tbuckley/cabot-search huggingface dataset:
Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study
Authors: Frederick A. Spencer, Jeanna Allegrone, Robert J. Goldberg, Joel M. Gore, Keith A.A. Fox, Christopher B. Granger, Rajendra H. Mehta, David Brieger
Journal: Annals of Internal Medicine (2004)

Background: Statins administered early in patients with acute coronary syndromes may lead to modest reductions in recurrent ischemic events. Objective: To examine the association between previous and early in-hospital statin therapy and the presentation and outcomes of an acute coronary syndrome. Design: Cohort study. Setting: 94 hospitals in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE). Patients: 19 537 patients with an acute coronary syndrome who were enrolled from April 1999 to September 2002. Measurements: Statin use before and after presentation with an acute coronary syndrome and associated rates of myocardial infarction, hospital complications, and hospital mortality. The composite end point included death, in-hospital myocardial infarction, and stroke. Results: Patients who were already taking statins when they presented to the hospital were less likely to have ST-segment elevation (odds ratio [OR], 0.79 [95% CI, 0.71 to 0.88]) or myocardial infarction (OR, 0.78 [CI, 0.70 to 0.86]). Patients who continued to take statins in the hospital were less likely to experience complications or die than patients who never received statins (OR, 0.66 [CI, 0.56 to 0.77]). Patients not previously taking statins who began statin therapy in the hospital were less likely to die than patients who never received statin therapy (OR, 0.38 [CI, 0.30 to 0.48]). However, adjustment for the hospital of admission attenuated the association between initiation of statin therapy and the composite end point (OR, 0.84 [CI, 0.65 to 1.10]). Limitations: This observational study cannot exclude confounding by clinical and hospital factors. Conclusions: These data support the hypothesis that statin therapy can modulate early pathophysiologic processes in patients with acute coronary syndromes. A randomized trial of statin therapy in acute myocardial infarction is warranted. *For a list of the members of the GRACE Scientific Advisory Committee, see the Appendix.
Recurrent Flares of Pancreatitis Predict Development of Exocrine Insufficiency in Chronic Pancreatitis
Authors: Bimaljit S. Sandhu, William A. Hackworth, Stacie Stevens, Doumit S. Bouhaidar, Alvin M. Zfass, Arun J. Sanyal
Journal: Clinical Gastroenterology and Hepatology (2007)
Bronchopulmonary Segmental Lavage with Surfaxin (KL<sub>4</sub>-Surfactant) for Acute Respiratory Distress Syndrome
Authors: THOMAS E. WISWELL, ROBERT M. SMITH, LAURENCE B. KATZ, LISA MASTROIANNI, DAVIES Y. WONG, DAVID WILLMS, STEPHEN HEARD, MARK WILSON, R. DUNCAN HITE, ANTONIO ANZUETO, SUSAN D. REVAK, CHARLES G. COCHRANE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We performed a trial to assess the safety and tolerability of sequential bronchopulmonary segmental lavage with a dilute synthetic surfactant (Surfaxin) in 12 adults with ARDS. Patients received one of three dosing regimens in which aliquots of Surfaxin were administered via a wedged bronchoscope to each of the 19 bronchopulmonary segments. Suctioning was performed 10–30 s after instillation of individual aliquots. Group 1 patients (n = 3) received one 30-ml aliquot of a 2.5-mg/ml concentration of Surfaxin in each segment, followed by a second 30-ml aliquot with a 10-mg/ml concentration. Group 2 patients (n = 4) received two 30-ml aliquots of the 2.5-mg/ml concentration followed by a third lavage with the 10-mg/ml concentration. Group 3 patients (n = 5) received therapy identical to that received by patients in Group 2 and were eligible for repeat dosing 6 to 24 h later. All patients tolerated the procedure. There were no serious adverse experiences ascribed to either the procedure or the surfactant. In the 96 h after treatment initiation, Fi O2 decreased from 0.80 to 0.52 and PEEP decreased from 10.3 to 7.6 cm H2O. Bronchoscopic "cleansing" of the lungs with dilute Surfaxin may offer a safe and feasible approach to improving outcomes in patients with ARDS. Wiswell TE, Smith RM, Katz LB, Mastroianni L, Wong DY, Willms D, Heard S, Wilson M, Hite RD, Anzueto A, Revak SD, Cochrane CG. Bronchopulmonary segmental lavage with Surfaxin (KL4-surfactant) for acute respiratory distress syndrome.
Thyroid peroxidase is a molecular mimicry target of anti-hepatitis C virus humoral response
Authors: D.P. Bogdanos, M. Lenzi, M. Okamoto, Y. Ma, P. Aluigi, F. Lari, L. Muratori, R. Williams, F.B. Bianchi, D. Vergani
Journal: Journal of Hepatology (2000)
National Survey of Coronary Artery Bypass Grafting for Coronary Stenosis Caused by Kawasaki Disease in Japan
Authors: Etsuko Tsuda, Soichiro Kitamura
Journal: Circulation (2004)

