tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Inhaled calcium based dry powder inhibits rhinovirus-induced inflammation and exacerbation in a mouse model of allergic airway inflammation
Authors: Paulette Wright, Sophanna Kong, Tim Brogan, Stephen Arold, Pamela Okerholm, Faith Saia, Robert Clarke, David Hava
Journal: European Respiratory Journal (2011)

Acute exacerbations (AE) in asthma are associated with rhinovirus (Rv) infection. AEs drive disease progression and cause loss of lung function, yet no current therapies target this infectious component. Calcium (Ca) based dry powder (DP) formulations were developed as host-targeted therapies that broadly reduce viral infection  in vitro , including Rv. Here, a lead Ca-based DP (PUR118) was tested for efficacy against Rv in a mouse model of infection and AE using Rv1B infection in naive and ovalbumin (OVA)-challenged mice (Bartlett NW et al Nat Med 2008). Mice (Balb/c) were treated with PUR118 or control DP by whole body exposure, twice daily (BID) 2d prior to Rv infection (5×10 6  TCID50) and BID on day of infection. Bronchoalveolar lavage (BAL) inflammation was evaluated 24h post-infection. Additional indices of infection and exacerbation included: viral titers, and expression of relevant cytokines and chemokines. Rv infection caused significant neutrophilic inflammation in naive mice (7.5×10 5  BAL neutrophils/ml) and exacerbated inflammation in OVA challenged mice (44% increase over control) with increased neutrophils, cytokines and chemokines. In naive mice, PUR118 treatment reduced neutrophilic inflammation by 38%, which correlated with reduced cytokine and chemokine expression. Similar results were observed in OVA mice where PUR118 treatment reduced neutrophilic inflammation by 40%. The data show Ca-based DP significantly inhibits Rv-induced airway inflammation and Rv-driven exacerbation responses in an asthma-like mouse model. These data support the development of inhaled Ca-based DP to treat infectious causes of AEs in respiratory disease.
Accident prevention in recreational alpine skiing: how good is the familiarity about the fis-regulations?
Authors: C Hildebrandt, E Mildner, C Höbenreich, C Raschner
Journal: British Journal of Sports Medicine (2011)

Background The conduct of participants in snow sport depends on the knowledge of the existing rules. Accidents can be avoided if there is sufficient familiarity with the skier's code published by the International Ski Federation (FIS). Objective We aimed to find out the knowledge of the FIS regulations, the intuitive behaviour in given situations and the general sense of security on ski slopes dependent on age, skiing ability and origin. Design Prospective, randomly survey. Setting recreational alpine skiers in 17 Tyrolean ski resorts. Participants 1450 recreational skiers were interviewed. More than 95% agreed to answer the questionnaire. Interventions Interviews were conducted during the winter season 2008/2009 assessing personal data, knowledge about existing rules and the general perception of safety. Main outcome measurements The knowledge of existing rules on the ski slope. Results A total of 75.0% were aware that rules exist, 33.9% knew that they are termed FIS-Rules. 10.7% thought that no rules exist on the ski slope and 14.3% had no opinion. Young skiers (p=0.000) and beginners (p=0.001) possessed the least knowledge whereas local residents (p=0.000) and experts evidenced the best knowledge. Several risk-carrying situations were assessed incorrectly by a high percentage. 29.8% think that stopping on the slope is possible without any restrictions and 22.1% assume that they have priority when moving upwards. A low skiing ability seems to have the biggest influence. Conclusion The present study revealed that beginners, young skiers and non-local residents had insufficient knowledge. Ski resorts and schools should target these high-risk groups. Better awareness of the FIS-Rules is possible with media campaigns.
New Advances in Gene Therapy: The Use of MGMT <sup>P140K</sup> -Mediated Stem Cell Selection in Nonhuman Primates
Authors: Andrew A. Bremer
Journal: Science Translational Medicine (2010)

In vivo selection with MGMT P140K enhances gene transfer efficiency in nonhuman primates, demonstrating the utility of this system for a variety of human conditions amenable to autologous gene-modified cell therapy.
Operating practices of and precautions taken by orthopaedic surgeons to avoid infection with HIV and hepatitis B virus during surgery.
Authors: M J Porteous
Journal: BMJ (1990)

