bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scintigraphic assessment of the intragastric distribution and gastric emptying of an encapsulated drug: the effect of feeding and of a proton pump inhibitor
Authors: ATHERTON J. C. , WASHINGTON N. , BRACEWELL M. A. , SUTTON L. J. , GREAVES J. L. , PERKINS A. C. , HAWKEY C. J. , SPILLER R. C. 
Published: July 2010

SUMMARYBackground: Local delivery of therapeutic agents to the stomach may be a useful strategy in the treatment of Helicobacter pylori infection. We aimed to see whether the intragastric distribution and gastric retention of a therapeutic agent could be improved, either by giving omeprazole or by dosing after a meal.Methods: Twelve healthy volunteers took part in this double‐blind placebo‐controlled crossover study comparing the effects of omeprazole 20 mg twice daily for 5 days with placebo, and the fasted with the fed state, on the gastric emptying and intragastric distribution of a soluble scintigraphic marker contained in a drug capsule.Results: Dosing after food profoundly prolonged gastric residence of the drug label, prolonging mean time to 50% emptying (T50) from 0.5 ± 0.1 h in the fasted state to 2.0 ± 0.2 h when given after food. Food also improved intragastric distribution by increasing delivery to the body and fundus. Omeprazole enhanced the effect of food, prolonging T50 to 2.9 ± 0.3 h, but had no effect in fasted subjects.Conclusions: Dosing after food markedly improves the aspects of local drug delivery to the stomach investigated in this study, and omeprazole enhances this effect. Post‐prandial dosing may, therefore, be useful for improving delivery of some anti‐Helicobacter agents.
Amoxycillin capsules with omeprazole for the eradication of Helicobacter pylori. Assessment of the importance of antibiotic dose timing in relation to meals
Authors: ATHERTON J. C. , HUDSON N. , KIRK G. E. , HAWKEY C. K. , SPILLER R. C. 
Published: July 2010

SUMMARYBackground: Giving antibiotics after meals prolongs their gastric residence time and improves their intragastric distribution. We aimed to see whether this would result in improved eradication of Helicobacter pylori.Methods: Eighty patients with H. pylori infection were treated with 40 mg omeprazole in the morning for 28 days and amoxycillin 500 mg q.d.s. for days 15–28. Amoxycillin dosing was randomised to either 1 h before or 10 min after food. Good compliance was pre‐defined as missing less than four doses of amoxycillin or two of omeprazole.Results: Amoxycillin dosing after meals was shown not to affect H. pylori eradication rate either when results were analysed on an intention‐to‐treat basis [amoxycillin before meals successful in 63% (25/40), after in 65% 26/40)] or for good compliers only [before meals 81% (17/21), after 71% (20/28)]. This excludes, with 95% confidence, a benefit of greater than 18% from dosing before, or 23% from dosing after meals. Good compliance, however, was shown to be important, with H. pylori eradication in 76% (37/49) of good compliers compared with 48%(11/23) of others completing the protocol (P < 0.05).Conclusions: The timing of antibiotic administration in relation to meals is not important in the treatment of H. pylori infection with this regimen of amoxycillin capsules and omeprazole. Good compliance, is however, an important determinant of treatment success.
Low dose aspirin: selective inhibition of rectal dialysis thromboxane B2 in healthy volunteers
Authors: COLE A. T. , FILIPOWICZ B. , HYMAN‐TAYLOR P. , HAWKEY C. J. 
Published: July 2010

