tbuckley/cabot-search huggingface dataset:
Heart disease tests increase, but attack rate is unchanged
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

US and Canadian doctors ordered many more cardiac tests and procedures in 1993-2001, but the rate of acute myocardial infarction remained much the same, say two cross sectional population based studies published in Circulation (2006;113:374-9 and 380-7). Rates of testing and treatment were high in the United States: in 1993 they exceeded those of Canada in 2001.

The authors of the Canadian study said that the growing costs of health technology may threaten the Canadian health insurance system. Ischaemic heart disease is the leading cause of death in Canada, and Canada spends more on cardiovascular technology than on …
DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins
Authors: Zoltan Balazs, Roberto A.S. Schweizer, Felix J. Frey, Franc[COMBINING CEDILLA]oise Rohner-Jeanrenaud, Alex Odermatt
Journal: Journal of the American Society of Nephrology (2007)

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2 catalyze the interconversion of inactive and active glucocorticoids. Impaired regulation of these enzymes has been associated with obesity, diabetes, hypertension, and cardiovascular disease. Previous studies in animals and humans suggested that dehydroepiandrosterone (DHEA) has antiglucocorticoid effects, but the underlying mechanisms are unknown. In this study, DHEA treatment markedly increased mRNA expression and activity of 11beta-HSD2 in a rat cortical collecting duct cell line and in kidneys of C57BL/6J mice and Sprague-Dawley rats. DHEA-treated rats tended to have reduced urinary corticosterone to 11-dehydrocorticosterone ratios. It was found that CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and C/EBP-beta regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-beta mRNA and protein expression. Moreover, it is shown that C/EBP-alpha and C/EBP-beta differentially regulate the expression of 11beta-HSD1 and 11beta-HSD2. In conclusion, DHEA induces a shift from 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids. This provides a possible explanation for the antiglucocorticoid effects of DHEA.
Nasal inflammatory and respiratory parameters in human volunteers during and after repeated exposure to chlorine
Authors: R.P.F. Schins, H. Emmen, L Hoogendijk, P.J.A Borm
Journal: European Respiratory Journal (2000)

The objectives of this study were: 1) to determine if chlorine exposure at low levels induces nasal effects in humans as it does in rodents; and 2) to establish a possible occurrence of respiratory effects in human volunteers exposed to chlorine vapour at concentrations of 0, 0.1, 0.3 and 0.5 ppm. The study was conducted in a double-blind fashion in 8 male volunteers using a repeated measures design, with randomly selected exposure sequences. Subjects were exposed for 6 h x day(-1) on 3 consecutive days to each of the 4 exposure conditions. In nasal lavage, interleukin-8 (IL-8), albumin, total cell number, and percentages of neutrophils, lymphocytes, monocytes, eosinophils, and epithelial cells were determined. The lung function parameters that were analysed included forced vital capacity (FVC), forced expiratory volume in first second (FEV1), FEV1/FVC ratio, and maximal mid expiratory flow (MMEF). Data analysis was limited to 7 subjects since one volunteer decided to stop participating for reasons not related to the study. Nasal lavage measurements did not support an inflammatory response or irritant effects on the nasal epithelium. For FVC, FEV1, and FEV1/FVC, no significant differences were found. MMEF was significantly different between the 0 and 0.5 ppm exposure, but this was attributed to an unexplained shift in baseline values during control (0 ppm) exposure. The present data does not support an inflammatory effect in the nose nor shows changes in respiratory function at repeated exposure up to 0.5 ppm. This discrepancy with previous data in rodents can be attributed at least in part to differences in respiratory tract airflow characteristics.
A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy
Authors: M. Aapro, H. Rugo, G. Rossi, G. Rizzi, M.E. Borroni, I. Bondarenko, T. Sarosiek, C. Oprean, S. Cardona-Huerta, V. Lorusso, M. Karthaus, L. Schwartzberg, S. Grunberg
Journal: Annals of Oncology (2014)

Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways.
Growth Differentiation Factor-15 for Prognostic Assessment of Patients with Acute Pulmonary Embolism
Authors: Mareike Lankeit, Tibor Kempf, Claudia Dellas, Mayumi Cuny, Heike Tapken, Timo Peter, Manfred Olschewski, Stavros Konstantinides, Kai C. Wollert
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Growth differentiation factor (GDF)-15 is a cytokine induced in the heart after ischemia or pressure overload. Circulating levels of GDF-15 provide independent prognostic information in patients with acute coronary syndromes or heart failure.Objectives: We investigated the prognostic value of GDF-15 in acute pulmonary embolism.Methods: In a prospective cohort study, plasma levels of GDF-15 were determined by immunoradiometric assay in 123 consecutive patients with confirmed acute pulmonary embolism.Measurements and Main Results: GDF-15 concentrations on admission ranged from 553 to 47,274 ng/L; 101 patients (82%) had GDF-15 levels above the upper limit of normal (1,200 ng/L). Patients who experienced pulmonary embolism–related complications during the first 30 days had higher baseline levels of GDF-15 (median, 6,039 [25th to 75th percentiles, 2,778 to 19,772] ng/L) compared with those with an uncomplicated course (median, 2,036 [25th to 75th percentiles, 1,279 to 3,176] ng/L; P < 0.001). By multivariable logistic regression analysis, which included clinical characteristics, cardiac biomarkers (troponin T and NT-proBNP [N-terminal propeptide of B-type natriuretic peptide]), and echocardiographic findings, GDF-15 emerged as an independent predictor of a complicated 30-day outcome (P = 0.033). The c-statistic for GDF-15 was 0.84 (95% confidence interval, 0.76–0.90), as compared with 0.72 for cardiac troponin T, and 0.65 for NT-proBNP. The ability of troponin T, NT-proBNP, and echocardiographic findings of right ventricular dysfunction to predict the risk of a complicated 30-day outcome was enhanced by GDF-15. Furthermore, multivariable Cox regression identified baseline levels of GDF-15 as an independent predictor of long-term mortality (P < 0.001).Conclusions: GDF-15 is a promising new biomarker for risk stratification of pulmonary embolism.
Enhanced myocardial salvage by maintenance of microvascular patency following initial thrombolysis with recombinant tissue plasminogen activator
Authors: D. J Longridge, M. J Follenfant, M. P Maxwell, A. J Ford, B. Hughes
Journal: Cardiovascular Research (1990)

Journal Article Enhanced myocardial salvage by maintenance of microvascular patency following initial thrombolysis with recombinant tissue plasminogen activator Get access David J Longridge, David J Longridge D J Longridge, M J Follenfant, M P Maxwell, A J Ford, B Hughes, Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, United Kingdom Correspondence to: Dr Longridge Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael J Follenfant, Michael J Follenfant D J Longridge, M J Follenfant, M P Maxwell, A J Ford, B Hughes, Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Miles P Maxwell, Miles P Maxwell D J Longridge, M J Follenfant, M P Maxwell, A J Ford, B Hughes, Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Alison J Ford, Alison J Ford D J Longridge, M J Follenfant, M P Maxwell, A J Ford, B Hughes, Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernadette Hughes Bernadette Hughes D J Longridge, M J Follenfant, M P Maxwell, A J Ford, B Hughes, Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 9, September 1990, Pages 697–706, https://doi.org/10.1093/cvr/24.9.697 Published: 01 September 1990 Article history Received: 09 March 1990 Accepted: 01 May 1990 Published: 01 September 1990
Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells
Authors: Aline Schögler, Brigitte S. Kopf, Michael R. Edwards, Sebastian L. Johnston, Carmen Casaulta, Elisabeth Kieninger, Andreas Jung, Alexander Moeller, Thomas Geiser, Nicolas Regamey, Marco P. Alves
Journal: European Respiratory Journal (2014)

Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells. Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry. RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses. Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations.
Red-Blood-Cell Augmentation of Hypoxic Pulmonary Vasoconstriction
Authors: STEVEN DEEM, ERIK R. SWENSON, MICHAEL K. ALBERTS, RICHARD G. HEDGES, MICHAEL J. BISHOP
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Red blood cells (RBCs) are known to augment hypoxic pulmonary vasoconstriction (HPV ). To determine whether this phenomenon is hematocrit (Hct) dependent and related to alterations of either nitric oxide (NO) or adenosine metabolism, we studied mechanically ventilated, pump-perfused lungs from euthanized New Zealand White rabbits. Lungs were perfused in situ in a recirculating manner at constant flow; perfusates consisted of Krebs–Henseleit buffer or buffer plus washed RBCs at a Hct of 10% or 30%. HPV was quantitated as the increase in pulmonary artery pressure (Ppa) from baseline after 5 min of hypoxia. In three experimental sets, we studied the effects of Hct on HPV and expired NO, the effects of nitric oxide synthase (NOS) inhibition, and the effects of adenosine receptor blockade. HPV was greater at a higher Hct, and expired NO varied inversely with Hct and decreased with hypoxia. NOS inhibition eliminated RBC-dependence of HPV. Adenosine-receptor blockade did not affect the RBC-dependence of HPV. We conclude that HPV is dependent on Hct, and that this phenomenon may be related to scavenging of NO but not adenosine by RBCs.
Diabetes mellitus and ventilatory capacity: a five year follow-up study
Authors: P Lange, S Groth, J Mortensen, M Appleyard, J Nyboe, P Schnohr, G Jensen
Journal: European Respiratory Journal (1990)

During a five year observation period, declines of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were investigated in 200 subjects with diabetes mellitus (DM), 126 subjects who developed DM during that period and 9,051 nondiabetic subjects. After statistical adjustment for age, sex, height, and tobacco consumption we found that the subjects who developed DM during the observation period had the steepest declines of ventilatory function. Their annual declines of FVC (and FEV1) were on average 29 ml (and 25 ml) greater than the declines observed among the nondiabetic subjects. The subjects who had DM during the whole observation period experienced a decline of ventilatory function which was not significantly greater than the decline among the nondiabetic subjects. Our results suggest that DM, at its onset, is associated with a significantly accelerated decline of ventilatory function. If DM has been present for some years, its impact on the decline of ventilatory function is small.
Differentiation of Lung Adenocarcinoma, Pleural Mesothelioma, and Nonmalignant Pulmonary Tissues Using DNA Methylation Profiles
Authors: Brock C. Christensen, Carmen J. Marsit, E. Andres Houseman, John J. Godleski, Jennifer L. Longacker, Shichun Zheng, Ru-Fang Yeh, Margaret R. Wrensch, Joseph L. Wiemels, Margaret R. Karagas, Raphael Bueno, David J. Sugarbaker, Heather H. Nelson, John K. Wiencke, Karl T. Kelsey
Journal: Cancer Research (2009)

