bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trial: randomized controlled study of zidovudine and lamivudine for patients with primary biliary cirrhosis stabilized on ursodiol
Authors: MASON A. L. , LINDOR K. D. , BACON B. R. , VINCENT C. , NEUBERGER J. M. , WASILENKO S. T. 
Published: September 2008

SummaryBackground  A human betaretrovirus has been characterized from patients with primary biliary cirrhosis (PBC). Uncontrolled studies using combination anti‐retroviral therapy have reported significant biochemical and histological improvement.Aim  To conduct a double‐blind, randomized controlled trial as a proof of principal to link infection with PBC.Methods  Fifty‐nine patients with an alkaline phosphatase level >1.5 upper limits of normal stabilized on ursodeoxycholic acid therapy were randomized to either 300 mg zidovudine and 150 mg lamivudine b.d. or placebo for 6 months.Results  None of the patients normalized alkaline phosphatase and no significant differences were observed in normalizing serum aminotransferase levels. Significant differences were observed in the anti‐viral vs. placebo arms with improvements in serial alkaline phosphatase (P < 0.04), alanine aminotransferase (P < 0.03) and aspartate aminotransferase (P < 0.04) levels as well as clinical score (P < 0.02). After 6 months, 25% of patients in the placebo arm and 4% in the anti‐viral arm had evidence of virus in serum.Conclusions  The study endpoints for normalizing hepatic biochemistry were too stringent to show efficacy for zidovudine and lamivudine therapy despite the demonstrable impact on clinical and biochemical improvement. Accordingly, more potent anti‐viral regimens will be required to confirm the efficacy of anti‐viral therapy in PBC patients with human betaretrovirus infection.
Review article: the psychoneuroimmunology of irritable bowel syndrome – an exploration of interactions between psychological, neurological and immunological observations
Authors: AREBI N. , GURMANY S. , BULLAS D. , HOBSON A. , STAGG A. , KAMM M. 
Published: September 2008

SummaryBackground  The pathogenesis of irritable bowel syndrome (IBS) is founded on interactive mechanisms. Disentangling these processes is a prerequisite for the development of effective drug therapy.Aim  To identify the interaction between the various factors implicated in IBS.Methods  Articles pertaining to IBS pathogenesis focusing on psychoneuroimmunology were identified using following search terms: IBS, animal models, microbiota, probiotics, immunology, visceral hypersensitivity, imaging, psychology and visceral pain.Results  Cerebral imaging using MRI and proton emission tomography scanning has revealed differential regional cerebral activation, whereas stimuli induced activation has been captured by both MRI and cortical evoked potentials. At the peripheral neurological level, the concept of visceral hypersensitivity has been challenged as perhaps representing psychological traits with symptom over‐reporting or hyper‐vigilance. Gut mucosal immunology is thought to be relevant with immunological changes reflected as peripheral blood cytokine level changes. Molecular technology advances suggest a role for microbiota by activating the gut immunological system. These interactions have been examined in IBS animal models.Conclusions  Translation of animal model findings to humans is needed to link the various psychological, neurological and immunological changes noted in IBS. This analysis may identify patient sub‐groups, which will ultimately be critical for drug testing to be focused accordingly.
Antipsychotic drugs and short‐term mortality after peptic ulcer perforation: a population‐based cohort study
Authors: CHRISTIANSEN C. , CHRISTENSEN S. , RIIS A. , THOMSEN R. W. , JOHNSEN S. P. , TONNESEN E. , SORENSEN H. T. 
Published: September 2008

