tbuckley/cabot-search huggingface dataset:
Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomised controlled trial
Authors: Neal Navani, Matthew Nankivell, David R Lawrence, Sara Lock, Himender Makker, David R Baldwin, Richard J Stephens, Mahesh K Parmar, Stephen G Spiro, Stephen Morris, Sam M Janes
Journal: The Lancet Respiratory Medicine (2015)

The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis. We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer.In this open-label, multicentre, pragmatic, randomised controlled trial, we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer, from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or conventional diagnosis and staging (CDS), for further investigation and staging. If a target node could not be accessed by EBUS-TBNA, then endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was allowed as an alternative procedure. Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre. We used a telephone randomisation method with permuted blocks of four generated by a computer. Because of the nature of the intervention, masking of participants and consenting investigators was not possible. The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose. This trial is registered with ClinicalTrials.gov, number NCT00652769.Between June 10, 2008, and July 4, 2011, we randomly allocated 133 patients to treatment: 66 to EBUS-TBNA and 67 to CDS (one later withdrew consent). Two patients from the EBUS-TBNA group underwent EUS-FNA. The median time to treatment decision was shorter with EBUS-TBNA (14 days; 95% CI 14-15) than with CDS (29 days; 23-35) resulting in a hazard ratio of 1·98, (1·39-2·82, p<0·0001). One patient in each group had a pneumothorax from a CT-guided biopsy sample; the patient from the CDS group needed intercostal drainage and was admitted to hospital.Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer, because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques.UK Medical Research Council.
Long-Term Exposure to Air Pollution and Incidence of Cardiovascular Events in Women
Authors: Kristin A. Miller, David S. Siscovick, Lianne Sheppard, Kristen Shepherd, Jeffrey H. Sullivan, Garnet L. Anderson, Joel D. Kaufman
Journal: New England Journal of Medicine (2007)

Fine particulate air pollution has been linked to cardiovascular disease, but previous studies have assessed only mortality and differences in exposure between cities. We examined the association of long-term exposure to particulate matter of less than 2.5 μm in aerodynamic diameter (PM2.5) with cardiovascular events.
Familial Risks in Cancer of Unknown Primary: Tracking the Primary Sites
Authors: Kari Hemminki, Jianguang Ji, Jan Sundquist, Xiaochen Shu
Journal: Journal of Clinical Oncology (2010)

Cancer of unknown primary (CUP) is diagnosed at the metastatic stage, and despite extensive diagnostic work-up, the primary tumor often remains unidentified. No data are available on familial clustering of CUP. We hypothesize that familial clustering of CUP with other cancers may be informative of the primary sites.A total of 35,168 patients with CUP were identified in the Swedish Family-Cancer Database, and risks between family members were calculated for concordant (CUP-CUP) and discordant (CUP-any other cancer) cancers using standardized incidence ratio (SIR).Familial cases of CUP accounted for 2.8% of all CUP cases in the offspring generation. Familial SIR for CUP was 1.69 when a sibling was diagnosed with CUP. As to discordant associations between siblings, CUP was associated with lung (SIR, 1.87), kidney (SIR, 1.82), liver (SIR, 1.67), ovarian (SIR, 1.45), colorectal (SIR, 1.26), and breast (SIR, 1.15) cancers and melanoma (SIR, 1.26). Upper aerodigestive tract, bladder, pancreatic, and prostate cancers were additionally associated with CUP. Notably, CUP was associated with families of kidney, lung, and colorectal cancers.The present data show that CUP is not a disease of random metastatic cancers but, instead, a disease of a defined set of cancers. The association of CUP with families of kidney, lung, and colorectal cancers suggests a marked genetic basis and shared metastatic mechanisms by many cancer types. Familial sites shared by CUP generally match those arising in tissue-of-origin determinations and, hence, suggest sites of origin for CUP. Mechanistic exploration of CUP may provide insight into defense against primary tumors and the metastatic process.
Investigative Use of Bronchoscopy in Asthma
Authors: NIZAR N. JARJOUR, STEPHEN P. PETERS, RATKO DJUKANOVIĆ, WILLIAM J. CALHOUN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The incorporation of bronchoscopy and bronchoscopic procedures into the investigation of asthma mechanisms, treatment, and in particular, the role of airway inflammation has contributed significantly to the enhanced understanding of this disease. Carefully drafted guidelines have allowed the gradual inclusion of subjects with more severe disease in studies utilizing bronchoscopic investigative tools. Many more questions remained unanswered, including the importance of persistence of airway inflammation in asymptomatic asthma, the specific antiinflammatory effects of new (and old) asthma therapies, the contribution of airway structural changes (subepithelial fibrosis) to nonreversible obstruction, the role of antiinflammatory versus proinflammatory cytokines in the pathogenesis of airway inflammation and the heterogeneity of disease expression in various groups of subjects. We are confident that current and future meticulously designed and executed research studies utilizing bronchoscopic techniques will significantly add to our knowledge of disease mechanisms and lead us to new and improved treatments for asthma.
TRIAL OF HIGH-DOSE EDMONSTON-ZAGREB MEASLES VACCINE IN GUINEA-BISSAU: PROTECTIVE EFFICACY
Authors: Peter Aaby, HenrikLyngbeck Hansen, Jesper Thårup, Morten Sodemann, ThøgerGorm Jensen, Hans Kristiansen, Anja Poulsen, Marianne Jakobsen, Kim Knudsen, MariaClotilde Da Silva, Hilton Whittle
Journal: The Lancet (1988)
Legionella pneumophila Serogroup 9: A Cause of Human Pneumonia
Authors: PAUL H. EDELSTEIN
Journal: Annals of Internal Medicine (1984)

