bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: alginate‐raft formulations in the treatment of heartburn and acid reflux
Authors: Mandel  , Daggy  , Brodie  , Jacoby  
Published: March 2003

Alginate‐based raft‐forming formulations have been marketed word‐wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate‐based raft‐forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate‐based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH‐neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro‐oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate‐based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents.The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate‐containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate‐based raft‐forming formulations can additionally provide longer‐lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms.Alginate‐based, raft‐forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate‐rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non‐systemic mechanism of action provides rapid and long‐duration relief of heartburn and acid reflux symptoms.
Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study
Authors: Graham  , Osato  , Hoffman  , Opekun  , Anderson  , Kwon  , El‐Zimaity  
Published: March 2003

Background:Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy).Aim:To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States.Methods:Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d.Results:A total of 26 patients were entered into the study; 22 for their first treatment and four as re‐treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78–99%). Both treatment failures reported full compliance to 14 days of therapy. Side‐effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate.Conclusion:Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice‐a‐day combination therapies.
A placebo‐controlled study to assess the effects of 7‐day dosing with 10, 20 and 40 mg rabeprazole on 24‐h intragastric acidity and plasma gastrin in healthy male subjects
Authors: Williams  , Blanshard  , Millson  , Sercombe  , Pounder  
Published: March 2003

Aim:To compare the effects of rabeprazole 10, 20 and 40 mg o.d. on 24‐h intragastric acidity and plasma gastrin concentration in a randomized, double‐blind placebo‐controlled trial.Methods:Twenty‐four healthy male volunteers were studied on the 7th day of morning dosing with either placebo or rabeprazole 10, 20 or 40 mg in a crossover fashion. On day 7, hourly intragastric acidity was measured for 24 h from 08.00 hours by gastric aspiration. Plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, and 2‐hourly thereafter.Results:Compared with placebo, rabeprazole 10, 20 and 40 mg produced significant dose‐related decreases in intragastric acidity (median 24‐h integrated acidity=697, 186, 129 and 82 mmol h/L, respectively). This was associated with significant elevation of plasma gastrin concentration (median 24‐h integrated gastrin=141, 1184, 1484 and 1763 pmol.h/L, respectively). Rabeprazole 40 mg resulted in significantly decreased acidity compared with both 10 and 20 mg, and in longer times for which intragastric pH was maintained at > 3 (19.2 h vs. 17.3 h and 17.5 h) and > 4 (17 h vs. 14.2 h and 15.2 h), but was accompanied by significantly increased plasma gastrin. There was a consistent trend for greater antisecretory activity for 20 mg compared with 10 mg, but these differences did not reach statistical significance. The interindividual variability in antisecretory response was greatest with 10 mg.Conclusions:Rabeprazole 10, 20 and 40 mg produce significant, profound dose‐related inhibition of gastric acid secretion. Taking into account reciprocal increases in plasma gastrin and the interindividual variation in antisecretory response, 20 mg appears to be the preferred dose for routine clinical use.
Effects of interferon‐beta on plasma lipid and lipoprotein composition and post‐heparin lipase activities in patients with chronic hepatitis C
Authors: Andrade  , García‐Escaño  , Valdivielso  , Alcántara  , Sánchez‐Chaparro  , González‐Santos  
Published: March 2003

Background:Interferon therapy has been shown to induce lipid abnormalities.Aim:We assessed the effects of interferon‐β on the lipoprotein profile and post‐heparin lipase activities in 26 normolipaemic patients with chronic hepatitis C.Methods:Interferon‐β was administered subcutaneously at doses of 6 × 106 U (units) three times a week, over 6 months, and lipoproteins and post‐heparin lipases were measured at baseline and at the end of therapy.Results:Plasma triglycerides increased by 21% due to preferential enrichment in those contained in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The concentration of cholesterol decreased slightly in the high density lipoprotein (HDL) subfractions. Lipoprotein lipase, but not hepatic lipase activity decreased by a 36%, and this change showed a significant negative correlation with changes in plasma triglycerides. Five patients (19.5%) responded to interferon‐β therapy. The lipoprotein profile was no different between responders and non‐responders to therapy.Conclusions:Interferon‐β treatment in normolipaemic patients with chronic hepatitis C induced moderate disturbances in plasma lipoproteins, associated with inhibition of lipoprotein lipase activity.
Pantoprazole versus one‐week Helicobacter pylori eradication therapy for the prevention of acute NSAID‐related gastroduodenal damage in elderly subjects
Authors: Pilotto A. , Di Mario F. , Franceschi M. , Leandro G. , Battaglia G. , Germanà B. , Marin R. , Valerio G. 
Published: March 2003

