tbuckley/cabot-search huggingface dataset:
Exercise during pregnancy and risk of maternal anaemia: a randomised controlled trial
Authors: R Barakat, J R Ruiz, A Lucia
Journal: British Journal of Sports Medicine (2009)

The purpose of this randomised controlled trial was to examine the effect of regular exercise (three times/week) performed during the second and third trimester of pregnancy on the risk of prepartum maternal anaemia (haemoglobin <11 g/dl). 160 sedentary healthy women were randomly assigned either to a training or a control group (n = 80 each). Haematological variables were recorded at baseline (first trimester) and the beginning of the second and third trimesters. The frequency of participants with maternal anaemia was similar in the two groups over gestation (and consistently <10%). The course of haematological adaptations was normal and similar in both groups, reflecting a steady fall in haemoglobin concentration over the second trimester due to haemodilution and a rise later in gestation due to haemoconcentration. In summary, regular exercise during the second half of pregnancy does not increase the risk of maternal anaemia nor does it alter haematological variables.
Interindividual and intra-articular variation of proinflammatory cytokines in patients with rheumatoid arthritis: potential implications for treatment
Authors: A.-K. Ulfgren
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> Assessment of the numbers and spatial distribution of cells producing interleukin 1α (IL1α), interleukin 1β (IL1β), tumour necrosis factor α (TNFα), and interleukin 6 (IL6) in the synovial membranes of patients with rheumatoid arthritis (RA). <h3>METHODS</h3> Synovial tissue specimens from 40 patients with RA and eight patients with non-rheumatic disease were obtained by arthroscopy guided biopsy techniques or during joint surgery. A modified immunohistochemical method detecting cytokine producing rather than cytokine binding cells was applied to determine cytokine synthesis in fixed cryopreserved sections. Computerised image analysis methods provided comparative quantitative assessments. <h3>RESULTS</h3> A wide variation between subjects was recorded for both quantities and profiles of expressed cytokines, despite similar macroscopic and histopathological features of inflammation. IL1α and IL1β were the most abundant monokines identified, though produced at different sites. IL1α was predominantly seen in vascular endothelial cells, whereas IL1β staining was mainly shown in macrophages and fibroblasts. Concordant results for the detection of TNFα at protein and mRNA levels were obtained with an unexpectedly low number of TNFα producing cells compared with IL1 expressing cells in many patients with RA. Specimens acquired arthroscopically from areas with maximum signs of macroscopic inflammation showed an increased number of TNFα producing cells in pannus tissue compared with that occurring in synovial villi of a given joint. This clustered distribution was not found for cells expressing any of the other studied cytokines. <h3>CONCLUSION</h3> The recorded heterogeneous profile of proinflammatory cytokine synthesis in the synovial membrane among patients with RA may provide a clue for an understanding of the wide variation in responsiveness to different modes of antirheumatic treatment between patients.
Rapid Validation of Cancer Genes and Drug Targets in Genetically Engineered Mouse Models of Cancer
Authors: I.J. Huijbers, R. Bin Ali, C. Pritchard, M. Cozijnsen, N. Proost, J.Y. Song, P. Krimpenfort, E. Michalak, J. Jonkers, A. Berns
Journal: Annals of Oncology (2013)
The impact of inspiratory effort on inspiratory flow through Turbuhaler in asthmatic patients
Authors: G Persson, B Olsson, S Soliman
Journal: European Respiratory Journal (1997)

To investigate the impact of the inhalation effort on the peak inspiratory flow through Turbuhaler, 100 asthmatics having a wide range of asthma severity (baseline forced expiratory volume in one second 28-127% of predicted normal) were studied. Each patient inhaled through four modifications of empty Turbuhaler inhalers, using first a "deep" inhalation and then a "forceful and deep" inhalation manoeuvre. Peak inspiratory flow increased by an average of 20% using a "forceful and deep" as compared to a "deep" inhalation, with a markedly higher increase for the patients who had a low peak inspiratory flow using the deep inhalation. Virtually all patients (97-100%) attained a peak inspiratory flow > or = 40 L x min(-1) after a "forceful and deep" inhalation. This study demonstrates that instructing the patient to take a "forceful and deep" inhalation optimizes the use of Turbuhaler. Irrespective of asthma severity, the vast majority of patients could attain a sufficiently high peak inspiratory flow with a "forceful and deep" inhalation.
Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group
Authors: Howard I. Scher, Susan Halabi, Ian Tannock, Michael Morris, Cora N. Sternberg, Michael A. Carducci, Mario A. Eisenberger, Celestia Higano, Glenn J. Bubley, Robert Dreicer, Daniel Petrylak, Philip Kantoff, Ethan Basch, William Kevin Kelly, William D. Figg, Eric J. Small, Tomasz M. Beer, George Wilding, Alison Martin, Maha Hussain
Journal: Journal of Clinical Oncology (2008)

Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as “new lesions” or “no new lesions,” changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.
Establishing a Diagnostic Road Map for <i>MUTYH</i>-Associated Polyposis
Authors: Ester Borras, Melissa W. Taggart, Patrick M. Lynch, Eduardo Vilar
Journal: Clinical Cancer Research (2014)

Abstract The analysis of MUTYH-associated polyposis cases of the EPIPOLIP cohort confirms the importance of including serrated polyps in the diagnostic work-up of patients with oligopolyposis, suggests a role for screening polyps for the somatic c.34G&amp;gt;T KRAS mutation, and allows the implementation of a genetic testing strategy based on population data. Clin Cancer Res; 20(5); 1061–3. ©2014 AACR.
Percutaneous Transarterial Aortic Valve Replacement in Selected High-Risk Patients With Aortic Stenosis
Authors: John G. Webb, Sanjeevan Pasupati, Karin Humphries, Christopher Thompson, Lukas Altwegg, Robert Moss, Ajay Sinhal, Ronald G. Carere, Brad Munt, Donald Ricci, Jian Ye, Anson Cheung, Sam V. Lichtenstein
Journal: Circulation (2007)

Background— Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. Methods and Results— Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 ( P =0.10), and 30-day mortality fell from 16% to 8% ( P =0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6±0.2 to 1.7±0.4 cm 2 . Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction ( P &lt;0.0001), mitral regurgitation ( P =0.01), and functional class ( P &lt;0.0001). Improvement was maintained at 1 year. Structural valve deterioration was not observed with a median follow-up of 359 days. Conclusion— Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.
Long-Term Outcomes of Mechanical Valve Replacement in Patients With Atrial Fibrillation
Authors: Joon Bum Kim, Joon Suk Moon, Sung-Cheol Yun, Wan Kee Kim, Sung-Ho Jung, Suk Jung Choo, Hyun Song, Cheol Hyun Chung, Jae Won Lee
Journal: Circulation (2012)

Background— The long-term benefits of the maze procedure in patients with chronic atrial fibrillation undergoing mechanical valve replacement who already require lifelong anticoagulation remain unclear. Methods and Results— We evaluated adverse outcomes (death; thromboembolic events; composite of death, heart failure, or valve-related complications) in 569 patients with atrial fibrillation–associated valvular heart disease who underwent mechanical valve replacement with (n=317) or without (n=252) a concomitant maze procedure between 1999 and 2010. After adjustment for differences in baseline risk profiles, patients who had undergone the maze procedure were at similar risks of death (hazard ratio, 1.15; 95% confidence interval, 0.65–2.03; P =0.63) and the composite outcomes (hazard ratio, 0.82; 95% confidence interval, 0.50–1.34; P =0.42) but a significantly lower risk of thromboembolic events (hazard ratio, 0.29; 95% confidence interval, 0.12–0.73; P =0.008) compared with those who underwent valve replacement alone at a median follow-up of 63.6 months (range, 0.2–149.9 months). The effect of superior event-free survival by the concomitant maze procedure was notable in a low-risk EuroSCORE (0–3) subgroup ( P =0.049), but it was insignificant in a high-risk EuroSCORE (≥4) subgroup ( P =0.65). Furthermore, the combination of the maze procedure resulted in superior left ventricular ( P &lt;0.001) and tricuspid valvular functions ( P &lt;0.001) compared with valve replacement alone on echocardiographic assessments performed at a median of 52.7 months (range, 6.0–146.8 months) after surgery. Conclusion— Compared with valve replacement alone, the addition of the maze procedure was associated with a reduction in thromboembolic complications and improvements in hemodynamic performance in patients undergoing mechanical valve replacement, particularly in those with low risk of surgery.
Symptomatic fluid retention in patients on continuous peritoneal dialysis.
Authors: A H Tzamaloukas, M C Saddler, G H Murata, D Malhotra, P Sena, D Simon, K L Hawkins, K Morgan, M Nevarez, B Wood
Journal: Journal of the American Society of Nephrology (1995)

