tbuckley/cabot-search huggingface dataset:
A Phase 2, double-blind, placebo-controlled study of N–acetylcysteine in combination with pirfenidone in patients with idiopathic pulmonary fibrosis
Authors: Jürgen Behr, Elisabeth Bendstrup, Bruno Crestani, Andreas Günther, Horst Olschewski, Magnus Skoeld, Athol Wells, Wim Wuyts, Helen Tang, Jürgen Beck, Carlo Albera
Journal: European Respiratory Journal (2014)

Introduction: Pirfenidone (Esbriet®; PFD) is the only drug indicated for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF). Due to the complex pathophysiology of IPF involving multiple pathways, combination therapy seems to be the future. A candidate drug is N-acetylcysteine (NAC), a mucolytic and antioxidant agent extensively studied in respiratory disorders, including IPF. The design of an on-going study of NAC and PFD in IPF is presented.

Aims and objectives: To evaluate the safety and tolerability of NAC in combination with PFD when PFD is prescribed as the standard of care in IPF patients.

Methods: In this Phase 2, double-blind, placebo-controlled trial, patients are randomized (1:1, ∼125 per group) to receive either NAC (1800 mg/day) or placebo in combination with PFD (2403 mg/day orally). Eligible patients (40–80 years) have IPF diagnosed according to current guidelines and baseline pulmonary function tests in the range 50% ≤FVC ≤90%, [FEV1/FVC] ≥0.75, and 30% ≤DLCO ≤90% (assessed by central review). Important exclusion criteria are history of significant environmental exposure known to cause pulmonary fibrosis and a known cause of interstitial lung disease. The study consists of 3 periods: washout and screening (days -42 to -28); treatment (24 weeks); follow-up (28 days after treatment completion).

Results: Since June 2013 approximately 100 patients have been enrolled. Baseline data will be presented. They show that the patient population is comparable to those of previous PFD studies.

Conclusions: This is the first safety and tolerability study of NAC in combination with PFD for the treatment of IPF.
Epidemiological study of a large cluster of fungaemia cases due to Kodamaea ohmeri in an Indian tertiary care centre
Authors: A. Chakrabarti, S.M. Rudramurthy, P. Kale, P. Hariprasath, M. Dhaliwal, S. Singhi, K.L.N. Rao
Journal: Clinical Microbiology and Infection (2013)
Effect of doxofylline on LPS-induced leukocyte migration to the lung
Authors: Yanira Vasquez, Francis Man, Clive Page
Journal: European Respiratory Journal (2013)

Doxofylline is a xanthine drug that shows bronchodilator and anti-inflammatory activity. However, the precise mechanism of action of doxofylline is unknown and its anti-inflammatory activity has not been widely investigated.  Methods : Doxofylline (0.3 mg/kg i.p.) was given -24, -1 and 6 h after LPS (10 µg/mice, i.n.) in Balb/c mice. Lung lavage was performed 24 h later. Lungs were collected for immunohistochemistry staining of ICAM-1 and VE-cadherin expression. Bone marrow cells were collected and stained for the expression of the markers of activation CD11b and CD62L after stimulation with TNF-a and measured by flow citometry.  Results : LPS recruited significantly higher number of neutrophils (PMN) to the lung (mean±SEM) compared to saline (saline:0±0  vs  LPS:2.8±0.12 x10 6 cells/ml, n=9). Doxofylline (Doxo) significantly inhibited the recruitment of PMN (LPS/Doxo:1.02±0.1 x10 6 cells/ml, n =8; p vs  LPS alone). Immunostaining demonstrated that doxofylline (0.3 mg/kg) inhibits the expression of ICAM-1, but does not alter the expression of VE-cadherin in the lung vascular tissue (ICAM-1 LPS:34.4±1.2  vs  Doxo:19.9±2.6 % mean brightness, p=0.001, n=4). Pre treatment with doxofylline (0.1-10 µM) did not significantly alter the expression of CD11b or CD62L on the surface of bone marrow leukocytes.  Conclusion:  Doxofylline inhibits LPS-induced inflammation in the lung by regulating the expression of certain adhesion molecules on the surface of the endothelial layer of the lung vasculature.
Wilm's tumor with pulmonary metastases at diagnosis: the significance of primary chemotherapy. International Society of Pediatric Oncology Nephroblastoma Trial and Study Committee.
Authors: J de Kraker, J Lemerle, P A Voûte, J M Zucker, M F Tournade, M Carli
Journal: Journal of Clinical Oncology (1990)

