tbuckley/cabot-search huggingface dataset:
Ambulatory oxygen improves quality of life of COPD patients: a randomised controlled study
Authors: T. Eaton, J.E. Garrett, P. Young, W. Fergusson, J. Kolbe, S. Rudkin, K. Whyte
Journal: European Respiratory Journal (2002)

It is unknown whether acute response to ambulatory oxygen (O 2 ) predicts longer term improvement in health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) patients. The aims of this study were 1) to assess the short-term clinical impact, as determined by HRQL, of ambulatory O 2 in a 12-week, double-blind, randomised crossover study of O 2 ( versus cylinder compressed air) of dyspnoeic but not chronically hypoxic COPD patients with exertional desaturation ≤88% (n=41), and 2) to determine whether either baseline characteristics or acute response to O 2 predicts short-term (12 weeks) response. Primary outcome measures were Chronic Respiratory Questionnaire (CRQ), Hospital Anxiety and Depression scale and the short form (SF)-36. Improvements were seen in all domains of the CRQ for cylinder O 2 compared with cylinder air. Significant improvements were also noted in anxiety and depression and in certain domains of the SF-36. There were 28 (68%) acute responders to cylinder O 2 (defined as increase in 6‐min walk ≥54 m or decrease in post-Borg dyspnoea ≥1) and 23 (56%) short-term responders (defined as clinically significant improvement in CRQ). However, acute and short-term responses were not correlated with no predictors of short-term response identified. At study completion, 14 (41%) of acute or short-term responders did not want to continue therapy, with 11 citing poor acceptability or tolerability. Short-term ambulatory oxygen is associated with significant improvements in health-related quality of life. These benefits cannot be predicted by baseline characteristics or acute response. Despite acute or short-term response, a substantial proportion of patients declined ambulatory oxygen.
Activin-A induces human regulatory T cells that control allergic asthma
Authors: Sofia Tousa, Maria Semitekolou, Ioannis Morianos, Konstantinos Samitas, Giannis Paraskevopoulos, Mina Gaga, Catherine M. Hawrylowicz
Journal: European Respiratory Journal (2012)

Activin-A is a cytokine involved in essential biological processes.Our previous studies have uncovered activin-A as a controller of experimental asthma through the induction of mouse regulatory T cells (Tregs).Here, we studied the role of activin-A in the induction of human Tregs suppressive against allergic responses in asthmatics.Peripheral blood CD4+ T cells were stimulated with a clinically-relevant allergen in the presence of activin-A (or control).The phenotype of activin-A-treated T cells and their suppressive function on human T cell responses and in asthma protection in a humanized mouse model were investigated.Our data reveal that activin-A greatly inhibits human T cell proliferation and Th2 cytokine release.Activin-A-treated T cells remain hyporesponsive after allergen restimulation and do not express effector cytokines. Still, they express significantly increased amounts of immunosuppressive IL-10.Notably, activin-A-treated T cells are suppressive against allergic responses of atopics and asthmatics, pointing to the generation of a Treg subset (act-A-iTregs). Act-A-iTregs also restrain Th2 responses in the bronchoalveolar lavage (BAL) of severe asthmatics.Using a humanized model of asthma, we show that, co-transfer of act-A-iTregs with human T effectors confers protection against asthma in vivo, as shown by greatly decreased airway hyperresponsiveness, BAL, lung inflammation and Th2 responses in the lungs and draining lymph nodes.Our data reveal that activin-A generates IL-10-producing Tregs that suppress human allergen-driven responses and protect against asthma.Our findings may facilitate the use of act-A-iTregs in adoptive-transfer therapies aiming to re-establish tolerance in asthma.
Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2–6: TMC435-C202, a phase IIa, open-label study
Authors: Christophe Moreno, Thomas Berg, Tawesak Tanwandee, Satawat Thongsawat, Hans Van Vlierberghe, Stefan Zeuzem, Oliver Lenz, Monika Peeters, Vanitha Sekar, Goedele De Smedt
Journal: Journal of Hepatology (2012)
Changes of Boundary Layer Flow in Model Systems
Authors: Heinz Scharfstein, William H. Gutstein, Leon Lewis
Journal: Circulation Research (1963)

