bluuebunny/crossref_metadata_2025 huggingface dataset:
Spiramycin in triple therapy of Helicobacter pylori‐associated peptic ulcer disease. An open pilot study with 12‐month follow‐up
Authors: BERSTAD A. , BERSTAD K. , WILHELMSEN I. , HATLEBAKK J. G. , NESJE L. B. , HAUSKEN T.
Published: July 2010

Background: Spiramycin (Rovamycin) is a well‐established macrolide antibiotic with good anti‐Helicobacter pylori activity in vitro. It is acid‐stable and found in high concentration in various body fluids and cells after oral administration. Its anti‐H. pylori activity in vivo has not yet been tested.

Methods: Twenty‐five consecutive patients with endoscopically verified peptic ulcer and a positive biopsy urease test were given spiramycin tables 1.5 MIU instead of oxytetracycline 500 mg q.d.s. in our triple therapy regimen with bismuth subnitrate suspension 10 mL (150 mg bismuth subnitrate) q.d.s. and metronidazole 400 mg t.d.s. for 10 days. Bismuth was taken between meals and spiramycin and metronidazole with meals. Re‐endoscopy and 14C‐urea breath test were performed 4 weeks after completion of therapy. Those who were H. pylori negative according to the breath test returned for 1‐year follow‐up.

Results: Per protocol analysis at 4 weeks showed that 21 out of 23 patients were H. pylori negative and had healed ulcers. These 21 patients were persistingly H. pylori negative and had no ulcers at 1‐year follow‐up. H. pylori eradication and ulcer healing rates were thus 91.3%; 95 % confidence interval from 72.0% to 98.9%. Side‐effects limiting daily activity were significantly less frequent than we have experienced previously using oxytetracycline in triple therapy.

Conclusions: Spiramycin appears to be an alternative to tetracycline in the triple therapy of H. pylori infection. Further studies to position spiramycin as an anti‐H. pylori drug are warranted.
A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori
Authors: KATELARIS P. H. , PATCHETT S. E. , ZHANG Z. W. , DOMIZIO P. , FARTHING M. J. G.
Published: July 2010

Aim: To compare H. pylori eradication rates using omeprazole in conjunction with either amoxycillin or clarithromycin.

Background: Omeprazole with amoxycillin is the most widely used dual therapy regimen for eradication of H. pylori. A recent open study suggested a high eradication rate combining omeprazole with the newer macrolide, clarithromycin.

Methods: A randomized prospective trial in 54 patients was conducted to compare 2 weeks of treatment with omeprazole 40 mg once daily and either amoxycillin 500 mg three times daily or clarithromycin 500 mg three times daily. H. pylori eradication was assessed using the 13C urea breath test.

Results: Eradication was achieved in 18/26 (69.2%) of subjects treated with omeprazole and amoxycillin and 18/25 (72.0%) of those treated with omeprazole and clarithromycin (P= N.S.). Minor side effects, most commonly altered taste, were reported by 16% of patients and were more frequent in those randomized to clarithromycin (P= 0.01).

Conclusions: These regimens are similarly effective. However, clarithromycin is more expensive, associated with a greater frequency of side effects and, unlike amoxycillin, resistance by H. pylori has been reported. This suggests that clarithromycin may be a useful alternative when there is penicillin allergy or previous treatment failure, but it should not replace amoxycillin as first choice in omeprazole‐based dual therapy.
quantitative tests of liver function
Authors: JALAN R. , HAYES P. C.
Published: July 2010

The search continues for a single reliable test of liver function that provides accurate prognostic information in chronic liver disease, in acute liver failure, and about graft function following orthotopic liver transplantation. Although transaminases, the commonly used markers of hepatocellular injury, have a high sensitivity in screening for liver disease, they do not provide any information about prognosis. Rational assessment of liver function using bilirubin, serum albumin and prothrombin‐time is limited by the relative lack of sensitivity of these measurements and their inability to identify the functional reserve of the liver. Dynamic liver function tests are an improvement on the static tests but are generally cumbersome.

