tbuckley/cabot-search huggingface dataset:
How long does it take for supine TLNO & TLCO to become stable after sitting upright?
Authors: Liam O'Reilly, Helen Ward, Martin Miller, Brendan Cooper
Journal: European Respiratory Journal (2012)

Introduction:   We previously investigated (ERS Congress, 2011) the change in gas transfer for carbon monoxide (TLCO) from sitting to supine in healthy subjects, but were unable to find published studies showing how long subjects should be supine before a stable TLNO measurement could be made.    Method:   We measured single breath TLCO & TLNO in 13 healthy subjects (5F:8M; ages 23-57 years; mean height (SD) 1.77 m (0.10)) using a Master Screen lung function system (Jaeger Ltd, Hochberg, Germany), twice sitting at rest and then after 10,15,20,25 & 30 mins respectively lying supine.    Results:   Table 1 shows mean (SD) for TLCO and TLNO    Discussion   :  We have shown that when supine for 30 mins TLCO changes but TLNO remains stable. We confirm TLCO increases from sitting to supine but that TLNO, which reflects membrane function, remains unchanged. TLNO/TLCO demonstrates a small decrease followed by an accommodation in pulmonary capillary blood volume.    Conclusion:   Supine gas transfer using TLNO + TLCO show physiological changes consistent with changes in pulmonary capillary blood volume when subjects lie supine. Measurements before 20 mins are transients and suggest care should be taken when making supine gas transfer estimations.
Regulation of Cell-Mediated Immunologic Reactivity to Moloney Murine Sarcoma Virus-Induced Tumors. III. Further Characterization of Tumor-Specific Serum Blocking Factors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: William J. Halliday, Thelma A. Koppi, Ian F. C. McKenzie
Journal: JNCI Journal of the National Cancer Institute (1982)

Blocking factors in the sera of inbred CBA mice bearing either Moloney murine sarcoma virus-induced tumors or transplanted 3-methylcholanthrene-induced tumors specifically blocked in the leukocyte adherence inhibition reaction between tumor-sensitized peritoneal cells and tumor antigens. These factors were absorbed from serum by treatment with anti-Ia antibodies and could be eluted in a partially purified form. Chromatography on Sephacryl S-200 columns demonstrated blocking activity in fractions of high and low molecular weight (greater than 100,000 and 40,000--50,000, respectively) derived from whole sera or eluates. Active fractions from serum appeared to retain the tumor specificity of the original material.
Abstract 9591: A Novel Quantitative Trait Locus for Coronary Flow
Authors: Rizwan Ahmed, Stuart Cook
Journal: Circulation (2011)

Background: Coronary flow (CF) is fundamental for normal cardiac function but the genetic determinants of CF are uncharacterized. We examined the heritability of CF, taking into account blood pressure (BP) effects to discover new Quantitative Trait Loci (QTLs) and candidate genes for CF regulation. Methods: We studied in vivo BP and ex vivo CF in normotensive Brown Norway (BN) rat and Spontaneously Hypertensive Rat (SHR), a model of impaired CF, and F1 and F2 progeny of these strains. In vivo BP was measured by carotid artery cannulation in anaesthetized animals. Ex vivo Langendorff perfusion measurements of CF were characterized at baseline, during coronary ligation and following cardiac reperfusion at a controlled heart rate. DNA was extracted and genotyping performed using Illumina's custom 768-plex Goldengate assay. Results: 1) The broad sense heritability (H2) of CF was 30% at baseline indicating significant and previously unappreciated genetic regulation of CF. 2) CF exhibited no significant correlation with systolic or diastolic BP (baseline: p = 0.18, r = 0.10, n = 172; reperfusion: p = 0.30, r = 0.07, n = 172). 3) Linkage analysis revealed a highly significant CF QTL on rat chromosome 2 (LOD = 5.1), which is the first locus for CF. 4) At the CF locus adenosine monophosphate deaminase 1 (ampd1) and the adenosine A3 receptor (adora3) were identified as candidate genes and are the subject of ongoing studies. Conclusion: Our data show that CF is a highly heritable trait and is BP-independent in our experimental model. We identified the first QTL for CF in any species and prioritized candidate genes for CF at the locus. Overall, these data provide the first insights into the genetic control of CF with implications for treatment of conditions characterized by impaired CF.
Efficacy of an anti-IL13 monoclonal antibody, lebrikizumab, in adults with inadequately controlled asthma is enhanced in those with high periostin levels
Authors: Nicola A. Hanania, Robert F. Lemanske, Phillip E. Korenblat, Joseph R. Arron, Jeffrey M. Harris, Zheng Su, Sofia Mosesova, John G. Matthews, Merdad V. Parsey, Sean Bohen, Michelle M. Freemer
Journal: European Respiratory Journal (2011)

