bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indomethacin‐induced morphological changes in the rat gastric mucosa, with or without prior treatment with two proton pump inhibitors
Authors: MORINI G. , GRANDI D. , ARCARI M. LUISA , BERTACCINI G. 
Published: July 2010

SUMMARYBackground: The mechanisms responsible for the gastric ulcerogenic effect of indomethacin are unclear. The importance of basal acid secretion on morphological changes by indomethacin was investigated.Methods: Gastric lesions were macroscopically evaluated 6 h after indomethacin, 20 mg/kg intragastrically, in rats pre‐treated with omeprazole (10–100μmol/kg intragastrically) or lansoprazole (3–30μmol/kg intragastrically). Glandular mucosa was processed for light, scanning and transmission electron microscopy 3 and 6 h after indomethacin in rats pre‐treated with omeprazole (100μmol/kg) or lansoprazole (30μmol/kg).Results: After 3 h, indomethacin caused extensive vasocongestion, oedema in the subepithelial region and superficial erosions. After 6 h, deeply extending focal necrosis involved 11 % of the tissue. Leukocyte margination was occasionally seen at 3 h and consistently present at 6 h. Only at 6 h were endothelial cells altered. In rats pre‐treated with omeprazole (100μmol/kg) or lansoprazole (30μmol/kg) grossly visible lesions were prevented. Oedema, erosions and necrosis were absent. Vasocongestion, vascular leakage and leukocytic margination were seen both at 3 and 6 h while no major damage of endothelial cells was observed.Conclusion: Indomethacin appears primarily to alter microcirculation, and microcirculation damage is dependent on acid for the progression to haemorrhagic lesions.
Only four days of quadruple therapy can effectively cure Helicobacter pylori infection
Authors: DE BOER W. A. , DRIESSEN W. M. M. , TYTGAT G. N. J. 
Published: July 2010

SUMMARY Aim: To determine whether 4 days of quadruple therapy using bismuth, tetracycline and metronidazole combined with omeprazole is effective treatment for Helicobacter pylori infection. Methods. Non‐ulcer dyspepsia, as well as chronic peptic ulcer patients with biopsy‐proven H. pylori infection received 4 days of quadruple therapy. They were pre‐treated with 3 days of omeprazole. At least 5–6 weeks later, endoscopy was repeated with 10 biopsies for urease test, histology and culture to establish cure of infection. Results: None of the 54 patients included was lost to follow‐up but two had a 14C‐urea breath test instead of endoscopy. Side‐effects did not interfere with compliance. Forty‐nine out of 54 patients (91 %; 95% Cl: 80–97 %) were cured. Metronidazole susceptibility data were available from 43 pre‐treatment isolates. Of these 38/40 (95 %) with a metronidazole‐sensitive strain, and one of three with a metronidazole‐resistant strain were cured. Conclusions: Four days of quadruple therapy after omeprazole pre‐treatment is a feasible, well tolerated, and effective treatment for N. pylori infection, especially in those carrying a metronidazole‐sensitive strain. It seems that in quadruple therapy, cure rate and treatment duration have a non‐linear relation. Our results need confirmation, but for patients suffering from side‐effects with the 7‐day regimen stopping treatment after 4 days is justified.
Gastric microbleeding following single and repeated dosing with naproxen
Authors: McALINDON M. E. , COOK G. A. , ELLIOTT S. L. , HAWKEY C. J. , YEOMANS N. D. 
Published: July 2010

SUMMARY Background: Adaptation to gastric damage from nonsteroidal anti‐inflammatory drugs (NSAID) has been observed during ongoing dosage in rats and humans. However, this does not always occur, and our previous data suggest that NSAID half‐life may be a determining factor. Aim: To investigate whether adaptation occurs during 1 week of naproxen administration in humans. Subjects: Thirteen healthy volunteers were studied at baseline, and after me or seven daily doses of naproxen 750 mg. Gastric microbleeding was measured 4 h after naproxen in gastric washings collected during a 30‐min period. Serum thromboxane B concentrations were also assayed, as a marker of cyclo‐oxygenase inhibition. Results: Mean blood loss after placebo was 0.60, μL/10 min (95% CI: 0.21–0.98). This rose to 2.15 (0.73–3.57) and 1.75 (0.74–2.76) μL/10 min after one and seven daily doses of naproxen, respectively (P < 0.05 vs. baseline: day 1 vs. 7 not significant). Thromboxane B concentrations were < 10% of control at both day 1 and 7 of dosing. Conclusion: In accord with our findings in rats, adaptation to this moderately long acting NSAID in humans was not apparent. We conclude that any adaptation to naproxen is unlikely to be clinically important.
Mesalazine (Mesasal/Claversal) 1.5 g b.d. vs. placebo in the maintenance of remission of patients with Crohn's disease
Authors: THOMSON A. B. R. , WRIGHT J. P. , VATN M. , BAILEY R. J. , RACHMILEWITZ D. , ADLER M. , WILSON‐LYNCH K. A. ,   on behalf of The International Mesasal Maintenance Study Group
Published: July 2010