A new serogroup of Legionella pneumophila was isolated from bronchoscopic washings and an open-lung biopsy specimen of a patient from California with pneumonia. A serologically identical isolate was obtained from tap water of a hospital ward in the Netherlands, and a fatal case of pneumonia in a patient from Virginia was shown retrospectively to have been caused by this new organism. The type strain of what is now serogroup 9 of L. pneumophila is IN-23-G1-C2 (American Type Culture Collection no. 35289). Disease caused by L. pneumophila serogroup 9 is not apparently different from that caused by other L. pneumophila serogroups.
Le coude en pratique rhumatologique (The Elbow in Rheumatological Practice)
Authors: A. St. J. Dixon
Journal: Annals of the Rheumatic Diseases (1961)

The authors set out to give a concise survey of modern views on articular function.At the outset let it be said that each of them has, in his own particular field, made a number of original contributions in one or more aspects of the structure or function of synovial joints.
Classification, diagnosis, and approach to treatment for angioedema: consensus report from the <scp>H</scp>ereditary <scp>A</scp>ngioedema <scp>I</scp>nternational <scp>W</scp>orking <scp>G</scp>roup
Authors: M. Cicardi, W. Aberer, A. Banerji, M. Bas, J. A. Bernstein, K. Bork, T. Caballero, H. Farkas, A. Grumach, A. P. Kaplan, M. A. Riedl, M. Triggiani, A. Zanichelli, B. Zuraw
Journal: Allergy (2014)

Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.
Prostanoid F receptors elicit an inotropic effect in rat left ventricle by enhancing myosin light chain phosphorylation
Authors: J. Riise, C. H.T. Nguyen, E. Qvigstad, D. L. Sandnes, J.-B. Osnes, T. Skomedal, F. O. Levy, K. A. Krobert
Journal: Cardiovascular Research (2008)