Introduction: IL13 is a key mediator in asthma pathogenesis. We evaluated lebrikizumab (LB) efficacy in adults with asthma inadequately controlled by inhaled corticosteroids (ICS). We prospectively evaluated whether LB was more efficacious in participants (prts) with increased IL13-driven inflammation, measured by the serum biomarker periostin.  Methods: Phase II study of 180 adults with asthma inadequately controlled by ICS, randomized 1:1 to LB (n=88) or placebo (PB; n=92). The primary outcome was change in forced expiratory volume/second (FEV1) from baseline (BL) to Week (Wk) 12. Secondary outcomes included change in FEV1 from BL to Wk 24 and rate of severe exacerbations (SE) in the 24-wk treatment period. Prts with BL periostin levels above the median value were classified as “periostin-high” (PH).  Results: Compared with PB prts, mean improvement in FEV1 from BL was 6% greater in LB prts (95% CI 1%, 11%) at Wk 12 and 5% (95% CI 0%, 9%) greater at Wk 24; the rate of SE was 51% lower in LB prts (0.11 vs 0.23 events/24 wks, 95% CI –33%, 82%). FEV1 improved significantly in PH-LB prts compared with PH-PB prts: 11% greater at Wk 12 and 7% greater at Wk 24. PH-LB prts had 81% fewer SE than PH-PB prts (0.04 vs 0.22 events/24 wks, 95% CI –17%, 97%). The overall rate of serious adverse events was 5%; none were attributed to study drug.  Conclusions: Lebrikizumab had a clinically meaningful benefit in prts with asthma inadequately controlled by ICS, especially among PH prts with greater IL13-driven inflammation. No drug-associated safety signals were identified.
Reference intervals of complete blood count constituents are highly correlated to waist circumference: Should obese patients have their own “normal values?”
Authors: Jennifer Vuong, Yuelin Qiu, Myanh La, Gwen Clarke, Dorine W. Swinkels, George Cembrowski
Journal: American Journal of Hematology (2014)

Body mass index (BMI), the prevalent indicator of obesity, is not easily grasped by patients nor physicians. Waist circumference (WC) is correlated to obesity, is better understood and has a stronger relationship to the metabolic syndrome. We compiled WC, complete blood count (CBC) parameters as well as other pertinent data of 6766 25-55-year-old US volunteers sampled in the US National Health and Nutrition Examination Survey, in the years 2005-2010. To determine reference intervals of typical US patients visiting their clinician, we used minimal exclusion criteria. We compiled hemoglobin, red blood cell count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration, mean cell hemoglobin (MCH), red cell distribution width (RDW), platelet count, mean platelet volume, and counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils. In addition, we also compiled serum C reactive protein and serum iron. The three major US races were studied and reference interval diagrams were constructed for each CBC parameter plotted against WC. WBC count, RDW, lymphocyte, neutrophil, and red blood cell count increase with WC. Conversely, serum iron and MCH and MCV decrease. These relationships may be related to insulin resistance and chronic activation of the immune system and the resulting low-grade inflammatory state. WC is a strong predictor for many CBC parameters, suggesting that WC should be taken into account when evaluating blood count results. Clinicians who take care of obese patients should be aware of altered hematology and investigate and treat accordingly.
Aspergillus tracheobronchitis. Analysis of our experience in a tertiary care centre
Authors: Maria Beatriz Arias Arcos, Ricardo García Luján, Mario Fernández-Ruiz, Eduardo de Miguel Poch, Manuel Lisazoaín, Jose María Aguado
Journal: European Respiratory Journal (2012)

