tbuckley/cabot-search huggingface dataset:
Renal Sympathetic Denervation for Treatment of Drug-Resistant Hypertension
Authors: Murray D. Esler, Henry Krum, Markus Schlaich, Roland E. Schmieder, Michael Böhm, Paul A. Sobotka
Journal: Circulation (2012)

Background— Renal sympathetic nerve activation contributes to the pathogenesis of hypertension. Symplicity HTN-2, a multicenter, randomized trial, demonstrated that catheter-based renal denervation produced significant blood pressure lowering in treatment-resistant patients at 6 months after the procedure compared with control, medication-only patients. Longer-term follow-up, including 6-month crossover results, is now presented. Methods and Results— Eligible patients were on ≥3 antihypertensive drugs and had a baseline systolic blood pressure ≥160 mm Hg (≥150 mm Hg for type 2 diabetics). After the 6-month primary end point was met, renal denervation in control patients was permitted. One-year results on patients randomized to immediate renal denervation (n=47) and 6-month postprocedure results for crossover patients are presented. At 12 months after the procedure, the mean fall in office systolic blood pressure in the initial renal denervation group (−28.1 mm Hg; 95% confidence interval, −35.4 to −20.7; P &lt;0.001) was similar to the 6-month fall (−31.7 mm Hg; 95% confidence interval, −38.3 to −25.0; P =0.16 versus 6-month change). The mean systolic blood pressure of the crossover group 6 months after the procedure was significantly lowered (from 190.0±19.6 to 166.3±24.7 mm Hg; change, −23.7±27.5; P &lt;0.001). In the crossover group, there was 1 renal artery dissection during guide catheter insertion, before denervation, corrected by renal artery stenting, and 1 hypotensive episode, which resolved with medication adjustment. Conclusions— Control patients who crossed over to renal denervation with the Symplicity system had a significant drop in blood pressure similar to that observed in patients receiving immediate denervation. Renal denervation provides safe and sustained reduction of blood pressure to 1 year. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00888433.
Nosocomial transmission of NDM-1-producing Escherichia coli within a non-endemic area in France
Authors: C. Denis, L. Poirel, A. Carricajo, F. Grattard, P. Fascia, P. Verhoeven, P. Gay, C. Nuti, P. Nordmann, B. Pozzetto, P. Berthelot
Journal: Clinical Microbiology and Infection (2012)
Effect of disease severity on rheumatoid arthritis concordance in same sexed siblings.
Authors: C M Deighton, D F Roberts, D J Walker
Journal: Annals of the Rheumatic Diseases (1992)

To assess the factors in a proband with rheumatoid arthritis (RA) that might predict the occurrence of the disease in siblings, 240 same sexed sibships (190 female, 50 male) in which the proband had classical or definite RA were clinically and immunologically documented. Sibship concordance rates were consistently higher for features of severe disease in the proband, reaching statistical significance for a clinical score of disease severity (the SS index). This trend for increasing disease severity to be associated with increasing sibship concordance rates could not be accounted for by age or disease duration of the proband. These results suggest that siblings of probands with severe RA are at greater risk of developing RA than those of probands with mild disease.
Omega-3 Treatment of Childhood Depression: A Controlled, Double-Blind Pilot Study
Authors: Hanah Nemets, Boris Nemets, Alan Apter, Ziva Bracha, R H Belmaker
Journal: American Journal of Psychiatry (2006)

Objective: Major depressive disorder in children may be more common than previously thought, and its therapeutics are unclear. Because of success in a previous study on omega-3 fatty acids in adult major depressive disorder, the authors planned a pilot study of omega-3 fatty acids in childhood major depression. Method: Children who entered the study were between the ages of 6 and 12. Ratings were performed at baseline and at 2, 4, 8, 12, and 16 weeks using Children’s Depression Rating Scale (CDRS), Children’s Depression Inventory (CDI), and Clinical Global Impression (CGI). Children were randomized to omega-3 fatty acids or placebo as pharmacologic monotherapy. Twenty-eight patients were randomized, and 20 completed at least 1 month’s ratings. Results: Analysis of variance showed highly significant effects of omega-3 on symptoms using the CDRS, CDI, and CGI. Conclusions: Omega-3 fatty acids may have therapeutic benefits in childhood depression.
High ambulatory blood pressure in male professional football players
Authors: Hilde Moseby Berge, Thor Einar Andersen, Erik E Solberg, Kjetil Steine
Journal: British Journal of Sports Medicine (2013)

