tbuckley/cabot-search huggingface dataset:
Abstract 5141: Guanylyl Cyclase Activation Using HMR1766 Improves Endothelial Function and Reduces Platelet Activation in Congestive Heart Failure
Authors: Andreas Schaefer, Daniela Fraccarollo, Johann Bauersachs
Journal: Circulation (2009)

Background: Endothelial dysfunction and platelet activation are part of the cardiovascular phenotype of severe congestive heart failure(CHF). An association between reduced endothelium-dependent NO-bioavailability and platelet activation has been described in experimental CHF. We investigated, whether chronic activation of soluble guanylyl cyclase using HMR1766 increases vascular NO-bioavailability and reduces platelet activation in experimental CHF. Methods and results: Chronic myocardial infarction was induced in male Wistar rats by coronary ligation. Rats were randomised to placebo or HMR1766 (10mg/kg twice daily). After 10 weeks, haemodynamics were measured and endothelial function was assessed in organ bath studies. Only animals were included in the CHF groups, when left-ventricular infarct size was &gt;45% and left-ventricular end-diastolic pressure was &gt;15 mmHg. Endothelium-dependent, acetylcholine-induced and NO-mediated relaxation of the aorta was significantly attenuated in CHF-Placebo compared to Sham-operated rats (Rmax: Sham 83.9±1.4%, CHF-Placebo 56.9±5.9%, p&lt;0.01) and markedly improved in CHF-HMR1766 (Rmax 75.4±4.6% p&lt;0.01 vs. CHF-Placebo). Basal NO-bioavailability in vivo was determined by the extent of phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets from whole blood fixed in formaldehyde immediately following collection. Platelet in vivo-VASP phosphorylation was attenuated in CHF-Placebo compared to Sham animals (mean fluorescence intensity: Sham 16.4±1.0%, CHF-Placebo 13.4±0.3%, p&lt;0.05), and normalised by HMR1766 treatment (17.1±1.2% p&lt;0.05 vs. CHF-Placebo). Activation of circulating platelets was determined measuring P-selectin surface-expression on platelets by flow-cytometry. P-selectin surface-expression was significantly increased in CHF-Placebo (mean fluorescence intensity: Sham 14.2±0.4%, CHF-Placebo 16.0±0.4%, p&lt;0.05) and reduced following treatment with HMR1766 (14.5±0.3% p&lt;0.05 vs. CHF-Placebo). Conclusion: Chronic guanylyl cyclase activation using HMR1766 significantly improved endothelial function, enhanced systemic NO-bioavailability and reduced platelet activation in CHF rats.
Understanding costs and cost-effectiveness in critical care: Report from the second american thoracic society workshop on outcomes research
Authors: Derek C. Angus, Gordon D. Rubenfeld, Mark S. Roberts, Randall Curtis, Alfred F Connors, Deborah J. Cook, Judith R. Lave, Michael R. Pinsky
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Economic evaluations are increasingly common in the critical care literature, although approaches to their conduct are not standardized. The American Thoracic Society convened a workshop to address methodologic and reporting issues for economic analyses in critical care and to determine how guidelines from the U.S. Public Health Service Panel on Cost-effectiveness in Health and Medicine (PCEHM) were applicable to critical care. We identified several issues that hamper cost-effectiveness analyses (CEAs) in the critically ill. Data on the effectiveness of intensive care unit (ICU) interventions are often lacking; ICU patients are complex, with multiple concurrent problems and interventions; most ICU therapies are only supportive, and therefore may not individually result in improved outcome; accurate cost data are not commonly available and are difficult to obtain; there is no standardized approach for measuring or valuing costs across countries; typical outcomes in ICU studies (e.g., short-term mortality) are not ideal for CEAs while preferred outcomes for CEAs (e.g., long-term quality-adjusted survival) are rarely collected; valuing the importance of appropriate end-of-life care, an important aspect of ICU care, is difficult, and the burden of critical illness on family members is not easily captured in a CEA. Nevertheless, many of these problems are not unique to critical care, and we believe the PCEHM guidelines can be adapted to the critical care setting. We recommend all CEAs in the critically ill include a PCEHM reference case, where the cost-effectiveness ratio is calculated by adopting a societal perspective, estimating long-term costs and quality of life after ICU care, applying a 3% annual discount rate to costs and effects, and conducting multiway sensitivity analyses. Because elements of the reference case, such as long-term costs and quality of life, may only be estimated using modeling and assumptions, we also recommend inclusion of a data-rich case, where the cost-effectiveness ratio is generated as closely as possible from data on actual patient outcomes and costs (e.g., hospital costs per hospital survivor). We recommend that investigators conducting a CEA concurrently with a randomized trial make the proposed model available (e.g., via the Internet) before unblinding of trial data to minimize bias. Adopting a standard approach to CEAs of ICU therapies will provide a valid and more transparent evidence base for health care policy with regard to care of the critically ill.
Laboratory capability in Europe for foodborne viruses
Authors: B A Lopman, Y van Duynhoven, F X Hanon, M Reacher, M Koopmans, D W Brown
Journal: Eurosurveillance (2002)