Data from patients with pulmonary metastases (PM) from Wilms' tumor at diagnosis (stage IV) were collected from six European centers. All patients were pretreated with a chemotherapy (CT) regimen consisting of vincristine (VCR), dactinomycin (AD), and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). After nephrectomy, local therapy for residual pulmonary disease was considered to avoid whole-lung irradiation. Only four of 36 patients still had multiple inoperable metastases after preoperative CT. Thirty patients survived. Four of them were irradiated. Of the six patients who died, four died of PM, one died of abdominal recurrence, and one of therapy-related disease. Disease-free survival and actuarial survival rates are 83% with a mean follow-up of 4 years postnephrectomy.
Fournier's Gangrene: Non-Clostridial Gas Gangrene of the Perineum and Diabetes Mellitus
Authors: A J Lamerton
Journal: Journal of the Royal Society of Medicine (1986)

Three successfully managed cases of Fournier's gangrene, all with diabetes, are reported. A simple bacteriological classification is offered and the importance of diabetes mellitus as a predisposing factor is stressed.
SRT1720 counteracts glucosamine-induced endoplasmic reticulum stress and endothelial dysfunction
Authors: Teresa Vanessa Fiorentino, Teresa Procopio, Elettra Mancuso, Gaetano Paride Arcidiacono, Francesco Andreozzi, Franco Arturi, Angela Sciacqua, Francesco Perticone, Marta Letizia Hribal, Giorgio Sesti
Journal: Cardiovascular Research (2015)

AimsWe hypothesized that a disproportionate activation of the glucosamine (GlcN) pathway, caused by a prolonged exposure to hyperglycaemia, could impair endothelial integrity promoting endoplasmic reticulum (ER) stress. We also tested the possibility that SRT1720 may be able to counteract GlcN-induced ER stress.
Interrelationship between clinical symptoms expressiveness and brush-biopsy cell count and proteinases and its inhibitors in sputum at smokers and nonsmokers with COPD
Authors: Ekaterina Bukreeva, Raisa Pleshko, Gulnara Seitova
Journal: European Respiratory Journal (2011)

We study relationship between clinical picture and expressiveness of inflammatory changes in bronchi at COPD smokers and nonsmokers.  Endobronchial biopsy and brush-biopsy cytological research and definition of elastase and its inhibitors in sputum were conducted at 46 COPD patients. To reveal correlations we used Spearman coefficient. At COPD nonsmokers the expressiveness of cough and dyspnoe has positive correlation with neutrophiles count (R=0.95), dystrophical epithelial cell count (R=0.95) and negative correlation with eosinophiles count (R=-0.95). COPD nonsmokers have positive correlation between elastase activity and goblet cell count (R=0.81) and atrophical epithelial ciliated cell count (R=0.83). It is evidence of influence of elastase on development of atrophy and hypersecretion in COPD exacerbation. COPD smokers have no correlation between cough expressiveness and brush-biopsy cell count, but dyspnoe expressiveness has positive correlation with neutrophiles count (R=0.42), and negative with lymphocytes count (R=-0.70). At COPD smokers the negative correlation was revealed between FEV 1  and dystrophical epithelial cell count (R=-0.40), between a2MG and reserved cell count (R=-0.42), positive correlation between a2MG and typical epithelial ciliated cell count (R=0.46), proliferated epithelial ciliated cell (R=0.56). That may be caused by capacity of a2MG to increase count of cell mitoses. Smoking influences on inflammation mechanisms at COPD patients, that is reflected on correlations between brush-biopsy cell count, proteinases and its inhibitors in sputum and clinical symptoms expressiveness.
Improved survival with increased IC/TLC ratio, DLCO and FEV1 in an analysis of a COPD pulmonary function database
Authors: David Balfe, Zab Mosenifar
Journal: European Respiratory Journal (2011)