SummaryBackground  Peptic ulcer perforation is a serious surgical emergency with a substantial short‐term mortality, but the influence of antipsychotic drug use on the prognosis remains unknown.Aim  To examine the association between antipsychotic drug use and 30‐day mortality following peptic ulcer perforation.Methods  This cohort study comprised 2033 patients with a first‐time hospitalization with peptic ulcer perforation, in Northern Denmark, between 1991 and 2004. Data on preadmission use of antipsychotics and other medications, psychiatric disease, other comorbidities and mortality were obtained through population‐based medical databases. We used Cox regression analyses to compute adjusted mortality rate ratios (MRRs).Results  One hundred and sixteen (5.7%) patients with peptic ulcer perforation were current users of antipsychotic drugs at the time of hospital admission and 205 (10.1%) were former users. The overall 30‐day mortality was 27%. Among current users of antipsychotics 30‐day mortality was 39%. The adjusted 30‐day MRR for current users of antipsychotic drugs compared with non‐users was 1.7 (95% CI: 1.2–2.3). Former use was not a predictor of mortality. The increase in mortality was equal in users of conventional and atypical antipsychotics.Conclusion  Use of antipsychotic drugs is associated with substantially increased mortality following peptic ulcer perforation.
Systematic review: persistence and severity in gastro‐oesophageal reflux disease
Authors: ARMSTRONG D. 
Published: September 2008

SummaryBackground  Management strategies for gastro‐oesophageal reflux disease (GERD) are often inconsistent with the proposition that it is a persistent or chronic disease.Aim  To determine the persistence of reflux symptoms and complications associated with GERD.Methods  Systematic searches of Medline and EMBASE.Results  In longitudinal studies, 65% (95% CI 54–75%) of patients with complicated GERD and 70% (95% CI 57–83%) of patients with ‘defined’ GERD had persistent disease at follow‐up, whereas 34% (95% CI 27–40%) with infrequent or mild reflux symptoms at baseline had persistent symptoms. Clinical trials of maintenance treatment for at least 6 months after healing of oesophagitis reported mean relapse rates of 75% (95% CI 68–82%) in patients taking placebo and 28% (95% CI 21–35%) in those taking proton pump inhibitors. Retrospective studies reported that 34–41% of individuals with GERD recalled experiencing their symptoms for >10 years. The prevalence of GERD is high (10–20%), whereas the incidence is low (4.5–19.6 cases per 1000 person‐years), suggesting that GERD is likely to persist for at least 18 years.Conclusions  Individuals with GERD have persistent reflux symptoms that merit management as a chronic disease; infrequent reflux symptoms are less likely to be chronic and may respond to different management strategies.
A multinational survey of prevalence and patterns of laxative use among adults with self‐defined constipation
Authors: WALD A. , SCARPIGNATO C. , MUELLER‐LISSNER S. , KAMM M. A. , HINKEL U. , HELFRICH I. , SCHUIJT C. , MANDEL K. G. 
Published: September 2008

SummaryBackground  While numerous studies report prevalence of constipation, use of laxatives is poorly understood.Aim  To conduct a survey in seven countries evaluating prevalence of constipation and laxative use in its treatment.Methods  Thirteen thousand eight hundred seventy‐nine adults [approximately 2000 each from US, UK, Germany (GE), France (FR), Italy (IT), Brazil (BR) and South Korea (SK)] completed questionnaires assessing occurrence, frequency, duration and laxative use for treating constipation.Results  Overall, 12.3% of adults had constipation [range: 5% (GE) to 18% (US)] in the prior year. A greater percent of women from all countries and elderly from all except SK and BR reported constipation; odds ratios for constipation among women and elderly were 2.43 (95% CI: 2.18–2.71) and 1.5 (95% CI: 1.25–1.73) vs. men and young subjects. Among those with constipation, 16% (SK) to 40% (US) used laxatives. Laxative use was generally associated with increasing age, symptom frequency and lower income and education. A similar percentage of men and women with constipation reported using laxatives; a greater percentage of women used laxatives for a longer time.Conclusions  Prevalence of self‐defined constipation and laxative use varies among countries. Prevalence is generally related to gender and age, whereas laxative use is related to age, but not to gender.
Meta‐analysis: high‐dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication
Authors: VILLORIA A. , GARCIA P. , CALVET X. , GISBERT J. P. , VERGARA M. 
Published: September 2008