This report describes a survey of national laboratory capabilities of diagnostics and surveillance databases for foodborne viruses among the &amp;quot;Foodborne Viruses in Europe&amp;quot; consortium. All the countries have laboratories that can test for HAV antibody in human serum. Eight of the ten surveyed European countries maintain a national database of HAV cases. Food can be tested for the presence of HAV in Finland, Italy, Spain, France and Denmark. All surveyed countries have at least one laboratory that tests for Norwalk-like virus (NLV) by reverse transcriptase-polymerase chain reaction and all also have the capability to use electron microscopy. Five countries maintain a national database of NLV cases and nine maintain a national database of NLV outbreaks. Almost all participant countries have laboratories that can test for NLV in food items including shellfish.
Data From The Russian Cohort Of The International Disease Registry For Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Igor Lisukov, Alexander Kulagin, Alexey Maschan, Elena Shilova, Kudrat Abdulkadyrov, Andrey Zaritskiy, Valentina Ivanova, Yulia Bogdanova, Svetlana Volkova, Andrey Gavrilenko, Tatyana S Kaporskaya, Sergey Meresiy, Tatyana Schneider, Svetlana Yakupova, Ludmila Anchukova, Bulat Bakirov, Natalia Kosacheva, Tatiana Krinitsina, Viktoria Ustyantseva, Yuriy Shatokhin, Alexander Rumyantsev, Boris Afanasyev
Journal: Blood (2013)
A Phase II Study of S-1 (S) Plus Cisplatin (P) with Concurrent Thoracic Radiotherapy (TRT) for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) West Japan Oncology Group (WJOG) 3706 Trial
Authors: Yamanaka T, Ichinose Y, Nishimura Y, Nakagawa K, Sasaki T, Seto T, Tanaka M, Sawa T, Kokubo M, Katakami N
Journal: Journal of Thoracic Oncology (2010)
Abstract 2289: Charlson Comorbidity Index Predicts Early Mortality Among ICD patients
Authors: Jose Mauricio Sanchez, Roger Kerzner, Scott L Greenberg, Jane Chen, Mitchell N Faddis, Marye J Gleva, Bruce D Lindsay, Timothy W Smith
Journal: Circulation (2006)

Background Limitations of current methods to predict who will benefit from an implantable cardioverter-defibrillator (ICD) are widely recognized. Prediction of early mortality could identify patien...
Abstract 5200: Octyl-D-Carnosine Attenuates Atherogenesis in ApoE Null Mice Fed a Western Diet
Authors: Giuseppe Pugliese, Carla Iacobini, Carlo Ricci, Angela Scipioni, Andrea Giaccari, Enrica Salomone, Renato Canevotti, Annunziata Lapolla, Marica Orioli, Giancarlo Aldini, Stefano Menini
Journal: Circulation (2009)