The ideal liver function test would be cheap, easy to perform and analyse, safe, have a simple pharmacokinetic profile with minimal drug interactions, have a high predictive value and provide quick results. Numerous quantitative liver function tests have been developed and have shown promise in some studies. The aim of this review is to assess the place of these tests in the practical management of liver disease.
Short‐chain fatty acid topical treatment in distal ulcerative colitis
Authors: VERNIA P. , MARCHEGGIANO A. , CAPRILLI R. , FRIERI G. , CORRAO G. , VALPIANI D. , PAOLO M. C. DI , PAOLUZI P. , TORSOLI A.
Published: July 2010

Background: Some evidence indicates that short‐chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis.

Methods: In a randomized, double‐blind, placebo‐controlled study, we tested the efficacy of a 6‐week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study.

Results: Fourteen patients on SCFA improved (overall score 11.3 ± 2.0 vs. 7.4 ± 3.5) as compared to five in the placebo group (overall score 10.0 ± 1.9 vs. 8.9 ± 2.5). In the SCFA‐treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self‐evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA‐treated group, thus causing pre‐trial differences between the two groups.

Conclusion: the present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.
Release of 5‐ASA from Pentasa in patients with Crohn's disease of the small intestine
Authors: LAROUCHE J. , MORAIS J. , PICARD M. , LAMBERT C. , SPÉNARD J. , LANDRIAULT H. , KENNEDY G. , POITRAS P.
Published: July 2010

Background: Pentasa is a controlled‐release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5‐ASA (5‐aminosalicylic acid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5‐ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine.

Materials: Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium‐153 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5‐ASA and acetylated 5‐ASA was used to verify the liberation and absorption of 5‐ASA.

Results: The Pentasa tablet appeared completely dissolved in the stomach by 117 ± 18 min. Samarium oxide was first detected in the small intestine 60 ± 5 min after its ingestion; it reached the colon after 280 ± 13 min and it was completely absent from the small intestine at 360 ± 26 min. Plasma concentrations of 5‐ASA started to rise after 67 ± 7 min and were maximal at 222±25 min.

Conclusion: In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5‐ASA in the proximal small intestine, acting locally to exert its beneficial effect.
The continuing development of proton pump inhibitors with particular reference to pantoprazole
Authors: HUBER R. , KOHL B. , SACHS G. , SENN‐BILFINGER J. , SIMON W. A. , STURM E.
Published: July 2010

Inhibition of the gastric proton pump is gaining acceptance as the treatment of choice for severe gastrooesophageal reflux disease, and for treatment of duodenal and gastric ulceration. Three of these drugs are now available (omeprazole, lansoprazole and pantoprazole) and more are being developed. Proton pump inhibitors share the same core structure, but differ in terms of substituents on this core. The substitutions are able to modify some important chemical properties of the compounds. For example, pantoprazole is significantly more acid‐stable than omeprazole or lansoprazole. E3810 is significantly less stable than the other compounds. We present an explanation for this finding that depends on the relative pK values for the pyridine and benzimidazole nitrogens, especially the former.

Pantoprazole formulated in an enteric‐coated tablet displays high bioavailability and linear pharmacokinetics whether on single or multiple dose regimens. Although all three proton pump inhibitors provide a similar chemical conversion to sulphenamides, which are highly reactive cysteine reagents, these reagents derivatize different cysteines in the extracytoplasmic or membrane domain of the pump and inhibit the pump at different rates.

Whereas the differences in chemical reactivity can be explained by the solution chemistry of the compounds, selective derivatization of different cysteines on the protein argues for an involvement of pump structure in response to the presence of the proton pump inhibitor on its luminal surface. This suggests that the proton pump inhibitors, which were originally designed to take advantage of only the highly acidic space generated in the parietal cell by the production of the sulphenamide, are made even more selective by the protein they target.

Pantoprazole is metabolized by a combination of phase I and phase II metabolism, and has also been shown to have a very low potential for drug interaction. Studies of acid secretion in man have shown this compound to be an effective and long lasting inhibitor of acid secretion. The pharmacodynamics explain the cumulative effect of repeated doses and maximal acid secretory capacity with a once daily dosage.
Low dose famotidine in the prevention of sleep disturbance caused by heartburn after an evening meal
Authors: MANN S. G. , MURAKAMI† A. , McCARROLL† K. , RAO† A. N. , COTTRELL J. , MEHENTEE† J. , MORTON R.
Published: July 2010

Aim: To determine whether, in a susceptible opulation, dosing with 10 mg famotidine 1 h before an evening meal could decrease the interference with sleep caused by heartburn.