SUMMARYAim: To investigate the degree and selectivity of rectal thromboxane inhibition by low dose aspirin and there by investigate the contribution of platelet thromboxane to rectal thromboxane.Methods: The study was a randomized double‐blind placebo controlled crossover study. Twelve healthy volunteers were studied, each over four separate study periods with two weeks wash‐out between each period. Changes in levels of thromboxane (TX) B2, prostaglandin (PG) E2 and leukotriene (LT) B2 in rectal dialysates were measured in response to 5 days oral low dose aspirin therapy in one of three once‐daily formulations (plain 75 mg, plain 300 mg or enteric coated 300 mg), and compared to placebo. For each study period, rectal dialysates (4 h duration) were obtained at baseline and twice more after 5 days of aspirin or placebo therapy. Dialysate levels of thromboxane B2, leukotriene B4, prostaglandin E2, and serum thromboxane B2 were measured by radioimmunoassay.Results: Dialysate thromboxane B, levels were consistently inhibited by low dose aspirin (overall results of all formulations, 75 to 300 mg daily) from 1.06 ng/ml (geometric mean, 95 % CI:0.79–1.43 ng/ml) on placebo, by 29% (95% CI: 11–40%) to 0.75 ng/ml(0.56–1.01 ng/ml) (P= 0.046) on aspirin. In the absence of aspirin the level of prostaglandin E, was 1.47 ng/ml (0.97–2.23 ng/ml) and in the presence of aspirin was not significantly changed. The dialysate level of leultotriene B, was 0.45 ng/ml(0.34–0.61 ng/ml) in the absence of aspirin and there was no significant change on low dose aspirin. Serum thromboxane was inhibited by 80% to 20% of placebo values by plain aspirin 75 mg, by 95 % by plain aspirin 300 mg, and by 82 % by enteric coated aspirin 300 mg, respectively (P < 0.01). These results show that 29 % of the rectal thromboxane, but none of the rectal prostaglandin E2 or leukotriene B4, is inhibited by low dose aspirin. We infer that 34% of the rectal thromboxane B2 is platelet‐derived in our volunteers.Conclusion: Low dose aspirin will selectively inhibit a proportion of rectal thromboxane and may have prophylactic therapeutic potential in inflammatory bowel disease.
Practical management of the short bowel
Authors: LENNARD‐JONES J. E. 
Published: July 2010

SUMMARYA shortened small intestine may end at a stoma or be anastomosed to the colon. Patients with a jejunostomy, but not those with a colon, lose large amounts of sodium. The intake and absorption of sodium can be increased by sipping a sodium–glucose solution: stomal loss can be reduced by restricting water or low‐sodium drinks. If a stoma is situated less than 100 cm along the jejunum, a constant negative sodium balance may necessitate parenteral saline supplements. Gastric anti‐secretory drugs or a somatostatin analogue reduce jejunostomy losses in such patients but do not restore a positive sodium balance. Loperamide or codeine phosphate benefit some patients. Magnesium deficiency can usually be corrected by oral magnesium oxide supplements. An elemental or hydrolysed diet is not beneficial. Patients with a jejunostomy can maintain a normal diet without fat reduction.When the colon is present, unabsorbed carbohydrate is fermented to absorbable short chain fatty acids. Unabsorbed long chain fatty acids and bile salts cause watery diarrhoea and increased colonic oxalate absorption with hyperoxaluria. Such patients benefit from a high carbohydrate, low‐fat and low‐oxalate diet.Parenteral nutrition is needed only by the few patients unable to maintain health or avoid socially disabling diarrhoea despite these measures.
Review article: infective complications of therapeutic gastric acid inhibition
Authors: LARNER J. , HAMILTON M. I. R. 
Published: July 2010

SUMMARYGastric acid secretion has a non‐specific bactericidal action which contributes to gastrointestinal defence mechanisms against micro‐organisms. Therapeutic inhibition of acid secretion with histamine H2 receptor antagonists and proton pump inhibitors might therefore be expected to predispose to infection. This article reviews clinical reports of infection occurring during therapeutic gastric acid inhibition, and assesses the risk of infection incurred by such treatment. Non‐typhoid salmonelloses, Campylobacter infections, local candidiasis, and possibly Strongyloides hyperinfections may be more prevalent after acid inhibitory treatment, but concurrent impairment of other gastrointestinal defence mechanisms may be necessary to permit infection.
Dexamethasone promotes ulcer plugging in experimental enteritis
Authors: ANTHONY A. , DHILLON A. P. , SIM R. , POUNDER R. E. , WAKEFIELD A. J. 
Published: July 2010