Abstract Pathologic differentiation of tissue of origin in tumors found in the lung can be challenging, with differentiation of mesothelioma and lung adenocarcinoma emblematic of this problem. Indeed, proper classification is essential for determination of treatment regimen for these diseases, making accurate and early diagnosis critical. Here, we investigate the potential of epigenetic profiles of lung adenocarcinoma, mesothelioma, and nonmalignant pulmonary tissues (n = 285) as differentiation markers in an analysis of DNA methylation at 1413 autosomal CpG loci associated with 773 cancer-related genes. Using an unsupervised recursively partitioned mixture modeling technique for all samples, the derived methylation profile classes were significantly associated with sample type (P &amp;lt; 0.0001). In a similar analysis restricted to tumors, methylation profile classes significantly predicted tumor type (P &amp;lt; 0.0001). Random forests classification of CpG methylation of tumors—which splits the data into training and test sets—accurately differentiated mesothelioma from lung adenocarcinoma over 99% of the time (P &amp;lt; 0.0001). In a locus-by-locus comparison of CpG methylation between tumor types, 1266 CpG loci had significantly different methylation between tumors following correction for multiple comparisons (Q &amp;lt; 0.05); 61% had higher methylation in adenocarcinoma. Using the CpG loci with significant differential methylation in a pathway analysis revealed significant enrichment of methylated gene-loci in Cell Cycle Regulation, DNA Damage Response, PTEN Signaling, and Apoptosis Signaling pathways in lung adenocarcinoma when compared with mesothelioma. Methylation profile–based differentiation of lung adenocarcinoma and mesothelioma is highly accurate, informs on the distinct etiologies of these diseases, and holds promise for clinical application. [Cancer Res 2009;69(15):6315–21]
Laser beam microdissection in the diagnosis of cutaneous B-cell lymphoma
Authors: L. CERRONI, G. MINKUS, B. PÜTZ, H. HÖFLER, H. KERL
Journal: British Journal of Dermatology (1997)

Interpretation of molecular analyses of cutaneous lymphoid infiltrates may be difficult because a heterogeneous group of cells in usually present within the neoplasms. Extraction of DNA from tissue sections does not provide exact information about which cell population has been analysed. We present a laser microscope system that allows selective molecular analysis of single cells or small groups of cells in cases of cutaneous lymphoma. An ultraviolet (UV)-laser microscope system (PALM, Wolfratshausen, Germany) was used to isolate particular populations of cells from a routinely processed specimen of a cutaneous follicular lymphoid proliferation. Using the UV-laser beam, a circle was cut around a target germinal centre in order to separate it from neighbouring tissues and to isolate a pure population of germinal centre cells. Isolated cells were scraped off with a micromanipulator and placed in a proteinase-K solution. DNA was extracted and amplified by the polymerase chain reaction (PCR) technique. Analysis of immunoglobulin JH gene rearrangement showed a distinct monoclonal band. In a second phase, using the same procedure in the same specimen, mantle zone cells around a germinal centre and single interfollicular B lymphocytes were isolated for PCR analysis of immunoglobulin JH gene rearrangement. In this population of cells, no clonality could be detected. This new technique allows the selective elimination of undesired cells and tissue from cutaneous neoplasms. By destruction of unwanted tissues with laser-beam energy a contamination-free sample is obtained. Analysis of isolated cells in our case demonstrated a clonal rearrangement derived from germinal centre cells and not from other B lymphocytes in the specimen, confirming the diagnosis of cutaneous follicle centre lymphoma. The method described has exciting implications for dermatology and dermatopathology, allowing precise correlation of morphological features with findings by molecular genetics.
ABC of Liver, Pancreas and Gall Bladder: Edited by I Beckinham. London: BMJ Publishing Group, 2001, pound16.95, pp 54. ISBN 0-7279-1531-2
Authors: P Hungin
Journal: Gut (2003)

The ABC Series are well established as handy reference guides but they sometimes struggle from not being clear about their target readership. Midway between a textbook and an update, this publication follows the usual format. The topic is covered from investigations used in liver and biliary disease to the clinical conditions themselves, ranging from gall stones to liver and pancreatic transplantation. Because of the nature of the clinical area, the book will probably appeal more to the hospital clinician than the general practitioner although the latter …
No pain, no gain? Thoughts on the Caerphilly study
Authors: I-M Lee
Journal: British Journal of Sports Medicine (2004)

Greater duration and/or intensity of activity can bring additional health benefits