The aims of this study were to determine if the prostanoid F receptor (FPR)-mediated inotropic effect in rat ventricle is mediated by increased phosphorylation of myosin light chain-2 (MLC-2) and to elucidate the signalling pathway(s) activated by FPRs to regulate MLC-2 phosphorylation. Contractility was measured in left ventricular strips from adult male rats. Strips were also snap-frozen, and changes in the phosphorylation level of both MLC-2 and myosin phosphatase targeting subunit-2 (MYPT-2) were quantified. FPR stimulation with fluprostenol increased contractility by ∼100% above basal and increased phosphorylation of both MLC-2 (by ∼30%) and MYPT-2 (by ∼50%). The FPR-mediated inotropic effect and MLC-2 phosphorylation were reduced by a similar magnitude in the presence of the myosin light chain kinase (MLCK) inhibitor ML-7 (∼60–70%) and an inhibitor of Ca2+/calmodulin, W-7 (∼35%). Inhibition of Rho-associated kinase by Y-27632 reduced the FPR-mediated inotropic effect and MLC-2 phosphorylation by ∼40–45% and MYPT-2 phosphorylation by ∼70%. ML-7 and Y-27632 together reduced contractility and MLC-2 phosphorylation by ∼70–80%. The FPR-mediated inotropic effect was only modestly affected by high concentrations of the inositol tris-phosphate (IP3) receptor blocker 2-APB, but not by the protein kinase C (PKC) inhibitor bisindolylmaleimide. The FPR-evoked inotropic effect is mediated by increasing the phosphorylation of MLC-2 through regulation of both MLCK and myosin light chain phosphatase activities. The second messenger IP3 and PKC are unlikely to be involved in the signalling cascade of the FPR-mediated positive inotropic effect. Therefore, FPR signalling mechanism(s) regulating MLC-2 phosphorylation likely extend beyond those classically established for Gq/11-coupled receptors.
Forty-Year-Old Intrathoracic Gossypiboma After Cardiac Valve Surgery
Authors: Gilberto Szarf, Thais Caldara Mussi de Andrade, Edson Nakano, Denis Szjenfeld, Altair Silva Costa, Erica Rymkiewicz, Renato de Oliveira, Sergio Aron Ajzen, Luiz Eduardo Villaca Leao, Henrique M. Lederman
Journal: Circulation (2009)
Glycemic Index, Glycemic Load, Carbohydrates, and Type 2 Diabetes
Authors: Darren C. Greenwood, Diane E. Threapleton, Charlotte E.L. Evans, Christine L. Cleghorn, Camilla Nykjaer, Charlotte Woodhead, Victoria J. Burley
Journal: Diabetes Care (2013)

OBJECTIVE Diets with high glycemic index (GI), with high glycemic load (GL), or high in all carbohydrates may predispose to higher blood glucose and insulin concentrations, glucose intolerance, and risk of type 2 diabetes. We aimed to conduct a systematic literature review and dose–response meta-analysis of evidence from prospective cohorts. RESEARCH DESIGN AND METHODS We searched the Cochrane Library, MEDLINE, MEDLINE in-process, Embase, CAB Abstracts, ISI Web of Science, and BIOSIS for prospective studies of GI, GL, and total carbohydrates in relation to risk of type 2 diabetes up to 17 July 2012. Data were extracted from 24 publications on 21 cohort studies. Studies using different exposure categories were combined on the same scale using linear and nonlinear dose–response trends. Summary relative risks (RRs) were estimated using random-effects meta-analysis. RESULTS The summary RR was 1.08 per 5 GI units (95% CI 1.02–1.15; P = 0.01), 1.03 per 20 GL units (95% CI 1.00–1.05; P = 0.02), and 0.97 per 50 g/day of carbohydrate (95% CI 0.90–1.06; P = 0.5). Dose–response trends were linear for GI and GL but more complex for total carbohydrate intake. Heterogeneity was high for all exposures (I2 &amp;gt;50%), partly accounted for by different covariate adjustment and length of follow-up. CONCLUSIONS Included studies were observational and should be interpreted cautiously. However, our findings are consistent with protective effects of low dietary GI and GL, quantifying the range of intakes associated with lower risk. Future research could focus on the type of sugars and other carbohydrates associated with greatest risk.
Interleukin 6/gp130-dependent pathways are protective during chronic liver diseases
Authors: Konrad L. Streetz, Frank Tacke, Ludger Leifeld, Torsten Wüstefeld, Andrea Graw, Christian Klein, Kenjii Kamino, Ulrich Spengler, Hans Kreipe, Stefan Kubicka, Werner Müller, Michael P. Manns, Christian Trautwein
Journal: Hepatology (2003)