To assess the precautions being taken by orthopaedic surgeons to avoid becoming infected with HIV or hepatitis B virus by their patients during surgery.Pilot study of 50 surgeons selected at random followed by a postal questionnaire completed anonymously.All 1220 fellows and associates of the British Orthopaedic Association working in the United Kingdom.800 (67%) Questionnaires were returned. 511 Surgeons has sustained a needlestick injury or had got body fluid in their eye within the past month despite 430 regularly wearing eye protection during major surgery. Seven had definitely and four possibly been infected with hepatitis B virus by a patient while operating, and 582 had been immunised against hepatitis B. Only 75 surgeons were satisfied with the present guidelines on testing patients for HIV antibodies.Although most surgeons who replied took some precautions when operating, most still exposed themselves to considerable risk from patients not known to be infected with HIV or hepatitis B virus.
Immunolocalization of natriuretic peptide receptor B in the rat kidney.
Authors: M C Bonhomme, K L Grove, S Caron, C T Crilley, G Thibault, C F Deschepper, R Garcia
Journal: Journal of the American Society of Nephrology (1998)

The natriuretic peptide receptor (NPR) family consists of three receptor subtypes: two transmembrane forms that contain a guanylyl cyclase intracellular domain (NPR-A and NPR-B), and one truncated form (NPR-C). Because of the lack of specific agonists and antagonists for each receptor subtype and to the difficulty to detect the presence of small quantities of NPR-B by ligand binding studies, polyclonal antibodies against a peptide whose sequence was chosen from a region of the extracellular domain of rat NPR-B that is not homologous to sequences in NPR-A and NPR-C were developed. Western blotting with affinity-purified anti-NPR-B (413-426)-Tyr revealed a polypeptide of approximately 120 kD on COS-1 cell membranes transfected with rat NPR-B cDNA. The antibody recognized a second polypeptide, approximately 5 to 10 kD smaller, which probably represents the unglycosylated receptor. Anti-NPR-B (413-426)-Tyr did not show crossreactivity to any other NPR. Western blotting analysis with anti-NPR-B (413-426)-Tyr also identified a protein of appropriate size in renal vascular membranes. These results were supported by immunohistochemistry findings that demonstrated staining for NPR-B on papillary and medullary capillaries, glomeruli, and renal arteries. This study concludes that NPR-B is present in the rat kidney, although it was only detected in vascular structures.
Phase II Trial of Dasatinib in Patients with Metastatic Breast Cancer Using Real-Time Pharmacodynamic Tissue Biomarkers of Src Inhibition to Escalate Dosing
Authors: Christina I. Herold, Vijaya Chadaram, Bercedis L. Peterson, P. Kelly Marcom, Judith Hopkins, Gretchen G. Kimmick, Justin Favaro, Erika Hamilton, Renee A. Welch, Sarah Bacus, Kimberly L. Blackwell
Journal: Clinical Cancer Research (2011)

Abstract Purpose: A phase II study of dasatinib, an inhibitor of multiple oncogenic tyrosine kinases including Src, was conducted to evaluate 16-week progression-free rate and tolerability in patients with previously treated metastatic breast cancer (MBC). Real-time assessment of potential tissue biomarkers of Src inhibition was used to optimize dosing. Experimental Design: Eligibility criteria required that patients have measurable MBC, biopsiable tumor, and unlimited prior therapies. For the analysis of change in protein biomarkers of Src inhibition, focal adhesion kinase, paxillin, and p-Src, patients underwent metastatic biopsies at baseline and 4 weeks. Patients who tolerated the starting dose of dasatinib (50 or 70 mg orally twice daily) for the first 28-day cycle, and displayed suboptimal Src inhibition, were escalated to a higher dose (70 or 100 mg). Results: The trial was closed early with 31 patients because of a statistical boundary that required at least 4 (13%) patients without disease progression to continue accrual. These 31 patients had a median of 2 prior lines of chemotherapy for MBC. The most notable toxicity was pleural effusions in 16 patients (52%). Twenty patients had evaluable metastatic biopsies. None of the tumors showed the predefined optimal level of Src inhibition at week 4. Conclusions: Single-agent dasatinib did not exhibit significant antitumor activity in patients with heavily pretreated MBC. There were no clinically meaningful decreases before and after dasatinib exposure between exploratory tissue biomarkers of Src inhibition which may be attributable to challenges in defining biomarker endpoints for multitargeted tyrosine kinase inhibitors. Clin Cancer Res; 17(18); 6061–70. ©2011 AACR.
Low IGF-I and Elevated Testosterone During Puberty in Subjects With Type 1 Diabetes Developing Microalbuminuria in Comparison to Normoalbuminuric Control Subjects
Authors: Rakesh Amin, Carl Schultz, Ken Ong, Jan Frystyk, R. Neil Dalton, Les Perry, Hans Ørskov, David B. Dunger
Journal: Diabetes Care (2003)

