bluuebunny/crossref_metadata_2025_split huggingface dataset:
H‐89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes
Authors: Pearman Charles , Kent William , Bracken Nicolas , Hussain Munir 
Published: June 2006

Voltage clamp was used to investigate the effects of N‐[2‐p‐bromo‐cinnamylamino)ethyl]‐5‐isoquinolinesulfonamide (H‐89), a potent inhibitor of PKA, on transient outward K+ current (Ito) and inward rectifying K+ current (IK1) in rat cardiac muscle.
Initial experiments, performed using descending voltage ramps, showed that H‐89 inhibited both the outward and inward ramp currents in a concentration‐dependent manner at concentrations between 5 and 60 μmol l−1. A similar degree of inhibition was observed when Ito and IK1 were recorded using square wave depolarising and hyperpolarising voltage steps, respectively.
The IC50 was 35.8 μmol l−1 for Ito and 27.8 μmol l−1 for IK1 compared to 5.4 μmol l−1 for L‐type Ca2+ current (ICa). The Hill coefficients for Ito, IK1 and ICa were −1.97, −1.60 and −1.21, respectively. In addition to inhibiting Ito amplitude, H‐89 also accelerated the time to peak and the rate of voltage‐dependent inactivation so that the time course of Ito was abbreviated.
Paired‐pulse protocols were performed to study the effects of H‐89 on steady‐state activation and inactivation as well as recovery from voltage‐dependent inactivation. H‐89 produced a concentration‐dependent rightward shift in voltage‐dependent activation but had no significant effect on steady‐state inactivation. Recovery from voltage‐dependent inactivation was delayed, although this was only visible at the highest concentration (60 μmol l−1) used.
In experiments investigating the effects of elevated cyclic AMP, the β‐adrenergic agonist isoprenaline and the phosphatase inhibitor calyculin A had no major effects on Ito or IK1.
Data suggest that the effects of H‐89 on K+ currents are more complex than simple inhibition of PKA‐mediated phosphorylation.

British Journal of Pharmacology (2006) 148, 1091–1098. doi:10.1038/sj.bjp.0706810
The political contradictions of Algerian economic reforms
Authors: Addi Lahouari 
Published: June 2006

From the outset, independent Algeria's political economy was marked by a paradox, for which it is still, today, paying the price. In 1962, the State, which is essentially public, was privatised, while commercial activities, which are essentially private, were made public. That was the time when revolutionary elites in the Third World thought that faith alone was enough to develop the country, using the State but without setting up the institutions guaranteeing free expression for the social groups organised as parties, trade unions, vested interests in order to participate in the political process. In the Boumedienne-Abdeslam period (1965-1978), the economic sector of the State was expected to absorb all commercial activities, from the large-scale steel industry down to the small local bakery, preventing the different social groups from enjoying any economic autonomy. Nor were they expected to make any claims on the political order. The State had set itself the task of satisfying all social needs through the so-called public sector whose vocation was not to make any profits, but to serve the public and, as a priority, the most destitute among the population.
Cet article traite des réformes économiques en Algérie, à l'ordre du jour depuis les années 1980, non encore réalisées malgré les discours des gouvernements successifs. Visant formellement à opérer la transition de l'économie administrée vers l'économie de marché, ces réformes se heurtent à la nature autoritaire du régime dans lequel des clans puissants utilisent les institutions de l'Etat pour s'enrichir. Ils s'opposent à la concurrence et à la mise en place d'un capitalisme manufacturier productif, préférant la spéculation et le commerce comme seuls modes d'accumulation.
Par ailleurs, l'Etat refuse toujours de se débarrasser du secteur économique public déficitaire, craignant de faire exploser les chiffres déjà élevés du chômage. Il préfère continuer à financer les déficits des entreprises sous sa tutelle et à distribuer des salaires vidés de leur pouvoir d'achat par des dévaluations massives, tout en interdisant la liberté syndicale pour empêcher les travailleurs de s'opposer aux effets de ces dévaluations.
L'embellie financière, suite à l'augmentation spectaculaire des prix mondiaux des hydrocarbures à partir de 1999, n'est pas mise à profit pour augmenter les capacités productives du marché national. Un programme de reconstruction a été lancé, certes nécessaire, mais rien n'a été prévu pour encourager la production. Au lieu d'exploiter les formidables ressources financières pour modifier le caractère rentier de l'économie, le gouvernement a opté pour une politique distributive qui allège momentanément les effets du chômage et qui permet à une couche privilégiée de s'approprier une part importante de la rente énergétique.
Systematic review: the safety and tolerability of pharmacological agents for treatment of irritable bowel syndrome – a European perspective
Authors: HEADING R. , BARDHAN K. , HOLLERBACH S. , LANAS A. , FISHER G. 
Published: June 2006