The contribution of the acute phase inducer interleukin 6 (IL–6) in the pathogenesis of liver diseases is yet unclear. Our analysis showed enhanced expression of IL–6 in livers derived from patients with acute and chronic liver diseases. Additionally, IL–6 plasma levels were significantly increased in patients with chronic liver diseases and showed an inverse correlation with biochemical markers of liver function and a positive correlation with inflammatory markers, signs of portal hypertension, and the degree of liver fibrosis. To prove the relevance of these clinical findings, we applied the tetrachlorcarbonide (CCl 4 ) model to conditional knockout animals (Cre/loxP system) for gp130, the common signal transducer of IL–6 family cytokines. Cre recombinases were expressed through a hepatocyte (AlfpCre) and a ubiquitous (MxCre) control element. Gp130 deleted mice had a totally abolished STAT3 activation and acute phase response induction, but gp130 deletion had no effect on the degree of acute liver injury and subsequent hepatocyte proliferation. In contrast, during chronic liver injury induced by biweekly application of CCl 4 , deletion of the gp130 receptor in nonparenchymal liver cells and not hepatocytes resulted in fibrosis progression. In conclusion, our experiments indicate an involvement of IL–6 in the pathogenesis of liver diseases and suggest a protective role of IL–6/gp130–dependent pathways in nonparenchymal liver cells during fibrosis progression in chronic liver diseases.
Steroidogenic Enzyme AKR1C3 Is a Novel Androgen Receptor-Selective Coactivator that Promotes Prostate Cancer Growth
Authors: Muralimohan Yepuru, Zhongzhi Wu, Anand Kulkarni, Feng Yin, Christina M. Barrett, Juhyun Kim, Mitchell S. Steiner, Duane D. Miller, James T. Dalton, Ramesh Narayanan
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Castration-resistant prostate cancer (CRPC) may occur by several mechanisms including the upregulation of androgen receptor (AR), coactivators, and steroidogenic enzymes, including aldo keto reductase 1C3 (AKR1C3). AKR1C3 converts weaker 17-keto androgenic precursors to more potent 17-hydroxy androgens and is consistently the major upregulated gene in CRPC. The studies in the manuscript were undertaken to examine the role of AKR1C3 in AR function and CRPC. Experimental Design: LNCaP cells stably transfected with AKR1C3 and VCaP cells endogenously expressing AKR1C3 were used to understand the effect of AKR1C3 on prostate cancer cell and tumor growth in nude mice. Chromatin immunoprecipitation, confocal microscopy, and co-immunoprecipitation studies were used to understand the recruitment of AKR1C3, intracellular localization of AKR1C3 and its interaction with AR in cells, tumor xenograft, and in Gleason sum 7 CRPC tissues. Cells were transiently transfected for AR transactivation. Novel small-molecule AKR1C3-selective inhibitors were synthesized and characterized in androgen-dependent prostate cancer and CRPC models. Results: We identified unique AR-selective coactivator- and prostate cancer growth-promoting roles for AKR1C3. AKR1C3 overexpression promotes the growth of both androgen-dependent prostate cancer and CRPC xenografts, with concomitant reactivation of androgen signaling. AKR1C3 interacted with AR in prostate cancer cells, xenografts, and in human CRPC samples and was recruited to the promoter of an androgen-responsive gene. The coactivator and growth-promoting functions of AKR1C3 were inhibited by an AKR1C3-selective competitive inhibitor. Conclusions: AKR1C3 is a novel AR-selective enzymatic coactivator and may represent the first of more than 200 known nuclear hormone receptor coactivators that can be pharmacologically targeted. Clin Cancer Res; 19(20); 5613–25. ©2013 AACR.
CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease
Authors: D Laukens
Journal: Annals of the Rheumatic Diseases (2004)

The association between spondyloarthropathy and Crohn's disease is well known. A risk for evolution to Crohn's disease has already been shown in the subgroup of patients with spondyloarthropathy associated with chronic gut inflammation.To investigate whether the reported polymorphisms in the CARD15 gene, a susceptibility gene for Crohn's disease, are associated with the presence of preclinical intestinal inflammation observed in spondyloarthropathies.104 patients with spondyloarthropathies were studied. All underwent ileocolonoscopy with biopsies between 1983 and 2004. The prevalence of three single nucleotide polymorphisms in the CARD15 gene (R702W, G908R, and 1007fs) was assessed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR); the patients were compared with an ethnically matched Crohn's disease population and a control population.The carrier frequency of R702W, G908R, or 1007fs variants in the spondyloarthropathy populations (20%) was similar to the control population (17%), but increased to 38% in the spondyloarthropathy subgroup with chronic gut inflammation. This frequency was significantly higher than in the other spondyloarthropathy subgroups (p = 0.001) or the control group (p = 0.006), but not different from the Crohn's disease group (49%) (NS). This indicates that CARD15 polymorphisms are associated with a higher risk for development of chronic gut inflammation.CARD15 gene polymorphisms clearly identify a subgroup of patients with spondyloarthropathies associated with chronic intestinal inflammation.
Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey
Authors: Salim Yusuf, Shofiqul Islam, Clara K Chow, Sumathy Rangarajan, Gilles Dagenais, Rafael Diaz, Rajeev Gupta, Roya Kelishadi, Romaina Iqbal, Alvaro Avezum, Annamarie Kruger, Raman Kutty, Fernando Lanas, Liu Lisheng, Li Wei, Patricio Lopez-Jaramillo, Aytekin Oguz, Omar Rahman, Hany Swidan, Khalid Yusoff, Witold Zatonski, Annika Rosengren, Koon K Teo
Journal: The Lancet (2011)
Generation of T cells with lytic specificity for atypical antigens. III. Priming F1 animals with antigen-bearing cells also having reactivity for host alloantigens allows for potent lytic T cell responses.
Authors: J D Davies, D H Wilson, D B Wilson
Journal: The Journal of Experimental Medicine (1991)