Aspergillus   (AT) constitutes an infrequent and severe form of invasive pulmonary aspergillosis in which the fungal infection is predominantly confined to the tracheobronchial tree.   Population and methods:  We reviewed all cases of AT diagnosed in our center between April 1991 to December 2010. Aspergillus  tracheobronchitis was defined as the isolation of  Aspergillus  spp. from endobronchial specimens and the presence of ≥1 endobronchial lesions without an alternative diagnosis. In order to exclude simple colonization, all cases also had histopathological evidence of tissue invasion of the tracheobronchial tree with hyphae morphologically consistent with  Aspergillus  spp.   Results:  8 cases (6 male; mean age 55.5 years) of AT were diagnosed. Hematologic malignancy (n=4), solid organ transplantation (n=2), systemic lupus erythematosus (n=1) and nasopharyngeal carcinoma (n=1) treated with chemotherapy and radiotherapy, were the underlying conditions reported. Fever and respiratory complaints (cough, dyspnea, stridor or wheezing) were the most frequent symptoms but one case was asymptomatic.  A.fumigatus  constituted the unique specie in our study. In bronchoscopy the pseudomembranous form was the most commonly observed (4 cases).Two cases revealed necrotic lesions and two cases only showed multiple mucus plugs. All cases were diagnosed by broncohoalveolar lavage and bronchial biopsy. Two cases died so the overall intra-hospital mortality was 25%.   Conclusions:   Aspergillus   is an infrequent form of invasive pulmonary aspergillosis that would be suspected in some immunosupressed patients. It is mandatory histopathological evidence of tissue invasion to comfirm the diagnosis.
Ultrastructure of Cell Types Cultured During Preneoplasia From Implant Surfaces and Foreign-Body-Reactive Tissues in Mice23
Authors: Kenneth H. Johnson, Helmy K. G. Ghobrial, Lance C. Buoen, Inge Brand, K. Gerhard Brand
Journal: JNCI Journal of the National Cancer Institute (1980)

Cell types (I–IV), isolated and expanded in vitro from mouse foreign-body (FB)-reactive capsule tissue or from surfaces of FB segments, were sectioned en face and studied ultrastructurally. The macrophage-like and fibroblast-like nature of respectively, the euploid types I and II cells were substantiated by this ultrastructural study and thus confirmed earlier conclusions that were based on light microscopic morphology and in vitro growth characteristics. Particular emphasis was placed on the characterization and identification of type IV cells in that these aneuploid cells are sarcomagenic when implanted or injected sc into histocompatible recipient mice. The submicroscopic features of the aneuploid type IV cells included: 1) numerous microfilaments (diameter, 6–9 nm); 2) many plasmalemmal (pinocytotic) vesicles; 3) many surface microvilli, ruffles. or blebs; 4) formation of intercellular gap junctions; and 5) relatively extensive smooth-surfaced endoplasmic reticulum and significantly less rough-surfaced endoplasmic reticulum. The much smaller bipolar type III cells had several features in common with type IV cells: 1) an abundance of 6- to 9-nm (diameter) microfilaments, 2) moderate numbers of plasmalemmal vesicles, and 3) many evaginations of the plasma membrane to form microvilli or blebs. A relationship between types III and IV cells was considered likely on the basis of these morphologic similarities and other observations. The submicroscopic features of both types III and IV cells correlated closely with those present in FB-induced sarcoma cells. The specific in vitro characteristics of aneuploid type IV ceUs most closely resembled those of endothelial cells. The results of this study supported the hypothesis that the progenitor cells of FB-induced sarcomas were derived from primitive cells associated with the local microvasculature.
The Internet and the future of psychiatry
Authors: M P Huang, N E Alessi
Journal: American Journal of Psychiatry (1996)

The Internet is a rapidly growing communications resource that is beginning to have an impact on medicine, and it is anticipated that the Internet will soon have a major effect on psychiatry. It is essential for psychiatrists to have a conceptual framework for understanding the many aspects of the Internet.Using a four-layer model, the authors describe the components of the Internet and how these work together to establish communication. They discuss some of the practical implications of the model, potential future applications of the Internet, and some of the challenges its use will create.In the Internet model described, the bottom three layers involve hardware and modes of information transmission; the fourth layer is human interaction. The Internet has great potential in psychiatric education, clinical care, research, and administration, but major adjustments in individual and organizational expectations and responses will be needed. These changes relate to the speed, dispersion, volume, privacy, and permanence of communication.The growth of the Internet and related information technologies is inevitable and has diverse technical and social implications. As psychiatrists, we must remain effective communicators of information and adjust to a changing world with new roles and skills that will permit us to best serve our professional mission.
Anaphylaxis to Patent Blue V. I. Clinical aspects
Authors: A. S. Hunting, A. Nopp, S. G. O. Johansson, F. Andersen, V. Wilhelmsen, A. B. Guttormsen
Journal: Allergy (2009)