OBJECTIVE—To describe longitudinal variations in pubertal hormonal variables in subjects with and without microalbuminuria (MA). RESEARCH DESIGN AND METHODS—Blood samples collected annually from subjects recruited at diagnosis of type 1 diabetes and followed prospectively through puberty (median follow-up 9.3 years, range 4.7–12.8) were analyzed for total and free IGF-I, IGF binding protein-1, testosterone, sex hormone-binding globulin, and HbA1c. A total of 55 subjects who developed MA (MA+ group) were compared with 55 age-, sex-, and duration-matched control subjects who did not develop MA (MA− group). RESULTS—For female subjects, total IGF-I (MA+ 1.2 mU/l vs. MA− 1.4 mU/l, P = 0.03) and free IGF-I levels (MA+ 1,767 ng/l vs. MA− 2010 ng/l, P = 0.002) were lower, whereas the free androgen index (MA+ 2.4 vs. MA− 2.0, P = 0.03) was higher in those with MA. These changes were less pronounced in male subjects. For both sexes, in a Cox model after adjusting for puberty, the presence of MA was associated with lower free IGF-I levels, higher testosterone standard deviation score (SDS), and poor glycemic control. We found that 22 of 55 case subjects (40%) developed persistent MA, whereas 33 (60%) had transient MA. In the persistent MA group compared with the transient and control groups, total IGF-I levels were lower (1.1 vs. 1.3 vs. 1.4 mU/l, P = 0.002) as were free IGF-I levels (1,370.9 vs. 1,907.3 vs. 1,886.7 ng/l, P &amp;lt; 0.001), whereas HbA1c levels were higher (11.8 vs. 10.3 vs. 9.9%, P &amp;lt; 0.001). CONCLUSIONS—Poor glycemic control and differences in IGF-I levels and androgens, particularly in female subjects, accompany development of MA at puberty. These differences may in part account for the sexual dimorphism in MA risk during puberty and could relate to disease progression.
Early Recurrent Ischemic Stroke in Stroke Patients Undergoing Intravenous Thrombolysis
Authors: Dimitrios Georgiadis, Stefan Engelter, Barbara Tettenborn, Hansjörg Hungerbühler, Regina Luethy, Felix Müller, Marcel Arnold, Christian Giambarba, Christian Rainer Baumann, Hans-Christian von Büdingen, Philipp Lyrer, Ralf Werner Baumgartner
Journal: Circulation (2006)

Background— We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator (tPA) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage (ICH). Methods and Results— Prospectively collected, population-based data for 341 consecutive acute stroke patients (62% men; mean age, 66 years) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerland (3 academic and 5 community) between January 2001 and November 2004 were retrospectively analyzed. The primary outcome measure was neurological deterioration ≥4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke (defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans, in the absence of ICH) or by ICH. Early recurrent ischemic stroke was diagnosed in 2 patients (0.59%; 95% confidence interval, 0.07% to 2.10%) and symptomatic ICH in 15 patients (4.40%; 95% confidence interval, 2.48% to 7.15%). Both recurrent ischemic strokes occurred during thrombolysis, whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion. Conclusions— Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis, with a different temporal pattern compared with that of symptomatic ICH.
Sleisenger and Fordtran's Gastrointestinal and Liver Disease
Authors: D. H Adams
Journal: Gut (2007)

Edited by Mark Feldman, Lawrence S Friedman, Lawrence J Brandt. Philadelphia: Saunders Elsevier, 2006, £180 (hardback), pp 1–1540 and 1541–2890. ISBN 1-4160-0245-6

The 8th edition of this famous textbook is the first not to be edited by either of the original editors and the 3rd edition to include hepatology as well as gastroenterology, with 38 of the 124 chapters focused on liver and biliary disease. This book thus provides a comprehensive reference for general gastroenterologists as well as more specialised practitioners in gastroenterology and hepatology. The two volumes are presented in a modern glossy style with clear figures and plenty of high-quality line drawings and tables which make the individual chapters easy to read.