Introduction:  COPD is the fourth leading cause of death worldwide. FEV1 is predictive of COPD mortality. The IC/TLC is a measure of static lung hyperinflation.   Aims:  Analysis of a pulmonary function (PF) database evaluating the influence of FEV1, DLCO, IC/TLC and other variables on survival.   Design:  Retrospective analysis of PF data base (31 year). 984 PF9s with a reduced FEV1/FVC, increased TLC and reduced DLCO were analyzed. The date of initial PF test was used as the initiation of the survival analysis. 596 subjects had dates of death. Kaplan-Meier survival plots, in addition to Cox analysis was performed to evaluate the relationship of age, FEV1 (GOLD stage), DLCO and IC/TLC ratio on survival, in addition multivariate analyses was performed assessing the effects of age, FEV1, gender, DLCO and BMI with the IC/TLC ratio.   Results:  Cox analysis for the risk of death, revealed that a reduced IC/TLC ratio (≤ 25%) [HR 1.69, p   Conclusion:  Analysis of a PF database reveals statistically significant associations of a number of measured and demographic variables with survival. IC/TLC ratio > 25%, DLCO ≥ 22%, Mild FEV1, Female gender, and BMI >25 is associated with survival.
Effects of ivabradine on exercise endurance and VO2 kinetic in chronic ischemic heart disease
Authors: Andrea Porto, Mattia Internullo, Elisa Pagliaroli, Paolo Marinelli, Matteo Bonini, Paolo Palange
Journal: European Respiratory Journal (2013)

Background: Elevated heart rate (HR) represents an independent risk factor for morbidity and mortality in chronic ischemic heart disease (CIHD). Βeta-blockers (βB) are considered the first choice medication to control HR in CIHD, however some patients have contraindications to their use. Ivabradine inhibits the If current of sinoatrial cells and controls HR avoiding βB collateral effects.  Aim and Methods: We evaluated the short term effect of 5 mg of ivabradine b.i.d. on exercise endurance at cardiopulmonary exercise test (CPET), in 6 patients (age 59±12) with CIHD (NYHA I-II), sinus rhythm and contraindications to βB. Each patient performed an incremental workload test (IWT) and a constant workload test (CWT) at 85% of his maximal O2 consumption (VO2max) in two separate days, before and after 7 days of ivabradine. We analysed standard CPET variables at IWT. O2 kinetic and Time to limitation (TLim) were evaluated at CWT.  Results: Ivabradine induced a significant reduction in rest and maximal HR (83±12 vs 69±13 bpm, 123±9 vs 106±13 bpm; p  Conclusions: Seven days of ivabradine positively influenced baseline and maximal HR in CIHD patients. Furthermore, sub-maximal exercise tolerance was significantly improved, although no changes in VO2max were observed at IWT.
Outcome of Postchemotherapy Surgery After Treatment With Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Patients With Unresectable or Metastatic Transitional Cell Carcinoma
Authors: Paul M. Dodd, John A. McCaffrey, Harry Herr, Madhu Mazumdar, Jennifer Bacik, Geralyn Higgins, Mary G. Boyle, Howard I. Scher, Dean F. Bajorin
Journal: Journal of Clinical Oncology (1999)

The role of postchemotherapy surgery for patients with metastatic transitional cell carcinoma (TCC) is controversial. We retrospectively analyzed our experience with patients who underwent postchemotherapy surgery after methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy to assess an impact on long-term survival.This report is based on the retrospective analysis of 203 patients with unresectable primary tumors or metastatic TCC, previously reported in five trials of M-VAC chemotherapy. Fifty patients underwent postchemotherapy surgery for suspected or known residual disease. Characteristics of patients selected for surgery, results of surgery, and the impact of surgery on survival were assessed.In 17 patients, no viable tumor was found at postchemotherapy surgery, pathologically confirming a complete response to chemotherapy. Three patients had unresectable residual TCC. In 30 patients, residual, viable TCC was completely resected, which resulted in a complete response to chemotherapy plus surgery. Ten (33%) of these 30 patients remained alive at 5 years, similar to results observed for patients who attained a complete response to chemotherapy alone (41%). Analysis by baseline extent of disease suggested that patients with unresectable primary tumors or with metastases restricted to lymph node sites were most likely to survive for 5 years.Postchemotherapy surgical resection of residual cancer may result in 5-year disease-free survival in some patients who would otherwise succumb to disease. Optimal candidates include patients whose prechemotherapy sites of disease are restricted to the primary or lymph node sites and who have a major response to chemotherapy.
Alcohol--who is paying the price?
Authors: I. Gilmore
Journal: BMJ (2015)