Methods: Patients with a history of frequent heartburn (n= 309) were randomized to receive 10 mg famotidine or placebo 1 h before an evening meal likely to induce symptoms. Patients assessed the efficacy of the treatment in preventing heartburn after the meal, at bedtime and during the night. The number of awakenings due to heartburn and the consumption of antacid tablets taken to alleviate symptoms were also recorded.

Results: Treatment groups were well matched and data from 302 patients were available for analysis. Compared to placebo, famotidine treated patients had: less heartburn after the meal (P < 0.0001 mean global scores), less interference with getting to sleep (P= 0.0156 mean global scores), fewer awakenings (P= 0.0001 difference in mean number) and better control of heartburn during the night (P < 0.0001 mean global scores). They were also almost three times less likely to need antacid treatment than the placebo group during the night (relative odds for no antacid 2.78 (95% CI: 1.29–5.96). Only four patients in each group suffered adverse events.

Conclusion: Taking a 10 mg dose of famotidine 1 h before an evening meal appears to be a successful and well tolerated strategy for preventing post‐prandial heartburn and avoiding the associated interference with sleep.
drug development in gastroenterology—the changing view of industry
Authors: PARSONS M. E. , GARNER A.
Published: July 2010

Rationalization within the pharmaceutical industry to combat escalating costs has included the close examination of research portfolios. Gastroenterology has been one of the casualties of this exercise and few companies currently retain a specific gastrointestinal research programme.

Acid‐peptic disease has been the victim of its own success, since the availability of a range of extremely effective drugs largely satisfies current medical needs. A safe, convenient and effective monotherapy able to eradicate Helicobacter pylori would be a commercially viable alternative to antisecretory drugs, leading to further expansion of the anti‐ulcer market. The irritable bowel syndrome is probably too diverse a target for logical research; inflammatory bowel disease is probably too small a market to be attractive.

Potentially effective drugs to treat these and other gastrointestinal diseases could emerge from broader research programmes, provided that companies retain the expertise and desire to develop such agents for gastrointestinal indications. Cancer of the gastrointestinal tract and associated organs undoubtedly represents a commercially attractive target, but new anti‐tumour drugs are more likely to arise from generic research rather than programmes specifically directed at tumours of the gastrointestinal tract.

The changing view of the pharmaceutical industry towards the development of gastrointestinal drugs is likely to have a negative impact on both fundamental and clinical research in gastroenterology.
artificial nutritional support for improved patient care
Authors: PENNINGTON C. R. , POWELL‐TUCK† J. , SHAFFER J.
Published: July 2010

Malnutrition is common and undiagnosed in the majority of affected hospital patients; it is associated with impaired organ function, morbidity, and increased length of hospital stay. Artifical nutritional support in malnourished patients leads to improvement in nutritional status and clinical outcome.

Nutritional support is required in malnourished patients, patients who are unable to take normal diet and patients with intestinal failure. Gastroenterologists are required to supervise patients with intestinal failure, to insert endoscopic feeding devices, and increasingly to participate in, or lead, nutritional support teams.

Major developments in nutrient delivery have included percutaneous endoscopic feeding devices, the recognition that enteral feeding is possible in patients with gastric stasis, and that nutrient needs can be met by peripheral parenteral nutrition. There is much interest in the use of new substrates, or substrates delivered in pharmacological doses such as glutamine and arginine, to manipulate the response to disease.

Many hospitals lack an organized approach to artificial nutritional support. Patients continue to suffer from a lack of treatment or the consequences of inappropriate or inadequate treatment. This article reviews the current status of artificial nutritional support and provides guidelines for patient managment.
The effects of aminosalicylic acid derivatives on nitric oxide in a cell‐free system
Authors: REYNOLDS P. D. , MIDDLETON S. J. , SHORTHOUSE M. , HUNTER J. O.
Published: July 2010

Aims and Methods: To determine the effect of aminosalicylic acid derivatives on the concentration of nitric oxide produced in a cell‐free system, by the use of a sensitive and specific polarographic meter.