Background No data exist on ambulatory blood pressure (ABP) in athletes. Objectives To identify ABP and examine recommended follow-up of high office blood pressure (OBP) in male professional football players and secondary study indicators of sympathetic activity. Methods Players with high OBP (cases) from a previous screening of 594 players (n=28) were matched for age and ethnicity with players with optimal OBP (controls). High ABP was defined as a mean of ≥135/85 mm Hg during daytime and ≥120/75 mm Hg during night-time. The players replied to questions regarding follow-up of high OBP. High night-time ABP and lack of nocturnal dip (≤10% decline in average BP) were taken as indicators of increased sympathetic activity. Results 26 cases and 26 controls, mean age 28±4 years, were included. 15 (58%) of the cases had sustained hypertension and 11 (42%) white coat hypertension. Among the controls, 17 (65%) had normotension and 9 (35%) masked hypertension. ABP during night-time was high in 23 (88%) of the cases and in 16 (64%) of the controls, and nocturnal dip was absent in 9 (35%) and 11 (42%), respectively. 10 (38%) of the cases had no follow-up of high OBP. Conclusions More than one-third of the players with optimal OBP had masked hypertension during daytime and more than half of all players had high ABP during night-time, which are novel findings in athletes. Together with the reduced nocturnal dip, this might indicate increased sympathetic activity. Follow-up of high OBP after preparticipation screening is random and should be organised.
Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study
Authors: R. Munro, R. Hampson, A. McEntegart, E A. Thomson, R. Madhok, H. Capell
Journal: Annals of the Rheumatic Diseases (1998)

To determine whether there is a relation between disease duration and functional outcome in patients with rheumatoid arthritis (RA) treated with intramuscular sodium aurothiomolate (gold) for five years.440 patients with RA were enrolled in a prospective trial of gold treatment. Initial demographic details were recorded. Disease activity was assessed at yearly intervals using a combination of clinical (pain score, Ritchie articular index, duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C reactive protein) parameters. Change in functional status was assessed using the health status questionnaire (HAQ). Patients were stratified according to disease duration at outset (group 1 = 0-2 years n = 106, group 2 = > 2-5 years n = 93, and group 3 = > 5 years n = 235).There were no significant differences between the groups at outset. A total of 160 patients completed five years of treatment (group 1 n = 44 (42%), group 2 n = 37 (40%), and group 3 n = 79 (34%)). Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a mean improvement of 30% at the end of the study (p < 0.001). Neither group 2 nor group 3 had a significant change in their HAQ at study end. There were significant improvements in all other variables (p < 0.05) in each group apart from pain in group 2.Patients with early RA have a larger reversible component to their HAQ. Only patients with disease duration of up to two years have a longlasting improvement in their functional ability after starting intramuscular gold treatment.
Comorbidity in Bipolar Disorder Among the Elderly: Results From an Epidemiological Community Sample
Authors: Benjamin I Goldstein, Nathan Herrmann, Kenneth I Shulman
Journal: American Journal of Psychiatry (2006)

