bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: esomeprazole − the first proton pump inhibitor to be developed as an isomer
Authors: Kendall M. J. 
Published: March 2003

SummaryOmeprazole is a racemate, from which the R‐ and S‐isomers can be isolated. At the cellular level, both of these isomers convert to the same inhibitor of the H+,K+‐ATPase and produce the same reduction in gastric acid secretion. However, the S‐isomer, esomeprazole, is metabolized more slowly and reproducibly than the R‐isomer and omeprazole, and therefore produces higher plasma concentrations for longer and, as a result, inhibits gastric acid production more effectively and for longer. Thus, esomeprazole has the pharmacological properties of a more effective form of treatment for disorders related to gastric acid secretion. Clinical studies have confirmed the anticipated increased efficacy, but have shown no evidence of impaired tolerability or increased toxicity when compared with omeprazole.
The management of acid‐related dyspepsia in general practice: a comparison of an omeprazole versus an antacid‐alginate/ranitidine management strategy
Authors: Mason  , Millar  , Sheikh  , Evans  , Todd  , Turbitt  , Taylor  
Published: March 2003

Background:There is need for an evidence‐based comparison of clinical management strategies to provide the rationale for selection of a particular therapeutic approach to treatment. Ideal dyspepsia treatment should quickly and conveniently alleviate patient symptoms whilst also minimizing the use of healthcare resources.Aim:To examine dyspepsia symptom relief over 16 weeks and compare an omeprazole clinical management strategy with a commonly used combination of antacid–alginate followed by H2‐antagonist.Methods:Seven hundred and twenty‐five patients participated in this randomized, open, parallel group comparison over 16 weeks. Patients were randomized to receive either an omeprazole treatment strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as required, or an antacid–alginate/ranitidine treatment strategy (362) consisting of antacid–alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg q.d.s. as required.Results:A greater proportion of patients receiving the omeprazole clinical management strategy had achieved the stringent health target of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty‐six per cent of omeprazole‐treated patients were symptom free after the first 10 mg step compared to only 17% in the antacid–alginate treated group (P = 0.0001). Total relief of heartburn, the most common symptom at entry, was achieved by more patients in the omeprazole treatment group than the antacid–alginate/ranitidine treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks (P = 0.0001).Conclusion:Treatment with the omeprazole clinical management strategy was superior to the antacid–alginate/ranitidine management strategy in providing relief of acid‐related dyspepsia symptoms after 16 weeks. In addition, the omeprazole treatment strategy involved fewer GP consultations and thus minimized the use of other healthcare resources.
Nitric oxide and gall‐bladder motor function
Authors: Luman  , Ardill  , Armstrong  , Smith  , Brett  , Lessells  , Haynes  , Gray  , Mickley  , Webb  , Palmer  
Published: March 2003

Background:The L‐arginine: nitric oxide (NO) pathway has been shown to be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission.Aim:To determine the role of the L‐arginine: NO pathway in gall‐bladder motor function.Methods:Strips of fresh bovine and human gall‐bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb’s solution upon CCK‐stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L‐NG‐monomethyl‐arginine (L‐NMMA) upon basal muscle tone was also examined. Ten human gall‐bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall‐bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L‐NMMA.Results:In the in vitro study, GTN and SNP significantly reduced the tension of CCK‐stimulated muscle contraction whilst Kreb’s solution had no effect. L‐NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall‐bladders. In the in vivo study, both GTN and SNP caused significant impairment of gall‐bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L‐NMMA.Conclusion:Pharmacological doses of NO donors impair postprandial gall‐bladder emptying in vivo and relax gall‐bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall‐bladder motility.
Treatment of Helicobacter pylori infection in infants in rural Bangladesh with oral immunoglobulins from hyperimmune bovine colostrum
Authors: Casswall  , Sarker  , Albert  , Fuchs  , Bergström  , Björck  , Hammarström  
Published: March 2003