Lipid endoperoxides resulting from oxidation of unsaturated lipids are further metabolized to reactive carbonyl species (RCS), which react with proteins to generate advanced lipoxidation endproducts (ALEs). ALEs are believed to evoke an inflammatory response which participates in all stages of atherosclerosis. The endogenous dipeptide L-carnosine was shown to act as quencher of RCS derived from lipoxidation. Since it is rapidly inactivated by carnosinase, we evaluated the effect of the carnosinase-resistant octyl ester of D-carnosine (ODC, Flamma SpA, 60 mg/kg in the drinking water) vs. vehicle on the development of atherosclerosis in female apoE null mice fed a western diet (42% fat) vs. standard chow for 12 weeks. Oil red O staining of en-face aorta preparations showed a significant reduction of lipid accumulation in ODC-treated vs. untreated ApoE null mice on western diet (13.2±2.5 vs. 19.2±2.0 %, P&lt;0.001). Morphometric evaluation of aortic lesions in sections stained with the Weigert-Van Gieson method showed significantly reduced lesion area in ODC-treated mice at the level of the aortic sinus and, particularly, of the brachiocephalic artery. ODC treatment also resulted in a more stable plaque phenotype, with less inflammation and apoptosis, and more collagen and VSMCs, resulting in reduced necrotic core formation (11.8±3.8 vs. 25.3±5.4%, P&lt;0.0001). The gene expression level of the markers of inflammation and lesion progression F4/80, MCP-1, VCAM –1, TNF- α , IFN- γ and matrix metalloproteinase-2 and 9 and the RCS- and ALE-receptors CD36, RAGE and gelectin-3 was significantly decreased and even normalized in western diet-fed ApoE null mice treated with ODC. These data indicate that generation of RCS and ALEs from lipid peroxidation plays a major role in atherogenesis and that quenching of these compounds with a D-carnosine ester may represent a promising approach to the prevention and treatment of vascular disease.
Low Back Pain
Authors: Roger Chou
Journal: Annals of Internal Medicine (2014)

This issue provides a clinical overview of Low Back Pain focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.
Abstract 5449: Diagnostic Performance of Perfusion Cardiovascular Magnetic Resonance Compared With Gated Myocardial Perfusion SPECT in Patients With Known or Suspected Coronary Artery Disease
Authors: Chiara Bucciarelli-Ducci, Jonathan Lyne, Eliana Reyes, Ravi Assomull, Joanna Petryka, Stuart Watkins, Peter Gatehouse, Micheal Roughton, Karen Symmonds, Eleni Asimacopoulos, Sanjay Prasad, S Richard Underwood, Dudley Pennell
Journal: Circulation (2009)

Background: Perfusion cardiac magnetic resonance (CMR) is emerging a clinically valuable imaging technique in patients with known or suspected coronary artery disease (CAD) and it has some potential advantages over myocardial perfusion scintigraphy. Aim : To evaluate the diagnostic performance of adenosine perfusion CMR vs gated single-photon emission computed tomography (SPECT) compared with the gold-standard of quantitative coronary angiography (QCA) in patients with known or suspected CAD. Methods : Ninety-five patients scheduled for coronary angiography underwent both adenosine perfusion CMR and adenosine technetium-99m-tetrofosmin SPECT. Stress CMR perfusion imaging was performed with a hybrid-EPI sequence after 4 minutes of 140 μ g/kg/min adenosine and 0.1mmol/kg of gadolinium, and followed by late enhancement imaging. Tc-99m SPECT was performed with a 1day stress-rest protocol. CAD was defined as diameter stenosis ≥50% on QCA. Two blinded observers per modality analyzed the images both qualitatively (presence/absence of inducible ischemia) and quantitatively: myocardial perfusion reserve index (MPRI) by CMR and sum difference score (SDS) by SPECT. A MPRI ≤2 by CMR was considered abnormal. The comparison of CMR vs SPECT was based on receiver operating characteristic (ROC) analysis. Results : Analysis of all patients showed that perfusion CMR had similar diagnostic performance to SPECT: area under ROC curve (AUC): 0.74±0.050 vs 0.683±0.052 for SPECT, p=0.29 based on qualitative assessment and 0.675±0.054 vs 0.583±0.024 for SPECT, p=0.10 based on MPRI and SDS. Similar results were observed in the subgroup of patient with previous myocardial infarction. (n=34, 38%-defined as the presence of late myocardial enhancement by CMR). However, in the subgroup of patients without previous myocardial infarction, CMR MPRI had significantly better diagnostic performance than SPECT SDS: AUC 0.695±0.063 vs 0.552±0.029, respectively, p=0.027. Conclusions : In patients with known or suspected CAD, perfusion CMR has a similar diagnostic performance to Tc-99m gated SPECT and has particular advantage in patients without previous infarction. CMR represents a valuable alternative imaging modality to assess CAD.
Increased Hepcidin Expression in β-Thalassemic Mice Treated with Apo-Transferrin Is Associated with Increased Smad1/5/8 and Decreased Erk1/2 Pathway Activation
Authors: Huiyong Chen, Tenzin Choesang, Petra Pham, Weili Bao, Maria Feola, Huihui Li, Mark Westerman, Guiyuan Li, Antonia Follenzi, Lionel Blanc, Stefano Rivella, Robert E Fleming, Yelena Ginzburg
Journal: Blood (2014)
Like should be compared with like
Authors: D. J Goldie, A. Gunneberg
Journal: BMJ (1995)