SUMMARY Aim: We investigated the effect of dexamethasone on indomethacin‐induced ulceration in the rat. Methods: Groups of four rats received oral indomethacin (15 mg/kg) and the jejunal mucosa was examined 24 h later for mucosal ulceration. Three of the groups received oral dexamethasone (1,3 and 6 mg/kg) 0.5 h prior to indomethacin, while the fourth received vehicle. Haematological evaluation was performed and ulcers were assessed both histologically and immunohistochemically. Results: Indomethacin caused multifocal jejunal ulceration that was reduced only by the highest dose of dexamethasone (6 mg/kg). Indomethacin caused a significant fall in the blood haemoglobin concentration that was prevented by dexamethasone at all doses. The ulcers induced by indomethacin alone were deep, punched‐out and haemorrhagic while the ulcers arising in rats pre‐treated with dexamethasone (all doses) were‘plugged‘ by a white fibrino‐purulent exudate. Histologically, the dexamethasone ulcer exudate was composed of bacteria, fibrin, mucus and a significant increase in the numbers of neutrophils. Dexamethasone alone had no significant pathological effect on the small intestine. Conclusions: We report the observation that examethasone at high doses inhibits indomethacin‐induced jejunal ulceration in the rat while at low doses it promotes‘plugging‘ of ulcers with bacteria, fibrin, mucus and neutrophils that probably reduces haemorrhage from the ulcer base.
Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis
Authors: NYMAN‐PANTELIDIS M. , NILSSON Å. , G‐WAGNER Z. , BORGA O. 
Published: July 2010

SUMMARY Methods: The retrograde spread of two budesonide enema formulations with different viscosities was investigated. The study design was open, randomized and two‐period crossover. Three female and two male patients (age range: 35–45 years) with distal ulcerative colitis or proctitis participated. Both enema formulations contained a dose of 2 mg budesonide/100 mL. An unabsorbable radioactive marker (99mTc‐labelled human serum albumin microcolloid) was added to the enema just before administration. All doses were given in the evening with the patients lying in a supine position during the whole investigation. The intestinal spread was followed for 8 h using scintigraphic imaging. Plasma samples for budesonide assay were taken during the 12 h after administration of the low viscosity enema. Results: Budesonide plasma levels were measurable for up to 4–6 h. Cmax was 2.5 nmol/L (range:0.9–4.5 nmol/L) and was attained in 1.5 h (range 1–3 h). The patients had no difficulty in retaining the enemas. There was a statistically significant difference in spread between the low and high viscosity enema. The low viscosity enema spread over an area situated between the rectum and the splenic flexure. The spread occurred mainly in the first 15 min after administration. In contrast, the high viscosity enema, in most cases, spread only over a minor part of this area and the rate and extent of spreading was also more variable with this formulation. Conclusion: The spread of a low viscosity enema appears to be well suited for the treatment of proctitis and distal colitis.
Omeprazole and the cytochrome P450 system
Authors: PETERSEN K.‐U. 
Published: July 2010

SUMMARYEnzymes of the cytochrome P450 superfamily play a key role in xenobiotic metabolism. Their properties and significance are discussed with particular reference to interactions with the H+, K+‐ATPase blocker, omeprazole. Such interactions include both inhibitory (subfamily 2C) and inducing effects (subfamily 1A). Delayed metabolic elimination of diazepam, warfarin, carbamazepin and phenytoin is probably due to omeprazole competition for the concerned isoform of subfamily 2C; however, these effects are modest to negligible in magnitude and, for phenytoin, not consistently reproducible. Also, induction of subfamily 1A is only minor as assessed from the resultant changes inN‐3‐demethylation of caffeine, a reaction specific to this subfamily. Concerns about a possible activation of procarcinogens that might arise from subfamily 1A induction appear ill‐founded given the fact that cruciferous vegetables such as broccoli and Brussels sprouts are potent inducers, but rather seem to lower the incidence of certain types of cancer. Likewise, the idea that the toxicity of acetaminophen might increase upon subfamily 1A induction appears far‐fetched, mainly because much stronger inducers of subfamily 1A (cigarette smoke and charcoaled beef) are unable to alter acetaminophen metabolism.
Successful Helicobacter pylori eradication incorporating a one‐week antibiotic regimen
Authors: HUDSON N. , BRYDON W. G. , EASTWOOD M. A. , FERGUSON A. , PALMER K. R. 
Published: July 2010