Background:Antibodies from hyperimmune bovine colostrum have been shown to be effective in treatment against a variety of microorganisms, including Helicobacter pylori in adults.Aim:To test this form of treatment in a small group of H. pylori infected children in a periurban community in Bangladesh.Methods:Twenty‐four infants, 4–29 months old (mean age 16.5 ± 7.7 months) and infected with H. pylori, were treated with purified immunoglobulins from hyperimmune bovine colostrum for 1 month, in a placebo‐controlled, double‐blind pilot study. Diagnosis was established with 13C‐urea breath test (UBT) before and after the treatment period and at a 1‐month follow‐up.Results:None of the hyperimmune bovine colostrum‐treated children became UBT negative. Five children initially positive in the UBT screening spontaneously became negative by the start of the study with hyperimmune bovine colostrum/placebo. At the end of the 1‐month study period, three had became positive again.Conclusion:Hyperimmune bovine colostrum does not eradicate H. pylori infection in infants. Transient H. pylori infection is common among infants in high endemic areas, as is reinfection after clearance. This presents obstacles to evaluation of therapeutic investigations in young children in areas where H. pylori is prevalent.
The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients
Authors: Ottesen  , Flyvbjerg  , Møller  , Bendtsen  
Published: March 2003

Background:Intravenous octreotide is an established treatment of oesophageal variceal haemorrhage in the cirrhotic patient.Aim:To examine the organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients with portal hypertension.Methods:Thirteen patients with cirrhosis had hepatic venous catheterization performed. Hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and hepatic blood flow (HBF) were determined in the basal state and during 60 min of octreotide infusion by bolus injection (0.75 μg/kg) followed by continuous infusion of 0.75 μg/kg.h. Blood samples were simultaneously drawn from the femoral artery and the hepatic and renal veins.Results:The extraction fraction of octreotide in the liver was 0.05 (− 0.01–0.14) (median (interquartile range)) and in the kidneys 0.16 (− 0.06–0.35). The extraction fraction ratio (Eliver/Ekidney) was 0.69 (− 0.20–1.06). Hepatic clearance was 47 mL/min (3–88) (n = 11). No correlations were found between liver biochemistry or galactose elimination capacity (GEC; a metabolic measure of liver function) and renal extraction fraction or liver clearance. Octreotide had no effect on HVPG or wedged hepatic venous pressure although free hepatic venous pressure increased during octreotide infusion: 6 mmHg (5–9) vs. 7 mmHg (6–10) (P = 0.02). No effect on HBF was observed while ICG clearance decreased significantly.Conclusions:Octreotide is extracted in cirrhotic patients by both the liver and the kidney, the latter being the most important organ of elimination. Octreotide decreases liver metabolic activity determined by the ICG clearance technique, but no significant effects of octreotide on HVPG or HBF could be demonstrated.
Variation in taste of topical lignocaine anaesthesia for gastroscopy
Authors: Asante  , Northfield  
Published: March 2003

Aim:To study the distribution and determinants of taste variation for lignocaine spray (Xylocaine; Astra Pharmaceuticals, King’s Langley, UK).Methods:Sixty‐nine patients (male:female 49:20, mean age 48.5 years) attending for open access upper gastrointestinal endoscopy were studied. Taste perceived after applying 4 doses (40 mg) of lignocaine spray to the oro‐pharynx was recorded prior to endoscopy.Results:37/69 (54%, 95% CI: 41–66%) perceived the taste of the lignocaine spray as bitter, whilst 24/69 (35%, 95% CI: 24–47%) and 6/69 (9%, 95% CI: 3–18%) perceived the taste as either fruity/sweet or tasteless. The variation in taste did not correlate with either demographic features or H. pylori infection, but duodenal ulceration was slightly more common amongst bitter tasters.Conclusion:The taste of lignocaine is not uniform, but the basis of this variability is uncertain.
Relationship between fundic endocrine cells and gastric acid secretion in hypersecretory duodenal ulcer diseases
Authors: Annibale  , Aprile  , Ferraro  , Marignani  , Angeletti  , D′ambra  , Caruana  , Bordi  , Fave G. Delle 
Published: March 2003