EDITOR,—Eric S Kilpatrick and colleagues conclude that measurement of haemoglobin A1c (HbA1c) concentration is to be preferred to measurement of haemoglobin A1 (HbA1 concentration on the grounds that the former classified a higher proportion of diabetic patients as having poorly controlled disease.1 But the basis of this classification—poor control being equated with a glycated haemoglobin concentration >5 SD from the reference population mean—is flawed because the coefficient of variation of the reference population mean is not the same for the methods of measurement compared. Inevitably, if (as is the case) the SD is much smaller for HbA1c than for HbA1 measured by electrophoresis but the means differ proportionately much less, any criterion of poor control based on the same number of SDs above the mean …
Abstract 17407: Right Ventricular Systolic Function in Subjects with HFpEF: A Community Based Study
Authors: Selma F Mohammed, Veronique L Roger, Omar F Abou Ezzeddine, Margaret M Redfield
Journal: Circulation (2011)

Background: Pulmonary hypertension is common in HFpEF and is associated with increased mortality. Pulmonary hypertension can lead to right ventricular systolic dysfunction. However, the magnitude and prognostic significance of RV dysfunction in the HFpEF population are unclear. Hypothesis: RV systolic dysfunction is common in HFpEF and is associated with increased mortality. Methods: RV size and systolic function were assessed qualitatively (as normal or abnormal) and pulmonary artery systolic pressure (PASP) was estimated using echocardiography in 548 consecutive HFpEF subjects (Framingham criteria and EF ≥50%) from a prospective population based study (Olmsted County, Minnesota). Control group was a retrospectively identified random sample of age and sex matched hypertensive (N=360) and normotensive subjects (N=168) from Olmsted County. HFpEF group was followed for up to 5 years (median follow up 4.4 years). Results: See table and figure. RV enlargement and systolic dysfunction were more prevalent in HFpEF compared with age and sex matched hypertensive and normotensive controls. In HFpEF subjects with PASP above the median, RV systolic dysfunction was associated with poor survival compared with normal RV function. RV systolic dysfunction was a significant predictor of mortality even after adjustment for age and PASP in a Cox regression model (Hazard Ratio=1.4, p=0.02). Conclusions: In the community, RV systolic dysfunction is common in HFpEF and is associated with higher mortality. Although quantitative assessment of RV function is difficult owing to its complex geometry, qualitative assessment is feasible on the majority of subjects and provides significant prognostic information.
Abstract 15373: Transition to Adult Congenital Heart Disease Care for Young Adults with Repaired Transposition of the Great Arteries is Better in Canada versus the United States in a Large Cohort: a Multi-institutional Congenital Heart Surgeons' Society Study
Authors: Anusha Jegatheeswaran, Karl F Welke, Eugene H Blackstone, Paul M Kirshbom, Linda M Lambert, Stephanie Fuller, Christo I Tchervenkov, Ronald K Woods, Kathleen A Mussatto, Timothy B Cotts, James D St. Louis, Jeffrey P Jacobs, Marshall L Jacobs, Christopher A Caldarone, William G Williams, Brian W McCrindle
Journal: Circulation (2011)

Objectives: Improved survival after congenital heart disease (CHD) surgery has led to the need for successful transition to adult congenital heart disease (ACHD) care. We sought patterns and associ...
Abstract 15057: Left Atrial Reverse Remodeling and Outcome in Patients with Heart Failure
Authors: Kazuto Yamaguchi, Hiroyuki Yoshitomi, Tomoko Adachi, Saki Ito, Nobuhiro Kodani, Takashi Sugamori, Masatake Sato, Nobuyuki Takahashi, Hidetoshi Sato, Kazuaki Tanabe
Journal: Circulation (2010)
Abstract 5404: Perturbation of Tropomyosin Amino Acid Residues Binding to Actin at the “Off” State of Tropomyosin Increase Cardiac Muscle Dynamics
Authors: Mariappan Muthuchamy, Rochelle Dowdie, Xin Wu, Scott Zawieja, Kuppan Gokulan, Carl Tong, Richard Moss
Journal: Circulation (2008)