SUMMARY Investigators: This multicentre study was conducted by 29 principal investigators in 11 countries. Aims: To compare the safety and efficacy of oral mesalazine (Mesasal/Claversal, 5‐ASA) 1.5 g b.d. in comparison with placebo in the maintenance of remission in 286 patients with Crohn's disease. Materials and Methods: Patients had to score less than 150 in their Crohn's Disease Activity Index (CDAI), and had to have had one period of clinical activity (CDAI > 150) within 18 months of the study start. Patients were randomized to receive 5‐ASA 1.5 g b.d. daily or matching placebo for 12 months. Study visits were scheduled for months 1, 3, 6, 9 and 12, or when symptoms suggested a relapse of the disease. Relapse was defined as a CDAI score greater than 150, with at least a 60‐point increase from the baseline index score. None of the patients used glucocorticoids or immunosuppressants during the trial. Results: In the first group, 207 patients with Crohn's colitis or ileocolitis were randomized: there were 101 females and 106 males, in age range 18–71 years. A total of 106 patients (51 in the 5‐ASA group and 55 in the placebo group) were withdrawn from the study due to adverse events, insufficient therapeutic effect, or for other reasons. This left 101 patients (51 in the 5‐ASA group and 50 in the placebo group) who completed the 12‐month trial. In the second group, 79 patients with Crohn's ileitis were randomized to treatment. There were 53 females and 26 males, age range 18–66 years. A. total of 41 patients (19 in the 5‐ASA group and 22 in the placebo group) were withdrawn from the study. This left 38 patients (17 in the 5‐ASA group and 21 in the placebo group) who completed the 12‐month trial. the primary efficacy variable was the CDAI. A protocol‐eligible analysis and an intent‐to‐treat analysis were performed. No statistical differences were noted Between the two analyses. In patients with Crohn's colitis or ileocolitis, or in those with ileitis, no statistically significant differences were noted with: espect to the relapse rates between the 5‐ASA and the, placebo treatment groups. Adverse events in the gastrointestinal system were the most frequently, eported in both treatment groups. Many of the events such as diarrhoea or abdominal pain are symptoms of crohn's disease. The majority of the events reported were mild or moderate in severity. In neither study was he prevalence of adverse events or the proportion of drop‐outs different between patients in the treatment or in the placebo groups. The site of the Crohn's disease had no effect on the frequency of adverse events. conclusion: The relapse rates of Crohn's disease were similar for up to 12 months in both the 5‐ASA 1.5 g b.d. and the placebo treatment groups.
Milk and egg phospholipids act as protective surfactants against luminal acid in Necturus gastric mucosa
Authors: KIVINEN A. , TARPILA S. , KIVILUOTOS T. , MUSTONENS H. , KIVILAAKSOS E. 
Published: July 2010

SUMMARY Background: Our previous studies indicate that milk phospholipids have anti‐ulcer properties in rats and humans, possibly by forming a hydrophobic surfactant layer at the epithelial surface. In the present study we measured intracellular pH and parameters of membrane resistances in gastric epithelium exposed to luminal acid using a microelectrode technique. Methods: Chambered isolated Necturus maculosus antral mucosa was exposed to pH 2.3, with or without 20–2 5 min pre‐treatment with milk or egg phospholipids. The pH in surface epithelial cells was measured with double‐barrelled liquid sensor pH/PDmicroelectrodes. Results: Pre‐treatment with phospholipids (2500–5000 μg P/mL) significantly (P < 0.01 n = 14) opposed intracellular acidification. Phospholipids significantly (P < 0.05 n = 14) increased the ratio of apical and basal membrane resistances, suggesting that they primarily affect the apical cell membrane. In contrast, there was no significant change in transmucosal resistance suggesting lack of effect on paracellular shunts in the‘leaky’ epithelium. Conclusions: Exogenous phospholipids of dietary origin may be used to form a protective layer in the gastric mucosa against irritants.
Morning or evening dosage of omeprazole for gastro‐oesophageal reflux disease?
Authors: HENDEL J. , HENDEL L. , AGGESTRUP S. 
Published: July 2010