SummaryAimTo use an evidence‐based approach to evaluate the safety and tolerability of the treatments available for irritable bowel syndrome (IBS), or in clinical development, in Europe. A separate review appraises the evidence for the efficacy of these therapies.MethodsA literature search (for 1980 to 2005) was completed for all relevant clinical trial data and other articles which included safety information on the use of pharmacological IBS therapies. Clinical trials were scored according to the level of safety information, and adverse event incidence reported when possible.ResultsThe tolerability of many of the agents used to treat IBS in Europe is poorly understood. However, serotonergic agents, such as tegaserod and alosetron, which are currently unavailable in Europe, have undergone rigorous assessment in IBS and their benefits have been established. Following initial marketing of alosetron for use in patients with IBS with diarrhoea, concerns about severe constipation and ischaemic colitis resulted in restriction of its use to women with severe IBS symptoms. This highlights the importance of post‐marketing surveillance and post‐marketing studies in refining the therapeutic indication of new IBS therapies, which will help to identify appropriate recipients for the drug and establish the impact of adverse reactions in clinical practice.ConclusionsThere is a significant lack of data on the safety and tolerability of the therapies currently used routinely to treat IBS in Europe. The newer agents have undergone rigorous assessment, such that their benefits and risks in treating IBS are established. Defining their place among the spectrum of available therapies remains challenging when the benefits and risks of the older treatments are so poorly characterized.
Systematic review: the efficacy of treatments for irritable bowel syndrome – a European perspective
Authors: TACK J. , FRIED M. , HOUGHTON L. A. , SPICAK J. , FISHER G. 
Published: June 2006

SummaryBackgroundIrritable bowel syndrome (IBS) is a common, chronic disorder, characterized by abdominal pain/discomfort, bloating and altered bowel habit.AimTo conduct a systematic evidence‐based review of pharmacological therapies currently used, or in clinical development, for the treatment of IBS in Europe. The safety and tolerability of these therapies are the subject of an accompanying review.MethodsA literature search was completed for randomized controlled studies which included adult patients with IBS and an active or placebo control, assessed IBS symptoms, and were published in English between January 1980 and June 2005. The level of evidence for efficacy was graded according to the quality of the trial design and the study outcome.ResultsThere is some evidence for improvement of individual IBS symptoms with antidiarrhoeals (diarrhoea), antispasmodics (abdominal pain/discomfort), bulking agents (constipation), tricyclic antidepressants (abdominal pain/discomfort) and behavioural therapy. In contrast, there is strong evidence for the improvement of global IBS symptoms with two new serotonergic agents: the 5‐HT4 selective agonist tegaserod (IBS with constipation) and the 5‐HT3 antagonist alosetron (IBS with diarrhoea). Further data are required for the 5‐HT3 antagonist, cilansetron, and the mixed 5‐HT3antagonist/5‐HT4 agonist renzapride before their utility in IBS can be appraised.ConclusionsThere is limited evidence for the efficacy, safety and tolerability of therapies currently available in Europe for the treatment of IBS. Overall, there is an absence of pharmacological agents licensed specifically for the treatment of IBS subtypes, and new agents are awaited in Europe that will allow changes in clinical practice to focus on and improve global IBS symptoms.
Significance of Rome II‐defined functional constipation in Taiwan and comparison with constipation‐predominant irritable bowel syndrome
Authors: LU C.‐L. , CHANG F.‐Y. , CHEN C.‐Y. , LUO J.‐C. , LEE S.‐D. 
Published: June 2006