The dye Patent Blue V (PBV) is increasingly used for staging procedures in operable breast cancer, but is reported to cause adverse reactions. The aim of this study was to present the clinical features and the results of follow-up examinations in patients with such reactions.We studied nine patients with hypersensitivity reactions to PBV between 1999 and 2006 who were identified through the Norwegian network for reporting and investigating allergic reactions during anesthesia.We observed incidences of 0.5% (7/1418) for all kinds of PBV reactions and 0.4% (5/1418) for anaphylaxis. Typical clinical features included: (i) cardiovascular and/or cutaneous symptoms, (ii) a delay in symptoms, compared to the time of dye injection, (iii) poor response to ephedrine and intravenous fluid, and (iv) need for adrenaline administration, sometimes prolonged, for circulatory stabilization. Cutaneous manifestations were noted in five of the seven patients with anaphylaxis and two additional patients without circulatory instability. During anaphylactic reactions, serum tryptase was increased in six patients and normal in one. Serum tryptase was normal in one patient with skin symptoms only. Skin prick tests to PBV were positive in all eight patients tested, including the two with skin manifestations only.The clinical features and the results of follow-up studies strongly suggest that these reactions are IgE mediated.
Phase II Trial of Weekly Irinotecan Plus Cisplatin in Advanced Esophageal Cancer
Authors: David H. Ilson, Leonard Saltz, Peter Enzinger, Ying Huang, Alice Kornblith, Marc Gollub, Eileen O'Reilly, Gary Schwartz, Julia DeGroff, Gladys Gonzalez, David P. Kelsen
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the response, toxicity, survival, and quality of life in patients with unresectable or metastatic esophageal cancer treated with weekly irinotecan and cisplatin. PATIENTS AND METHODS: Thirty-five patients with metastatic or unresectable esophageal adenocarcinoma (23 patients) or squamous cell carcinoma (12 patients) were treated. No prior chemotherapy was allowed. The majority of patients had metastatic and bidimensionally measurable disease (34 patients each [97%]). Patients were treated with cisplatin 30 mg/m 2 and irinotecan 65 mg/m 2 , repeated weekly for 4 weeks, followed by a 2-week rest period. Treatment was recycled every 6 weeks. Degree of dysphagia relief was monitored, and quality of life was measured prospectively using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 and Functional Assessment of Cancer Therapy–General instruments. RESULTS: Thirty-five patients were assessable for response and toxicity. Major objective responses were observed in 20 patients (57%; 95% confidence interval, 41% to 73%), including two complete responses (6%). Similar response rates were observed for adenocarcinoma (12 of 23 patients; 52%) and squamous carcinoma (eight of 12 patients; 66%). The median duration of response was 4.2 months (range, 1 to 8.8+ months). Median actuarial survival was 14.6 months (range, 1 to 15.2+ months). In 20 patients with dysphagia assessable at baseline, 18 (90%) noted either improvement or resolution of dysphagia on chemotherapy. Global quality of life improved in responding patients, primarily because of improvements in pain, emotional state, and relationships with family and friends. Toxicity was relatively mild and included only three patients (9%) with grade 4 neutropenia and four (11%) with grade 3 diarrhea. There were no treatment-related deaths. CONCLUSION: The combination of weekly cisplatin plus irinotecan had significant activity in metastatic esophageal carcinoma and resulted in significant relief of dysphagia. The regimen was well tolerated, with acceptable myelosuppression and rare treatment-related diarrhea. Further evaluation of the combination of weekly irinotecan and cisplatin, including the addition of other agents to this regimen, is indicated.
Abstract 541: Differential Effects of IGF-1 and VEGF on Migration, Proliferation and Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells
Authors: Yangxin Li, Jane Titterington, Yao-Hua Song, Roxanne Reger, Patrick Delafontaine
Journal: Circulation (2006)