Here, we explore the conditions required for generating two different highly potent F1 antiparental killer cell populations to unusual antigens in rats. The first, L/DA anti-DA, has lytic specificity for two antigen systems: MTA, a mitochondrial antigen expressed on DA and DA Lewis (L) target cells restricted by RT1A class I molecules; and H, an antigen that maps to the class I-like RT1C region and is present only on parental target cells from donors homozygous at the major histocompatibility complex. The second killer population is generated in the reciprocal DA/L anti-DA combination and has lytic specificity only for the H antigen system. We show that the killer cells are T cells, and that generation of these F1 cytotoxic T lymphocytes (CTL) requires an in vivo priming step in which it is essential that the inoculated parental cells bear the relevant target antigens and possess alloreactivity for F1 host antigens. The requirement for alloreactivity and antigen on the same priming cell population suggests that these potent lytic responses depend on a situation akin to a hapten-carrier effect that bypasses otherwise ineffective helper responses by the host to these unusual antigens. Restimulation of F1 lymphocytes in culture is also necessary, requiring the presence of antigen on irradiated lymphoblast stimulator cells, but alloreactivity to responder cell antigens is not necessary; normal, nonactivated lymph node cells are completely ineffective as stimulators. For effective lysis, the target cells need not possess the potential for alloreactivity to responder F1 CTL. We also demonstrate in a preliminary way additional antigen systems defined by killer populations raised with other F1 antiparental strain combinations.
Contribution of Exercise-Induced Mitral Regurgitation to Exercise Stroke Volume and Exercise Capacity in Patients With Left Ventricular Systolic Dysfunction
Authors: Rigobert Lapu-Bula, Annie Robert, David Van Craeynest, Anne-Marie D’Hondt, Bernhard L. Gerber, Agnès Pasquet, Jacques A. Melin, Martine De Kock, Jean-Louis Vanoverschelde
Journal: Circulation (2002)

Functional mitral regurgitation (MR) is common in patients with heart failure and left ventricular (LV) dysfunction, and its severity may vary over time, depending primarily on the loading conditions. Because dynamic changes in the severity of functional MR may affect forward stroke volume, we hypothesized that exercise-induced changes in MR severity influence the stroke volume response of patients with LV dysfunction to exercise, and hence their exercise capacity.Heart failure patients (n=25; mean age 53+/-12 years) with LV dysfunction underwent dynamic bicycle exercise at steady-state levels of 30%, 60%, and 90% of predetermined peak VO2. During each exercise level, right heart pressures, cardiac output, VO2, and MR severity were measured simultaneously. During exercise, MR severity, as evaluated by the ratio of MR jet over left atrium area, increased from 15+/-8% to 33+/-15%. Peak VO2, exercise-induced changes in stroke volume, and those in capillary wedge pressure correlated with the changes in MR (r=-0.55, -0.87, and 0.62, respectively, P<0.01). The changes in MR severity also correlated with those in end-diastolic (r=-0.75, P<0.01) and end-systolic (r=-0.72, P<0.01) sphericity indexes and those in the coaptation distance (r=0.86, P<0.01).Our data indicate that in patients with LV dysfunction, exercise-induced changes in MR severity limit the stroke volume adaptation during exercise and therefore contribute to limitation of exercise capacity.
Chemoembolization improves survival in patients with unresectable hepatocellular carcinoma (HCC)
Authors: J.M. Llovet, M.I. Real, R. Vilana, R. Planas, S. Coll, J.J. Aponte, C. Ayuso, M. Sala, J. Muchart, R. Sola, J. Rodes, J. Bruix
Journal: Journal of Hepatology (2001)