Summary>BackgroundThe epidemiology and impact of functional constipation on Asians remain unclear.>AimTo determine the prevalence of functional constipation, its social/medical impact, and its distinction from constipation‐predominant irritable bowel syndrome (C‐IBS) in Taiwan.>MethodsA Rome II questionnaire was administered to an apparently healthy adult Chinese population (n = 2865).>ResultsThe prevalence of functional constipation was 8.5% and it was 2.7% for C‐IBS. The functional constipation subjects were predominantly female and had excessive gastrointestinal‐related doctor visits, absenteeism and sleep disturbance compared with controls (P < 0.01). Among functional constipation subjects, approximately 40% were ‘consulters’ with excessive doctor consultations, absenteeism and sleep disturbance. Female gender, the presence of sleep difficulty and higher constipation symptom scores were predictive of their consultation behaviour (P < 0.05). No differences existed in demographic variables, doctor consultations and absenteeism between 172 functional constipation and 54 C‐IBS subjects. However, the C‐IBS subjects experienced more severe constipation symptoms and sleep disturbance than functional constipation subjects.>ConclusionsFunctional constipation in Taiwan is comparable with that in other countries. The clinical presentation of constipation‐predominant irritable bowel syndrome differ somewhat from that of functional constipation.
Meta‐analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma
Authors: BJELAKOVIC G. , NAGORNI A. , NIKOLOVA D. , SIMONETTI R. G. , BJELAKOVIC M. , GLUUD C. 
Published: June 2006

SummaryBackgroundColorectal cancer may be prevented by reducing the development of adenomatous polyps.AimTo assess the benefits and harms of antioxidant supplements in preventing colorectal adenoma.MethodsUsing the Cochrane Collaboration methodology we reviewed all randomized clinical trials comparing antioxidant supplements with placebo or no intervention. We searched electronic databases and the reference lists until October 2005. Outcome measures were development of colorectal adenoma adverse events. We analysed dichotomous outcomes with fixed‐ and random‐effects model meta‐analyses and calculated the relative risk with 95% confidence interval.ResultsWe identified eight randomized trials (17 620 participants). Neither fixed‐effect (relative risk: 0.93, 95% CI: 0.81–1.1) nor random‐effect model meta‐analyses (0.82, 0.60–1.1) showed statistically significant effects of supplementation with β‐carotene, vitamins A, C, E and selenium alone or in combination. Antioxidant supplements seemed to increase the development of colorectal adenoma in three low‐bias risk trials (1.2, 0.99–1.4) and significantly decrease its development in five high‐bias risk trials (0.59, 0.47–0.74). The estimates difference is significant (P < 0.0001). There was no significant difference between the intervention groups regarding adverse events, including mortality (0.82, 0.47–1.4).ConclusionWe found no convincing evidence that antioxidant supplements have significant beneficial effect on primary or secondary prevention of colorectal adenoma.
Systematic review: sphincter of Oddi dysfunction – non‐invasive diagnostic methods and long‐term outcome after endoscopic sphincterotomy
Authors: SGOUROS S. N. , PEREIRA S. P. 
Published: June 2006

