan  , Sloan  , Chen  
Published: March 2003

Background:The incidence of both gastro‐oesophageal reflux disease (GERD) and upper gastrointestinal motility disorders appears to increase with age. However, there is a dearth of data concerning the utility of a prokinetic agent such as cisapride in the treatment of older adults with symptomatic GERD.Aim:To investigate the incidence of electrogastrographic abnormalities in older adults with and without GERD symptoms, as well as the effect of cisapride therapy on symptoms of GERD and electrogastrographic responses.Methods:We report on 18 older adults with symptomatic GERD and 10 older adult controls (mean ages 71 and 75 years, respectively). Subjects underwent electrogastrographic evaluation pre‐ and postprandially under baseline conditions and after 1 month of treatment with 10 mg q.d.s. of cisapride.Results:Heartburn frequency and postprandial fullness were both significantly (P < 0.05) reduced after cisapride treatment. Acid contact time was not significantly changed. The percentage of 2–4 cpm activity in the electrogastrographic analysis was significantly (P < 0.05) increased with cisapride treatment, and the instability coefficient was significantly (P < 0.05) diminished with cisapride treatment.Conclusions:Enhanced gastric functioning and reduction in heartburn suggest that cisapride is efficacious in the treatment of older adults with symptomatic GERD, and that gastric dysrhythmias and postprandial fullness are resolved with cisapride treatment.
The effects of meloxicam, indomethacin or NS‐398 on eicosanoid synthesis by fresh human gastric mucosa
Authors: Tavares  
Published: March 2003

Background:In the stomach, constitutive cyclooxygenase (COX‐1) synthesizes prostaglandins that maintain the integrity of the gastric mucosa, while their inhibition contributes to gastric mucosal damage. In contrast COX‐2, an inducible enzyme, forms prostanoids involved in pain and inflammation.Aim:To compare prostaglandin synthesis inhibition by meloxicam, a selective COX‐2 NSAID reported to have better gastric tolerability, with indomethacin and NS‐398 in human gastric mucosa and in whole blood assays.Methods:Meloxicam, indomethacin or NS‐398 were incubated with fresh human gastric mucosa pieces (100 mg in 1 mL phosphate buffered saline, pH 7.4, 37 °C, 30 min), clotting human blood (1 mL, 37 °C, 60 min) or with lipopolysaccharide‐stimulated heparinized blood (1 mL, 37 °C, 24 h). Prostanoids were analysed by radioimmunoassay.Results:Meloxicam was a less potent inhibitor of gastric mucosal eicosanoid compared to indomethacin, showing a sixfold difference in IC50 with gastric mucosal prostaglandin E (PGE) (11.8 and 1.8 μM, respectively). In the whole blood assays, the COX‐2/COX‐1 ratio for meloxicam was 0.2 compared to 0.9 for indomethacin confirming meloxicam’s COX‐2 selectivity.Conclusion:The results with human mucosa pieces would suggest that the better gastric tolerability of meloxicam compared to indomethacin is related to its relatively lower inhibition of gastric mucosal PGE synthesis by COX‐1.
The effectiveness of omeprazole, clarithromycin and tinidazole in eradicating Helicobacter pylori in a community screen and treat programme
Authors: Moayyedi  , Feltbower  , Crocombe  , Mason  , Atha  , Brown  , Dowell  , Richards  , Axon  ,   ON BEHALF OF THE LEEDS HELP STUDY
Published: March 2003

Introduction: Helicobacter pylori screening and treatment has been proposed as a cost‐effective method of preventing gastric cancer.Aim:To assess, in a randomized controlled trial, the efficacy of therapy in eradicating H. pylori as part of a screening programme, and to report the adverse events associated with this strategy.Methods:Subjects between the ages of 40–49 years were randomly selected from the lists of 36 primary care centres. Participants attended their local practice and H. pylori status was determined by 13C‐urea breath test. Infected subjects were randomized to receive omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days (OCT) or identical placebos. Eradication was determined by a 13C‐urea breath test 6 months and 2 years after the first visit. Successful eradication was defined as two negative 13C‐urea breath tests or one negative and one missing test. Adverse events and compliance were assessed at the 6‐month visit.Results:A total of 32 929 subjects were invited to attend, 8407 were evaluable, and 2329 (28%) of these were H. pylori‐positive. A total of 1161 subjects were randomized to OCT and 1163 to placebo; over 80% returned for a repeat 13C‐urea breath test on at least one occasion. The eradication rates in those allocated to OCT were as follows: intention‐to‐treat, 710 out of 1161 (61%; 95% confidence interval: 58–64%); evaluable 710 out of 967 (73%; 95% CI: 71–76%); took all medication 645 out of 769 (84%; 95% CI: 81–87%). Adverse events occurred in 45% of the treatment group and in 18% of the placebo group (relative risk 2.5; 95% CI: 2.1–2.9). Compliance, male gender, no antibiotic prescription in the subsequent 2 years and experiencing a bitter taste with the medication were independently associated with treatment success.Conclusions:The OCT regimen has an eradication rate of 61% in intention‐to‐treat analysis and is therefore less successful in treating H. pylori as part of a screening programme compared with hospital studies in dyspeptic patients.
Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: a double‐blind, randomized, placebo‐controlled study
Authors: Pokrotnieks  , Marlicz  , Paradowski  , Margus  , Zaborowski  , Greinwald  
Published: March 2003

Background:Rectal formulations of mesalazine are the treatment of choice in mildly to moderately active ulcerative colitis. A new foam formulation of mesalazine was developed to improve both drug delivery and patient acceptance.Methods:In this multicentre, randomized, double‐blind, parallel‐group study, 111 patients with mildly to moderately active proctitis, proctosigmoiditis, or left‐sided ulcerative colitis received mesalazine foam enema or placebo enema (2 g mesalazine per day) for 6 weeks. Disease activity was monitored on the basis of the Clinical Activity Index, Endoscopic Index, Histological Index, and global efficacy assessment by the investigators. Safety assessments included the recording of adverse events, laboratory variables and vital signs.Results:Clinical remission was more frequent in the mesalazine group than the placebo group (65% vs. 40%; P=0.0082), particularly in patients with mild disease and patients with proctosigmoiditis. The frequency of patients with an endoscopic remission was higher in the mesalazine group (57%) than in the placebo group (37%). Similarly, 59% of patients receiving mesalazine but only 41% of those receiving placebo showed an improved Histological Index. The foam enemas were generally well‐tolerated, and no treatment‐related changes on laboratory variables and vital signs were noted.Conclusions:Mesalazine foam enema was well‐tolerated and was more effective than placebo in the treatment of patients with distal ulcerative colitis.
Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors
Authors: Stedman C. A. M. , Barclay M. L. 
Published: March 2003

Proton pump inhibitors have dramatically influenced the management of acid‐peptic disorders in recent years. They all have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4. There is some variation in their potential for drug interactions due to differences in enzyme inhibition. Relatively few serious adverse effects have been reported for the proton pump inhibitors.Comparative studies of acid suppression suggest that lansoprazole and pantoprazole have a potency similar to that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset of maximal acid suppression than the other proton pump inhibitors.Comparative studies using proton pump inhibitors for the treatment of reflux oesophagitis, duodenal ulcer healing and Helicobacter pylori eradication show little overall difference in outcome between the proton pump inhibitors when used in their standard doses. Lansoprazole and rabeprazole provide earlier and better symptom relief than the other proton pump inhibitors in some studies of peptic ulcer treatment. The few studies of gastric ulcer treatment suggest that there is an advantage in using the proton pump inhibitors that have a higher standard daily dose.