Results: The aminosalicylic acid derivatives 3‐ASA (IC50100 μm), 4‐ASA (IC50350 μm) and 5‐ASA (IC505 μm) all decreased the nitric oxide signal. These drugs had a similar inhibitory effect on the formationin vitroof nitrite from sodium nitroprusside (IC50200 μm, 500 μmand 100 μm, respectively). Sulphasalazine (31.1 ± 5% decrease in signal at 1 mm) was less effective than 5‐ASA, but sulphapyridine, N‐acetyl 5‐ASA, indomethacin and hydrocortisone produced no decrease in nitric oxide signal at all.

Conclusions: Nitric oxide binding may be part of the mechanism by which ASA derivatives exert their therapeutic effect, and this work suggests that it may be an important factor in the pathogenesis of ulcerative colitis.
GR122311X (ranitidine bismuth citrate), a new drug for the treatment of duodenal ulcer
Authors: BARDHAN K. L. D. , DEKKERS C. P. M. , LAM S. K. , NOWAK A. , MUCKADELL O. B. SCHAFFALITZKY DE , SCHUTZE K. , TILDESLEY G. , KLER L. , FORSTER J. K. , LACEY M. F. , ROBERTS P. M. , ISAL J. P.
Published: July 2010

Background: Ranitidine bismuth citrate (GR122311X) is a new drug which offers potential benefits in healing duodenal ulcers and prevention of relapse.

Methods: This randomized, multi‐centre double‐blind study of 1620 patients compared the effect of 4 weeks of treatment with GR122311X 200 mg b.d. (n= 401), 400 mg b.d. (n= 404) or 800 mg b.d. (n= 404) or ranitidine hydrochloride 150 mg b.d. (n= 411) on the rates of duodenal ulcer healing and of overall success (ulcers healed and remaining ulcer free in the 24‐week follow‐up phase).

Results: All four treatments were equally effective at ulcer healing (79%, 85%, 84% and 81% of patients, respectively). GR122311X 400 mg b.d. (38%) and 800 mg b.d. (37%) were significantly more effective than ranitidine hydrochloride 150 mg b.d. (32%) with respect to overall success (P = 0.050 and P = 0.030, respectively) but there was no difference with GR122311X 200 mg b.d. (31%). GR122311X caused effective, dose‐related suppression of H. pylori (47%, 61% and 74%); H. pylori eradication rates were 18%, 21% and 22%. GR122311X was safe and well tolerated, with an adverse event profile similar to that of ranitidine hydrochloride 150 mg b.d. Median week 4 trough plasma bismuth levels were 1.3 ng/mL, 2.3 ng/mL and 3.3 ng/mL with GR122311X 200 mg b.d., 400 mg b.d. and 800 mg b.d. respectively. No individual plasma bismuth concentrations were of clinical concern.

Conclusions: GR122311X is a safe and effective ulcer healing drug, and provides a platform on which anti‐H. pylori therapy can be based.
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

Background: 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

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

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

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

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

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

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

Sulphasalazine‐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

There 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

Virtually 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

A 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

Drugs 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

The 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

Background

Recent 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.

Aim

To 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 Methods

The 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.

Results

Immunopositive 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.

Conclusion

These findings indicate that the HO‐CO system is induced in UC.
Endoscopic classifications as diagnostic factors of peptic ulcer and early gastric cancer – a possible reason why Helicobacter pylori infection causes gastric ulcers along lesser curvature
Authors: YOSHIDA M. , SAIKAWA Y. , HOSODA S. , KUMAI K. , KUBOTA T. , ISHIKAWA H. , NAKAMURA T. , NAKAMURA R. , KAMEYAMA K. , TAKAHASHI S. , KURIHARA N. , KITAJIMA M.
Published: July 2010

Background

Endoscopic classifications were reported to reflect the pathophysiology of gastric mucosa. However, relationship between gastric lesions and classifications has not been examined well.

Aim

To investigate the relationship between endoscopic classifications and cancers or ulcers.

Methods

In this study, 487 patients undergoing upper gastrointestinal endoscopy in Takahashi Clinic and 257 patients with early gastric cancer in Keio University Hospital were enrolled.

Results

Incidence of reflux oesophagitis was higher in Helicobacter pylori‐negative patients. K‐form was better in the H. pylori‐positive patients. Most cancers in the patients with the closed‐type or reflux oesophagitis were of undifferentiated types. Incidences of ulcers were highest in C‐2 and C‐3 in which the borders of atrophy cross the medial oblique muscle bundle, the border circular muscle bundle or both, and 94% of ulcers in C‐2 and C‐3 stomach were located along the lesser curvature.