SummaryBackgroundSphincter of Oddi dysfunction is a benign, functional gastrointestinal disorder for which invasive endoscopic therapy with potential complications is often recommended.AimsTo review the available evidence regarding the diagnostic accuracy of non‐invasive methods that have been used to establish the diagnosis and to estimate the long‐term outcome after endoscopic sphincterotomy.MethodsA systematic review of English language articles and abstracts containing relevant terms was performed.ResultsNon‐invasive diagnostic methods are limited by their low sensitivity and specificity, especially in patients with Type III sphincter of Oddi dysfunction. Secretin‐stimulated magnetic resonance cholangiopancreatography appears to be useful in excluding other potential causes of symptoms, and morphine‐provocated hepatobiliary scintigraphy also warrants further study. Approximately 85%, 69% and 37%, of patients with biliary Types I, II and III sphincter of Oddi dysfunction, respectively, experience sustained benefit after endoscopic sphincterotomy. In pancreatic sphincter of Oddi dysfunction, approximately 75% of patients report symptomatic improvement after pancreatic sphincterotomy, but the studies have been non‐controlled and heterogeneous.ConclusionsPatients with suspected sphincter of Oddi dysfunction, particularly those with biliary Type III, should be carefully evaluated before considering sphincter of Oddi manometry and endoscopic sphincterotomy. Further controlled trials are needed to justify the invasive management of patients with biliary Type III and pancreatic sphincter of Oddi dysfunction.
Early treatment with ursodeoxycholic acid for cholestasis in children on parenteral nutrition because of primary intestinal failure
Authors: DE MARCO G. , SORDINO D. , BRUZZESE E. , DI CARO S. , MAMBRETTI D. , TRAMONTANO A. , COLOMBO C. , SIMONI P. , GUARINO A. 
Published: June 2006

SummaryBackgroundThere is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition‐associated cholestasis.AimTo investigate the efficacy of UDCA on parenteral nutrition‐associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes.MethodsChildren with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition‐associated cholestasis was evaluated at 6 months of therapy and at the last follow‐up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal.ResultsTwelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition‐associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment.ConclusionsUrsodeoxycholic acid was effective in controlling parenteral nutrition‐associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.
Prospective assessment of the impact of feedback on colonoscopy performance
Authors: HAREWOOD G. C. , PETERSEN B. T. , OTT B. J. 
Published: June 2006

SummaryBackgroundColonoscopy is an operator‐dependent procedure. The medical literature describes disparity in colonoscopy performance with respect to polyp detection, caecal intubation rates and procedural times.AimTo assess prospectively the impact of feedback among a large cohort of colonoscopists on three performance parameters: caecal intubation rate, insertion time and withdrawal time.MethodIn a prospective clinical study, procedural data from all out‐patient colonoscopies performed by attending gastroenterologists at our institution were recorded routinely in a computerized database. Enhanced serial feedback was provided on a quarterly basis for three procedure parameters: intubation to caecum, insertion time and withdrawal time. Feedback (absolute value, % rank and group distribution) was sent by email every 3 months beginning with January 2005 feedback for all of 2004, and subsequently quarterly in April 2005 (for January–March 2005), July 2005 (for April–June 2005) and October 2005 (for July–September 2005).ResultsFeedback was provided to 58 endoscopists with a median experience level of 8 years. There was a relative decline of 19% in incomplete procedures, with median caecal non‐intubation rates decreasing from 4.7% to 3.8% following the introduction of feedback while median insertion times declined from 10.6 to 9.5 mins, P = 0.02. Median withdrawal times did not change significantly, 9.1–8.9 mins, P = 0.6.ConclusionsFeedback by email appears to improve colonoscopy performance, enhancing completion rates and shortening insertion times without compromising withdrawal times.
Papillotomy Performance Scoring Scale – a pilot validation study focused on the cut axis
Authors: LEUNG J. W. , LEUNG F. W. 
Published: June 2006