We surveyed the national experience of coronary artery bypass grafting (CABG) for coronary sequelae of Kawasaki disease (kDa) in 2002.A questionnaire was returned from 323/552 (59%) institutions. Two hundred forty-four patients (188 male 56 female) since 1975 were identified. The mean number of grafts was 1.8 and the age at operation ranged from 1 to 44 years (median 11 years). The interval from the onset of kDa to operation ranged from 1 month to 42 years (median 8 years), whereas the follow-up period was from 7 days to 25 years (median 5 years). Previous myocardial infarction was found in 70 patients (28%). When the age at operation was older than 12 years, patency rates for internal thoracic artery grafts (ITA) at 1, 5, and 15 years were 95%, 91%, and 91%, respectively (n=156). When the age at operation was younger than 12 years, the corresponding values were significantly lower, with 1, 5, and 15 years being 93%, 73%, and 65%, respectively (n=146) (P<0.05). Reoperation was performed in 14 patients (6%). Death occurred in 15 patients (6%). Nine of the 14 late deaths were sudden. Six of 8 patients with a left ventricular ejection fraction (LVEF) <40% died.The results of ITA in those aged 12 years or older were favorable. LVEF influenced prognosis.
Partial versus complete control of blood pressure in the prevention of hypertensive complications.
Authors: J Taguchi, E D Freis
Journal: Circulation Research (1975)

The data from the Veterans Administration Cooperative Study on Antihypertensive Agents Prevention of Morbidity Trial were reviewed from the point of view of the importance of normalizing the blood pressure in preventing cardiovascular complications. The treated group of patients was subdivided into three subgroups on the basis of the diastolic blood pressures recorded at the fourth month after randomization as follows: subgroup A, the poorly controlled patients whose diastolic blood pressures were 90 mm Hg or higher, an intermediate subgroup B with diatolic levels of 81 to 89 mm Hg, and subgroup C, the best controlled patients, all of whom exhibited diastolic blood pressures of 80 mm Hg or less. While the incidence of morbid events was slightly higher in subgroup A than in the other subgroups, the differences were not statistically significant. On the other hand, the incidence of morbid events in subgroup A was significantly lower (P less than 0.05) than in the untreated control patients (14.9% in subgroup A vs. 28.9% in the control group). While normalization of blood pressure is a desirable goal of treatment, even partial reduction appears to exert significant therapeutic benefit.
P33 Improving medicines management in COPD: identifying and addressing sub-optimal treatment
Authors: C Blackaby, P Duncan, A Porter
Journal: Thorax (2012)

Medicines for Chronic Obstructive Pulmonary Disease (COPD) cost the NHS £317m pa. A national improvement programme worked with primary care sites to test practical ways to identify and address potentially sub-optimal prescribing, with a view to improving outcomes and containing cost. Building on learning from initial test sites, selected practises in three CCG areas were supported to analyse primary care data for patients on the COPD disease register and optimise care for these patients. Practises process mapped their current system for managing COPD patients to identify potential improvements. Different methods for data extraction were used to audit diagnosis, disease severity and treatment in relation to NICE guidance. Patients identified as potentially sub optimally treated were called in for review with support of local nurse specialists. Data was collected on respiratory chapter prescribing costs per month per practize, patients reviewed, reasons and outcome. At CCG level, appropriate tools, training and support were developed to help sustain and spread improvement. Early findings from data analysis and patient review identified up to 20% of patients with scope for optimisation of treatment, for reasons including inaccurate diagnosis, poor interpretation of spirometry, and over- or under-treatment in relation to assessment of disease severity. Detailed analysis of patient records required significant input of time and skills, but data extraction tools allowed groups of patients to be targeted more quickly. Review of patients is ongoing. <h3>Conclusions</h3> Data analysis and practical support at practise level can identify and address existing problems of misdiagnosis and sub optimal treatment, but are labour intensive and reactive. It is essential to develop a reliable pathway to ensure accurate and timely diagnosis and treatment are maintained for the future. Tools, guidelines, and ongoing education and support can help sustain this. NHS Improvement acknowledges the contribution of project teams from Mansfield and Ashfield CCG, Godiva CCG and University Hospitals Coventry &amp; Warwickshire, &amp; NHS Isle of Wight in this work.
Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure
Authors: C M Chu
Journal: Thorax (2004)

