tbuckley/cabot-search huggingface dataset:
Mast cell generated cyclooxygenase products protect from airway hyperresponsiveness in a model of chronic asthma
Authors: Barbara Fuchs, Lisa Sjöberg, Christine Möller Westerberg, Maria Ekoff, Linda Swedin, Sven-Erik Dahlén, Mikael Adner, Gunnar Nilsson
Journal: European Respiratory Journal (2011)

The cyclooxygenase (COX) product prostaglandin (PG) E2 is known to act bronchoprotective in asthmatics. Recent preclinical studies identified the COX-terminal microsomal PGE synthase-1 to contribute to the formation of protective PGE2. This study investigated whether the release of bronchoprotective COX products is mast cell (MC) dependent.  Chronic allergic airway inflammation in mice was induced by ovalbumin/alum injections and repeated challenges during 90 days. COX-inhibition with diclofenac (DFC) was performed. Airway hyperresponsiveness (AHR) was assessed applying forced-oscillation technique in response to methacholine. Contribution of MC-COX-products to AHR was resolved by comparing Wsh (MC-deficient) to C57BL/6 wildtype (WT) mice (MCs around central airway).  Central airway resistance, R n  was pronounced in allergen-challenged WT mice and increased in WT-DFC [cmH2O/s*mL, mean± SEM: 1.3±0.1  vs  1.6±0.2, p=0.04]. Wsh displayed comparable resistance [1.7±0.1] as WT-DFC. R n  in Wsh was not changed after treatment [1.9±0.2].  Both mouse strains lack MCs in peripheral lung tissue. Consequently, tissue resistance was not changed in WT and Wsh [8.5±0.5  vs  7.8±0.6], nor after treatment [WT-DFC 7.8±0.5, Wsh-DFC 7.6±0.6]. Although a shift in baseline tissue elastance was observed between WT and Wsh [21.9±1.4  vs  17.7±0.4, p=0.02], treatment did not affect baseline [WT-DFC 21.4±1.2; Wsh-DFC 17.6±0.9], nor was the reactivity changed.  The data indicates that the bronchoprotective role of PGE2 is MC dependent. It remains to be seen if this is due to PGE2 or other COX products released by MCs, or if modulating COX products are released by other cells in response to MC activation.
Abstract 20772: Antiarrhythmic Effect of Mesenchymal Stem Cells in Myocardial Infarction is Dependent on Surrounding Environment Through Altered Paracrine Action
Authors: Hye Jin Hwang, Heesang Song, Il-Kwon Kim, Byeong-Wook Song, Min-Ji Cha, Eun Ju Choi, Onju Ham, Boyoung Joung, Hui-Nam Pak, Sung Soon Kim, Yangsoo Jang, Moon-Hyoung Lee, Ki-Chul Hwang
Journal: Circulation (2010)

Background:  Mesenchymal stem cells (MSCs) can provide paracrine factor support for other cells in injured myocardium. We hypothesized that anti-arrhythmic effect of MSCs might depend on the environment through different paracrine action.   Methods:  Sham (n=23), paracrine media (PM) secreted from MSCs under hypoxia (hypoxic PM group, n=12), PM secreted under normoxia (normoxic PM group, n=14) were administrated at border zone in rats with MI. At 7–10 days, we performed optical mapping, histological analysis, immunostaining, measurement of cytosolic free Ca 2+ , RT-PCR, and proteomics analysis.   Results:  Survival curves revealed a marked reduction of sudden deaths in hypoxic PM, compared to normoxic PM (8.3% in hypoxic PM vs. 35.7% in normoxic PM, p=0.1) and sham-operated group (8.3% in hypoxic PM vs. 52.2% in sham, p=0.016). In optical mapping, pacing protocol induced VT in 77.8 % of sham-operated (n=9), 14.3 % of hypoxic PM (n=7), and 50 % of normoxic PM group (n = 6). Conduction velocity (CV) was markedly restored in hypoxic PM treated lesion compared to normoxic PM treated lesion (0.8±0.1m/s vs. 0.37±0.09 m/s, p 2+  overload, and an increase of Ca 2+  related protein expression underlay this electrophysiological alteration. It was identified to be mediated by substances such as bFGF, IGF-1, HGF and EF hand domain containing 2. To assess the cellular effect of MSCs, we compared MSCs -injected rats (m=24) with normoxic PM-treated rats (n=15) after 1hr injury and treatment. CV were similar in MSCs engrafted and normoxic PM treated lesions (0.42±0.1m/s in MSCs vs. 0.37±0.09 m/s in normoxic PM, p>0.05), but APD80 increased in MSCs-engrafted lesion (98±12 ms vs. 78±21ms, p 0.05).   Conclusions:  PM secreted from MSCs showed different preventive effect in sudden death and arrhythmogenicity according to hypoxic or normoxic environment, suggesting that antiarrhythmic effect of MSCs may depend on the surrounding environment.
A comparison of QuantiFERON-TB Gold In-Tube test and new QuantiFERON-Microtube assay in children suspect of active TB and adults with active TB
Authors: Michala Vaaben Rose, Inge Kroidl, Michal Hoelscher, Godfry Mfinanga, Pernille Ravn
Journal: European Respiratory Journal (2011)