This study sought to determine psychiatric comorbidity among elderly individuals with bipolar disorder.An epidemiological community survey identified 84 elderly (ages >/=65) respondents with bipolar disorder, 1,327 younger adults with bipolar disorder, and 8,121 elderly respondents without bipolar disorder.Elderly respondents with bipolar disorder reported lifetime and 12-month rates of comorbid alcohol use disorders (38.1%, 38.1%, respectively), dysthymia (15.5%, 7.1%), generalized anxiety disorder (20.5%, 9.5%), and panic disorder (19.0%, 11.9%) that were significantly higher than among elderly respondents without bipolar disorder. They had lower lifetime and 12-month rates of alcohol use disorders and lower 12-month rates of dysthymia and panic disorder than younger adults with bipolar disorder. Elderly men with bipolar disorder reported a greater prevalence of alcoholism; women reported a greater prevalence of panic disorder.Comorbid axis I disorders, including panic disorder, are common among elderly individuals with bipolar disorder.
Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study
Authors: Ragnar Gunnarsson, Trond Mogens Aaløkken, Øyvind Molberg, May Brit Lund, Georg Karl Mynarek, Åse Stavland Lexberg, Kari Time, Alvilde Sofie Strand Dhainaut, Liv-Turid Bertelsen, Øyvind Palm, Karen Irgens, Andrea Becker-Merok, Jan Leidulf Nordeide, Villy Johnsen, Sonja Pedersen, Anne Prøven, Lamya Samir Noori Garabet, Jan Tore Gran
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Mixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown cause. <h3>Objective</h3> To assess the prevalence, pattern and severity of interstitial lung disease (ILD) in a cross-sectional study of the nationwide, Norwegian MCTD cohort. <h3>Methods</h3> 126 patients with MCTD were systematically examined for ILD by high-resolution CT (HRCT), pulmonary function tests (PFT), 6 min walk test (6MWT) and by the New York Heart Association (NYHA) functional classification of dyspnoea. The extent and type of HRCT lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society. <h3>Results</h3> All 126 patients were Caucasian, 75% women. At the time of the cross-sectional ILD study, the patients had a mean disease duration of 9.0 years. 52% of the patients had abnormal HRCT findings, most commonly reticular patterns consistent with lung fibrosis (35%). Lung fibrosis was quantified as minor in 7%, moderate in 9% and severe in 19% of the patients. Fibrosis was uniformly concentrated in the lower parts of the lungs and was not associated with smoking. Patients with severe lung fibrosis had lower PFT values, shorter 6MWT and a higher mean NYHA functional class. After a mean 4.2 years9 follow-up, overall mortality was 7.9%. Mortality in patients with normal HRCT was 3.3%, as compared with 20.8% in patients with severe lung fibrosis (p&lt;0.01). <h3>Conclusions</h3> Severe lung fibrosis is common in MCTD, has an impact on pulmonary function and overall physical capacity and is associated with increased mortality.
Exhaled volatile organic compounds predict exacerbations of childhood asthma in a 1-year prospective study
Authors: Charlotte M. Robroeks, Joep J. van Berkel, Quirijn Jöbsis, Frederik-Jan van Schooten, Jan W. Dallinga, Emiel F. Wouters, Edward Dompeling
Journal: European Respiratory Journal (2013)

The hypothesis was that prediction of asthma exacerbations in children is possible by profiles of exhaled volatile organic compounds (VOCs), a noninvasive measure of airway inflammation. The aims of the present study were to determine: 1) whether VOCs in exhaled breath are able to predict asthma exacerbations; and 2) the time course and chemical background of the most predictive VOCs. A prospective study was performed in 40 children with asthma over 1 year. At standard 2-month intervals, exhaled nitric oxide fraction (FeNO), VOC profiles in exhaled breath samples, lung function and symptoms were determined in a standardised way. VOC profiles were analysed by gas chromatography-time-of-flight mass spectrometry. 16 out of 40 children experienced an exacerbation. With support vector machine analysis, the most optimal model of baseline measurements versus exacerbation within patients was based on six VOCs (correct classification 96%, sensitivity 100% and specificity 93%). The model of baseline values of patients with compared to those without an exacerbation consisted of seven VOCs (correct classification 91%, sensitivity 79% and specificity 100%). FeNO and lung function were not predictive for exacerbations. This study indicates that a combination of different exhaled VOCs is able to predict exacerbations of childhood asthma.
Role of nosocomial hospital transmission in acute hepatitis C
Authors: Thierry Morin, Alexandre Pariente, Jean François Cadranel, Jacques Denis
Journal: Journal of Hepatology (2008)