Britain can’t afford to foot the £21bn bill that alcohol delivers annually to the economy

The toll of alcohol on individual health and on healthcare systems has been well highlighted. Alcohol sits in the top five causes of death and disability globally, responsible for 5.9% of deaths and 5.1% of disability adjusted life years (DALYs) lost each year.1 However, many policy makers have not yet accepted the economic arguments for tougher action to reduce this burden. The European Commission has ignored calls from members of the European Parliament (MEPs) and member states for a new alcohol strategy,2 and the new UK government seems unlikely to prioritise public health interests over lobbying from the drinks industry, even though alcohol harm costs our economy more than £21bn (€29bn; $32bn) a year.3

The UK has a relatively “light touch” system of regulation compared with many developed countries. The last government cut alcohol taxes and abolished the alcohol duty escalator, in a move that will cost the public purse more than £1.5bn over five years.4 Liberalising …
Global, regional, and national levels and trends in under-5 mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation
Authors: Danzhen You, Lucia Hug, Simon Ejdemyr, Priscila Idele, Daniel Hogan, Colin Mathers, Patrick Gerland, Jin Rou New, Leontine Alkema
Journal: The Lancet (2015)
Adjuvant Treatment and Onset of Menopause Predict Weight Gain After Breast Cancer Diagnosis
Authors: Pamela J. Goodwin, Marguerite Ennis, Kathleen I. Pritchard, David McCready, Jarley Koo, Saul Sidlofsky, Maureen Trudeau, Nicky Hood, Sheila Redwood
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m 2 . Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P ≤ .05). Caloric intake decreased (P &lt; .01) and physical activity increased (P &lt; .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.
P-247 A follow-up results of team management approach for XELOX therapy in patients with advanced/recurrent colorectal cancer: the SMILE Study (Study of Metastatic colorectal cancer to investigate Impact of Learning Effect)
Authors: Y. Shibata, H. Matsuoka, Y. Munemoto, H. Bando, G. Nishimura, Y. Ogata, H. Okuda, M. Nakamura, I. Terada, H. Uchida, T. Shiroiwa, J. Kishimoto, K. Maeda
Journal: Annals of Oncology (2015)
Ecto-5′ -Nucleotidase. I. Expression in Human Normal and Neoplastic Lymphoid Cell Lines Representing Sequential Stages of 8-Cell Differentiation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Sutapa SenGupta, Toshifumi Hibi, Alison MacKay, Vera Markovic, Leonard D. Stein, Nolan Sigal, Erwin W. Gelfand, Boris E. Chechik
Journal: JNCI Journal of the National Cancer Institute (1984)

The possible association of ecto-5'-nucleotidase (5'-NT) with differentiation of B-cells was explored with the use of normal and neoplastic lymphoblastoid cell lines representing sequential stages of B-cell maturation. There was no relationship between patterns of enzyme expression in the cell lines and immunoglobulin (Ig) secretion, chromosome constitution, proliferative rate, cell volume, or the presence of B1 and B2 antigens. Pre-B-cell lines, which were negative for surface Ig or Ig secretion but positive for cytoplasmic mu-chains, showed the presence of 5'-NT, whereas 9 of 11 lymphoma cell lines, Burkitt's or non-Burkitt's type, both secreting and nonsecreting, did not exhibit enzyme activity. Four myeloma cell lines and 13 of 15 normal B-cell lines were positive for 5'-NT. These results suggested that 5'-NT was present in pre-B-cells and in some very early B-cells. 5'-NT usually disappeared from early and some intermediate B-cells and reappeared in mature B-cells and plasmacytoid cells.
Exercise-induced pulmonary hypertension: at last!
Authors: Robert Naeije, Anton Vonk Noordegraaf, Gabor Kovacs
Journal: European Respiratory Journal (2015)