Background:  The use of Quantiferon-TB Gold In-Tube test (QFT) in children is limited by volume of blood required. A Quantiferon Microtube (QFT-MT) using only 0.9ml of blood is being evaluated.   Objective:  Comparing performance of QFT and QFT-MT for diagnosing TB infection in children and adults.   Methods:  160 children suspected for TB and104 adults with smear-positive TB were tested with QFT, QFT-MT, and TST.   Results:  Among 160 children, 24 (15%) were QFT and 30 (18.8%) QFT-MT-positive, p=0.37 and 40 (25%) were QFT- and 34 (21.3%) QFT-MT-indeterminate, p=0.43.  Among 104 adults 76 (73.1%) were QFT- and 81 (77.9%) QFT-MT positive; p=0.42; 21 (20.2%) and 7 (6.7%) were QFT- and 10 (9.6%) QFT-MT-indeterminate, p=0.41. The proportions of positive, negative and indeterminate results of QFT were similar between the two IGRA.  In children clincially diagnosed with active TB, positivity rates of QFT and QFT-MT were surprisinly low; 21.4% and 31.1% (p=0.29) and much higher in adults with microscopy confirmed TB (84.6% and 95.2% respectively (p=0.05). Test performance between the two IGRAs was comparable with moderate concordance (76.3%, k=0.57) in children and 80.8%, k=0,52) in adults. The study team found it easy to use the QFT-MT system   Conclusion:  Overall the performance of the QFT-MT test using 0.9ml of blood was equal to the QFT test using 3 ml of blood. The low sensitivity of both tests in children suggests difficulties in diagnosing TB in children as often descirbed. Considering the potential benefits of QFT-MT in testing young children and infants we suggests that further investigations of the test performance are warranted.
Role of the nitric oxide in the lung function and airway hyperreactivity in silicotic mice
Authors: Davidson Dias, Tatiana Ferreira, Bianca Ciambarella, Ana Arantes, Patrícia Silva, Marco Aurélio Martins
Journal: European Respiratory Journal (2013)

Introduction:  Silicosis is an inflammatory restrictive pulmonary disease caused by silica particle inhalation, characterized by intense fibrosis and granuloma formation. Several inflammatory mediators are involved in this disease, including nitric oxide (NO).   Aim:  To investigate the involvement of NO in silica-induced changes in lung function, hyperreactivity and airway morphology.   Methods:  Male wild-type C57BL/6 (iNOS+/+) and iNOS ko (iNOS-/-) mice were anesthetized and received a single intranasal instillation of silica (10 mg/50 µL) or saline (control). The analyzes were made 7 and 28 days after silica provocation and included: i) lung function and airways hyperrreactivity to methacholine, ii) quantification of nitric oxide levels in the bronchoalveolar lavage (BAL), iii) morphological and morphometric analyses and iv) treatment with NO donor DETANonoate (0.61 µmol/animal).   Results:  The animals exposed to silica showed higher lung function and airway response than the controls. In 7 days (11.5±2.6) (mean ± SEM) as soon as 28 days (7.8±0.6), the NO in BAL fluid was greater in silicotic mice as compared respectively to those of the controls (5.5±0.7) and (4.7±0.2). Instillation of DETANonoate led to an increase in lung resistance and elastance to methacholine. Yet all silica effects were abolished in iNOS -/- mice.   Conclusion:  Silica induced lung function compromise and airways hyperreactivity is directly associated with inflammation and granuloma formation. These responses were markedly suppressed in iNOS knockout mice, indicating that NO seems to significantly contribute to several features of the silicosis, including airways hyperreactivity and inflammation.  Financial support: FAPERJ, CNPq.
Lung clearance index predicts pulmonary exacerbations in cystic fibrosis
Authors: Joerg Grosse-Onnebrink, Florian Stehling, Uwe Mellies
Journal: European Respiratory Journal (2014)