To the Editor: We read with great interest the provocative paper by Martinez-Bauer and the Spanish Acute HCV Group attributing two-thirds of 109 cases of acute hepatitis C to hospitalization [[1]Martinez-Bauer E. Forns X. Armelles M. Planas R. Sola R. Vergara M. et al.Hospital admission is a relevant cause of hepatitis C virus acquisition in Spain.J Hepatol. 2008; 48: 20-27Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. We have not observed this predominant role of nosocomial hospital transmission in our cohort of 126 patients prospectively recorded in the French Observatory of Acute Hepatitis C: in this cohort, nosocomial transmission was suspected in 24 of our patients (19%), a professional role was attributed in 15 (12%), drug use being responsible for 48 cases (38%) and sexual contacts for 26 (20%). The proportion of suspected nosocomial transmission was a little bit higher (18 patients, 29%) in our first, retrospective study of 62 cases [[2]Morin T. Pariente A. Acute hepatitis C: a retrospective study of 62 cases.Gastroenterol Clin Biol. 2002; 26: 994-1000PubMed Google Scholar], after excluding transfusion-related cases. The probable overestimation of the relative role of hospital nosocomial transmission in the Spanish study could have three main causes: (1) the inclusion of two “large” epidemics (totalizing 12/73 cases), related to obviously unsafe procedures, (2) a recruitment bias (patients being regularly admitted having systematic determinations of liver tests, which is exceptional after drug injection for example), and (3) recall bias (patients probably remembered and reported more easily hospitalization than a single act of sexual intercourse act with a poorly risk-defined partner). Hospital nosocomial transmission of hepatitis C virus certainly persists, but it is probably not so high, and it has to be maintained at its very low level by regular reminders and observance of universal hygiene precautions and disinfection procedures.
Outlet obstruction constipation (anismus) managed by biofeedback.
Authors: B M Kawimbe, M Papachrysostomou, N R Binnie, N Clare, A N Smith
Journal: Gut (1991)

Fifteen subjects presenting with intractable constipation due to obstructive defecation, mean (SEM) duration 8.8 (1.8) years, had the inappropriate contraction and electromyographic changes in the pelvic floor muscles and external and sphincter typical of this condition. An electromyographically derived index was used to grade its severity. A self applied biofeedback device was used to allow electromyographic recording of the abnormal external anal sphincter. The subjects were encouraged to reduce the abnormal electromyographic activity on straining after instruction and training. The procedure was intended as a relearning process in which the non-relaxing activity of the pelvic floor was gradually suppressed. Biofeedback training was maintained on a domiciliary basis for a mean time of 3.1 weeks and resulted in a significant reduction in the anismus index (mean (SEM) 69.9 (7.8)% before biofeedback, mean 14 (3.9)% after biofeedback, p less than 0.01). There was an associated reduction in the time spent straining at stool and in the difficulty of defecation and an increased frequency of defecation. Defecatory video proctograms in six subjects showed improvements in the anorectal angle during straining and evacuation. The clinical benefit to the patients persisted after a mean follow up of 6.2 months.
Analysis of Transcriptome Complexity Through RNA Sequencing in Normal and Failing Murine Hearts
Authors: Jae-Hyung Lee, Chen Gao, Guangdun Peng, Christopher Greer, Shuxun Ren, Yibin Wang, Xinshu Xiao
Journal: Circulation Research (2011)

Accurate and comprehensive de novo transcriptome profiling in heart is a central issue to better understand cardiac physiology and diseases. Although significant progress has been made in genome-wide profiling for quantitative changes in cardiac gene expression, current knowledge offers limited insights to the total complexity in cardiac transcriptome at individual exon level.To develop more robust bioinformatic approaches to analyze high-throughput RNA sequencing (RNA-Seq) data, with the focus on the investigation of transcriptome complexity at individual exon and transcript levels.In addition to overall gene expression analysis, the methods developed in this study were used to analyze RNA-Seq data with respect to individual transcript isoforms, novel spliced exons, novel alternative terminal exons, novel transcript clusters (ie, novel genes), and long noncoding RNA genes. We applied these approaches to RNA-Seq data obtained from mouse hearts after pressure-overload-induced by transaortic constriction. Based on experimental validations, analyses of the features of the identified exons/transcripts, and expression analyses including previously published RNA-Seq data, we demonstrate that the methods are highly effective in detecting and quantifying individual exons and transcripts. Novel insights inferred from the examined aspects of the cardiac transcriptome open ways to further experimental investigations.Our work provided a comprehensive set of methods to analyze mouse cardiac transcriptome complexity at individual exon and transcript levels. Applications of the methods may infer important new insights to gene regulation in normal and disease hearts in terms of exon utilization and potential involvement of novel components of cardiac transcriptome.
STRUCTURE-BASED DRUG DESIGN:Computational Advances
Authors: Tami J. Marrone, James M. Briggs, and, J. Andrew McCammon
Journal: The Annual Review of Pharmacology and Toxicology (1997)

