tbuckley/cabot-search huggingface dataset:
Biomarkers and community-adquired pneumonia (CAP) etiology
Authors: Elisa Minchole, Sergio Fandos, Ana Simon, Carolina Panadero, Ana Lasierra, Maria Angeles Ruiz, Guillermo Hernandez, David Nieto, Clara Viñado, Salvador Bello
Journal: European Respiratory Journal (2012)

INTRODUCTION  It is a controversial matter if virus alone, without a copathogen is able to cause pneumonia in immuncompetent adults. We studied leukocyte count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) serum levels to test their behaviour in each etiologic group.  MATERIALS AND METHODS  In a prospective study, we obtained serum CRP, PCT, WBC and PADM from 282 patients with CAP at their admittance. A complete test battery was performed, including two multiple polimerase chain reaction (PCR) for respiratory viruses.  RESULTS  PCT had significant higher levels in bacteria-involved CAP (bacterial an mixed) than viral/atypical ones. Mixed bacterial/viral CAP had a similar value for PCT, whereas viral pneumonias showed lower PCT levels. CRP values were also different between viral and mixed CAP. When Influenza was removed from viral group, differences were maintained. ROC curve to try to discriminate bacteria-involved from viral CAP, had an AUC for PCT of 0.658 (p  CONCLUSION  Biomarkers CRP and specially, PCT have a different behavior in viral than mixed bacterial/virus CAP, even without including Influenza. That suggests that viruses can be, without associated copathogen, cause of CAP.  Levels of PCT are similar in bacterial CAP than mixed virus/bacterial CAP, and higher than the viral pneumonia ones, and it can help us to differentiate bateria-involved pneumonia from viral CAP.
A new pathogenicity island carrying an allelic variant of the Subtilase cytotoxin is common among Shiga toxin producing Escherichia coli of human and ovine origin
Authors: V. Michelacci, R. Tozzoli, A. Caprioli, R. Martínez, F. Scheutz, L. Grande, S. Sánchez, S. Morabito
Journal: Clinical Microbiology and Infection (2013)
A model-based analysis of the effect of hypoxia on regional pulmonary blood flow
Authors: Kelly Burrowes, Alys Clark, Annalisa Swan, Merryn Tawhai
Journal: European Respiratory Journal (2011)

Hypoxic pulmonary vasoconstriction (HPV) diverts blood from hypoxic regions of the lung, optimising ventilation/perfusion (V/Q) matching and gas exchange. In whole lung hypoxia (i.e. high altitude) HPV becomes less effective but still impacts on gas exchange by redirecting blood flow to regions of higher oxygen partial pressure (PO2). The combination of events leading to this response on a regional level is not well understood and is difficult to investigate experimentally, particularly in humans.  In this study we use a structure-based model to investigate the interacting mechanisms that contribute to regional development of HPV under low inspired PO2 (PiO2) to understand its effect on perfusion redistribution in the pulmonary circulation. The mathematical model couples ventilation (V), perfusion (Q), and gas exchange within a patient-specific anatomical structure. Regional alveolar PO2 (PAO2) is simulated for various levels of PiO2. An empirically-derived model of HPV [J Appl Physiol:1988;64(1):68-77] is included in an existing multi-scale model of the pulmonary circulation [doi:10.1152/japplphysiol.00775.2010] and the resultant blood flow predicted.  During hypoxia pulmonary artery pressure and pulmonary vascular resistance increased exponentially with decrements in PiO2. Regions with lower baseline V/Q had lower predicted PAO2 and hence greater vasoconstriction; blood was therefore redistributed preferentially to the gravitationally non-dependent tissue (decreased gravitational flow gradient), in agreement with experimental measurements in animals. Shear stress in the non-dependent region increased proportionately. The resultant decreased blood flow gradient results in a more efficient V/Q matching.
Contribution of Transient Receptor Potential Ankyrin 1 to Chronic Pain in Aged Mice With Complete Freund's Adjuvant–Induced Arthritis
Authors: Sheldon R. Garrison, Cheryl L. Stucky
Journal: Arthritis & Rheumatology (2014)