Aim:To compare the efficacy of pantoprazole vs. a one‐week Helicobacter pylori eradication therapy for the prevention of NSAID‐related gastroduodenal damage.Methods:Patients over 60 years old with symptoms and/or a history of ulcer who needed NSAID treatment were evaluated by endoscopy. H. pylori positive subjects who had no severe gastroduodenal lesions were randomized to take, concomitantly with NSAID therapy, either: (i) pantoprazole 40 mg daily plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. for 1 week (35 subjects, Group PAC) or (ii) pantoprazole 40 mg daily for 1 month (34 subjects, Group P). Endoscopy was repeated after 1 month.Results:A significantly higher incidence of severe gastroduodenal damage was found in Group PAC than in Group P (29% vs. 9%, P < 0.05). The percentages of patients worsened, unchanged and improved after 1 month were, respectively: Group PAC: 46%, 46%, and 9% and Group P: 7%, 65%, and 29% (P < 0.0008). The percentage of H. pylori‐negative subjects was 89% in Group PAC and 52% in Group P (P=0.0009). The incidence of gastroduodenal damage was higher in Group PAC treatment failures than in cured patients (50% vs. 25.8%, P=ns).Conclusion:One month of pantoprazole was more effective than a proton pump inhibitor‐based triple therapy in the prevention of gastroduodenal damage in elderly H. pylori‐positive NSAID users.
Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta‐analysis of eradication of Helicobacter pylori
Authors: Gisbert J. P. , González L. , Calvet X. , García N. , López T. , Roqué M. , Gabriel R. , Pajares J. M. 
Published: March 2003

Aim:To perform a meta‐analysis of studies comparing twice daily, one‐week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication.Review methods:Selection criteria: Comparative randomized trials of PCA vs. PCN were included. Data sources: PubMed database and abstracts from congresses until September 1999. Statistics: Meta‐analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention‐to‐treat (ITT) and on a per protocol (PP) basis.Results:Twenty‐two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79–83%) ITT, and 84% (82–86%) PP with PCA, and 81% (78–83%) ITT and 84% (82–86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83–1.22) on an ITT, and 0.98 (0.8–1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78–85%) ITT, vs. 86% (83–89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48–0.98). Finally, when comparing PC(500 b.d.)A against PC(250 b.d.)N ITT cure rates were 77% (74–80%), and 75% (72–78%) with an odds ratio of 1.18 (0.93–1.5).Conclusion:Overall, one‐week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.).
A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease
Authors: Salvatore S. , Heuschkel R. , Tomlin S. , Davies S. E. , Edwards S. , Walker‐Smith J. A. , French I. , Murch S. H. 
Published: March 2003

Background:The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease activity may be effective in treating chronic inflammation.Aim:To report an alternative approach, using the nutriceutical agent N‐acetyl glucosamine (GlcNAc), an amino‐sugar directly incorporated into glycosaminoglycans and glycoproteins, as a substrate for tissue repair mechanisms.Methods:GlcNAc (total daily dose 3–6 g) was administered orally as adjunct therapy to 12 children with severe treatment‐resistant inflammatory bowel disease (10 Crohn’s disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or proctitis resistant to steroids and antibiotics. Where pre‐ and post‐treatment biopsies were available (nine cases), histochemical assessment of epithelial and matrix glycosaminoglycans and GlcNAc residues was made.Findings:Eight of the children given oral GlcNAc showed clear improvement, while four required resection. Of the children with symptomatic Crohn’s stricture, only 3 of 7 have required surgery over a mean follow‐up of > 2.5 years, and endoscopic or radiological improvement was detected in the others. Rectal administration induced remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement, and a significant increase in epithelial and lamina propria glycosaminoglycans and intracellular GlcNAc.Conclusions:GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. It may have the potential to be helpful in stricturing disease. However, controlled trials and an assessment of enteric‐release preparations are required to confirm its efficacy and establish indications for use.
The prevalence of gastro‐oesophageal reflux symptoms in a UK population and the consultation behaviour of patients with these symptoms
Authors: Kennedy T. , Jones R. 
Published: March 2003

Background:Patients consulting with gastro‐oesophageal reflux symptoms (GORS) may differ from nonconsulters.Aim:To describe these differences in a UK population.Methods:A postal questionnaire was sent to 4432 adults. Definitions used were GORS (either heartburn or acid regurgitation on more than six occasions during the previous year), dyspepsia (upper abdominal pain or discomfort on more than six occasions during the previous year) and irritable bowel syndrome (abdominal pain with three or more Manning criteria). Socio‐economic status was identified by the Standard Occupational Classification.Results:With a 71.7% response, GORS were reported by 28.7% of the sample, it was unaffected by gender and age but was more common among the socially disadvantaged (P < 0.005). Less than 25% of GORS patients consulted during the previous year. Increasing age (χ2 for trend; P < 0.001) and coexisting upper abdominal symptoms (χ2P < 0.001) positively influenced consultation behaviour, but it was unaffected by socio‐economic status, gender, or the coexistence of irritable bowel syndrome. Dyspepsia and nausea independently predicted consultation.Conclusions:GORS are especially common among the deprived. Socio‐economic variables do not affect consultation behaviour, but the patient’s age and the burden (number and type) of associated symptoms do.
Review article: healing after inflammatory injury – coordination of a regulatory peptide network
Authors: Podolsky D. K. 
Published: March 2003