Background:Acid hypersecretion is associated with duodenal ulcer disease in the following conditions: Zollinger–Ellison syndrome (ZES) and antral gastrin cell hyperfunction (AGCH) due to hypergastrinaemia, or hypersecretory duodenal ulcer (HDU) without hypergastrinaemia.Aim:To evaluate whether quantitative changes in fundic ECL and D cells may be involved in acid hypersecretion.Patients and Methods:Seven ZES, six AGCH and six HDU Helicobacter pylori‐positive patients were compared. Basal (BAO) and pentagastrin‐stimulated gastric acid secretions (PAO), and morphometry of fundic ECL and D cells were performed. The six AGCH and six HDU patients were investigated again using the same tests 1 year after H. pylori eradication.Results:Median PAO values were no different in all the hypersecretory conditions studied. The median volume density of ECL cells in ZES was significantly higher than in controls (2.75, range 1.74–5.8 vs. 0.73, 0.52–1.11; P < 0.05), whereas it was in the control range in AGCH and HDU patients (0.77, range 0.20–1.39 and 0.99, range 0.42–1.51; respectively). The count of fundic D cells was significantly lower in AGCH patients than in all other investigated groups (median 0.16, range 0.1–0.52; P < 0.05). Cure of infection in AGCH and HDU patients did not modify the ECL cell volume density, whereas a significant increase in the count of fundic D cells was observed in AGCH patients. Thus, the ECL/D cell index was significantly affected in AGCH patients (P < 0.05), being higher during H. pylori infection (median 6, range 0.7–9.25) than after the cure (median 2.12, range 1.10–3.5). BAO and PAO were not affected by H. pylori eradication in either group.Conclusions:The study provides evidence, for the first time, that quantitative alterations in the fundic endocrine cells are not involved in acid hypersecretion of patients with hypersecretory states, and that eradication of H. pylori does not restore normal acid secretion values.
Estimating the cost of lost productivity in dyspepsia
Authors: Severens J. L. , Laheij R. J. F. , Jansen J. B. M. J. , Lisdonk E. H. Van Der , Verbeek A. L. M. 
Published: March 2003

Background:In the field of gastrointestinal disease, productivity costs are highly relevant because work loss is substantial in dyspeptic patients. Productivity costs are normally calculated by multiplying days absent valued by gross earnings. This, however, might lead to an overestimation.Aim:To use a conservative approach to calculating productivity costs, taking absence compensating mechanisms into account.Methods:Patients who visited their general practitioner for the first time with dyspeptic complaints and patients who were known to have persistent dyspeptic complaints were enrolled in two studies. In total, 136 patients completed a questionnaire about their employment situation, absence from work and absence compensating mechanisms.Results:Sixty‐six of the respondents had a paid job, of which 25 (38%) reported absence from work during the previous 4 weeks (average 3.0 days, 1.9 days related to dyspeptic complaints). More than 50% of the employed respondents answered that absence could be compensated for by colleagues, and only in 8% of the cases was absence compensated for by overtime. Using our conservative approach, only one‐quarter of the productivity costs remained, compared to the current approach of valuing each day absent as a loss of productivity.Conclusions:We suggest using both the current and the conservative approaches, analogous to the principles of sensitivity analysis, to avoid overestimation of productivity costs.
Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine
Authors: Sinha L. , Liston R. , Testa H. J. , Moriarty K. J. 
Published: March 2003

Background:Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition.Aim:To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine.Method:Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed.Results:Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3–12.6). Their median daily faecal weight was 285 g (range 85–676) and median faecal fat output was 17 mmol/24 h (range 8.3–38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre‐treatment 5/day vs. 2/day post‐treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea.Conclusions:Idiopathic bile acid malabsorption, once suspected, especially by documenting true ‘large volume’ watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.
Short‐ and long‐term outcome of patients treated with cyclosporin for severe acute ulcerative colitis
Authors: Stack  , Long  , Hawkey  
Published: March 2003