Background:  The lung clearance index (LCI) is increasingly used as an endpoint in clinical trials, but data showing its associations with clinical endpoints and its prognostic value are spares.  Objectives:  We aimed to show whether the LCI is associated with clinical parameters supposed to reflect lung disease in cystic fibrosis and whether the LCI predicts subsequent pulmonary exacerbations (PE).  Methods:  Baseline LCI, spirometry parameters and clinical data were obtained and PE per year were prospectively recorded in 59 patients with proven cystic fibrosis. Linear regression models were used to explore associations between baseline data and LCI and between LCI and PE.  Results:  59 Patients with a mean age of 17.8 years (range 6.3; 44.6) with a mean baseline FEV1 of -3.1 z-score (-13.2; 2.7) and a mean LCI of 9.9 (6.2; 18.6) were evaluated for a mean of 3.1 years (1.5; 3.5) years. 165 PE were recorded, the mean annual PE rate was 2.8 (0; 14). PO2 (β =-0.124; 95%CI -0.188; -0.060), FEV1 z-score (β= -0.288 95%CI -0.534; -0.041) and status of infection with Pseudomonas aeruginosa (β= -1,759 95%CI -3.029; -0.489) were independent predictors of LCI (r=0.779; r 2 =0.606). LCI was the only predictor of subsequent PE (β=0.306 95%CI 0.196; 0.415, r=0.629; r 2 =0.40).  Conclusion:  We show that the LCI is associated with surrogate parameters of lung disease. By predicting PE the LCI is also associated with markers of clinical deterioration in cystic fibrosis patients. Our data support the use of LCI as a valuable endpoint in clinical trials.
Cardiovascular regulation effects of CPAP therapy in obstructive sleep apnea patients with and without hypertension during daytime
Authors: Thomas Penzel, Christoph Schöbel, Carmen Garcia, Martin Glos, Niels Wessel, Ingo Fietze
Journal: European Respiratory Journal (2012)

Obstructive sleep apnea can cause changes in cardiovascular regulation during the night and during daytime. Altered regulation may not be visible in absolute values of heart rate and blood pressure but in a changed coupling between the heart beat and the respiration. In a controlled randomized study we investigated effects of CPAP therapy on daytime cardiovascular regulation.  Twenty-eight patients with OSA in total, thereof 18 with arterial hypertension and 10 with normal blood pressure, were studied at baseline and at a follow up date with three months of CPAP. Ten age and sex matched healthy control subjects were investigated using the same protocol. All subjects underwent cardiorespiratory polysomnography. In addition we recorded 20 minutes quiet breathing at rest and a bicycle ergometry with ECG and blood pressure (Portapres). Cardiorespiratory coupling was investigated using symbolic coupling traces, a new developed technique which can reveal causality between signals.  The stress test showed a significant reduction of the diastolic blood pressure at a work load of 50W and 100W (p  The results indicate a reduction of vascular resistance and sympathetic activity during daytime. The coupling analysis of the resting periods by means of symbolic coupling traces approach indicated an effect of the CPAP therapy on the baroreflex reaction in hypertensive patients where influences of the systolic blood pressure on the heart rate changed from pathological patterns to adaptive mechanisms of the normotensive patients (p
QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION
Authors: Michael Heidelberger, Forrest E. Kendall
Journal: The Journal of Experimental Medicine (1932)

A method, based on the precipitin reaction, is given for the micro determination of the specific polysaccharide of Type III pneumococcus. As little as 0.01 mg. of S III can be determined. The method should be applicable to any specific polysaccharide upon standardization of an homologous antibody solution or antiserum in the region of excess antibody.
The wow factor as a determinant of funding for disorders of the skin
Authors: Terence J. Ryan
Journal: Military Medical Research (2015)

As people live beyond 100 years, there is an extended period of impaired quality of life for the increasing numbers of individuals with skin disorders. There is also a growing work force of fit elderly individuals who are able to provide low technology skin care and who can teach self-help if well instructed. The International Society of Dermatology's sub-committee Skin Care for All: Community Dermatology seeks to bring together those who care for skin diseases and those who manage wounds, burns, lymphoedema and neglected tropical diseases affecting the skin for the purpose of skin care. Their focus is the repair of four functions: barrier, thermoregulation, sensory perception and communication. The curriculum includes low cost self-help and the restoration of absent skin. The care expectation is one of technical proficiency integrated with kindness and altruism. The concept is attracting wide attention but needs to develop compelling and persuasive arguments ("wow factors") regarding why it should be funded. There is probably no greater wow factor than tracing the path of a severely injured patient from the battlefield through the course of immediate first aid by paramedics to the surgeon in the frontline tent who can almost guarantee survival. Seeing these disfigured persons winning trophies at the Olympic Games has garnered the admiration of millions of viewers.
Leukotriene pathway and asthma in children with sickle cell disease
Authors: Mattia Guerra, Anna Pusiol, Raffaello Tosolini, Barbara Toffoletto, Daniela Cesselli, Angelo Rosolen
Journal: European Respiratory Journal (2013)

Asthma is a common comorbidity in sickle cell disease (SCD) with a prevalence of 20-48%. Recent evidence suggests that features of asthma, such as airway hyperresponsiveness, may be related to the underlying haematological disease.1Cysteinyl leukotrienes (CysLT) levels are increased both in asthma and in SCD, but the relationship between CysLT and SCD is poorly defined.

Aim To analyze steady-state plasma LTE4 in SCD children; to assess the relationship between LTE4 levels and features of asthma

Methods SCD children at steady state and healthy subjects matched for age and race underwent blood tests, prick tests, exhaled nitric oxide and spirometry. Plasma was obtained within 2 hours from collection, stored at -80°C until purification and examination (EIA test). Exclusion criteria: <5 yrs, hydroxyurea or regular blood transfusion therapy, controller medications for asthma

Results Ten SCD patients (80%SS; mean age 6.8yrs) and 7 controls were enrolled. LTE4 levels were higher in SCD compared with controls (median 130.2 vs. 74.1pg/ml); in controls mean LTE4 was 73.3±10.7. Asthma features in SCD cohort are shown

View this table:



Conclusion Baseline LTE4 in plasma is elevated in SCD. No signs of an allergic diathesis seem to be associated with increased LTE4 levels. Due to sample size type I and II errors should be considered. [1]Field JJ et al. Chest 2011;139:563-568.
Definition and validation of a predictive model to identify COPD patients from administrative databases
Authors: Lisa Bauleo, Nera Agabiti, Ursula Kirchmayer, Valeria Belleudi, Luigi Pinnarelli, Silvia Cascini, Danilo Fusco, Massimo Arcà, Marina Davoli
Journal: European Respiratory Journal (2011)

Background:  Large administrative databases are increasingly used to identify patients with chronic conditions, however the best methodology for Chronic Obstructive Pulmonary Disease (COPD) is still debated.   Objective:  To develop and validate a predictive model to identify patients with COPD in Lazio region (2,625,102 residents over 45) linking clinical and administrative data.   Methods:  From regional hospitalizations and drug prescriptions, through record linkage, we identified patterns of specific drug use (minimum 2 prescription during 12 months) and COPD hospitalizations during a 9-year period in 428 patients with COPD, who attended an outpatient clinic in 2006, and in 2140 people without COPD (selection from outpatients9 specialized health care registry). Through a Bootstrap-Stepwise procedure we analyzed COPD associated factors. We validated the algorithm through internal (cross-validation-bootstrap, jack-knife) and external validation (comparison with COPD patients with confirmed diagnosis).   Results:  Prevalence of COPD was 7.8%. Factors associated with COPD were prescription of beta2-agonists, anticholinergics, corticosteroids, oxygen, previous hospitalization for COPD and respiratory failure. For each patient we estimated an expected probability to suffer from COPD. Depending on the cut-point of expected probability, sensibility ranged from 74.5 to 99.6%, specificity from 37.8 to 86.2%. We defined a cut-point of 0.30 to identify COPD patients. Applying our algorithm on external COPD patients we succeeded to identify 70%.   Conclusion:  The predictive model showed good performance to identify COPD patients confirming the strength of administrative data for monitoring chronic diseases.
Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Mona Bafadhel, Susan McKenna, Sarah Terry, Vijay Mistry, Carlene Reid, Pranabashis Haldar, Margaret McCormick, Koirobi Haldar, Tatiana Kebadze, Annelyse Duvoix, Kerstin Lindblad, Hemu Patel, Paul Rugman, Paul Dodson, Martin Jenkins, Michael Saunders, Paul Newbold, Ruth H. Green, Per Venge, David A. Lomas, Michael R. Barer, Sebastian L. Johnston, Ian D. Pavord, Christopher E. Brightling
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology.Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated.A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively.The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
The TORCH (TOwards a Revolution in COPD Health) survival study protocol: Fig. 1.—
Authors: J Vestbo
Journal: European Respiratory Journal (2004)

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.
Metastatic Breast Cancer, Version 1.2012
Authors: Robert W. Carlson, D. Craig Allred, Benjamin O. Anderson, Harold J. Burstein, Stephen B. Edge, William B. Farrar, Andres Forero, Sharon Hermes Giordano, Lori J. Goldstein, William J. Gradishar, Daniel F. Hayes, Clifford A. Hudis, Steven Jay Isakoff, Britt-Marie E. Ljung, David A. Mankoff, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Lori J. Pierce, Elizabeth C. Reed, Mary Lou Smith, Hatem Soliman, George Somlo, Richard L. Theriault, John H. Ward, Antonio C. Wolff, Richard Zellars, Rashmi Kumar, Dorothy A. Shead
Journal: Journal of the National Comprehensive Cancer Network (2012)

These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.