The first section on basic biology is relatively brief, but this is supplemented by introductions to the subsequent sections that include anatomical, embryological and developmental aspects for each organ. The book is multi-authored with 177 contributors, and …
Case of Foreign Body in the Bronchus: Tracheotomy: Recovery
Authors: F. B. J. Baldwin
Journal: BMJ (1901)

IN the following case there was no history of alcolholism, and arsenic could not be found in any of the beer or foods that the patient had been in tlle habit of taking.She was not a teetotaller, but on tlle other hand lhad never taken alcohol to excess.Histo -Mrs. A. P., aged 45, had had nine children.An uncle died of cancer of the tlhroat, but otherwise thc family hiistory was unimportanit.As a baby it is stated tlhat she hald some- thing the matter with her spine, but its niature is unknown.At the age of I4 she had a very severe attack of bronchitis, but beyond that slhe had always enijoyed good healtlh until the birtlh of her second child.This pulled lier down a good deal and tlle other children following eacll otlher quickly she had never been quite strong since.She got more and miiore nervous and easily worried.At the beginniing of 1896, dring lactatioin, slhe felt a smiiall hard lumiip in her right breast.This was excised by her doctor.A year later a large fungatiing tuimiour appeared in her left breast, wllich was diagnosed as carcinoma, and the whole breast was removed.She was so afraid of recurrence that for the next twelve months
Response of Non–Small Cell Lung Cancer Cells to the Inhibitors of Phosphatidylinositol 3-Kinase/Akt- and MAPK Kinase 4/c-<i>Jun</i> NH2-Terminal Kinase Pathways: An Effective Therapeutic Strategy for Lung Cancer
Authors: Ho-Young Lee, Seung-Hyun Oh, Young-Ah Suh, Jin Hyen Baek, Vali Papadimitrakopoulou, Suyun Huang, Waun Ki Hong
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We previously showed that phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways cooperate to promote non–small cell lung cancer (NSCLC) cell proliferation in vitro. This study was designed to explore whether inhibition of these pathways effectively inhibits NSCLC tumor growth in vivo. Experimental Design: The effects of PI3K/Akt inhibitors {LY294002, adenoviruses expressing dominant-negative mutant of the p85α adaptor subunit of PI3K (Ad-dnp85α), dominant-negative Akt [Ad-HA-Akt(KM)], or PTEN (Ad-PTEN)}, MKK4/c-jun NH2-terminal kinase (JNK) inhibitor [SP600215, adenovirus expressing dominant-negative MKK4, Ad-MKK4(KR)], and their combinations on proliferation and apoptosis in NSCLC cells were tested in vitro and in vivo using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a flow cytometry-based terminal deoxynucleotidyl transferase–mediated nick-end labeling assay, Western blot and immunohistochemical analyses, and an NSCLC xenograft tumor model. Results: Ad-dnp85α significantly inhibited proliferation of a subset of NSCLC cell lines used in our study. Intratumoral injection of Ad-dnp85α induced a significant decrease in the growth of H1299 NSCLC xenograft tumors. Concurrent inhibition of the PI3K/Akt and MKK4/JNK pathways showed enhanced antiproliferative effects on H1299 cells in vitro and in vivo by increasing apoptosis. Conclusions: PI3K/Akt and MKK4/JNK pathways cooperate to stimulate NSCLC cell proliferation by maintaining cell survival, suggesting that simultaneously targeting these two pathways might be an effective therapeutic strategy against NSCLC.
Therapeutic surgical resection of primary pulmonary artery sarcoma
Authors: Helen Jo, Chuong Bui, Anabelle Maher, Wai Kuen Chow
Journal: European Respiratory Journal (2013)

Introduction: Primary pulmonary artery (PA) sarcoma is an atypical and rare malignancy. The disease is often extensive and aggressive surgical resection is an infrequent intervention.