Insulin-like growth factor 1 (IGF-1) induces proliferation, differentiation and survival of multiple cell types, but its effects on stem cells have not been addressed. We determined the effects of ...
Mitochondrial thioredoxin reductase regulates major cytotoxicity pathways of proteasome inhibitors in multiple myeloma cells
Authors: E E Fink, S Mannava, A Bagati, A Bianchi-Smiraglia, J R Nair, K Moparthy, B C Lipchick, M Drokov, A Utley, J Ross, L P Mendeleeva, V G Savchenko, K P Lee, M A Nikiforov
Journal: Leukemia (2015)
<i>TOLLIP</i>, <i>MUC5B</i>, and the Response to <i>N</i>-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis
Authors: Justin M. Oldham, Shwu-Fan Ma, Fernando J. Martinez, Kevin J. Anstrom, Ganesh Raghu, David A. Schwartz, Eleanor Valenzi, Leah Witt, Cathryn Lee, Rekha Vij, Yong Huang, Mary E. Strek, Imre Noth
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. The genes TOLLIP and MUC5B play important roles in lung host defense, which is an immune process influenced by oxidative signaling. Whether polymorphisms in TOLLIP and MUC5B modify the effect of immunosuppressive and antioxidant therapy in individuals with IPF is unknown.To determine whether single-nucleotide polymorphisms (SNPs) within TOLLIP and MUC5B modify the effect of interventions in subjects participating in the Evaluating the Effectiveness of Prednisone, Azathioprine, and N-Acetylcysteine in Patients with Idiopathic Pulmonary Fibrosis (PANTHER-IPF) clinical trial.SNPs within TOLLIP (rs5743890/rs5743894/rs5743854/rs3750920) and MUC5B (rs35705950) were genotyped. Interaction modeling was conducted with multivariable Cox regression followed by genotype-stratified survival analysis using a composite endpoint of death, transplantation, hospitalization, or a decline of ≥ 10% in FVC.Significant interaction was observed between N-acetylcysteine (NAC) therapy and rs3750920 within TOLLIP (P interaction = 0.001). After stratifying by rs3750920 genotype, NAC therapy was associated with a significant reduction in composite endpoint risk (hazard ratio, 0.14; 95% confidence interval, 0.02-0.83; P = 0.03) in those with a TT genotype, but a nonsignificant increase in composite endpoint risk (hazard ratio, 3.23; 95% confidence interval, 0.79-13.16; P = 0.10) was seen in those with a CC genotype. These findings were then replicated in an independent IPF cohort.NAC may be an efficacious therapy for individuals with IPF with an rs3750920 (TOLLIP) TT genotype, but it was associated with a trend toward harm in those with a CC genotype. A genotype-stratified prospective clinical trial should be conducted before any recommendation regarding the use of off-label NAC to treat IPF.
Neu3 Activity Enhances Egfr Activation Without Affecting Egfr Expression
Authors: A. Riva, A. Mozzi, M. Forcella, C. Difrancesco, F. Molinari, N. Papini, B. Bernasconi, V. Martin, L. Mazzucchelli, E. Monti, P. Fusi, M. Frattini
Journal: Annals of Oncology (2014)
Effect of noninvasive ventilation on thoracoabdominal kinematics in patients with heart failure associated to cardiomegaly: A controlled randomized clinical trial
Authors: Larissa Andrade, Jasiel Nascimento-Junior, Daniella Brandão, Andrea Aliverti, Guilherme Fregonezi, Shirley Campos, Taina Vidal, Silvia Martins, Wilson Oliveira, Armele Dornelas de Andrade
Journal: European Respiratory Journal (2014)

Introduction: Dyspnea and fatigue determine exercise intolerance in heart failure (HF) subjects, hampering performance in activities of daily living.In this context,noninvasive ventilation (NIV) has been used to minimize such impairment, increasing functional capacity.  Aim:  To evaluate the impact of NIV on exercise performance in HF individuals.  Methods:  A randomized crossover clinical trial with allocation concealment consisted of two experimental phases: NIV and control, 7 days apart of each other. During NIV phase, 30 minutes of bi-levelventilation was performed. Any type of ventilator support was offered during control phase.Functional capacity was assessed by cardiopulmonary exercise test on a treadmill.  Results: 24 subjects, 7 (24%) females were evaluated, with a mean ejection fraction of 36.04 + 8.46%, and mean age of 51.83 + 10.23 years. NIV determined an increase of maximal oxygen consumption (VO2max) (control: 18.35 +4.44 ml/kg/min X NIV: 20.61 +4.90 ml/kg/min,  p ≤ 0.01); in heart rate (HR) (control: 127.33 +20.96 bpm X NIV: 134.78 +19.53 bpm, p ≤ 0.04) and in heart rate variation (Δ HR) (control: 63.35 +19.34% X NIV : 69.76 +16.66 %,  p  ≤ 0.02). Also, differences between cardiopulmonary exercise time (CPX-T) (control: 444.50 +90.53s X NIV 501.05 +103.05s,  p =0.01) and recovery time of oxygen consumption (T1/2/VO2) (control: 171,33 +61, 04s X NIV : 144.91 +49.26s , p= 0.01) were found.  Conclusion: NIV promotes a beneficial effect in HF population by increasing exercise tolerance, optimizing time recovery and improving chronotropic and respiratory reserve.