SummaryBackground  The evidence on whether high‐dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed.Aim  To evaluate the evidence on the usefulness of high‐dose PPI in standard triple therapy by performing a systematic review and a meta‐analysis.Methods  A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high‐dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager.Results  Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention‐to‐treat cure rate of 82% was achieved with high‐dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01–1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg.Conclusion  High‐dose PPI seems more effective than standard‐dose for curing H. pylori infection in 7‐day triple therapy.
Clinical trial: the incidence and early mortality after peptic ulcer perforation, and the use of low‐dose aspirin and nonsteroidal anti‐inflammatory drugs
Authors: TAHA A. S. , ANGERSON W. J. , PRASAD R. , MCCLOSKEY C. , GILMOUR D. , MORRAN C. G. 
Published: September 2008

SummaryBackground  It is not clear whether the incidence or early mortality related to peptic ulcer perforation has changed.Aim  To evaluate the incidence and mortality related to peptic ulcer perforation while considering the intake of low‐dose aspirin and nonsteroidal anti‐inflammatory drugs (NSAIDs).Methods  We recorded the numbers and details of all patients presenting in our region of Scotland with perforation between 1997 and 2006 including demography, drug usage and 30‐day mortality.Results  In subjects aged >65 years, the annual incidence of perforation was 32.7 per 105 of the age‐specific population, of whom 10.7 per 105 were taking low‐dose aspirin and 12.0 taking NSAIDs. These were all significantly higher (P < 0.001) than the corresponding incidence in subjects aged ≤65 years (6.6 per 105 overall, 1.1 taking aspirin and 2.5 taking NSAIDs). There was an increasing trend with time in the number of patients taking NSAIDs (χ2 = 4.57, P = 0.03). Using univariate analysis, 30‐day mortality was associated with aspirin [odds ratio, 2.32 (95% C.I., 1.20–4.47), P = 0.01] but not with NSAIDs. The strongest predictors of mortality were increasing age and comorbidity.Conclusions  Perforation remains common in elderly patients including users of NSAIDs and aspirin. Early mortality is also noted in association with increasing age and comorbidity, but not independently with drug intake.
A new concept in colonic drug targeting: a combined pH‐responsive and bacterially‐triggered drug delivery technology
Authors: IBEKWE V. C. , KHELA M. K. , EVANS D. F. , BASIT A. W. 
Published: September 2008

SummaryBackground Current approaches to colonic drug delivery exploit one of two main physiological characteristics: the pH change or increase in bacterial numbers along the gastrointestinal tract. Here, we describe a new concept in targeted delivery, which combines these triggers to improve colonic delivery.Aim To assess thein‐vivotargeting performance of a novel colonic delivery coating comprising a mixture of pH‐responsive enteric polymer (Eudragit S) and biodegradable polysaccharide (resistant starch) in a single layer matrix film.Methods Tablets (radio‐labelled) were film‐coated with the dual‐mechanism coating and administered in a three‐way crossover study to eight healthy volunteers (i) without food, (ii) with breakfast or (iii) 30 min before breakfast. The site of intestinal disintegration was assessed using gamma scintigraphy.Results The coated tablets were able to resist breakdown in the stomach and small intestine. Consistent disintegration of the dosage form was seen at the ileocaecal junction / large intestine. The site of disintegration remained unaffected by feeding.Conclusions The dual‐mechanism (pH/bacterial) coating provides colon‐specificity. Each trigger mechanism has the capacity to act as a failsafe, ensuring appropriate targeting in the gastrointestinal tract. This platform technology has potential for systemic applications or the treatment of local disorders of the large intestine, such as inflammatory bowel disease.
The role of inherited extensional fault segmentation and linkage in contractional orogenesis: a reconstruction of Lower Cretaceous inverted rift basins in the Eastern Cordillera of Colombia
Authors: Mora Andrés , Gaona Tatiana , Kley Jonas , Montoya Diana , Parra Mauricio , Quiroz Luis Ignacio , Reyes German , Strecker Manfred R. 
Published: September 2008