A model system using fluid driven through glass and plastic tubes coated with resin, demonstrated augmentation of the viscous shearing stresses at the inner surface of the wall when variations in shape were introduced into the tube and at branch points. The hydrodynamic basis of these increased stresses is presented from the point of view of boundary layer theory, and the relevance for initiation of arterio-atherosclerosis is discussed.
Cerebral blood flow and metabolism in fulminant liver failure
Authors: Julia A. Wendon, Phillip M. Harrison, Richard Keays, Roger Williams
Journal: Hepatology (1994)

Fulminant liver failure is a syndrome that is frequently complicated by cerebral edema and increased intracranial pressure. Cerebral blood flow has been reported as high in some studies but low in others. This study undertook to measure cerebral blood flow and cerebral metabolic rate for oxygen in 30 patients with fulminant liver failure in grade 4 encephalopathy and to assess these parameters after intervention with hyperventilation and infusions of mannitol, epoprostenol and acetylcysteine. Cerebral blood flow varied widely, from 14 to 71 ml/100 gm/min (normal range, widely, from 14 to 71 ml/100 gm/min (normal range, 41 to 66), whereas the cerebral metabolic rate for oxygen was low in all patients, 0.16 to 2.03 ml/100 gm/min (normal range, 3.12 to 3.96). Twenty-one of the 30 patients had evidence of anaerobic metabolism with cerebral lactate production. Hyperventilation resulted in a significant decrease in both cerebral blood flow (median, 36 to 28 ml/100 gm/min) and cerebral metabolic rate for oxygen (median, 0.92 to 0.65 ml/100 gm/min); mannitol and acetylcysteine infusions resulted in significant increases in both of these parameters. Prostaglandin I2 infusion did not significantly after cerebral blood flow, but there was a significant increase in cerebral metabolic rate for oxygen. The depressed cerebral metabolic rate for oxygen in patients with fulminant liver failure is inappropriate to metabolic requirements, as demonstrated by both cerebral lactate production and the increase in cerebral oxygen consumption after improvement in cerebral blood flow. Mannitol infusion should remain the main treatment of the cerebral complications of fulminant liver failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Laminar Shear Stress Upregulates Integrin Expression
Authors: Carmen Urbich, Dirk H. Walter, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2000)

Abstract —Laminar shear stress exerts important effects on endothelial cell (EC) function and inhibits apoptosis of ECs induced by various stimuli. The mechanism by which hemodynamic forces, such as shear stress, are transduced into cellular signaling is still not known. Located at the cell surface, integrins, which are required for cell adhesion and cell survival, are potential mechanotransducers. Therefore, we investigated the effect of shear stress on integrin expression in ECs. Shear stress time-dependently increased the mRNA expression of the fibronectin receptor subunits α 5 and β 1 with a maximum at 6 hours (283±41% and 215±27% of control, respectively). In addition, the protein levels of the fibronectin receptor subunits α 5 and β 1 were enhanced with a maximum at 12 hours of shear stress exposure (343±53% and 212±38% of control, respectively). The shear stress–induced upregulation of integrins is independent of nitric oxide. Furthermore, we confirmed the enhanced functional activity of α 5 β 1 integrin expression by FACS analysis. As a functional consequence, human umbilical vein ECs, which were preexposed to shear stress, revealed a significantly increased attachment (178±10% of static controls) and a more pronounced extracellular signal–regulated kinase 1 and 2 activation in response to cell attachment. Finally, we demonstrated that shear stress requires RGD-sensitive integrins to mediate its antiapoptotic effect. Taken together, these results define a novel mechanism by which shear stress may exert its atheroprotective effects via upregulation of integrins to support EC adhesion and survival.
Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection
Authors: Fanny Tzelepis, Mark Verway, Jamal Daoud, Joshua Gillard, Kimya Hassani-Ardakani, Jonathan Dunn, Jeffrey Downey, Marilena Elena Gentile, Joanna Jaworska, Anthony Michel Jean Sanchez, Yohann Nédélec, Hojatollah Vali, Maryam Tabrizian, Arnold Scott Kristof, Irah Luther King, Luis Bruno Barreiro, Maziar Divangahi
Journal: Journal of Clinical Investigation (2014)