To investigate age-related differences in mechanical sensitivity to inflammatory pain and determine the contribution of transient receptor potential ankyrin 1 (TRPA1) to mechanical hypersensitivity during chronic inflammation in young and aged mice with complete Freund's adjuvant (CFA)-induced arthritis.Mechanical sensitivity in young (3-month-old) and aged (24-month-old) wild-type (TRPA1(+/+) ) mice and TRPA1-deficient (TRPA1(-/-) ) mice was measured behaviorally for 8 weeks following injection of CFA into the plantar hind paw. The severity of inflammation was evaluated by histologic analyses and hind-paw measurements. Ex vivo preparations of the skin saphenous nerve from mice were assessed for C-fiber sensitivity.Among naive (uninjured) wild-type mice, aged animals were less sensitive than young animals to mechanical stimuli. Afferent recordings of C-fibers from TRPA1(-/-) mice indicated that TRPA1 contributes to the normal mechanical sensitivity in both age groups. Following injection of CFA, both young and aged TRPA1(+/+) mice exhibited mechanical hypersensitivity. In young TRPA1(-/-) mice injected with CFA, peak development of mechanical hypersensitivity was delayed until week 4, when they exhibited a sharp decrease (9-fold) in the mechanical paw withdrawal threshold, whereas aged TRPA1(-/-) mice did not exhibit mechanical hypersensitivity at any time during the 8 weeks after CFA injection. Recordings of C-fibers from the saphenous nerve supported these findings, with results indicating that both young and aged TRPA1(+/+) mice exhibited increased action potential firing at 8 weeks after CFA injection (increases of 25% and 60%, respectively). Interestingly, among TRPA1(-/-) mice injected with CFA, mechanical firing was increased markedly in the C-fibers of young mice (increase of 80%) but not in the C-fibers of aged mice.These findings reveal marked differences in the long-term mechanical behavioral sensitivity of aged and young mice, and suggest that TRPA1 may be a key contributor to the transition from acute to chronic inflammatory pain in response to mechanical stimuli as well as to the development of nociceptor sensitization selectively in aged mice.
Three-dimensional reconstruction of the right ventricle from two-dimensional echocardiographic images: Validation of volume measurements against MRI
Authors: Nicole Bhave, Benjamin Freed, Amit Patel, Megan Yamat, Lynn Weinert, James Bodtke, Roberto Lang, Mardi Gomberg-Maitland
Journal: European Respiratory Journal (2012)

Assessment of right ventricular (RV) function is an essential component of the diagnosis and management of patients with Pulmonary Arterial Hypertension (PAH). Today, this assessment is performed using two-dimensional echocardiography (2DE), which is challenging due to the complex geometry of the right ventricle. We hypothesized that 3D reconstruction of RV endocardium from 2DE images would provide accurate RV volume measurements. The aim of this study was to validate these measurements in against cardiac magnetic resonance (CMR) reference. Methods. Eleven PAH patients were recruited for same day 2DE and CMR imaging. 2DE images of the right ventricle were acquired in standard imaging planes using a 3D spatial localization device. 3D reconstruction was performed using dedicated software to obtain end-systolic and end-diastolic volumes (ESV, EDV). (VentriPoint). CMR images were analyzed to provide RV volume reference values using Simpson9s method of disks. Results. Image acquisition was feasible in all 11 patients allowing reconstruction of the ventricular cast and volume measurements at end-systole and end-diastole.  Both ESV and EDV correlated highly between modalities. Bland Altman analysis showed minimal biases and narrow limits of agreement. Conclusion. This study indicates that this novel technique may provide accurate measurement of RV volumes in PAH patients.
Imbalance between circulating endothelial cells and endothelial progenitors in idiopathic pulmonary fibrosis
Authors: David Smadja, Laetitia Mauge, Hilario Nunes, Clement d'Audigier, Karine Juvin, Raphael Borie, Zohra Carton, Olivier Sanchez, Bruno Crestani, Dominique Valeyre, Pascale Gaussem, Dominique Israel-Biet
Journal: European Respiratory Journal (2011)

Background:  Fibrogenesis during idiopathic pulmonary fibrosis (IPF) is associated with abnormal vascular remodeling. Respective abundance of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the balance between vascular injury and repair and potentially serve as a biomarker of the disease.   Objectives:  We postulated that CEC and all EPC subtypes might be differently modulated in IPF. We aimed at 1) assessing them in early stages of IPF and 2) searching for correlations with disease severity.   Methods:  64 consecutive patients with newly diagnosed IPF and 10 healthy age-matched volunteers were studied. CEC were isolated with CD146-coated beads. CD34, CD133 and KDR antigens, characterizing EPC, were assessed through flow cytometry. EPC (early CFU-Hill and late endothelial cells forming colonies (ECFC)) were also counted using cell culture.   Results:  CEC numbers were significantly increased in IPF (p=0.004) whereas EPC assessed using both flow cytometry (CD34+KDR+) and cell culture were decreased vs controls (p  or  40%). ECFC was the only cell type found to be correlated to DLCO (Spearman correlation test, p=0.04).   Conclusion:  IPF is associated with markers of vascular injury and with a global decrease in EPC. Disease severity is associated with an EPC mobilization whose mechanisms and clinical impact need to be explored.
Effectiveness of a sleep disorders center: a 9-month follow-up
Authors: P J Hauri, B Hayes, M Sateia, C Hellekson, L Percy, E Olmstead
Journal: American Journal of Psychiatry (1982)