ABSTRACTLower Cretaceous early syn‐rift facies along the eastern flank of the Eastern Cordillera of Colombia, their provenance, and structural context, reveal the complex interactions between Cretaceous extension, spatio‐temporal trends in associated sedimentation, and subsequent inversion of the Cretaceous Guatiquía paleo‐rift. South of 4°30′N lat, early syn‐rift alluvial sequences in former extensional footwall areas were contemporaneous with fan‐delta deposits in shallow marine environments in adjacent hanging‐wall areas. In general, footwall erosion was more pronounced in the southern part of the paleorift. In contrast, early syn‐rift sequences in former footwall areas in the northern rift sectors mainly comprise shallow marine supratidal sabkha to intertidal strata, whereas hanging‐wall units display rapid transitions to open‐sea shales. In comparison with the southern paleo‐rift sector, fan‐delta deposits in the north are scarce, and provenance suggests negligible footwall erosion. The southern graben segment had longer, and less numerous normal faults, whereas the northern graben segment was characterized by shorter, rectilinear faults. To the east, the graben system was bounded by major basin‐margin faults with protracted activity and greater throw as compared with intrabasinal faults to the west. Intrabasinal structures grew through segment linkage and probably interacted kinematically with basin‐margin faults. Basin‐margin faults constitute a coherent fault system that was conditioned by pre‐existing basement fabrics. Structural mapping, analysis of present‐day topography, and balanced cross sections indicate that positive inversion of extensional structures was focused along basin‐bounding faults, whereas intrabasinal faults remained unaffected and were passively transported by motion along the basin‐bounding faults. Thus, zones of maximum subsidence in extension accommodated maximum elevation in contraction, and former topographic highs remained as elevated areas. This documents the role of basin‐bounding faults as multiphased, long‐lived features conditioned by basement discontinuities. Inversion of basin‐bounding faults was more efficient in the southern than in the northern graben segment, possibly documenting the inheritance and pivotal role of fault‐displacement gradients. Our observations highlight similarities between inversion features in orogenic belts and intra‐plate basins, emphasizing the importance of the observed phenomena as predictive tools in the spatiotemporal analysis of inversion histories in orogens, as well as in hydrocarbon and mineral deposits exploration.
Plio‐Quaternary sediment budget between thrust belt erosion and foreland deposition in the central Andes, southern Bolivia
Authors: Barnes J. B. , Heins W. A. 
Published: September 2008

ABSTRACTEstimates of the physical boundary conditions on sediment source and sink regions and the flux between them provide insights into the evolution of topography and associated sedimentary basins. We present a regional‐scale, Plio‐Quaternary to recent sediment budget analysis of the Grande, Parapeti and Pilcomayo drainages of the central Andean fold‐thrust belt and related deposits in the Chaco foreland of southern Bolivia (18–23°S). We constrain source‐sink dimensions, fluxes and their errors with topographic maps, satellite imagery, a hydrologically conditioned digital elevation model, reconstructions of the San Juan del Oro (SJDO) erosion surface, foreland sediment isopachs and estimated denudation rates. Modern drainages range from 7453 to 86 798 km2 for a total source area of 153 632 km2. Palaeo‐drainage areas range from 9336 to 52 620 km2 and total 100 706 km2, suggesting basin source area growth of ∼50% since ∼10 Ma. About 2.4–3.1 × 104 km3 were excavated from below the SJDO surface since ∼3 Ma. The modern foredeep is 132 080 km2 with fluvial megafan areas and volumes ranging from 6142 to 22 511 km2 and from 1511 to 3332 km3, respectively. Since Emborozú Formation deposition beginning 2.1 ± 0.2 Ma, the foreland has a fill of ∼6.4 × 104 km3. The volume and rate of deposition require that at least ∼40–60% of additional sediment be supplied beyond that incised from below the SJDO. The data also place a lower limit of ≥0.2 mm year−1 (perhaps ≥0.4 mm year−1) on the time‐ and space‐averaged source area denudation rate since ∼2–3 Ma. These rates are within the median range measured for the Neogene, but are up to 2 orders of magnitude higher than some observations, as well as analytic solutions for basin topography and stratigraphy using a two‐dimensional mathematical model of foreland basin evolution. Source‐to‐sink sediment budget analyses and associated interpretations must explicitly and quantitatively reconcile all available area, volume and rate observations because of their inherent imprecision and the potential for magnification when they are convolved.
Universality and variability in basin outlet spacing: implications for the two‐dimensional form of drainage basins
Authors: Walcott Rachel C. , Summerfield Michael A. 
Published: September 2008