The clinical features, pathogenesis, management, prognosis, and predictors of symptomatic fluid gain (SFR) were analyzed for 71 episodes occurring in 66 patients on continuous peritoneal dialysis, 94.4% on continuous ambulatory peritoneal dialysis (CAPD) and 5.6% on continuous cycling peritoneal dialysis. Compared with a control group of 149 CAPD patients, the SFR group had a higher percentage of diabetics (64 versus 46%) and a higher frequency of noncompliance with fluid restriction (76 versus 22%), salt restriction (74 versus 23%), and performance of dialysis (30 versus 7%) (all at P < or = 0.015). Peripheral edema (100%), pulmonary congestion (80%), pleural effusions (76%), and systolic (83%) and diastolic (66%) hypertension were the most common manifestations of SFR. The annual hospitalization rate for SFR was 4.1 +/- 5.8 days per patient. SFR resulted in the discontinuation of CAPD in 10 patients and death in 1 patient. Serum sodium concentration was not different between dry and maximal weight in the SFR group. Thirty-eight (58%) of SFR and 61 (41%) of control patients were evaluated by peritoneal equilibration tests (PET). SFR patients had lower PET drain volume (2.08 +/- 0.47 versus 2.54 +/- 0.23 L) and a higher frequency of high peritoneal solute transport (32.2 versus 2.4%). In this group, logistic regression identified dietary noncompliance, low PET drain volume, and young age as independent predictors of SFR. Response to management and preventive measures was inconsistent. The best results were obtained by the use of short dwell exchanges with hypertonic dialysate in compliant patients with high peritoneal solute transport. SFR has serious consequences in CAPD. (ABSTRACT TRUNCATED AT 250 WORDS)
Chronic graft-versus-host disease after allogeneic blood stem cell transplantation
Authors: Donna Przepiorka, Paolo Anderlini, Rima Saliba, Karen Cleary, Rakesh Mehra, Issa Khouri, Yang O. Huh, Sergio Giralt, Ira Braunschweig, Koen van Besien, Richard Champlin
Journal: Blood (2001)
Pulmonary haemodynamics after single-lung transplantation for end-stage pulmonary parenchymal disease
Authors: O Bjortuft, S Simonsen, OR Geiran, JG Fjeld, E Skovlund, J Boe
Journal: European Respiratory Journal (1996)

In a prospective study, we investigated the effect of single-lung transplantation (SLT) on pulmonary haemodynamics and the relationship between pulmonary hypertension (PH) and the fraction of perfusion to the transplant in patients with end-stage pulmonary parenchymal disease. Twenty four SLT recipients were included in the study, 19 with chronic obstructive pulmonary disease (COPD), two with sarcoidosis and three with fibrosing alveolitis. Spirometry, determination of arterial blood gas values, perfusion scintigraphy and right heart catheterization were performed before and 1, 6, 12 and 24 months after transplantation. Patients with a mean pulmonary artery pressure (Ppa) > or = 20 mmHg before transplantation were defined as having PH (PH group, 15 patients) and the remainder (9 patients) constituted the non-PH group. In the PH group, Ppa and pulmonary vascular resistance (PVR) were significantly decreased after transplantation: 28 +/- 2 to 18 +/- 1 mmHg and 288 to 161 +/- 11 dyne.s-1.cm-5, respectively (mean +/- SEM). In the non-PH group, the haemodynamic parameters were unchanged after transplantation. Over the 2 year follow-up period, no significant change was found in Ppa and PVR, nor any difference between the PH and non-PH group. There was no significant difference between the two groups in terms of pulmonary perfusion to the graft. In conclusion, patients with pulmonary hypertension obtain pulmonary haemodynamics within the normal range after single-lung transplantation. Presence or absence of pulmonary hypertension before transplantation does not influence perfusion to the graft. These findings persist up to 2 yrs, despite the coexistence of an "end-stage" native lung and a lung transplant.
Endothelial β <sub>3</sub> -Adrenoreceptors Mediate Nitric Oxide–Dependent Vasorelaxation of Coronary Microvessels in Response to the Third-Generation β-Blocker Nebivolol
Authors: Chantal Dessy, Julie Saliez, Philippe Ghisdal, Géraldine Daneau, Irina I. Lobysheva, Françoise Frérart, Catharina Belge, Karima Jnaoui, Philippe Noirhomme, Olivier Feron, Jean-Luc Balligand
Journal: Circulation (2005)