SUMMARY Background: The optimum regimen for the eradication of Helicobacter pylori remains unclear. The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks, plus amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. given for the first 7 days, in the treatment of H. pylori associated peptic ulcer disease. Results: One hundred and thirty‐two consecutive patients with peptic ulcer disease were entered into the study (89 male, 41 female; median age 47 years; inter‐quartile range: 36–58 years). H. pylori was eradicated successfully in 109 of 130 patients (intention‐to‐treat: 83%; 95% confidence limits: 76–89%); per protocol: 85% (95% CI: 78–91%)). Ninety per cent of patients completed the full course of therapy. Only four patients (3%) stopped treatment as a result of side effects although these occurred in 41% of patients. One patient developed pseudomembranous colitis requiring hospital admission. Conclusion: Omeprazole combined with one week of treatment of amoxycillin and metronidazole is an effective and well tolerated Helicobacter eradication regimen. Occasional severe side effects remain a risk, even when the duration of antibiotic exposure is reduced.
Review article: anti‐diarrhoeal pharmacology and therapeutics
Authors: SCHILLER L. R. 
Published: July 2010

SUMMARYAnti‐diarrhoeal drugs reduce the symptoms of diarrhoea (loose stool consistency, frequency of defecation and excessive stool weight) by effects on intestinal transit, mucosal transport or luminal contents. Opiates and opioids are the most useful anti‐diarrhoeal agents. Opiates have major effects on intestinal transit; pro‐absorptive and anti‐secretory effects are less well documented, but may be important for some of these drugs. Alpha‐adrenergic agonists, somatostatin analogues and several other agents have had limited clinical use; these drugs may modify mucosal transport in addition to slowing transit. Adsorbents, bismuth and stool texture modifiers are used frequently by the public, but their efficacy is largely unproven. Oral rehydration solutions have had the greatest impact in saving lives and continue to be improved. Many new approaches to the treatment of diarrhoea are yet to be exploited.
Effect of D2‐dopamine receptor antagonist levosulpiride on diabetic cholecystoparesis : a double‐blind crossover study
Authors: MANSI C. , SAVARINO V. , VIGNERI S. , SCIABÀ L. , PERILLI D. , MELE M. R. , CELLE G. 
Published: July 2010

SUMMARY Background: Abnormal gall‐bladder motility has been reported in diabetics. The objective was to evaluate the effect of chronic D2‐dopamine receptor inhibition on gall‐bladder emptying in diabetic patients. Methods: Under double‐blind placebo‐controlled conditions and according to a crossover design, patients were randomly assigned to receive either 4 weeks treatment with levosulpiride 25 mg t.d.s. or 4 weeks treatment with placebo, with an interval of 15 days. Twenty‐three consecutive long‐standing, insulin‐treated diabetics with autonomic neuropathy were studied. Measurements: At the beginning of the study and after levosulpiride or placebo treatment, gall‐bladder emptying was measured ultrasonically by evaluating the gall‐bladder volume in basal conditions and every 15 min for 90 min after the ingestion of a standard meal. Statistical analysis of the results was performed by means of analysis of variance. Results: Levosulpiride treatment reduced the basal mean gall‐bladder volume from 21.6 ± 2.3 to 18.6 ± 2.3 mL (P < 0.05). Furthermore, the residual gall‐bladder volume (9.3 ± 1.4 mL) was significantly reduced compared to the corresponding pre‐treatment volume (14.6 ± 1.5 mL (P < 0.05)). In placebo‐treated patients, no significant differences were observed in gall‐bladder volumes before and after treatment. Conclusion: These results show that chronic oral administration of the D2 dopamine antagonist levosulpiride has a significant effect on gall‐bladder motility in diabetic patients.
manipulation of cell death — the development of novel strategies for the treatment of gastrointestinal disease
Authors: WATSON A. J. M. 
Published: July 2010

SUMMARYThe mechanisms underlying cell death are reviewed in order to propose new targets for the therapy of gastrointestinal disease. Necrosis is a set of precise biochemical and cellular lesions which culminate in cell destruction. A number of potential targets for drug therapy are discussed which will inhibit necrosis, including preservation of cellular ATP by inhibition of poly(ADP‐ribose) polymerase. Such therapies may be useful either as adjuncts to other therapeutic modalities such as immunosuppressive agents for the treatment of inflammatory conditions or on their own for organ preservation prior to organ transplantation. Either excessive apoptosis or failure of apoptosis plays an important role in a variety of gastrointestinal diseases. Failure of apoptosis is of particular importance in the development of colorectal cancer. Mutations or deletions ofp53, bcl‐2andmycprevents the appropriate deletion of malignant cells and causes resistance to anti‐cancer drugs which act by the induction of apoptosis. Correction of these genetic defects or replacement of their function is a major strategy in cancer prevention and therapy. It is concluded that manipulation of cell death processes is an important new area for gastrointestinal research.
new insights into prostaglandins and mucosal defence
Authors: WALLACE J. L. , TIGLEY A. W. 
Published: July 2010