The phagocytosis of apoptotic cells and associated vesicles (efferocytosis) by DCs is an important mechanism for both self tolerance and host defense. Although some of the engulfment ligands involved in efferocytosis have been identified and studied in vitro, the contributions of these ligands in vivo remain ill defined. Here, we determined that during Mycobacterium tuberculosis (Mtb) infection, the engulfment ligand annexin1 is an important mediator in DC cross-presentation that increases efferocytosis in DCs and intrinsically enhances the capacity of the DC antigen-presenting machinery. Annexin1-deficient mice were highly susceptible to Mtb infection and showed an impaired Mtb antigen-specific CD8+ T cell response. Importantly, annexin1 expression was greatly downregulated in Mtb-infected human blood monocyte-derived DCs, indicating that reduction of annexin1 is a critical mechanism for immune evasion by Mtb. Collectively, these data indicate that annexin1 is essential in immunity to Mtb infection and mediates the power of DC efferocytosis and cross-presentation.
Cough hypersensitivity syndrome: towards a new approach to chronic cough
Authors: Roger Escamilla, Nicolas Roche
Journal: European Respiratory Journal (2014)

Although cough is a highly frequent motive for visiting the doctor among both adults and children in primary care [1, 2], it usually resolves spontaneously within a few days or weeks. Conversely, chronic cough, broadly defined as cough persisting for more than 8 weeks, is often a more difficult clinical situation from both diagnostic and therapeutic perspectives [3]. In many patients, the anatomical diagnostic workup introduced almost 40 years ago [4] rapidly unmasks a likely underlying cause, the involvement of which is confirmed by the effectiveness of aetiological treatment. However, in some cases, the initial workup does not reveal any convincing aetiology and cough remains refractory to treatments; the proportion of patients with so-called idiopathic cough varies markedly between series (0–46%) [5], leading authors to question whether this condition exists or is only the consequence of insufficient diagnostic workup, which should include various therapeutic trials before concluding as to the idiopathic nature of cough [6]. Whatever the answer is, such situations may be worrying, as, in parallel, chronic cough is a significant cause of quality-of-life impairment [7].

It has been hypothesised that some, if not all, cases of chronic refractory/idiopathic cough may belong to a specific phenotype and share some common pathophysiological mechanism, namely hypersensitivity of the cough reflex [6]. As such hypersensitivity is not restricted to idiopathic cough, it has been proposed that, in general, chronic cough is the result of an interaction between intrinsic cough reflex abnormalities ( i.e. hypersensitivity) and aggravating factors such as angiotensin-converting enzyme (ACE) inhibitors, gastro-oesophageal reflux disease (GORD), upper airway disorders, eosinophilic airway diseases and cigarette smoke/chronic obstructive pulmonary disease (COPD) [5]. The term “cough hypersensitivity syndrome” (CHS) was then proposed [8] to name the …
High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis
Authors: E. Dekker, K. Boparai, J. Poley, E. Mathus-Vliegen, G. Offerhaus, E. Kuipers, P. Fockens, J. Dees
Journal: Endoscopy (2009)

See also: Commentaire de travail de E. Dekker et al., pp. 935Endoscopy 2009; 41(08): 826-826DOI: 10.1055/s-0032-1306743
A Systems Approach to Designing Effective Clinical Trials Using Simulations
Authors: Vincent A. Fusaro, Prasad Patil, Chih-Lin Chi, Charles F. Contant, Peter J. Tonellato
Journal: Circulation (2012)

Background— Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit in comparison with standard clinical therapy. This study demonstrates a computational framework to systematically evaluate preclinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results— We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and nongenetic clinical-based, multiple-dose adjustment protocols, pharmacokinetic/pharmacodynamics modeling and international normalization ratio prediction, and various types of outcome measures. We validated the framework by conducting 1000 simulations of the Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin (CoumaGen) clinical trial primary end points. The simulation predicted a mean time in therapeutic range of 70.6% and 72.2% ( P =0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in the time in therapeutic range between the pharmacogenetic and standard arm (78.8% versus 73.8%; P =0.0065), respectively. Conclusions— We demonstrate that this simulation framework is useful in the preclinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk.
Indoor Radon and Lung Cancer in China
Authors: W J Blot, Z Y Xu, J D Boice, D Z Zhao, B J Stone, J Sun, L B Jing, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1990)