The Caerphilly study1 addresses an important question regarding physical activity and health: how intensely does one need to exercise in order to reduce the risk of premature mortality from cardiovascular disease (CVD)? In this study, 1975 men, aged 49–64 years and free of coronary heart disease (CHD), reported on their leisure time physical activities and were followed for an average of 10.5 years for mortality. The investigators concluded that “only leisure exercise classified as heavy or vigorous was independently associated with reduced risk of premature death from CVD”. When men were categorised into thirds of energy expended on vigorous activities requiring ⩾6 METs, the most active third (expending ⩾24 kcal/day in vigorous activities) experienced a 36% reduction in mortality from CVD compared with the least active third (expending hardly any energy in vigorous activities). However, when men were grouped into thirds of energy expended on light or moderate activities requiring <6 METs, similar rates of CVD mortality were observed in the most and least active thirds of men (expending ⩾343 and ⩽133 kcal/day respectively in light or moderate activities).

“If moderate intensity physical activity does not benefit health, should health professionals bother to prescribe such activities?” 

This surely comes as bad news for many, as most people living in developed countries are inactive. In the United Kingdom, only 33% of men and 21% of women meet guidelines for physical activity,2 and in the United States, a mere 36% of men and 28% of women engage in regular leisure time physical activity.3 In these largely sedentary societies, persuading those who are inactive to take up moderate intensity physical activity (such as brisk walking) for their health is more likely to meet with success than requiring inactive persons …
CO2 chemosensing in rat oesophagus
Authors: Y Akiba, M Mizumori, M Kuo, M Ham, P H Guth, E Engel, J D Kaunitz
Journal: Gut (2008)

Background: Acid in the oesophageal lumen is often sensed as heartburn. It was hypothesised that luminal CO2, a permeant gas, rather than H+, permeates through the epithelium, and is converted to H+, producing an afferent neural signal by activating chemosensors. Methods: The rat lower oesophageal mucosa was superfused with pH 7.0 buffer, and pH 1.0 or pH 6.4 high CO2 ( P CO2 = 260 Torr) solutions with or without the cell-permeant carbonic anhydrase (CA) inhibitor methazolamide (MTZ, 1 mM), the cell-impermeant CA inhibitor benzolamide (BNZ, 0.1 mM), the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ, 0.5 mM) or the acid-sensing ion channel (ASIC) inhibitor amiloride (0.1 mM). Interstitial pH (pHint) was measured with 5′,6′-carboxyfluorescein (5 mg/kg intravenously) loaded into the interstitial space, and blood flow was measured with laser-Doppler. Results: Perfusion of a high CO2 solution induced hyperaemia without changing pHint, mimicking the effect of pH 1.0 perfusion. Perfused MTZ, BNZ, CPZ and amiloride all inhibited CO2-induced hyperaemia. CA XIV was expressed in the prickle cells, with CA XII in the basal cells. TRPV1 was expressed in the stratum granulosum and in the muscularis mucosa, whereas all ASICs were expressed in the prickle cells, with ASIC3 additionally in the muscularis mucosa. Conclusions: The response to CO2 perfusion suggests that CO2 diffuses through the stratum epithelium, interacting with TRPV1 and ASICs in the epithelium or in the submucosa. Inhibition of the hyperaemic response to luminal CO2 by CA, TRPV1 and ASIC inhibitors implicates CA and these chemosensors in transduction of the luminal acid signal. Transepithelial CO2 permeation may explain how luminal H+ equivalents can rapidly be transduced into hyperaemia, and the sensation of heartburn.
[9] COMPARABLE ANTIVIRAL RESPONSE RATES WITH ALBUMIN INTERFERON ALFA-2B DOSED AT Q2W OR Q4W INTERVALS IN NAIVE SUBJECTS WITH GENOTYPE 2 OR 3 CHRONIC HEPATITIS C
Authors: V.G. Bain, P. Marotta, K. Kaita, E. Yoshida, M. Swain, R. Bailey, A. Neumann, P. Cronin, J. McHutchison, E. Pulkstenis, M. Subramanian
Journal: Journal of Hepatology (2007)