ABSTRACTIt has been observed that the distance between the outlets of transverse basins in orogens is typically half of the distance between the main divide and the range front irrespective of mountain range size or erosional controls. Although it has been suggested that this relationship is the inherent expression of Hack's law, and/or possibly a function of range widening, there are cases of notable deviations from the typical half‐width average spacing. Moreover, it has not been demonstrated that this general relationship is also true for basins in morphologically similar nonorogenic settings, or for those that do not extend to the main drainage divide. These issues are explored by investigating the relationship between basin outlet spacing and the 2‐dimensional geometric properties of drainage basins (basin length, main valley length and basin area) in order to assess whether the basin outlet spacing‐range width ratio is a universal characteristic of fluvial systems. We examined basins spanning two orders of magnitude in area along the southern flank of the Himalayas and the coastal zone of southeast Africa. We found that the spacing between basin outlets (Los) for major transverse basins that drain the main divide (range‐scale basins) is approximately half of the basin length (Lb) for all basins, irrespective of size, in southeast Africa. In the Himalayas, while this ratio was observed for eastern Himalayan basins (a region where the maximum elevations coincided with the main drainage divide), it was only observed in basins shorter than ∼30 km in the western and central Himalayas. Our analysis indicates that basin outlet spacing is consistent with Hack's law, apparently because the increase in basin width (represented by outlet spacing) with basin area occurs at a rate similar to the increase in main stream length (Lv) with basin area. It is suggested that most river systems tend towards an approximately diamond‐shaped packing arrangement, and this applies both to the nonorogenic setting of southeast Africa as well as most orogenic settings. However, in the western Himalayas shortening associated with localised rock uplift appears to have occurred at length scales smaller than most the basins examined. As a result rivers in basins longer than ∼30 km have been unable to erode in a direction normal to the range front at a sufficiently high rate to sustain this form and have been forced into an alternative, and possibly unstable, packing arrangement.
Phase II multicenter study of oblimersen sodium, a Bcl‐2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B‐cell non‐Hodgkin lymphoma
Authors: Pro Barbara , Leber Brian , Smith Mitchell , Fayad Luis , Romaguera Jorge , Hagemeister Fredrick , Rodriguez Alma , McLaughlin Peter , Samaniego Felipe , Zwiebel James , Lopez Adriana , Kwak Larry , Younes Anas 
Published: September 2008

SummaryOblimersen sodium plus rituximab was evaluated in relapsed/refractory B‐cell non‐Hodgkin lymphoma (NHL) patients. Oblimersen was administered as a continuous intravenous infusion at a daily dose of 3 mg/kg/d for 7 d on alternate weeks for 3 weeks. Rituximab was given at a weekly dose of 375 mg/m2 for six doses. Patients with stable disease or objective response were allowed to receive a second course of treatment. The overall response rate (ORR) was 42% with 10 complete responses (CR) and eight partial responses (PR). Twelve (28%) patients achieved a minimal response or stable disease. Among the 20 patients with follicular lymphoma the ORR was 60% (eight CR, four PR). Three of the responders were refractory to prior treatment with rituximab, and two of the responses occurred in patients who had failed an autologous stem cell transplant. Median duration of response was 12 months. Most toxicities were low grade and reversible. In conclusion, oblimersen sodium can be safely combined with rituximab. The combination appears to be most beneficial in patients with indolent NHL and warrants further investigation in a large randomized trial.