Stress tests are for the identification of silent pathology. Applications to medical diagnosis are numerous. For example, ventilation ( V ′E) and mean pulmonary artery pressure (mPAP) may overlap at rest, but markedly diverge during exercise in patients with pulmonary hypertension or heart failure and in healthy controls (figure 1). Accordingly, measurements of mPAP during exercise have been part of the diagnostic work-up of pulmonary hypertension since the early years of cardiac catheterisation, more than half a century ago [1]. Yet "exercise-induced pulmonary hypertension", defined by higher than normal mPAP during exercise has failed to gain acceptance [2]. Why is this? Two studies in the September issue of the ERJ support the recognition of exercise-induced pulmonary hypertension <http://ow.ly/Pk7xn>
Principles and Practice of Infectious Diseases.
Authors: Gerald L. Mandell, R. Gordon Douglas, John E. Bennett
Journal: Annals of Internal Medicine (1991)

This updated and expanded edition now offers 297 chapters that cover the basic principles of diagnosis and management, major clinical syndromes, all important pathogenic microbes and the diseases they cause, plus a number of specialised topics useful to the practitioner. It contains 24 totally-new chapters, offers a whole section on AIDS with seven chapters and a chapter Microsporidium Disease, which deals with a new disease just discovered because of AIDS. The text is designed for clinical pathologists, microbiologists, virologists, medical scientists, mycologists, allergists, general practitioners and lecturers of medicine.
A systems approach to identification and validation of biomarkers
Authors: Gordon B. Mills, UT M. D
Journal: Clinical Cancer Research (2010)

Abstract The realization of the promise of personalized molecular medicine will require the efficient development and implementation of novel targeted therapeutics. The goal will be to deliver the right drug to the right patient at the right time at the right dose. This effort will require an integration of information from the DNA, RNA, and protein level into predictors of which patients are likely to benefit from particular therapies. The overall likelihood of response to particular drugs represents the interaction between predictors of sensitivity with predictors of resistance. This session will use examples with predictors from the DNA, RNA, and protein level to illustrate some of the opportunities and challenges to the implementation of personalized medicine. It will demonstrate the need to integrate information from multiple technological platforms into visualizable pathways and networks as a key step in the process.
miRNome integrative analysis in ovarian cancer
Authors: Lin Zhang, Stefano Volinia, Tomas Bonome, George Adrian Calin, Nuo Yang, Vassilis Atlamazoglou, Chang-Gong Liu, Antonis Giannakakis, Joel Greshock, Barbara Weber, Michael Birrer, Artemis Hatzigeorgiou, Carlo Croce, George Coukos
Journal: Clinical Cancer Research (2008)

ED02-02   MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs that function as negative gene regulators. We present data from integrative genomic analysis of the miRNome in human epithelial ovarian cancer including miRNA microarray, array-based comparative genomic hybridization, cDNA microarray, and tissue array. miRNA expression was markedly downregulated with malignant transformation and tumor progression. A high proportion of genomic loci containing miRNA genes exhibited DNA copy number alterations in ovarian cancer (37.1%). Copy number alterations observed in >15% tumors were considered significant. We identified 41 miRNA genes with gene copy number changes that were shared among human ovarian cancer, breast cancer and melanoma (26 with gains and 15 with losses) as well as miRNA genes with copy number changes that were unique to each tumor type. miRNA gene copy changes correlate with miRNA gene expression in ovarian cancer. Thus, genomic copy number loss may account for downregulation of ~15% of miRNA genes. Additionally, epigenetic silencing may account for downregulation of at least ~36% of miRNA genes. miRNA downregulation contributes to genome-wide transcriptional deregulation. Eight miRNAs located in chromosome 14 miRNA cluster ( Dlk1-Gtl2  domain) were downregulated in advanced relative to early stage EOC; two of them, mir-495 and mir-410, are potential tumor suppressor genes and were predicted to target a large part of protein-coding genes that are upregulated in the same cancers. Additional miRNAs were found to be significantly associated with clinical outcome in late stage EOC.