Background:Recent evidence suggests that the immunosuppressive drug cyclosporin may be of benefit in treating patients with severe colitis who are steroid resistant. Although cyclosporin appears to be effective in reducing colectomy rates in the short term, few data are available on the long‐term follow‐up of such patients.Aim:To investigate the short‐ and long‐term outcome of patients with severe steroid‐resistant ulcerative colitis treated with cyclosporin who were otherwise being considered for colectomy.Methods:Twenty‐two patients with severe steroid‐resistant exacerbations of ulcerative colitis who were being considered for colectomy were treated with cyclosporin (4 mg/kg i.v.) daily for 7 days followed by oral treatment (6 mg/kg/day) if colectomy was avoided.Results:Twenty of 22 patients (91%) avoided colectomy during their initial hospital admission. With a mean follow‐up period of 39 months (range 31–59), eight of these patients have subsequently relapsed and required colectomy and 12 patients have avoided colectomy (53%). Of the 12 patients avoiding colectomy, seven have successfully been weaned on to azathioprine while five are maintained on an aminosalicylate alone. None of these long‐term responders require maintenance corticosteroids. The main side‐effects during treatment with cyclosporin were headaches (six patients, 27%), paraesthesia and tremors (four patients, 18%) and hypertension (four patients, 18%). Two patients developed renal impairment on cyclosporin which resolved on lowering the dose. In no case was cyclosporin discontinued because of an adverse reaction. No clinical or laboratory features could be identified that predicted which patients treated with cyclosporin would later require colectomy.Conclusion:This study shows that cyclosporin is a viable alternative to emergency colectomy in severe ulcerative colitis in the short term. Although these benefits are not maintained in all patients, more than half were found to avoid colectomy in the longer term.
First line treatment with omeprazole provides an effective and superior alternative strategy in the management of dyspepsia compared to antacid/alginate liquid: a multicentre study in general practice
Authors: Goves  , Oldring  , Kerr  , Dallara  , Roffe  , Powell  , Taylor  
Published: March 2003

BackgroundMany patients who present with dyspepsia are prescribed antacid/alginates as their first line and often mainstay therapy. This multicentre study was designed to assess whether early introduction of acid inhibition is an effective strategy in dyspepsia management.MethodsDyspeptic patients (n = 674) were randomized to receive either omeprazole 10 mg o.m. or antacid/alginate liquid 10 mL q.d.s. for 4 weeks in an open, parallel group study.ResultsComplete relief of the most common symptom at entry, heartburn, was greater in the omeprazole‐treated group compared with the antacid/alginate‐treated group (64 vs. 30%, respectively, at 4 weeks; P < 0.0001). The percentage of patients who met the stringent health target of complete relief of overall symptoms was higher in the omeprazole‐treated group (41% at 4 weeks) compared with the antacid/alginate group (16% at 4 weeks; P < 0.0001). Comparisons of quality of life scores between treatments favoured the omeprazole group at 2 and 4 weeks for both the Psychological General Well‐Being Index and the Gastrointestinal Symptom Rating Scale (each P ≤ 0.0009). In addition, a greater proportion of patients rated omeprazole to be more effective in symptom relief and more convenient to use (each P = 0.0001) than antacid/alginate.ConclusionThis study demonstrates that, compared to antacid/alginate liquid 10 mL q.d.s., omeprazole 10 mg o.m. is more effective in the management of dyspepsia symptoms and is the patients’ preferred treatment.
The monoethylglycinexylidide test for grading of liver cirrhosis
Authors: FABRIS  , JEMMOLO  , TOFFOLO  , PALEARI  , VIAGGI  , RIGON  , CASAGRANDE  , LIRUSSI  , STRAZZABOSCO  , COBELLI  , OKOLICSANYI  
Published: March 2003

Background:Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration.Aim:To determine the optimal sampling time for MEGX determination.Methods:A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score).Results:Only the MEGX fractional formation rate (kf) and formation delay (τ) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 ± 0.03 vs. 0.32 ± 0.10 min−1 (mean ± s.d.); τ = 7.7 ± 2.0 vs. 3.9 ± 2.9 min−1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method.Conclusion:The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.
Ranitidine bismuth citrate, tetracycline, clarithromycin twice‐a‐day triple therapy for clarithromycin susceptible Helicobacter pylori infection
Authors: Graham  , Hoffman  , Anderson  , Qureshi  , Osato  , El‐Zimaity  
Published: March 2003

Background:Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success.Aim:To investigate the role of the new soluble form of bismuth, ranitidine bismuth citrate, in twice‐a‐day therapy for Helicobacter pylori infection.Methods:Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients).Results:Sixty‐three patients completed the therapy, 59 men and four women (average age 56.7 years; range 31–75 years). All patients had clarithromycin‐susceptible strains prior to therapy. H. pylori infection was cured in 94% (95% CI: 85–98%). There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side‐effects. Three of the isolates from treatment failures were available post‐failure; two were clarithromycin‐resistant and one was susceptible. Side‐effects were severe in two patients (3%) and moderate in three (primarily diarrhoea).Conclusions:Twice‐a‐day ranitidine bismuth citrate, tetracycline, clarithromycin triple therapy was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin‐susceptible H. pylori.