<b>Background:</b> Non-invasive ventilation (NIV) has been shown to reduce intubation and in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF). However, little information exists on the outcomes following discharge. A study was undertaken to examine the rates of readmission, recurrent AHRF, and death following discharge and the risk factors associated with them. <b>Methods:</b> A cohort of COPD patients with AHRF who survived after treatment with NIV in a respiratory high dependency unit was prospectively followed from July 2001 to October 2002. The times to readmission, first recurrent AHRF, and death were recorded and analysed against potential risk factors collected during the index admission. <b>Results:</b> One hundred and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after NIV during the study period. One year after discharge 79.9% had been readmitted, 63.3% had another life threatening event, and 49.1% had died. Survivors spent a median of 12% of the subsequent year in hospital. The number of days in hospital in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the MRC dyspnoea score (p&lt;0.001) predicted early death. <b>Conclusions:</b> COPD patients with AHRF who survive following treatment with NIV have a high risk of readmission and life threatening events. Further studies are urgently needed to devise strategies to reduce readmission and life threatening events in this group of patients.
Mesenchymal chondrosarcoma of the pleura
Authors: G Luppi, AM Cesinaro, A Zoboli, U Morandi, L Piccinini
Journal: European Respiratory Journal (1996)

A 52 year old man developed an extraskeletal mesenchymal chondrosarcoma (ESMC) arising from the pleura. Clinically, the tumour mimicked a mesothelioma. Fine needle biopsy was consistent with the diagnosis of sarcomatoid mesothelioma. Histological examination of multiple tumour samples, supported by immunohistochemical characterization, made it possible to correctly diagnose extraskeletal mesenchymal chondrosarcoma.
Human Interleukin-10 Gene Transfer Is Protective in a Rat Model of Parkinson's Disease
Authors: Louisa C Johnston, Xiaomin Su, Kathleen Maguire-Zeiss, Karen Horovitz, Irina Ankoudinova, Dmitry Guschin, Piotr Hadaczek, Howard J Federoff, Krystof Bankiewicz, John Forsayeth
Journal: Molecular Therapy (2008)

In Parkinson's disease (PD) chronic inflammation occurs in the substantia nigra (SNc) concurrently with dopaminergic neurodegeneration. In models of PD, microglial activation precedes neurodegeneration in the SNc, suggesting that the underlying pathogenesis involves a complex response in the nigrostriatal pathway, and that the innate immune system plays a significant role. We have investigated the neuroprotective effect of an adeno-associated viral type-2 (AAV2) vector containing the complementary DNA (cDNA) for human interleukin-10 (hIL-10) in the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD. AAV2-hIL-10 reduced the 6-OHDA-induced loss of tyrosine hydroxylase (TH)-positive neurons in the SNc, and also reduced loss of striatal dopamine (DA). Pretreatment with AAV2-hIL-10 reduced glial activation in the SNc but did not attenuate striatal release of the inflammatory cytokine IL-1beta. Assessment of rotational behavior in response to apomorphine challenge showed absence of asymmetry, confirming protection of dopaminergic innervation of the lesioned striatum. At baseline, 6-OHDA-lesioned animals displayed a deficit in contralateral forelimb use, but pretreatment with AAV2-hIL-10 reduced this forelimb akinesia. Transcriptional analyses revealed alteration of a few genes by AAV2-hIL-10; these alterations may contribute to neuroprotection. This study supports the need for further investigations relating to gene therapies aimed at reducing neuroinflammation in early PD.
Functional neuroimaging demonstrates that ghrelin inhibits the central nervous system response to ingested lipid
Authors: Richard B Jones, Shane McKie, Nerys Astbury, Tanya J Little, Stacey Tivey, Daniel J Lassman, John McLaughlin, Simon Luckman, Steve R Williams, Graham J Dockray, David G Thompson
Journal: Gut (2012)