Case report: A 53 year old non-smoker female presented with recurring massive haemoptysis and dyspnoea. The CT pulmonary angiogram showed large filling defects in the main pulmonary arterial trunks extending to the segmental branches bilaterally, more prominent on the left. The left pulmonary artery had an unusual distortion with an expansile mass that had increased FDG avidity on Positron Emession Tomography (PET) imaging.

![Figure][1] 



Repeated bronchial artery embolisations provided temporary control of her recurring massive haemoptysis. The clinical suspicion of PA sarcoma was eventually confirmed on CT guided core biopsy after two separate failed attempts of endobronchial ultrasound guided biopsy (EBUS) of the left PA mass. Although her disease was extensive, she underwent a left pneumonectomy, debulking of right PA tumour and right endarterectomy at 2 months following her initial presentation.

Discussion: The indication for surgical resection was to alleviate the recurring symptoms of massive haemoptysis. It also provided histological specimen for definitive diagnosis.

Conclusion: Extensive disease of primary (PA) sarcoma may be amenable to therapeutic surgical resections.

 [1]: pending:yes
Clinical judgment in rheumatoid arthritis. III. British rheumatologists' judgments of 'change in response to therapy'.
Authors: J R Kirwan, D M Chaput de Saintonge, C R Joyce, H L Currey
Journal: Annals of the Rheumatic Diseases (1984)

A realistic analysis of the criteria used by rheumatologists in evaluating the progress of patients suffering from rheumatoid arthritis must be based on actual clinical judgments rather than on expressed opinions. A randomly selected 15% sample of British rheumatologists (48) recorded judgements on the progress of 50 9paper9 patients, based on data taken from actual patients participating in clinical trials. The rheumatologists differed markedly in their assessments of the progress of disease, with serious disagreements even when only 9clinically important9 changes were considered. Some clinicians showed little consistency in their judgments of duplicate cases. Multiple regression analysis of the patient data in relation to the disease assessments provided a model of each clinician9s judgment policy. These judgment policy models showed that the differences in clinical assessment were greater than could be explained by the inconsistent application of similar assessment policies, and were a consequence also of differences in the underlying judgment policies themselves. Judgments related more closely to changes in ESR and other process measures than to changes in functional ability.
Elastic recoil changes in early emphysema.
Authors: G W Silvers, T L Petty, R E Stanford
Journal: Thorax (1980)

An attempt was made to determine if emphysema and static lung recoil were related in a group of 65 excised human lungs. We studied 23 normal lungs, 24 lungs with an emphysema score of 5 or less, and 18 lungs with an emphysema score greater than 5. A comparison of the percentage of predicted elastic recoil revealed that both emphysema groups were significantly different from normal lungs. In addition, the total lung capacities were significantly different between the three groups. In the group with an emphysema score greater than 5 we found a linear negative correlation between the extent of emphysema and percent of predicted elastic recoil at 90% total lung capacity (r = -0.696, p &lt; 0.01). We found a negative correlation between the percentage of predicted elastic recoil and the lung volume (r = -0.612, p &lt; 0.01). We conclude that a significant loss of elastic recoil and a significant increase in total lung capacity occurs in the early stages of emphysema.
Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial
Authors: B. Trimbos, P. Timmers, S. Pecorelli, C. Coens, K. Ven, M. van der Burg, A. Casado
Journal: JNCI Journal of the National Cancer Institute (2010)

A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer followup with more events.In the ACTION trial, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation (no further treatment).The original analysis found that adjuvant chemotherapy improved recurrence-free survival but not overall survival and found in a subgroup analysis that completeness of surgical staging was an independent prognostic factor, with better recurrence-free and overall survival among those with complete (optimal) surgical staging.After a median follow-up of 10.1 years, we analyzed the more mature data from the ACTION trial and found support for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P = .05).More cancer-specific deaths were observed among nonoptimally staged patients (40 [27%] of the 147 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) than among optimally staged patients (seven [9%] of the 75 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) (two-sided x 2 test for heterogeneity, P = .06).Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging.