tbuckley/cabot-search huggingface dataset:
Abstract 134: Low Dose Particle Radiation Affects Long-Term Survival of Bone Marrow Progenitor Cell Populations
Authors: Sharath Sasi, Daniel Park, Maria A Zuriaga, Kenneth Walsh, Xinhua Yan, David A Goukassian
Journal: Circulation Research (2014)

Radiation-induced decreases in the number of bone marrow (BM)-derived endothelial progenitor cell (BM-EPCs) and their lineage precursors which include Early- and Late-Multi-Potent Progenitor cells (E-MPP and L-MPP) could contribute to the pathogenesis of ischemic and vascular diseases. We examined the effect of full-body single dose of proton (1H) at 0.5 Gy, 1 GeV and 0.15 Gy, 1 GeV/nucleon of iron (56Fe) - ionizing radiation (IR) on survival and proliferation of BM-EPCs. The survival of E-MPPs and L-MPPs in the BM after particle IR in C57BL/6 mice were determined at 1, 2, 4, 8, 12, 28 and 40 weeks post-IR. BM-derived mononuclear cells were triple-stained with RAM34 (CD34, c-kit, and Sca1), AC133, and hematopoietic lineage negative cocktail, then sorted by FASC for E- and L-MPP. BM EPCs ex-vivo - There was a transient 2.5-3.5-fold increase in BM-EPC apoptosis, with 3.5-fold increases for 56Fe and 1H at 5hrs and 24hrs, respectively that was no longer detected by day 7. Subsequently, there was a 3-fold increase in BM-EPC apoptosis on day 28 for both ion-IR mice. Compared to 24 hrs, there was a ~20% (1H) and ~45% (56Fe) increase in the rate of EPC proliferation on day 14 that returned to control levels on day 28. BM E-MPP and L-MPP in vivo - Compared to control mice, 1H-IR increased the number of both E-MPPs (665%) and L-MPPs (203%), whereas 56Fe-IR decreased E-MPP (74%) and L-MPPs (65%) at 1 week post-IR, suggesting stimulation by 1H but overt damage by 56Fe in the BM milieu. In 56Fe-IR mice, E-MPPs recovered between 4 and 12 weeks, followed by declines at later time points. In 1H-IR mice, E-MPPs were near control levels up to 4 weeks, but declined at later time points. The long-lasting and cyclical effects of IR on the BM E- and L-MPPs after a single 1H or 56Fe IR dose suggests the presence of prolonged and non-targeted effects in BM milieu, that occur in cells that were not traversed by IR, rather induced by signals from IR cells. Our studies showed that, both 1H- and 56Fe-IR has profound and long-lasting (28-40 months) negative effects on the number of E- and L-MPPs. Future longitudinal studies are necessary to determine whether BM progenitor cells may be affected after terrestrial IR exposure, such as cancer radiotherapy, CT and PET scans, and in astronauts after exploration-type space missions.
Biodiesel usage in Austria: Improving or deteriorating respiratory health?
Authors: Hans-Peter Hutter, Michael Kundi, Peter Wallner, Bernd Krüger, Irene Schicker, Hanns Moshammer
Journal: European Respiratory Journal (2011)

We estimated respiratory health outcomes for two scenarios for the fraction of biodiesel used in road vehicles: B10 a blend of 10% bio- and standard diesel; B100 biodiesel only.  Data of the composition of vehicle exhausts, vehicle frequency and exhaust volumes were entered into a dispersion model to obtain estimates for the change in particulate matter (PM10, PM2.5) and nitrogen dioxide (NO2) for Vienna and the surrounding region (Lower Austria). From established exposure-response-relationships the health impacts (respiratory mortality and hospital admissions) of the scenarios were expressed as a difference to the reference scenario (year 2007).  Impacts of B10 were very small. For B100 fine particles would decrease by 4 (countryside) to 8% (city of Vienna) while NO2 would increase by 11% in Vienna. Based on effect estimates for chronic exposure the reduction of PM2.5 would lead to 53 less cardiorespiratory annual deaths. Effect estimates based on time series studies resulted in smaller numbers: Reduction of ambient PM10 levels were estimated to result in 8 less annual respiratory hospital admissions. Concerning respiratory mortality the increase of NO2 could result in additional 20 premature deaths per year, while the beneficial effect of the reduction in particles only would lead to a reduction of one case per year.  If health impacts of these air pollutants were independent, the increase in NO2 would strongly outweigh the reduction of PM2.5. However, dose-response relationships of PM and NO2 are not independent and NO2 is indicating traffic related exposures as is PM2.5. Therefore the adverse impact might be less pronounced than indicated by the net difference.
Physical fitness and asthma development in a random population during three decades. The Odense schoolchild study
Authors: Jørgen Guldberg-Møller, Finn Rasmussen
Journal: European Respiratory Journal (2011)

Aim: To investigate the longitudinal association between physical fitness and the development of asthma and asthma-like symptoms in a general population sample. 1369 children from the Odense schoolchild study were assessed from 1985 to 2007 at age 9, 15, 20 and 29 years. The same physical fitness test was applied at all occasions and fitness was stratified into quintiles for each sex.

Results: The following analysis is based all subjects who performed a satisfactory fitness test: 1369 children at age 9 (mean 9.7), 1072 (78%) at age 15 (mean 15.6), 881 (64%) at age 20 (mean 20.3) and 814 (60%) at age 29 (mean 29.3) performed a satisfactory fitness test respectively. The results showed that fitness levels at each age was associated with lower lung function at same age (p<0.001). The was no significant difference in the occurrence of asthma or asthma-like symptoms in the sex specific fitness quintiles at age 9 years. Higher fitness at age 9 was associated with a lower occurrence of asthma at age 20 (p=0.001) and 29 years (p=0.04), but not significant at age 15 years. On the other hand, at age 15 there was a significant trend of higher occurrence of asthma-like symptoms the lower the fitness quintile at age 9 years (p<0.05). In the sex specific analyses the association between physical fitness at age 9 years and asthma at age 20 and 29 years was only significant in women (age 20; p=0.01); (age 29; p=0.04) and men (age 20; p=0.07); (age 29; p=0.7) respectively.

Conclusion: In conclusion, our results point toward the importance of a moderate-high fitness level before puberty to reduce the risk of asthma development in adulthood but this effects seems mainly present in women.
Abstract 14417: Association of QRS Duration with MRI Measures of Left Ventricular Structure and Function and Risk of Heart Failure in Middle-Aged and Older Adults: the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Leonard Ilkhanoff, Kiang Liu, Hongyan Ning, Saman Nazarian, David Bluemke, Elsayed Z Soliman, Donald M Lloyd-Jones
Journal: Circulation (2010)

Background: Prolonged QRS duration (QRSd) on the resting 12-lead ECG has been associated with incident heart failure (HF). Left ventricular (LV) structural and functional measures also are associated with incident HF. Whether QRSd, a marker of electrical and myocardial impulse propagation, is associated with incident HF independent of LV structure and function is unknown. Methods: We included participants who were 45-84 year old men and women free of cardiovascular disease from 4 race/ethnic groups in the NHLBI-funded MESA Study, and who had baseline ECG and cardiac MRI data available. We examined the association of QRSd with incident hospitalized HF over 5.5 years, unadjusted and after adjustment for demographic and clinical variables and each MRI LV measure of structure and function (separately). Results: A total of 4,621 participants were included (50.9% women; 26.2% black, 22.3% Hispanic, 12.5% Chinese; mean age 61.3 years); 84 participants developed incident HF. QRSd ≥ 100 msec was associated with in...
Evolution and Revolution
Authors: John F. Murray, Fran Du Melle, Philip C. Hopewell
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The American Thoracic Society (ATS), the preeminent professional organization in the field of respiratory, critical care, and sleep medicine, is now 107 years old. For the most part, the Society's administrative and medical-scientific interests evolved in an orderly fashion, but two "revolutions" took place that should be remembered. What ultimately metamorphosed into the ATS in 1960 began in 1905 as the 34-member American Sanatorium Association, which in 1915 became the medical section of the National Association for the Study and Prevention of Tuberculosis (NASPT). In 1918, the NASPT became the National Tuberculosis Association and in 1939, the ASA became the American Trudeau Society, cosmetic revisions having no effect on either the medical section-parent relationship or the one-disease orientation of both organizations. After World War II, the narrow focus of the ATS on tuberculosis was progressively enlarged through coalescence of several factors that transformed the practice of pulmonary medicine: the growth of intensive care units and pulmonary function laboratories and the advent of fiberoptic bronchoscopy; the rise of asthma, chronic obstructive pulmonary disease, and lung cancer coincident with the withering of tuberculosis; and the arrival of pulmonary physician-scientists who sought enrichment through a professional society. The newcomers found a home in the ATS, but it was slow to fulfill their needs for scientific communication and administrative responsibility. The first revolution, the formation of Scientific Assemblies, got the job done quickly and well, as described in Part 1 of this perspective. The second revolution, separation from the American Lung Association, is described in Part 2.
Nivolumab (Anti-Pd-1; Bms-936558, Ono-4538) in Combination with Platinum-Based Doublet Chemotherapy (Pt-Dc) or Erlotinib (Erl) in Advanced Non-Small Cell Lung Cancer (Nsclc)
Authors: S. Gettinger, N. Rizvi, L.Q. Chow, H. Borghaei, J.R. Brahmer, R. Juergens, F.A. Shepherd, S.A. Laurie, D.E. Gerber, J. Goldman, Y. Shen, C. Harbison, A. Chen, S.J. Antonia
Journal: Annals of Oncology (2014)
Microscopic colitis: a misnomer for a clearly defined entity?
Authors: Diana Yung, Anastasios Koulaouzidis, Paul Fineron, John Plevris
Journal: Endoscopy (2015)

In recent years, several endoscopic features of microscopic colitis have been noted. The pickup of these on colonoscopy depends on local expertise, endoscopic technology, and case volume. As the incidence of microscopic colitis has increased, we wanted to draw attention to endoscopists' ability to recognize such findings. We present eight cases of biopsy-proven microscopic colitis which demonstrate the spectrum of endoscopic findings. Endoscopists should actively search for such findings and target their biopsies, as new high-definition colonoscopes with sharper images, zoom capabilities, and high resolution allow a new vision into this syndrome.
Transplacental Induction of Primary Renal Tumors in Rabbits Treated With 1 -Ethyl-l-nitrosourea23
Authors: R. R. Fox, B. A. Diwan, H. Meier
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Transplacental Induction of Primary Renal Tumors in Rabbits Treated With 1 -Ethyl-l-nitrosourea Get access R. R. Fox, R. R. Fox Search for other works by this author on: Oxford Academic PubMed Google Scholar B. A. Diwan, B. A. Diwan Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Meier H. Meier Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 6, June 1975, Pages 1439–1447, https://doi.org/10.1093/jnci/54.6.1439 Published: 01 June 1975 Article history Received: 26 November 1974 Accepted: 25 February 1975 Published: 01 June 1975
Inspiratory or expiratory resistance during methacholine challenge in young children: Does it make a difference?
Authors: Iulia Marian, Nicole Beydon
Journal: European Respiratory Journal (2014)

Background It is recommended to measure interrupter resistance during expiration (RintExp) for bronchodilation test and during inspiration (RintInsp) for bronchial hyperreactivity (BHR) detection, to minimize laryngeal influence. But no study assessed the clinical implication of using RintInsp rather than RintExp to detect BHR.

Objectives To compare RintInsp and RintExp ability to correctly detect BHR defined as a 20% decrease in transcutaneous partial pressure in oxygen (TcPO2), in young children.

Methods Prospective monocentre study in children referred for methacholine challenge because of non specific chronic respiratory symptoms, and unable to perform reliable spirometry. Baseline Rint (MicroMedical, UK) measurement lay within the normal range. Methacholine was administered using the dosimeter method (Atomisor, France). Rint changes were considered consistent to that of TcPO2 if there was a 35% Rint increase from the post-diluant value at the dose TcPO2 decreased ≥20% or a less than 35% Rint increase in children without BHR.

Results 14 children (7 girls, median age 5.7 years) performed the test and 9 had BHR between 50 and 400µg of methacholine. Consistency between TcPO2 and Rint was present in 9 (RintIns) and 4 (RintExp) children, with no false positive with RintIns (vs 3 with RintExp).

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Conclusion Although Rint measurement cannot always, on its own, correctly detect BHR in young children, inspiratory measurement should be used as it is more often consistent with TcPO2 changes and do not falsely detect BHR compare to expiratory Rint measurement.
Diagnostic value of bronchoalveolar lavage and lymphocyte transformation test in drug-induced lung disease
Authors: Yoshifumi Kimizuka, Sadatomo Tasaka, Wakako Yamasawa, Makoto Ishii, Hirofumi Kamata, Hiroshi Fujiwara, Youhei Funatsu, Ho Namkoong, Naoki Hasegawa, Mitsuru Murata, Koichiro Asano
Journal: European Respiratory Journal (2011)

Background: The diagnostic strategy of the drug-induced lung disease (DILD) has not been established. It remains to be determined whether the lymphocyte transformation test (LTT) can be used for the diagnosis of DILD. Although bronchoalveolar lavage (BAL) is often performed, its usefulness in the diagnosis of DILD is still uncertain.  Aim: We aimed to evaluate the diagnostic values of BAL and LTT in patients with DILD.  Method: We retrospectively analyzed 47 patients who were suspected as DILD and underwent BAL and LTT between January 2004 and September 2009. The total cell number and the differential count of leukocytes in BAL fluid were determined. The levels of cytokines (eotaxin-1, -2, -3, and RANTES) in the supernatant were measured by ELISA. It was also evaluated whether these parameters were correlated with the outcome of the patients.  Results: The diagnostic sensitivity and specificity of LTT were 50% and 60%, respectively. These numbers were comparable to those in previous reports. The sensitivity of increased eosinophils (>0.5%) in BAL fluid was 90%, and the specificity was 22%. The sensitivity of increased lymphocytes (>50%) was 35%, and the specificity was 78%. Furthermore, the positive likelihood ratio of LTT and increased eosinophils and lymphocytes (>10%) in BAL fluid for the prediction of the patient recovery was 0.99, 6.22, and 5.54, respectively. On the other hand, cytokine levels in the supernatant were not correlated with the diagnosis or the prognosis.  Conclusion: It was suggested that BAL fluid findings, especially the differential count of leukocytes, may be useful for the diagnosis and the prediction of outcome of the patients with DILD.
COPD under invasive mechanical ventilation, in-hospital mortality rate: A retrospective study
Authors: Patricia Garrido, Susana Carreira, Andreia Gonçalves, Fernanda Paula, Leonardo Ferreira, Filipe Froes, Luis Telo
Journal: European Respiratory Journal (2011)

Background: The in-hospital mortality rate of patients with Chronic Obstructive Pulmonary Disease (COPD) submitted to Invasive Mechanical Ventilation (IMV) is recognized as being high.

The authors aim to characterize this population and to identify mortality predictive factors.

Methods: Retrospective study of the clinical records of 67 COPD patients with IMV admitted in the Respiratory Intensive Care Unit (ICU) of Lisbon-North Hospital Centre between January 2005 and August 2009.

Results: The majority were male (91%), with an average of 69±10 yrs and 25% were active smokers. The FEV1 was 40±18%, with 55% being subjected to Long Term Oxygen Therapy and 18% to domiciliary Non Invasive Ventilation (NIV).

The aetiology of exacerbation was mostly infectious (78%). They required 16±24 days of IMV. The ICU mortality rate was 24% and the global hospital mortality rate was 40%.

Two groups were evaluated concerning mortality.

The statistically significant (p<0,05) prognostic factors were: older patients (75 vs. 66 yrs), lower BMI (24 vs. 26 kg/m2), pneumonia (40% vs. 15%), longer in-hospital period before ICU admission (8 vs.3 days), previous acute NIV (67% vs. 33%) and higher severity score at admission (SAPS II 44 vs. 35; APACHE II 27 vs. 20).

A significant association with mortality, through binary logistic regression, was establish: NIV pre-IMV (OR=4.92; IC95%=1,42-16,98 p<0,012) and the APACHE II severity score (OR=1,13; IC95%=1,03-1,24 p<0,008).

Conclusions: Mortality was associated to a higher severity at admission and extended period under NIV whilst preceding the admission in ICU. The data may be relevant through an early recognition of failure situations in patients with previous NIV.
Prlx 93936 displays anti-tumor activity in vitro and in vivo against multiple models of human tumors
Authors: Paul Robbins, Michael Pierce, Christopher Clemens, Raj Gopal Venkat, Shuping Lai, Matthew Rebentisch, Anna Senina, John Peltier, Robert Selliah, Robert Becklin, Vlad O'Mel, Tracy Erkkila, Sudhir Sahasrabudhe
Journal: Cancer Research (2008)

5714  PRLX 93936 is a novel small molecule which exhibits therapeutic potential in a diverse array of in vitro and in vivo tumor models including examples with limited treatment options such as pancreatic cancer. Developed and characterized in cell-based phenotypic assays, PRLX 93936 is a product of extensive SAR work originating from a small molecule identified in a synthetic lethal screen against isogenic cell lines engineered to differentially express several genes including activated RasV12 (Dolma et.al, Cancer Cell 3: 285-296, 2003). A series of structural analogs were designed, synthesized and tested for antiproliferative activity against a panel of normal cell lines and lines derived from tumors with dissimilar causative mutations. The results indicate potent and selective activity against tumor cell lines derived from breast, colon, lung, melanoma, ovary, kidney and pancreas in addition to 100 and 1000 fold improvements in parameters such as potency and solubility respectively. In vivo test results in multiple tumor xenograft models mirrored the in vitro findings producing efficacy ranging from complete regression to tumor-growth inhibition in a dose-dependent manner following oral (PO), intravenous (IV), or intraperitoneal (IP) administration. In vivo efficacy testing of PRLX 93936 in parallel or in combination with other agents such as gemcitabine, bevacizumab, paclitaxel and irinotecan suggest that PRLX 93936 is an effective single agent but that its activity may be complemented by the presence of other drugs. Responsive in vivo tumor models include: HT1080 (fibrosarcoma), PANC-1 (pancreatic), OVCAR-5 (ovarian), DLD-1, Colo205 and HCT116 (colon), in addition to models of non small cell lung cancer, mesenchymal chondrosarcoma, leiomyosarcoma and multiple myeloma. Toxicology studies with mice, rats, dogs, and monkeys demonstrate drug tolerance at potentially therapeutic levels based on body surface area scaling. Although its mechanism of action is still under investigation, examination of the effects of compound treatment upon sensitive cells indicates that PRLX 93936 can rapidly affect ion flux, cell cycle, and mitochondrial membrane polarization ultimately inducing caspase dependent apoptosis. Mass spectrometry-based proteomics experiments indicate that both PRLX 93936 and its parent compound can bind to a mitochondrial protein VDAC (Voltage Dependent Anion Channel) which may be a molecular target (Yagoda et al., Nature. Jun 14;447(7146):864-8). Based on the results of the preclinical pharmacodynamic, pharmacokinetic and toxicological studies, Prolexys initiated Phase I studies with PRLX 93936 in August, 2007.
Abstract 10621: Trends of Early Coronary Revascularization With Acute Myocardial Infarction among Patients on Long-term Dialysis over 15 Years in the United States
Authors: Gautam R Shroff, Shuling Li, Charles A Herzog
Journal: Circulation (2013)

Introduction:  Acute myocardial infarction (AMI) is a catastrophic event associated with dismal long-term survival in dialysis pts. We have previously reported that 1yr mortality rates of STEMI but not NSTEMI pts have significantly reduced in the past 15 yrs. We evaluated the rates of early coronary revascularization in AMI pts to determine if increasing revascularization rates were associated with improved survival.   Methods:  Using the United States Renal Data System (USRDS) database, we identified prevalent ESRD pts hospitalized for an index AMI in 1993, 1998, 2003 and 2008. We identified patients undergoing coronary revascularization with thrombolytics, percutaneous intervention (PCI) or coronary bypass graft surgery (CABG) using ICD-9 procedure codes or CPT codes. We further evaluated whether revascularization occurred in the first day, first two hospital days, or during entire hospitalization.   Results:  Between 1993 & 2008, there was an increase in NSTEMI (1898 vs 13201) but not STEMI (1658 vs 1571) pts. Rates of in-hospital PCI increased steadily (Figure) but were more marked among STEMI (8% vs 38%, p   Conclusion:  There has been a significant increase in early coronary revascularization rates among dialysis AMI pts over 15 yrs, more marked in STEMI compared to NSTEMI pts. These increased revascularization rates are associated with improved 1 yr survival among dialysis STEMI but not NSTEMI pts. These trends probably reflect diffusion of evidence based guidelines to this high risk population.
Bacterial multidrug-resistance profile in a respiratory insufficiency unit - Analysis of 17 months
Authors: Marisa Anciães, Susana Carreira, Cecília Nunes, Fernanda Oliveira
Journal: European Respiratory Journal (2012)

Introduction : Multidrug-resistant bacteria (MRB) are a seriously growing public health threat.

Objectives: Characterize patients with MRB isolations, namely their risk factors. Evaluate frequency of MRB species. Assess influence of antibiotic (AB) therapy towards length of hospital stay (LOS) and mortality.

Methods: Retrospective identification of patients with MRB isolations admitted to Respiratory Insufficiency Unit (RIU) from Feb/10 to Jun/11, followed by medical records' analysis.

Results: MRB were isolated from 32 patients: male sex — 56.3%; mean age — 74.5 years; chronic respiratory disease — 81.3%; comorbidities — 93.8%, of which 65.6% were immunodepressions. Some (37.5%) were transferred to RIU with an average previous LOS of 42.3 days. At RIU admission 96.9% were/had been on AB and 40.6% had been discharged, in the previous month. 71.9% underwent invasive techniques.There were 44 MRB isolations: MRSA — 45.5%; Acinetobacter baumannii — 29.5%; Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa and Enterococcus faecium — ≤ 9.1% each. Pathogen directed-AB was introduced in 29 isolates (65.9%), but only 11 (37.9%) underwent post-AB control and only 3 of these (27.3%) became negative.There were 14 (43.8%) deaths, 78.6% due to infectious causes, of which 54.5% were attributed to MRB. We found no statistically significant differences between death and survival groups, however LOS was significantly longer in patients who had >1 isolation and whose post-AB control remained positive.

Conclusions: Every patient had at least 1 risk factor for infection. MRSA predominated. MRB were difficult to eradicate and responsible for a high mortality rate.