<h3>Objective</h3> Gut-derived humoural factors activate central nervous system (CNS) mechanisms controlling energy intake and expenditure, and autonomic outflow. Ghrelin is secreted from the stomach and stimulates food intake and gastric emptying, but the relevant mechanisms are poorly understood. Nutrient-activated CNS systems can be studied in humans by physiological/pharmacological MRI (phMRI). This method has been used to examine the CNS responses to exogenous ghrelin. <h3>Design</h3> phMRI was used to study the CNS responses in healthy people to a ghrelin bolus (0.3 nmol/kg, intravenous) in the post-prandial state, and an intravenous infusion of ghrelin (1.25 pmol/kg/min) alone and after intragastric lipid (dodecanoate, C12) in people who have fasted. <h3>Results</h3> A ghrelin bolus decreased the blood oxygenation level dependent (BOLD) signal detected by phMRI in feeding-activated areas of the CNS in the post-prandial state. Infusion of ghrelin reversed the effect of C12 in delaying gastric emptying but had no effect on hunger. Intragastric C12 caused strong bilateral activation of a matrix of CNS areas, including the brain stem, hypothalamus and limbic areas which was attenuated by exogenous ghrelin. Ghrelin infusion alone had a small but significant stimulatory effect on CNS BOLD signals. <h3>Conclusion</h3> Ghrelin inhibits activation of the hypothalamus and brain stem induced by ingested nutrients, suggesting a role in suppression of gut-derived satiety signals in humans.
Household Wealth and the Metabolic Syndrome in the Whitehall II Study
Authors: Pablo Perel, Claudia Langenberg, Jane Ferrie, Kath Moser, Eric Brunner, Michael Marmot
Journal: Diabetes Care (2006)

OBJECTIVE—The metabolic syndrome is more common in socially disadvantaged groups. Inequalities in household wealth are currently widening and may contribute to the increasing prevalence of the metabolic syndrome. RESEARCH DESIGN AND METHODS—This was a cross-sectional analysis of 1,509 women and 4,090 men (aged 45.2–68.9 years) of an occupational cohort study of 20 civil service departments located in London, U.K. Components of the metabolic syndrome were measured in 1997–1999 and defined using a modified World Health Organization definition. RESULTS—Own income, household income, and wealth were each strongly and inversely associated with the metabolic syndrome in both sexes (Ptrend &amp;lt; 0.001). Within each group of household wealth, the prevalence of the metabolic syndrome was higher in men than in women. Sex differences became smaller with decreasing household wealth, with the prevalence of the metabolic syndrome rising from 12.0 and 5.7% in the wealthiest men and women, respectively, to corresponding values of 23.6 and 20.1% in the poorest group. The odds ratio (95% CI) associated with each decrease of one category in household wealth was 1.25 (1.03–1.50) in men and 1.69 (1.18–2.41) in women, adjusting for age, household members, occupational grade, education, father’s social class, personal and household income, ethnic group, smoking, alcohol intake, diet, and physical activity. CONCLUSIONS— Household wealth, a measure of assets accumulated over decades and generations, is strongly and inversely associated with the metabolic syndrome. Future research should explore the potential mechanisms by which wealth inequalities are associated with the metabolic syndrome.
Fast High-Resolution Magnetic Resonance Imaging Demonstrates Fractality of Myocardial Perfusion in Microscopic Dimensions
Authors: Wolfgang R. Bauer, Karl-Heinz Hiller, Paolo Galuppo, Stefan Neubauer, Julian Köpke, Axel Haase, Christiane Waller, Georg Ertl
Journal: Circulation Research (2001)

Abstract —The fractal nature of heterogeneity of myocardial blood flow and its implications for the healthy and diseased heart is not yet understood. The main hindrance for investigation of blood flow heterogeneity and its role in physiology and pathophysiology is that conventional methods for determination of myocardial perfusion have severe limitations concerning temporal and spatial resolution and invasiveness. In isolated rat hearts, we developed a nuclear magnetic resonance technique that does not depend on contrast agents and in which the apparent longitudinal relaxation time is made perfusion sensitive by selective preparation of the imaging slice. This perfusion-sensitive relaxation time is determined within 40 seconds as a map with a high spatial in-plane resolution of 140×140 μm 2 and a thickness of 1.5 mm. Perfusion imaging was validated with the established microsphere technique. Additionally, the congruence between perfusion-sensitive T 1 maps and first-pass perfusion imaging was demonstrated. As an application of high-resolution perfusion imaging, fractal analysis of the spatial distribution of perfusion was performed. We were able to demonstrate that the fractality of this distribution exists even in microscopic dimensions. Vasodilation by nitroglycerin modulated the fractal pattern of perfusion, and the decrease of the fractal dimension indicated a shift toward homogeneity. This implies that parameters of the fractal distribution depend on the microvascular tone rather than on anatomic preformations; ie, fractality is a functional characteristic of perfusion.
Targeting Poly(ADP-Ribose) Polymerase: A Two-Armed Strategy for Cancer Therapy
Authors: Elizabeth Ruth Plummer, Hilary Calvert
Journal: Clinical Cancer Research (2007)

The DNA repair pathways are protective of the host genome in normal cells; however, in cancer cells, these pathways may be disrupted and predispose to tumorigenesis or their activity may overcome the potentially cytotoxic damage caused by anticancer agents and be a mechanism of resistance. Poly(ADP-ribose) polymerase inhibitors, which block base excision repair of single-strand breaks, have entered the clinic in the last few years. This article discusses the interactions between the pathways of single- and double-strand break repair, which explain the two clinical development strategies for this class of drugs.
Late-breaking abstract: Particle Emission of e-cigarette
Authors: Efthimios Zervas, Eleni Litsiou, Konstantinos Glynos, Eleni Chita, Ioannis Kalomenidis, Spyros Zakynthinos, Paraskevi Katsaounoou
Journal: European Respiratory Journal (2014)

The constituents (liquid, nicotine&flavours) of e-cigs are vaporized and thus particles are generated. Only passive inhalation of e-cig vapour has been studied.  METHODS  We studied direct particle emission of 7 e-cigs liquids  using a Scanning Mobility Particle Sizer in order to determine the number and size of particles inhaled by e-cigs users.  RESULTS  e-cigs emit 106 -107 particles with a size distribution peaked at 10-20nm & 100-500nm (Figure1) and a median diameter of 200-400nm (Figure2).  Particle size and number are shown in Tab1.  CONCLUSIONS  e-cigs liquids generate nano-particles (300-3000 more than ambient air) that could be inhaled.  Their composition has little or no impact on the distribution, size and number of emitted nano-particles.
Metastasis-Promoting protein S100A4 (MTS1) upregulates production of proinflammatory cytokines via TLR-4
Authors: L. Senolt, L. Cerezo, J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2010)

BackgroundThe authors have previously demonstrated that metastasis inducing protein S100A4 is upregulated in plasma, synovial fl uid as well as in synovial tissue from patients with rheumatoid arthritis (RA).This protein contributes to the pathogenesis of RA by inducing expression of matrix degrading enzymes and regulating apoptosis of synovial fi broblasts.Aim The authors hypothesised that S100A4 might also regulate function of other cells and therefore evaluated the effect of S100A4 on peripheral blood monocytes.
The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair
Authors: M.C. McElroy, M. Kasper
Journal: European Respiratory Journal (2004)

Alveolar epithelial type I cells cover most of the internal surface area of the lungs. Ultrastructural studies demonstrate that alveolar epithelial type I cell damage is frequently observed in acute and chronic lung diseases. This article discusses the use of cell-selective proteins as markers for the investigation of injury and repair of the alveolar epithelium. The utility of proteins specific to alveolar epithelial type I cells as diagnostic markers of alveolar epithelial injury in acute lung injury is considered, and expression of proteins selective for alveolar epithelial type I cells in lungs following injury and in fibrosis are discussed.
CAPON: A Protein Associated with Neuronal Nitric Oxide Synthase that Regulates Its Interactions with PSD95
Authors: Samie R Jaffrey, Adele M Snowman, Mikael J.L Eliasson, Noam A Cohen, Solomon H Snyder
Journal: Neuron (1998)

Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic GMP elevations. The coupling of NMDA receptor-mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein, PSD95, through a unique PDZ–PDZ domain interaction between PSD95 and nNOS. Here, we report the identification of a novel nNOS-associated protein, CAPON, which is highly enriched in brain and has numerous colocalizations with nNOS. CAPON interacts with the nNOS PDZ domain through its C terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95/nNOS complexes in transfected cells. CAPON may influence nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.