To assess the usefulness of a sleep disorders center the authors sent follow-up questionnaires to patients and referring physicians 9 months after each diagnostic evaluation. Findings suggest that sleep disorders centers provide a useful diagnostic service, especially for patients suffering from excessive daytime sleepiness. This problem usually has a medical etiology, and sleep laboratory evaluations seemed crucial for about two-thirds of all such patients. Insomnia was more likely to involve behavioral/psychological factors; about 30% of the patients with long-term, serious insomnia seemed to benefit markedly from the sleep center evaluation.
Effects of Arg16Gly polymorphism in ADRB2 gene on responses to salmeterol or montelukast added to inhaled corticosteroids in Japanese asthmatic subjects
Authors: Satoshi Konno, Hironi Makita, Nobuyuki Hizawa, Kaoruko Shimizu, Fumio Kokubu, Takefumi Saito, Takeo Endo, Hiroki Ninomiya, Hiroaki Iijima, Norihiro Kaneko, Masaharu Nishimura
Journal: European Respiratory Journal (2012)

Rationale: Long-acting b2-agonists (LABA) and leukotriene receptor antagonists (LTRA) are two recommended agents to add to inhaled corticosteroids (ICS) in asthma patients not adequately controlled by ICS alone. Conflict studies exist on whether the Arg16Gly genotype in b2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effect of b2-agonists, and some indicate that subjects with Arg/Arg show deterioration in pulmonary function with long-term LABA treatment.

Objective: We hypothesized that the Arg16Gly genotype might determine the differential response to either LABA (salmeterol, Sal) or LTRA (montelukast, Mon) when added to ICS in patients with asthma.

Methods: This study was a randomized, cross-over design and 62 mild to moderate asthma patients (26 patients with Arg/Arg, 36 patients with Gly/Gly) were enrolled. The primary endpoint was a difference of the change in the morning PEF at 16 weeks [ΔPEF (Sal) – ΔPEF (Mon)] between the two genotypes.

Results and Conclusion: The mean difference in [ΔPEF (Sal) – ΔPEF (Mon)] was 16 ± 50 (SD) in patients with Arg/Arg, and 16 ± 41(SD) in patients with Gly/Gly (P>0.05). This result suggests that the Arg16Gly genotype does not influence the preferential bronchodilator effect of Sal or Mon in mild to moderate persistent asthma patients, at least, in 16 weeks follow-up.
Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder
Authors: F X Castellanos, J N Giedd, P Eckburg, W L Marsh, A C Vaituzis, D Kaysen, S D Hamburger, J L Rapoport
Journal: American Journal of Psychiatry (1994)

Because the caudate nuclei receive inputs from cortical regions implicated in executive functioning and attentional tasks, caudate and total brain volumes were examined in boys with attention deficit hyperactivity disorder (ADHD) and normal comparison subjects. To gain developmental perspective, a wide age range was sampled for both groups.The brains of 50 male ADHD patients (aged 6-19) and 48 matched comparison subjects were scanned by magnetic resonance imaging (MRI). Volumetric measures of the head and body of the caudate nucleus were obtained from T1-weighted coronal images. Interrater reliabilities (intraclass correlations) were 0.89 or greater.The normal pattern of slight but significantly greater right caudate volume across all ages was not seen in ADHD. Mean right caudate volume was slightly but significantly smaller in the ADHD patients than in the comparison subjects, while there was no significant difference for the left. Together these facts accounted for the highly significant lack of normal asymmetry in caudate volume in the ADHD boys. Total brain volume was 5% smaller in the ADHD boys, and this was not accounted for by age, height, weight, or IQ. Smaller brain volume in ADHD did not account for the caudate volume or symmetry differences. For the normal boys, caudate volume decreased substantially (13%) and significantly with age, while in ADHD there was no age-related change.Along with previous MRI findings of low volumes in corpus callosum regions, these results support developmental abnormalities of frontal-striatal circuits in ADHD.
Intra-arterial cisplatin and FUDR in advanced malignancies confined to the head and neck.
Authors: A A Forastiere, S R Baker, R Wheeler, B R Medvec
Journal: Journal of Clinical Oncology (1987)

Twenty-seven patients with advanced malignancies confined to the head and neck region were treated with intra-arterial (IA) cisplatin and 5-fluorodeoxyuridine (FUDR) using implantable pumps or injection ports. Tumor histologies were: 16 squamous cell, one mucoepidermoid, one adenocarcinoma, one neuroendocrine, four adenoid cystic, two acinic cell, one fibrosarcoma, and one melanoma. All primaries originated from tissues in the head and neck area. Nineteen patients had received prior treatment, including chemotherapy in 13; eight were newly diagnosed. Responses in 26 evaluable patients were two complete (CR), ten partial (PR), six minor (MR), and eight progressions. The median duration of response was 5 months, with a range of 2 to 11 months. Sites of progression were within the infused volume in 13 patients and to uninfused local-regional or distant sites in eight. The response rate in the subset of 15 patients with squamous cell head and neck cancer was 47%. Toxicity in the 26 patients included stomatitis in 88%, nausea and vomiting in 64%, myelosuppression in 15%, and grade 1 nephrotoxicity in 1%. A regional advantage for IA cisplatin and FUDR can be calculated based on total body clearance rates (CLTB) for these agents and estimates of external carotid artery (ECA) blood flow. However, frequent progression of disease outside the infused volume to regional and distant sites limits the usefulness of this approach in recurrent disease patients.
Pooled safety results from SPIRITT: A multicenter, open-label, randomized, phase II study of FOLFIRI with panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: J. R. Hecht, S. R. Dakhil, M. N. Saleh, B. Piperdi, M. Cline-Burkhardt, D. M. Kocs, L. C. DeMarco, L. Chen, K. Krishnan, A. L. Cohn
Journal: Journal of Clinical Oncology (2011)

477 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR) approved as monotherapy in pts with chemorefractory mCRC. Many pts with mCRC who have progressed on a bev-containing regimen receive second-line bev + chemotherapy despite the lack of prospective, randomized data supporting this approach. A phase III study recently showed that pmab + second-line FOLFIRI improved progression-free survival (PFS) in pts with wild-type (WT) KRAS tumors vs chemotherapy alone. This study was amended after enrollment began to focus hypothesis testing on the WT KRAS population and is evaluating the safety and efficacy of pmab + FOLFIRI vs bev + FOLFIRI in pts who received first-line therapy with an oxaliplatin-based regimen + bev. Methods: This is a randomized, phase II, open-label study in pts with mCRC with disease progression or intolerability after ≥ 4 doses of first-line oxaliplatin-based chemotherapy + bev. Pts are randomized 1:1 to receive either 6 mg/kg pmab Q2W + FOLFIRI or bev (given at institutional standard dose Q2W) + FOLFIRI. Tx is administered until disease progression (PD), death, or withdrawal from study. The primary endpoint is PFS in patients with WT KRAS tumors. Other endpoints include objective response rate, overall survival, safety, and patient-reported outcomes. Results: At the time of data cutoff, 216 of 277 planned pts were enrolled. 175 (81%) pts discontinued study tx and 39 (18%) pts remain on tx. Any grade adverse events (AEs) were reported in 197 (92%) pts. 38 (18%) pts had AEs that led to withdrawal from tx or study. Serious AEs were reported in 66 (31%) pts and included gastrointestinal disorders (13%), infections and infestations (8%), respiratory disorders (7%), and metabolism and nutrition disorders (7%). Fatal AEs were reported in 18 (8%) pts of which 9 (4%) were related to disease progression. Conclusions: The aggregate safety profile is consistent with expected toxicities of FOLFIRI in combination with an anti-EGFR or an anti-VEGF targeted therapy in second-line mCRC. Detailed pooled safety results will be presented at the meeting. [Table: see text]
Are accelerometers a useful tool for measuring disease activity in children with eczema? Validity, responsiveness to change, and acceptability of use in a clinical trial setting
Authors: C.I. Wootton, K. Koller, S. Lawton, C. O’Leary, K.S. Thomas
Journal: British Journal of Dermatology (2012)

Actigraphy, which uses accelerometers to record movement, has been proposed as an objective method of itch assessment in eczema. Previous studies have found strong correlations with actigraphy and video surveillance, disease severity and biological markers in patients with eczema.To assess the validity of accelerometer data, its responsiveness to change and the practicality and acceptability of accelerometers when used as an outcome measure in a clinical trial.This study used data collected from 336 participants of the Softened Water Eczema Trial (SWET). Accelerometer data were compared with three standardized scales: Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score, Patient Oriented Eczema Measure (POEM) and Dermatitis Family Impact (DFI). Spearman's rank testing was used for correlations.Only 70% of trial participants had complete data, compared with 96% for the primary outcome (eczema severity - SASSAD). The convergent validity of accelerometer data with other measures of eczema severity was poor: correlation with SASSAD 0·15 (P = 0·02) and POEM 0·10 (P = 0·13). Assessing for divergent validity against quality of life measures, the correlation with the DFI was low (r = 0·29, P < 0·0001). Comparing the change scores from baseline to week 12 for SASSAD, POEM and DFI with the change in accelerometer scores we found low, negative correlations (r = -0·02, P = 0·77; r = -0·12, P = 0·06; and r = -0·01, P = 0·87, respectively). In general, the units were well tolerated but suggestions were made that could improve their usability in children.Actigraphy did not correlate well with disease severity or quality of life when used as an objective outcome measure in a multicentre clinical trial, and was not responsive to change over time. Further work is needed to establish why this might be, and to establish improved methods of distinguishing between eczema-related and eczema-nonrelated movements.
Respiratory events related arousals, what are we doing about them?
Authors: Margarida Aguiar, Richard Staats, Susana Moreira, Fatima Caeiro, João Valença, Antόnio Bugalho de Almeida
Journal: European Respiratory Journal (2011)

Respiratory events related arousals (RERAs) are a possible reason for excessive daytime sleepiness (EDS), fatigue and mood disturbances, a complex also known by the upper airway resistance syndrome.  Our aim was to detect the importance of this pathology within the overall sleep studies performed at our sleep laboratory.  Sleep and cardiorespiratory parameters were evaluated with standard polisonography (PSG) according to the recommendations of AASM. RERAs were identified by a flattening of the airflow registered by nasal cannula and/or a visible increase in thoraco-abdominal effort leading to an arousal.  All PSGs recorded during a period of 6 month with an apnea/hypopnea index of less than 15/h were reanalyzed by a single sleep specialist. Patients (pts) demonstrating RERAs in more than 50% of all breathing events were included for further study.  Within 303 sleep studies a total of 45 pts were included (14,8%), mean respiratory disturbance index 17,4±10,4/h. 71% were male, with a mean age of 54,6±14,8 years. In 42% of the pts sleep latency and in 63,8% sleep efficiency (mean 78.5±12.6%) were reduced. Decreased slow wave sleep was found in 55%. In 61% a reduced REM sleep was found and all pts had a high arousal index (41,6±18,3/hr).  Of the pts followed in our sleep clinic 50% showed an increased epworth scale (12.6±5.5), 56% were hypertensive and in 75% (BMI 2 ). 75% of the pts underwent a positive pressure therapy (ppt) with improvement of symptoms (ESE  As a conclusion, pts with RERAs should be evaluated for EDS for therapy with ppt improves daytime symptoms and is reasonably well tolerated.
Inhalation of terbutaline increases anaerobic performance and muscle strength in well-trained endurance athletes
Authors: Michael Kreiberg, Morten Hostrup, Anders Kalsen, Jens Bangsbo, Vibeke Backer
Journal: European Respiratory Journal (2013)

Background: The World Anti-doping Agency (WADA) recently loosened their restrictions towards inhaled beta2-agonists. Although, terbutaline still require athletes to provide evidence of asthma to get a dispensation (i.e. TUE) for inhaled use, WADA may in the coming years loosen their restrictions towards terbutaline as well. Before such an action is realized, more studies are needed investigating any performance-enhancing effect of terbutaline. The purpose of this study was to investigate if inhaled terbutaline in supratherapeutic doses is performance-enhancing in athletes.  Methods: Ten well-trained endurance athletes, all males and non-asthmatics, aged 24.4±3.3 yrs (Mean±SD), VO2max 67.4±4.9 ml/min/kg, were included in a randomized, double-blinded and placebo-controlled crossover study with inhaled terbutaline (40x0.5 mg) and placebo. At separate visits, isometric muscle strength of m.quadriceps, Wingate performance, VO2 kinetics at 70-75% of VO2max, and endurance at 110% of VO2max were measured.  Results: Terbutaline increased (p  Conclusion: Supratherapeutic inhalation of terbutaline provides an ergogenic effect on muscle strength and anaerobic performance, but decrease endurance due to side-effects.