SUMMARY Background and aims: When routinely checking patients receiving omeprazole treatment for gastro‐oesophageal reflux, we have been finding patients with surprisingly low nocturnal gastric pH. The aim of this study was to evaluate the impact of timing of the 40 mg omeprazole once daily regimen. Methods: We evaluated the difference in effect of 40 mg omeprazole, given as a morning or evening dose, in 17 patients with gastro‐oesophageal reflux disease. Gastric and oesophageal pH was recorded by portable 24‐h two‐channel pH‐metry in a cross‐over design of 14 days of morning and 14 days of evening administration. Results: In five patients pathological reflux was abolished by both regimens, four only during morning dosage, and three only during evening dosage. In the remaining five patients abolition of pathological reflux was not achieved. The therapeutic outcome and patient preference for morning or evening administration were closely related to the individual oesophageal pH curves. Patients with reflux induced by physical activity had a clear preference for morning dosage, patients with nocturnal reflux showed a clear preference for evening dosage. Gastric pH profiles showed a high inter‐individual variation; paired statistics, however, revealed a significant impact of dosage timing on the gastric pH profile. After morning dosage the work‐day part (the first 7 h) of the gastric pH profile is 0.72 ± 0.91 (mean difference of pairs ± s.d.) higher than after evening dosage (P < 0.01). After evening dosage the gastric pH during the supine period is 0.64 ± 0.83 (mean difference of pairs ± s.d.) higher than after morning dosage (P= 0.02). Conclusion: The timing of a 40 mg omeprazole dosage regimen has a clinically significant impact on the 24‐h pH profile, and that—by relating to the patient 24‐hour oesophageal pH‐metry in combination with the patient symptomatology—the timing of this dosage is highly important for therapeutic efficacy.
The influence of isolated doses of drugs, feeding and colonic bacterial ureolysis on urea breath test results
Authors: PERRI F. , MAES B. , GEYPENS B. , GHOOS Y. , HIELE M. , RUTGEERTS P. 
Published: July 2010

SUMMARY Background: Aim of this work was to improve standardization of the 13C‐urea breath test (13C‐UBT) by evaluating the effect of drug administration, feeding and colonic ureolysis on the UBT results. Methods: Three different studies were performed. First, a 13C‐UBT was performed in 41 Helicobacter pylori infected subjects before and after 1 day of therapy with sucralfate (5 g), colloidal bismuth (600 mg), amoxycillin (2.5 g) or omeprazole (40 mg). Second, a 13C‐UBT was performed in 10 H. pylori‐positive patients after an overnight fast and repeated 2 h after lunch. Finally, a 13C‐UBT was carried out in seven healthy volunteers, with breath sampling prolonged to 6 h to investigate colonic bacterial ureolysis. Results: Even a short course of drugs specific for H. pylori may result in a falsely negative 13C‐UBT. Feeding does not interfere with the 13C‐UBT in infected subjects. No significant 13C‐urea breakdown by colonic bacteria is observed during the 13C‐UBT when it is prolonged to 6 h. Conclusion: The 13C‐urea breath test is a sensitive clinical tool for the non‐invasive diagnosis of H. pylori infection. It is unaffected by feeding or colonic ureolysis. However, false negative results are likely even after 1 day of therapy with bactericidal, ‘cytoprotective’ or antisecretory drugs.
Treatment of sulphasalazine‐induced agranulocytosis with granulocyte macrophage‐colony stimulating factor
Authors: RODDIE P. , DORRANCE H. , COOK M. K. , RAINEY J. B. 
Published: July 2010

SUMMARYSulphasalazine‐induced agranulocytosis is a rare but potentially life threatening complication. A variable mortality rate has been reported, from 6% to 20%, and is related to the duration of neutropenia. Previous case reports have shown that the use of granulocyte macrophage‐colony stimulating factor (GM‐CSF) in treating drug‐induced agranulocytosis may shorten the period of neutropenia and hence lead to improved survival. It may also be a less costly treatment option that supportive care alone due to reduction of hospital stay as a consequence of a shortened duration of neutropenia. We report a case in which sulphasalazine had been used in the treatment of ulcerative colitis and the subsequent agranulocytosis was treated successfully with GM‐CSF, something which has hitherto been unreported.
Unanswered questions about Helicobacter pylori
Authors: WALSH J. H. 
Published: July 2010