SUMMARYA role for prostaglandins in maintaining mucosal integrity in the gastrointestinal tract is well documented. While traditionally the effects of prostaglandins on mucosal blood flow and epithelial function have been regarded as critical in the mechanism of action of these fatty acids, recent evidence that mucosal ulceration is almost invariably associated with mucosal inflammation has caused a reevaluation of the role of prostaglandins in mucosal defence. This review focuses on the ability of prostaglandins to exert anti‐inflammatory, and therefore anti‐ulcerogenic, effects in the gastrointestinal tract. These effects of prostaglandins are attributable to their ability to suppress the release of inflammatory mediators and reactive oxygen metabolites from a number of immunocytes, stromal cells and inflammatory cells. There is emerging evidence for cooperative interactions between prostaglandins and nitric oxide in maintaining mucosal integrity. Recent work on the inducible isoform of prostaglandin synthase as it pertains to mucosal defence is also reviewed.
osteoporosis, corticosteroids and inflammatory bowel disease
Authors: COMPSTON J. E. 
Published: July 2010

SUMMARYOsteoporosis is a serious complication of inflammatory bowel disease which has not received adequate recognition despite its high prevalence and potentially devastating clinical effects. Its pathogenesis remains poorly defined although corticosteroid therapy and sex hormone deficiency are likely to play a major role.Recent advances in the diagnosis and management of osteoporosis have facilitated early detection of bone loss and identified means by which this may be prevented. Bone density measurements to predict fracture risk and define thresholds for prevention and treatment should be performed routinely in patients with inflammatory disease. Hormone replacement therapy is effective in prevention of bone loss in peri‐ and post‐menopausal patients, but the treatment of younger women and men of all ages requires further study.
Prognostic factors for relapse and maintenance treatment with cisapride in gastro—oesophageal reflux disease
Authors: TYTGAT G. N. J. , BLUM† A. L. , VERLINDEN M. 
Published: July 2010

SUMMARYAim: To perform a further Cox proportional hazards logistic regression analysis of data from two large‐scale placebo‐controlled trials with cisapride as maintenance treatment in reflux disease.Results: Analysis of each of the two databases, allowing the model to operate freely, led to the identification of a number of unexpected putative predictors of outcome in the 6 to 12 months following initial healing of oesophagitis with an H2‐receptor antagonist or omeprazole. This allowed us to delineate more accurately the patient population that is likely to respond to long‐term continuous treatment with low or standard dose cisapride.The analysis revealed that symptom severity may be more useful than endoscopic severity in predicting relapse or in guiding therapy. Reflux oesophagitis outcome is particularly poor in the presence of treatment‐recalcitrant symptoms or severe mucosal damage.Analysis showed cisapride to be effective in the maintenance treatment of patients with non‐refractory symptoms, irrespective of the initial severity of oesophagitis, the healing agent used, or a history of previous endoscopic relapses.
Gastrin releasing peptide and its value in assessing gastric secretory function
Authors: McCOLL K. E. L. , EL‐OMAR E. 
Published: July 2010

SUMMARYGastrin releasing peptide (GRP) has proved to be a particularly valuable tool in detecting disturbances of gastric secretory function associated with duodenal ulcer disease and Helicobacter pylori infection, and it has furthered understanding of the pathophysiology of these conditions. Its attractiveness lies in the fact that it simultaneously activates many physiological control processes, both stimulatory and inhibitory. This facilitates the detection of a defect in any of the many controls involved in regulating biological function. Other gastrointestinal functions such as gall‐bladder contraction, pancreatic secretion and gastrooesophageal motility are also subject to complex regulatory controls, and GRP may also be of value in investigating disturbances of these processes.