Radon has long been known to contribute to risk of lung cancer, especially in undergound miners who are exposed to large amounts of the carcinogen. Recently, however, lower amounts of radon present in living areas have been suggested as an important cause of lung cancer. In an effort to clarify the relationship of low amounts of radon with lung cancer risk, we placed alpha-track radon detectors in the homes of 308 women with newly diagnosed lung cancer and 356 randomly selected female control subjects of similar age. Measurements were taken after 1 year. All study participants were part of the general population of Shenyang, People's Republic of China, an industrial city in the northeast part of the country that has one of the world's highest rates of lung cancer in women. The median time of residence in the homes was 24 years. The median household radon level was 2.3 pCi/L of air; 20% of the levels were greater than 4 pCi/L. Radon levels tended to be higher in single-story houses or on the first floor of multiple-story dwellings, and they were also higher in houses with increased levels of indoor air pollution from coal-burning stoves. However, the levels were not higher in homes of women who developed lung cancer than in homes of controls, nor did lung cancer risk increase with increasing radon level. No association between radon and lung cancer was observed regardless of cigarette-smoking status, except for a nonsignificant trend among heavy smokers. No positive associations of lung cancer cell type with radon were observed, except for a nonsignificant excess risk of small cell cancers among the more heavily exposed residents. Our data suggest that projections from surveys of miners exposed to high radon levels may have overestimated the overall risks of lung cancer associated with levels typically seen in homes in this Chinese city. However, further studies in other population groups are needed to clarify the carcinogenic potential of indoor radon.
Early postoperative serum cystatin C predicts severe acute kidney injury following pediatric cardiac surgery
Authors: Michael Zappitelli, Catherine D. Krawczeski, Prasad Devarajan, Zhu Wang, Kyaw Sint, Heather Thiessen-Philbrook, Simon Li, Michael R. Bennett, Qing Ma, Michael G. Shlipak, Amit X. Garg, Chirag R. Parikh
Journal: Kidney International (2011)
Psychological Outcomes in Long-Term Survivors of Childhood Brain Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Brad J. Zebrack, James G. Gurney, Kevin Oeffinger, John Whitton, Roger J. Packer, Ann Mertens, Norman Turk, Robert Castleberry, ZoAnn Dreyer, Leslie L. Robison, Lonnie K. Zeltzer
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate and compare psychological outcomes in long-term survivors of pediatric brain cancer and siblings of childhood cancer survivors, and to identify significant correlates of psychological distress. Methods One thousand one hundred one adult survivors of childhood brain cancer and 2,817 siblings completed a long-term follow-up questionnaire allowing assessment of symptoms associated with depression, somatization, and anxiety, as well as demographic, health, and medical information. Results A large majority of siblings and survivors report few, if any, symptoms of psychological distress. The prevalence of distress approximating clinically significant levels for both survivors (11%) and siblings (5%) reflects rates found in the general population. Yet when accounting for significant sociodemographic, socioeconomic, and health-status variables, survivors of childhood brain cancer, in the aggregate, appear to report significantly higher global distress and depression scores than do siblings. As in the general population, higher levels of distress among survivors and siblings were associated with female sex, low household income, lower educational attainment, being unmarried, not being employed in the past 12 months, and poor physical health status. No diagnostic or treatment-related variables were directly and significantly associated with increases in distress symptoms for survivors of childhood brain cancer. Conclusion Cancer treatment does not appear to contribute directly to increased psychological distress. Instead, distress appears to be associated with diminished social functioning that may be related to cancer type or treatment. Implementation and evaluation of supportive interventions that enhance survivors' social and vocational skills should be considered.
Treatment of Panic
Authors: Norman B. Schmidt, Meghan E. Keough
Journal: Annual Review of Clinical Psychology (2009)