SUMMARYThere is general agreement that Helicobacter pylori eradication is indicated in all infected patients with duodenal ulcer disease and is probably indicated in all infected patients with gastric ulcer disease. However, translation of treatment recommendations into practice leads to some difficult clinical decisions. Three of the more perplexing questions are whether or not all patients with dyspepsia and H. pylori should be treated, whether or not a definitive diagnosis of ulcer should be established by an invasive method, and whether H. pylori eradication is sufficient to prevent recurrence of bleeding ulcers, especially in patient groups that have a high frequency of nonsteroidal anti‐inflammatory drug (NSAID) use. Another common problem is the question of whether or not to establish the success of an eradication regimen in an individual patient and the choice of method to obtain this information. There is also an obvious need to develop better antimicrobial regimens aimed specifically at Helicobacter pylori.At the basic level, almost nothing is known about the mechanisms by which H. pylori produces peptic ulcer in 10–20% of infected patients while producing gastritis in all infected subjects. There is good evidence that host factors, including intrinsic rate of acid secretion, family history and smoking are independent additive risk factors for ulcer. Ingestion of NSAIDs appears to be an independent and separate risk factor. There is evidence that strains of H. pylori that lack certain genetic markers may have a reduced likelihood of causing ulcers, but the‘ulcer’ marker is present in the majority of infected subjects without ulcer. One goal of research in H. pylori‐infected subjects should be to identify those without ulcer who are at high risk of developing ulcer disease.
No Helicobacter pylori, no Helicobacter pylori‐associated peptic ulcer disease
Authors: TYTGAT G. N. J. 
Published: July 2010

SUMMARYVirtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUS) are the consequence of Helicobacter pylori‐associated inflammation. In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb. Gastrin homeostasis is disturbed by H. pylori gastritis and there is robust acid secretion. Successful eradication of the infection cures the ulcer diathesis. Amalgamated figures for ulcer relapse per year in H. pylori‐positive DUs are > 60% compared with 2.6% for H. pylori‐negative DU patients. The corresponding figures for GU are > 50% for H. pylori‐positive and 2.0% for H. pylori‐negative individuals. This striking difference in relapse rate persists, as the re‐infection rate in the developed world is < 1 % per year. Recurrent bleeding in bleeding‐prone DUs is essentially abolished after cure of the infection.Proton pump inhibitors (PPIs) are increasingly used in eradication regimens. PPIs have intrinsic antimicrobial activity. MICs for lansoprazole (LAN) are lower than for omeprazole (OME). Two weeks of triple therapy (bismuth, tetracycline, imidazole) has, on average, a superior eradication efficacy (± 90%) compared with dual therapy (PPI, amoxycillin or clarithromycin) (± 80%). When a combination of PPI and two antibiotics has been used, results comparable to triple therapy have been reported. However, the side‐effects profile and patient acceptability of PPI plus one or two antibiotic regimens are better than for traditional triple therapy. To date, published results with LAN‐antibiotic combinations are limited, but may be expected to be comparable to those obtained with OME combinations.
The role of acid in upper gastrointestinal haemorrhage due to ulcer and stress‐related mucosal damage
Authors: PETERSON W. L. 
Published: July 2010

SUMMARYA peptic ulcer is a lesion in which acid and pepsin are essential components of pathogenesis. Regardless of type of patient or the setting in which the ulcer presents, the basic pathogenetic scheme is the same. The primary event is disruption of mucosal integrity. In the presence of acid and pepsin, such disruption of integrity leads to an ulcer. While rarely sufficient by itself to cause ulceration, the presence of acid is a necessary cofactor.The causes of disruption of mucosal integrity include nonsteroidal anti‐inflammatory drugs (NSAIDs), Helicobacter pylori and critical illness. With the latter, tissue ischaemia may be the primary event, leading to back‐diffusion of H+ ions through increased membrane permeability. Impaired mucosal buffering then leads to intramural acidosis and cell death. Risk factors for bleeding peptic ulcer in the intensive care unit (ICU) include severe trauma, sepsis, respiratory failure, and coagulopathy.Potential roles for decreasing gastric acidity in the treatment of bleeding peptic ulcer include cessation of active bleeding, prevention of rebleeding in hospital and primary prevention of bleeding. Most published studies dealing with the first two situations suggest no benefit with antisecretory therapy. However, the optimal pH for clot and platelet function may be ± 7.0. Can such pH levels be maintained with antisecretory agents such as the proton pump inhibitors? Are the published trials adequate to demonstrate any benefit from antisecretory agents?Primary prevention of bleeding ulcer in the outpatient setting includes avoidance of NSAIDs, use of antisecretory agents and eradication of H. pylori. Antacids, antisecretory therapy and sucralfate have each been shown to reduce the incidence of bleeding ulcer in ICU patients. Which regimens are the most effective? Which are the safest? Does prevention of bleeding improve survival?
Review article: Drug‐induced pancreatitis
Authors: McARTHUR K. E. 
Published: July 2010