SummaryIntestinal epithelial cells are capable of producing a variety of cytokines and other regulatory factors that can affect functional regulation of the epithelium itself, through autocrine and paracrine mechanisms, as well as functional integration with lamina propria populations. The bi‐directional nature of this cytokine network is now apparent, with the demonstration that both rat and human intestinal epithelium‐derived cell lines possess a much greater array of cytokine receptors than previously anticipated.
The roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E2 in rat stomach
Authors: Araki H. , Ukawa H. , Sugawa Y. , Yagi K. , Suzuki K. , Takeuchi K. 
Published: March 2003

Summary Aim: To investigate the EP receptor subtype involved in the gastroprotective action of prostaglandin (PG) E2 using various EP receptor agonists in rats, and using knockout mice lacking EP1 or EP3 receptors. Methods: Male SD rats and C57BL/6 mice were used after an 18‐h fast. Gastric lesions were induced by oral administration of HCl/ethanol (150 m
m HCl in 60% ethanol). Rats were given various EP agonists i.v. 10 min before HCl/ethanol: PGE2, sulprostone (EP1/EP3 agonist), butaprost (EP2 agonist), 17‐phenyl‐ω‐trinorPGE2 (17‐phenylPGE2: EP1 agonist), ONO‐NT012 (EP3 agonist) and 11‐deoxyPGE1 (EP3/EP4 agonist). In a separate study, the effect of PGE2 on HCl/ethanol lesions was examined in EP1‐ and EP3‐receptor knockout mice. Results: Gastric lesions induced by HCl/ethanol were dose dependently prevented by PGE2; this effect was mimicked by sulprostone and 17‐phenylPGE2 and was significantly antagonized by ONO‐AE‐829, an EP1 antagonist. Neither butaprost, ONO‐NT012 nor 11‐deoxyPGE1 exhibited any protective activity against HCl/ethanol‐induced gastric lesions. PGE2 caused an inhibition of gastric motility as well as an increase of mucosal blood flow and mucus secretion, the effects being mimicked by prostanoids activating EP1 receptors, EP2/EP3/EP4 receptors and EP4 receptors, respectively. On the other hand, although HCl/ethanol caused similar damage in both wild‐type mice and knockout mice lacking EP1 or EP3 receptors, the cytoprotective action of PGE2 observed in wild‐type and EP3‐receptor knockout mice totally disappeared in mice lacking EP1 receptors. Conclusion: The gastric cytoprotective action of PGE2 is mediated by activation of EP1 receptors. This effect may be functionally associated with inhibition of gastric motility but not with increased mucosal blood flow or mucus secretion.
Review: pathogenesis of gallstones
Authors: Dowling R. H. 
Published: March 2003

SummaryThe aim of this article is to review selected aspects of the pathogenesis of cholesterol‐rich, gall‐bladder stones (GBS) – with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall‐bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development.In biliary cholesterol secretion, transport and satura‐ tion, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md‐2 gene, and in humans the MDR‐3 gene, encodes for a canalicular protein that acts as a ‘flippase' transporting phospholipids from the inner to the outer hemi‐leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospho‐ lipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have ‘lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation.The precipitation/nucleation of cholesterol micro‐ crystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original ‘nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid‐shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle‐, spiral‐ and tubule‐shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined.There are many situations where GB stasis in humans is associated with an increased risk of gallstone forma‐ tion – including iatrogenic stone formation in acro‐ megalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT‐treated patients all have ‘bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two‐fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT‐induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or ‘synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and ‘normalizes' the percentage of DCA in serum/bile.Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic Gram‐positive an‐ aerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone‐free controls. Together, these changes lead to increased DCA formation, solubilization and absorption. Thus, in addition to the ‘lithogenic liver' and ‘guilty gall‐bladder' one must now add the ‘indolent intestine' to the list of culprits in cholesterol gallstone formation.
Pre‐neoplastic states of the gastric mucosa–a practical approach for the perplexed clinician
Authors: Genta R.M. , Rugge M. 
Published: March 2003

The sequence leading to gastric cancer can be schematically reduced to Helicobacter pylori infection–chronic gastritis–atrophy–intestinal metaplasia–dysplasia–neoplasia. Although clinicians have not yet developed a uniform approach to the treatment of gastritis (when should H. pylori infection be treated?), the entity itself is not the subject of controversy. All other lesions are still the focus of debate. There are no guidelines for the management of patients with intestinal metaplasia; pathologists are still searching for universal diagnostic criteria for atrophic gastritis; dysplasia and early neoplasia have elicited scientific diatribes between Japanese and Western pathologists. Amidst such controversies and in the absence of guidelines to regulate the management of gastric lesions, the responsibility to provide sensible clinical advice is often bestowed upon pathologists.This review discusses whether pathologists have access to sufficient evidence to provide the requested advice, and whether a consensus on the management of gastric ‘pre‐neoplastic’ states is within reach. We conclude that, although many sensible and useful definitions, criteria and classifications are being generated, the final decision on how to manage the individual patient with gastric lesions will continue to be based on the communication between pathologist and clinician.