The therapeutic effects of nonspecific beta-blockers are limited by vasoconstriction, thus justifying the interest in molecules with ancillary vasodilating properties. Nebivolol is a selective beta1-adrenoreceptor antagonist that releases nitric oxide (NO) through incompletely characterized mechanisms. We identified endothelial beta3-adrenoreceptors in human coronary microarteries that mediate endothelium- and NO-dependent relaxation and hypothesized that nebivolol activates these beta3-adrenoreceptors.Nebivolol dose-dependently relaxed rodent coronary resistance microarteries studied by videomicroscopy (10 micromol/L, -86+/-6% of prostaglandin F2alpha contraction); this was sensitive to NO synthase (NOS) inhibition, unaffected by the beta(1-2)-blocker nadolol, and prevented by the beta(1-2-3)-blocker bupranolol (P<0.05; n=3 to 8). Importantly, nebivolol failed to relax microarteries from beta3-adrenoreceptor-deficient mice. Nebivolol (10 micromol/L) also relaxed human coronary microvessels (-71+/-5% of KCl contraction); this was dependent on a functional endothelium and NO synthase but insensitive to beta(1-2)-blockade (all P<0.05). In a mouse aortic ring assay of neoangiogenesis, nebivolol induced neocapillary tube formation in rings from wild-type but not beta3-adrenoreceptor- or endothelial NOS-deficient mice. In cultured endothelial cells, 10 micromol/L nebivolol increased NO release by 200% as measured by electron paramagnetic spin trapping, which was also reversed by NOS inhibition. In parallel, endothelial NOS was dephosphorylated on threonine(495), and fura-2 calcium fluorescence increased by 91.8+/-23.7%; this effect was unaffected by beta(1-2)-blockade but abrogated by beta(1-2-3)-blockade (all P<0.05).Nebivolol dilates human and rodent coronary resistance microarteries through an agonist effect on endothelial beta3-adrenoreceptors to release NO and promote neoangiogenesis. These properties may prove particularly beneficial for the treatment of ischemic and cardiac failure diseases through preservation of coronary reserve.
Cochrane corner: is integrated disease management for patients with COPD effective?: Table 1
Authors: Annemarije L Kruis, Nynke Smidt, Willem J J Assendelft, Jacobijn Gussekloo, Melinde R S Boland, Maureen Rutten-van Mölken, Niels H Chavannes
Journal: Thorax (2014)

Patients with COPD experience respiratory symptoms, impairments of daily living and recurrent exacerbations. The aim of integrated disease management (IDM) is to establish a programme of different components of care (ie, self-management, exercise, nutrition) in which several healthcare providers (ie, nurses, general practitioners, physiotherapists, pulmonologists) collaborate to provide efficient and good quality of care. The aim of this Cochrane systematic review was to evaluate the effectiveness of IDM on quality of life, exercise tolerance and exacerbation related outcomes. Searches for all available evidence were carried out in various databases. Included randomised controlled trials (RCTs) consisted of interventions with multidisciplinary (≥2 healthcare providers) and multitreatment (≥2 components) IDM interventions with duration of at least 3 months. Two reviewers independently searched, assessed and extracted data of all RCTs. A total of 26 RCTs were included, involving 2997 patients from 11 different countries with a follow-up varying from 3 to 24 months. In all 68% of the patients were men, with a mean age of 68 years and a mean forced expiratory volume in 1 s (FEV<sub>1</sub>) predicted value of 44.3%. Patients treated with an IDM programme improved significantly on quality of life scores and reported a clinically relevant improvement of 44 m on 6 min walking distance, compared to controls. Furthermore, the number of patients with ≥1 respiratory related hospital admission reduced from 27 to 20 per 100 patients. Duration of hospitalisation decreased significantly by nearly 4 days.
Reduction of Metacholine‐Induced Nasal Secretion by Treatment with a New Topical Steroid in Perennial Non‐Allergic Rhinitis
Authors: L. MALM, J. Å. Wihl, C. J. LAMM, N. Lindqvist
Journal: Allergy (1981)

The value of three objective tests of the nasal mucosa in 22 patients with perennial non-allergic rhinitis treated with a topical corticosteroid has been investigated. Placebo and three different dosages of a new steroid, budesonide, were administered intranasally using a double-blind, cross-over technique. Nasal airway resistance was not reduced by the steroid treatment as compared with the placebo treatment. Eosinophilia in nasal smears was reduced by budesonide. However, the value of this test was decreased by the fact that eosinophilia was found in less than 50% of the patients at the beginning of the trial. Metacholine-induced nasal secretion was significantly reduced by the budesonide treatment. Symptom scores for nasal obstruction, secretion and sneezing attacks were also significantly reduced by the steroid.
IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Igα/β
Authors: Ari Waisman, Manfred Kraus, Jane Seagal, Snigdha Ghosh, Doron Melamed, Jian Song, Yoshiteru Sasaki, Sabine Classen, Claudia Lutz, Frank Brombacher, Lars Nitschke, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2007)

We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin (Ig) gamma1 or mu heavy chains. Progenitor cells expressing gamma1 chains from the beginning generate a peripheral B cell compartment of normal size with all subsets, but a partial block is seen at the pro- to pre-B cell transition. Accordingly, gamma1-driven B cell development is disfavored in competition with developing B cells expressing a wild-type (WT) IgH locus. However, the mutant B cells display a long half-life and accumulate in the mature B cell compartment, and even though partial truncation of the Ig alpha cytoplasmic tail compromises their development, it does not affect their maintenance, as it does in WT cells. IgG1-expressing B cells showed an enhanced Ca(2+) response upon B cell receptor cross-linking, which was not due to a lack of inhibition by CD22. The enhanced Ca(2+) response was also observed in mature B cells that had been switched from IgM to IgG1 expression in vivo. Collectively, these results suggest that the gamma1 chain can exert a unique signaling function that can partially replace that of the Ig alpha/beta heterodimer in B cell maintenance and may contribute to memory B cell physiology.