SUMMARYDrugs are a relatively uncommon cause of pancreatitis in adult patients, but should be considered when other reasonable causes of pancreatitis are not present. A wide variety of drugs have been reported to cause pancreatitis. Drug–induced pancreatitis is almost always acute and may be mild to fatal in severity. Definite proof that a drug causes pancreatitis requires that pancreatitis develops during treatment with the drug, that other likely causes of pancreatitis are not present, that pancreatitis resolves upon discontinuing the drug, and that pancreatitis usually recurs upon readministration of the drug. For ethical reasons, rechallenge with the suspect drug can be done only if the drug is necessary to treat a serious condition: thus this highly convincing piece of evidence relating the drug to pancreatitis may not be available. Information about drug–related pancreatitis is often not readily available, particularly for newer drugs. Clinicians should consider obtaining information directly from regulatory agencies and manufacturers as well as the literature.
Review article: duodenal bicarbonate – mucosal protection, luminal chemosensing and acid–base balance
Authors: KAUNITZ J. D. , AKIBA Y. 
Published: July 2010

SummaryThe duodenum serves as a buffer zone between the stomach and the jejunum. Over a length of only 25 cm, large volumes of strong acid secreted by the stomach must be converted to the neutral–alkaline chyme of the hindgut lumen, generating large volumes of CO2.The duodenal mucosa consists of epithelial cells connected by low‐resistance tight junctions, forming a leaky epithelial barrier. Despite this permeability, the epithelial cells, under intense stress from luminal mineral acid and highly elevated Pco2, maintain normal functioning.Bicarbonate ion uniquely protects the duodenal epithelial cells from acid‐related injury. The specific protective mechanisms likely involve luminal bicarbonate secretion, intracellular pH buffering and interstitial buffering. Furthermore, the duodenum plays an active role in foregut acid–base homeostasis, absorbing large amounts of H+ and CO2.We have studied mucosal protection and acid–base balance using live‐animal fluorescence ratio microimaging and by performing H+ and CO2 balance studies on duodenal perfusates. On the basis of these data, we have formulated novel hypotheses with regard to mucosal protection.
Increased intestinal luminal carbon monoxide gas in patients with ulcerative colitis
Authors: TAKAGI T. , NAITO Y. , TSUBOI H. , ISOZAKI Y. , KATADA K. , SUZUKI T. , TERAO K. , HANDA O. , KOKURA S. , ICHIKAWA H. , YOSHIDA N. , OKUYAMA Y. , YAGI N. , UEDA H. , YOSHIKAWA T. 
Published: July 2010

SummaryBackgroundRecent studies in models of inflammatory bowel disease have demonstrated that heme oxygenase‐1 (HO‐1) induction, or its by‐products in this process such as carbon monoxide (CO), plays an important role in the intestinal inflammation. However, the distribution of HO‐1 in intestinal mucosa and the concentration of intestinal luminal CO in humans have not yet been investigated.AimTo detect the HO‐immunopositive cells in the intestine of normal subjects and in patients with ulcerative colitis (UC) and to measure intestinal luminal CO gas contents using gas chromatography.Materials and MethodsThe expression of HO‐1 in the intestine was determined using immunohistochemistry. Human colonic gas was collected using colonoscopy from healthy volunteers and patients with UC. Analysis of intestinal luminal gas was performed using a newly developed portable gas chromatograph.ResultsImmunopositive staining for HO‐1 was localized in the inflammatory cells, mainly mononuclear cells, and the number of cells that accepted stain was greater in patients with UC. CO level in the intestinal lumen significantly increased in patients in the active stage of UC.ConclusionThese findings indicate that the HO‐CO system is induced in UC.