SummaryBackgroundNo published Papillotomy Performance Scoring Scale exists.AimsTo develop such a scale and to apply it to stratify the quality of performance of recorded papillotomies.MethodExpert biliary endoscopists were polled regarding their opinion of a ‘perfect’ biliary papillotomy and experience with complications in relation to the cut axis. Based on these responses a scoring scale encompassing two components – wire alignment and cut orientation, was proposed. This scoring scale was presented to experienced and trainee endoscopists, who scored recording of five biliary papillotomies. The mean final combined score was used for stratification.ResultsThe experts’ opinion of a ‘perfect’ biliary papillotomy is one cut along the axis of the distal bile duct and papilla. Their reported experience with complications occurring outside of the perfect axis validated their consensus. Application of the scoring scale stratified recorded papillotomies based on the mean final combined scores.ConclusionsThese pilot data support the hypothesis that a scoring scale focused on the cut axis can be constructed based on expert opinion, experience and consensus. The possibility of stratification of mean final combined scores that are significantly different validates application of the scoring scale for assessment of papillotomy performance.
Healthcare seeking for constipation: a population‐based survey in the Mediterranean area of Spain
Authors: GÁLVEZ C. , GARRIGUES V. , ORTIZ V. , PONCE M. , NOS P. , PONCE J. 
Published: June 2006

SummaryBackgroundThe use of healthcare resources for the management of constipation is not well‐known.AimTo analyse healthcare seeking for constipation, defined by three different criteria, and its related factors and to assess the frequency of use of laxatives, suppositories and enemas for the treatment of constipation.MethodsA cross‐sectional study in the general community. A questionnaire comprising 21‐items was developed and delivered by mail to a random sample of 506 subjects aged 18–65 years, and belonging to a Spanish population.ResultsSeeking of health care was high in the sample (16%) and was similar for all definitions of constipation (over 40% of constipated subjects). It was associated with female gender, a higher educational level and two symptoms, such as prolonged defecation and abdominal pain. A 14% of the sample used laxatives, and about a 25% of constipated subjects used laxatives at least once a week. Utilization was more frequent in women, with no differences by age group.ConclusionsChronic constipation is a problem that causes an important consumption of resources in our setting, derived from laxative use and the seeking of medical help to combat the problem. The use of these resources is higher in women.
Persistence and adherence to proton pump inhibitors in daily clinical practice
Authors: VAN SOEST E. M. , SIERSEMA P. D. , DIELEMAN J. P. , STURKENBOOM M. C. J. M. , KUIPERS E. J. 
Published: June 2006

SummaryBackgroundProton pump inhibitors are widely used, but little is known about the usage pattern in different indications.AimTo analyse proton pump inhibitor usage patterns in the general population.MethodsA cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis.ResultsOne‐year persistence was 31% in patients using proton pump inhibitors for gastro‐oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non‐reflux dyspepsia or Helicobacter pylori‐associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent.ConclusionsA substantial proportion of patients with indications not requiring long‐term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on‐demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus.
Predictors of treatment response in patients with non‐erosive reflux disease
Authors: TALLEY N. J. , ARMSTRONG D. , JUNGHARD O. , WIKLUND I. 
Published: June 2006

SummaryBackgroundUp to 40% of patients with non‐erosive reflux disease (NERD) fail to respond to proton pump inhibitor therapy.AimTo determine useful prognostic factors for response to and suppression in NERD.MethodsA pooled analysis from three multicentre, double‐blind trials of patients with a normal endoscopy and heartburn for 4 days or more during the 7 days prior to the start of each treatment. Patients received omeprazole 20 mg, esomeprazole 20 mg or esomeprazole 40 mg/day for 4 weeks. Complete resolution of heartburn was defined as no heartburn during the last week.ResultsOf 2458 patients included, complete heartburn resolution was achieved in 63% at the end of 4 weeks treatment. Response on days 5–7 provided an 85% probability of complete resolution of heartburn at 4 weeks; the probability of complete heartburn resolution at 4 weeks in those with moderate to severe symptoms on days 5–7 was 22%. Sensitivity and specificity of no heartburn on days 5–7 was 55% and 83% respectively. Patient demographics, duration of symptoms, medications used, other symptoms and body mass index were not predictors.ConclusionAssessment of heartburn resolution during the first week of therapy was the best predictor of treatment success at 4 weeks in non‐erosive reflux disease, but was suboptimal as a test.