▪ Abstract Structure-based computational methods continue to enhance progress in the discovery and refinement of therapeutic agents. Several such methods and their applications are described. These include molecular visualization and molecular modeling, docking, fragment methods, 3-D database techniques, and free-energy perturbation. Related issues that are discussed include the use of simplified potential energy functions and the determination of the positions of tightly bound waters. Strengths and weaknesses of the various methods are described.
EGFR- and VEGF(R)-Targeted Small Molecules Show Synergistic Activity in Colorectal Cancer Models Refractory to Combinations of Monoclonal Antibodies
Authors: Virginie Poindessous, Djamila Ouaret, Karima El Ouadrani, Aude Battistella, Virginie F. Mégalophonos, Nyam Kamsu-Kom, Amélie Petitprez, Alexandre E. Escargueil, Pascaline Boudou, Sylvie Dumont, Pascale Cervera, Jean-François Fléjou, Thierry André, Christophe Tournigand, Benoist Chibaudel, Aimery de Gramont, Annette K. Larsen
Journal: Clinical Cancer Research (2011)

Epidermal growth factor receptor (EGFR) and VEGF(R) signaling show extensive cross-talk, providing a rationale for joint targeting of the two pathways. However, combinations of monoclonal antibodies (mAb) targeting EGFR and VEGF showed disappointing activity in patients with colorectal cancer (CRC). We speculated that inhibition of surface receptors and ligands might only partly prevent oncogenic signaling whereas small-molecule tyrosine kinase inhibitors (TKI) would also influence intracellular signaling.Mice with CRC xenografts were treated with two TKIs, vargatef and afatinib, or with two mAbs, bevacizumab and cetuximab, and their influence on tumor growth, viability, in vivo DNA synthesis, and the presence of phosphorylated EGFR and VEGFR was determined. The activity of the TKIs was further characterized in CRC cells with different KRAS status.Vargatef and afatinib together showed strong tumor growth inhibition toward HT-29 xenografts compared with either drug alone, which was associated with a 5-fold increase in apoptotic tumor cell death. In comparison, bevacizumab and cetuximab together were exclusively cytostatic with no more activity than either drug alone. Exposure to the two TKIs was accompanied by a marked decrease of tumor-associated intracellular phospho-VEGFR1 and phospho-EGFR, whereas similar exposure to the two mAbs had no detectable effect. A synergistic activity of vargatef plus afatinib was observed in all eight CRC cell lines examined, independent of KRAS status.Our results indicate that attenuation of intracellular EGFR and/or VEGF signaling is required for cytotoxic activity. These findings provide a rationale for trials of the TKIs, even in patients with mutant KRAS.
A Randomized Controlled Trial of Nurse-led Care for Symptomatic Moderate–Severe Obstructive Sleep Apnea
Authors: Nick A Antic, Catherine Buchan, Adrian Esterman, Michael Hensley, Matthew T Naughton, Sharn Rowland, Bernadette Williamson, Samantha Windler, Simon Eckermann, R Doug McEvoy
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Obstructive sleep apnea (OSA) is a prevalent disease. Often limited clinical resources result in long patient waiting lists. Simpler validated methods of care are needed.Objectives: To demonstrate that a nurse-led model of care can produce health outcomes in symptomatic moderate–severe OSA not inferior to physician-led care.Methods: A randomized controlled multicenter noninferiority clinical trial was performed. Of 1,427 potentially eligible patients at 3 centers, 882 consented to the trial. Of these, 263 were excluded on the basis of clinical criteria. Of the remaining 619, 195 met home oximetry criteria for high-probability moderate–severe OSA and were randomized to 2 models of care: model A, the simplified model, using home autoadjusting positive airway pressure to set therapeutic continuous positive airway pressure (CPAP), with all care supervised by an experienced nurse; and model B, involving two laboratory polysomnograms to diagnose and treat OSA, with clinical care supervised by a sleep physician. The primary end point was change in Epworth Sleepiness Scale (ESS) score after 3 months of CPAP. Other outcome measures were collected.Measurements and Main Results: For the primary outcome change in ESS score, nurse-led management was no worse than physician-led management (4.02 vs. 4.15; difference, −0.13; 95% confidence interval: −1.52, 1.25) given a prespecified noninferiority margin of −2 for the lower 95% confidence interval. There were also no differences between both groups in CPAP adherence at 3 months or other outcome measures. Within-trial costs were significantly less in model A.Conclusions: A simplified nurse-led model of care has demonstrated noninferior results to physician-directed care in the management of symptomatic moderate–severe OSA, while being less costly.Clinical trial registered with http://www.anzctr.org.au (ACTRN012605000064606)