Tropomyosin (TM), an essential thin filament protein, binds along F-actin in association with troponin and plays a central role in regulating cardiac muscle dynamics. Previous structural studies have shown that TM molecule consists of 14 negatively charged, alternating α- and β-bands along its length, responsible for binding to actin. The 7 α-bands of TM are implicated in the binding to actin at the “off” state where actomyosin crossbridging is blocked. The 7 β-bands of TM bind to actin at the “on” state that permits actomyosin interaction and results in force production. In this study, we hypothesize that if the α-bands are perturbed by changing the charged residues at that region, it will cause TM molecule “slipping” at the “off” state that will allow TM to be in an extended “on” state leading to enhanced cardiac muscle dynamics. To test this hypothesis we have generated TG mouse lines expressing α-TM with mutations in the α-bands located in the carboxy terminus (α-TM CTM). More specifically, codons encoding negatively charged amino acids (aspartate or glutamate) at positions 212, 219, 223, 255 and 259 were changed to lysine by site-directed mutagenesis. Molecular analyses revealed one of the TG lines α-TM CTM-6 expressed 100% of mutant protein. Echocardiogram data analyses showed that α-TM CTM-6 hearts exhibited significant decrease in heart rate (10%; p&lt;0.05, n=6)) in the absence or presence of dobutamine. Furthermore, the percentage fractional shortening and ejection fraction were significantly increased (13% and 15%, respectively, p&lt;0.05, n=6) in TG hearts when compared to non-transgenic (NTG) controls. To investigate the mechanisms for the increase in cardiac muscle dynamics in the TG hearts, we measured force and calcium levels in the papillary muscle fiber. Force- [Ca2+]i data analyses showed that the α-TM CTM TG hearts produced more force per given [Ca2+]i when compared to NTG hearts, indicating that α-TM CTM myofilaments exhibit an increase in Ca2+ sensitivity. Protein modeling analyses show surface charges of α-TM CTM molecule is altered. We propose that the changes in charged residues in the α-bands located in the C-terminus of TM molecule perturb the “off” state, which augment the crossbridge kinetics and lead to enhanced cardiac muscle performance.
Abstract P400: Potential Barriers to Cardiovascular Disease Risk Assessment Among Deaf Young Adults
Authors: Tamala David, Jane Tuttle, Steven Barnett, Harriett J Kitzman
Journal: Circulation (2012)

Objective: To address a potential barrier to preventing cardiovascular disease (CVD) among people deaf since childhood; the lack of validated health surveys that might be used for risk assessment. Background: CVD impacts the lives of many Americans, including socially or linguistically marginalized persons like those deaf since childhood. CVD risk assessment among young adults, including those who are deaf, is essential for early identification of CVD risk factors and establishment of risk-reduction interventions. Health surveillance approaches like the National College Health Assessment (NCHA) are useful for risk assessment, but young adults must be able to report health information using survey instruments. English literacy among deaf young adults is reportedly poor, and barriers to health surveillance with this group are ill-defined, so risk assessment via health surveillance can be problematic with this group. Methods: The survey response patterns of 191 deaf/hard of hearing (HOH) and 541 hearing college freshmen who completed a written health survey were examined. The survey was adapted from the NCHA and other surveys for use by deaf young adults, and it comprised 71 items covering 10 subject areas including tobacco use, weight, diet, and exercise. Language and literacy were examined as factors associated with students’ response patterns. Measures of reading skill were based on students’ California Achievement Tests and measures of survey readability were based on Flesch/ Flesch-Kincaid readability tests. Students’ responses were tallied to create continuous variables, such as “inconsistent response” scores, “don’t know response” scores, and “non-response” scores. Chi-Square was used to examine response patterns involving categorical variables and t-tests were used to examine patterns involving continuous variables. Results: Fewer deaf/HOH students (42%, n = 75) reported English, versus sign language, as their best language than hearing students (99%, n = 507). Deaf/HOH students who did report English, versus sign language, as their best language were significantly more likely (p = .027) to have estimated reading skills above the 8 th grade level. Thirty-one percent (n = 22) of the survey items had estimated readability above the 5 th grade level; remaining items were at or below 5 th grade. Deaf/HOH students were more likely to have inconsistent responses to related survey items and “don’t know” responses to survey items than hearing students (p &lt; .000 and p &lt; .000, respectively). Conclusion: Study results suggest that language and literacy are potential barriers to CVD assessment among deaf young adults, even high academic achievers like college students. Thus, for health surveillance, the readability of survey instruments and the language and literacy skills of deaf persons must be considered and alternatives to written surveys must be explored.