The present review summarizes empirical developments in the psychosocial treatment of panic and panic disorder by focusing on four key themes that have been emphasized in this literature: (a) treatment efficacy, effectiveness, and innovation; (b) modulating and process variables in treatment; (c) effective dissemination of treatment; and (d) prevention of panic. Cognitive behavioral treatments (CBTs) for panic are very good, even in the context of comorbidity, but the level of efficacy does not appear to be increasing over time. Unfortunately, there have been relatively few substantive innovations in CBT protocols since the 1980s, and despite progress in the use of computer technology, dissemination of these treatments is lagging. The prevention of panic-spectrum psychopathology is a promising area linked with advances in the identification of panic-relevant risk factors that appear to modulate CBT outcomes.
Renal risk and renoprotection among ethnic groups with type 2 diabetic nephropathy: A post hoc analysis of RENAAL
Authors: D. de Zeeuw, D. Ramjit, Z. Zhang, A.B. Ribeiro, K. Kurokawa, J.P. Lash, J. Chan, G. Remuzzi, B.M. Brenner, S. Shahinfar
Journal: Kidney International (2006)
Plasma cytomegalovirus (CMV) DNA load predicts CMV disease and survival in AIDS patients.
Authors: S A Spector, R Wong, K Hsia, M Pilcher, M J Stempien
Journal: Journal of Clinical Investigation (1998)

In this study, baseline plasma from 619 persons with acquired immunodeficiency syndrome (AIDS) (median CD4+ lymphocyte count -21/microl) who participated in a trial to determine the efficacy of oral ganciclovir for cytomegalovirus (CMV) disease prevention were evaluated for CMV DNA load by qualitative and quantitative polymerase chain reaction (PCR), and correlated with the development of CMV disease and survival. For participants without detectable plasma CMV DNA, the 12-mo Kaplan-Meier CMV disease event rate was 14% and 1% for the placebo and ganciclovir groups, respectively (P < 0.001). For PCR positive participants, CMV disease developed in 43% of placebo and 26% ganciclovir recipients (P < 0.017). Among placebo recipients, CMV PCR positivity was associated with a 3.4-fold increased risk of developing CMV disease (P < 0.001) whereas CD4+ lymphocyte count was not a useful predictor (P = 0.47). A positive plasma CMV DNA PCR was also associated with a 2.5-fold increased risk of death. Each log10 increase in baseline CMV DNA load was associated with a 3.1-fold increase in CMV disease (P < 0.001) and a 2.2-fold increase in mortality (P < 0.001). These data indicate that the risk of developing CMV disease and death in persons with advanced AIDS is directly related to the quantity of CMV DNA in plasma, and is a better predictor than CD4+ lymphocyte count in this population.
Identification of amplified and highly expressed genes in amplicons of the T-cell line huT78 detected by cDNA microarray CGH.
Authors: Bárbara Meléndez, Beatriz Martínez-Delgado, Marta Cuadros, Victoria Fernández, Ramón Díaz-Uriarte, Javier Benítez
Journal: Molecular Cancer (2005)

Conventional Comparative Genomic Hybridization (CGH) has been widely used for detecting copy number alterations in cancer and for identifying regions containing candidate tumor responsible genes. Recently, several studies have shown the utility of cDNA microarray CGH for studing gene copy changes in various types of tumors. However, no such studies on T-cell lymphomas have been performed. To date T-cell lymphomas analyzed by the use of chromosome CGH have revealed only slight copy number alterations and not gene amplifications. In the present study, we describe the characterization of three amplicons of the T-cell line huT78 located at 2q34-q37, 8q23-q24 and 20p, where new amplified and overexpressed genes are found. The use of a cDNA microarray containing 7.657 transcripts allowed the identification of certain genes, such as BCLX, PCNA, FKBP1A, IGFBP2 and cMYC, that are amplified, highly expressed, and also contained in the amplicons on 20p and 2q. The expresion of these genes was analyzed in 39 T-cell lymphomas and 3 other T-cell lines. By the use of conventional CGH and CGH and expression cDNA microarrays we defined three amplicons in the T-cell line huT78 and identified several novel gene amplifications (BCLX, PCNA, FKBP1A, IGFBP2 and cMYC). We showed that overexpression of the amplified genes could be attributable to gene dosage. We speculate that deregulation of those genes could be important in the development of T-cell lymphomas and/or in the maintenance of T-cell lines.