Conclusion

The predominant existence of undifferentiated types in patients with reflux oesophagitis or closed‐type stomach can be useful information for early diagnosis of cancers. The relationship between the Kimura–Takemoto classification and ulcer location may explain why H. pylori infection is related to ulcer formation along the lesser curvature.
Review article: the nature of oesophageal injury in gastro‐oesophageal reflux disease
Authors: DE HERTOGH G. , ECTORS N. , VAN EYKEN P. , GEBOES K.
Published: July 2010

The purpose of this review was to explore issues relating to the nature of oesophageal injury in gastro‐oesophageal reflux disease. Several structural and functional elements of the oesophageal epithelium provide for an inherent resistance against refluxed material. It is only when this defence is overcome that reflux‐induced damage ensues.

The light microscopic changes in reflux oesophagitis are manifold. Early changes are confined to the epithelium and consist of reactive changes and inflammatory cell infiltration. When the epithelial integrity can no longer be maintained, erosions and ulcers develop.

Recently, dilatation of the intercellular spaces was described as a sensitive early marker for gastro‐oesophageal reflux disease. This parameter was first identified by electron microscopy but can also be assessed by light microscopy in routinely stained tissue sections.

Some of the changes occurring in early gastro‐oesophageal reflux disease can be reproduced by incubating oesophageal mucosal biopsies in gastrointestinal fluids or their components. Activated pepsin, trypsin and conjugated bile acids at an acidic pH have been identified as probable causes of reflux‐induced damage.
Review article: complete gastro‐oesophageal reflux monitoring – combined pH and impedance
Authors: TUTUIAN R. , CASTELL D. O.
Published: July 2010

Gastroesophagel reflux disease (GERD) is a common condition encountered in clinical practice. Over the years there has been a continuous interaction between the understanding of the disease, the diagnostic tools and treatments of GERD. The use of proton pump inhibitor (PPI) trials by primary care physicians as diagnostic tool in patients with symptoms suspected to be due to GERD has led to a shift in the type of patients referred to specialists. Currently, gastrointestinal specialists are frequently asked to evaluate patients with persistent reflux symptoms despite acid suppressive therapy. In these patients symptoms can be associated with reflux (both acid and non‐acid) or not associated with reflux.

While conventional pH monitoring can quantify esophageal acid exposure and evaluate the association between symptoms and acid reflux, it cannot reliably detect reflux episodes with a pH >4 (i.e. non‐acid reflux). Detecting reflux episodes by changes in intraluminal resistance to alternating current (i.e. impedance), combined multichannel intraluminal impedance and pH (MII‐pH) monitoring offers the opportunity to detect both acid and non‐acid reflux episodes and to evaluate the relationship between symptoms and reflux. We believe that MII‐pH monitoring has become the new ‘‘gold standard’’ for clarifying the mechanisms of persistent symptom on PPI therapy.
Systematic review: fluoroquinolones for the treatment of intra‐abdominal surgical infections
Authors: FALAGAS M. E. , MATTHAIOU D. K. , BLIZIOTIS I. A.
Published: July 2010

Background

Intra‐abdominal infections result in substantial morbidity and mortality. Fluoroquinolones are among the various regimens that are used for the treatment of these infections.

Aim

To evaluate the available data from laboratory and clinical studies regarding the use of fluoroquinolones for the treatment of patients with intra‐abdominal infections.

Methods

We searched for relevant laboratory and clinical studies in the PubMed and the Cochrane Library databases.

Results

Good pharmacokinetic and pharmacodynamic properties of fluoroquinolones in inflamed abdominal tissue are reported in several laboratory studies. In six prospective non‐randomized clinical studies of patients with intra‐abdominal infections, the clinical success achieved with the use of fluoroquinolones ranged from 77% to 94%. In 10 randomized‐controlled trials fluoroquinolone‐based regimens were compared with other commonly used (mainly β‐lactam‐based) regimens. Clinical success, bacterial eradication, withdrawal because of toxicity and mortality were similar between the compared treatment arms except from two randomized‐controlled trials, in which clinical success was statistically higher in the fluoroquinolone treatment arm.

Conclusions

Fluoroquinolones seem to be an effective and relatively safe option for the treatment of patients with intra‐abdominal infections.