tbuckley/cabot-search huggingface dataset:
Abstract 17054: Variability of Platelet Inhibition as Determined by the VerifyNow Assay Among Patients Receiving Clopidogrel or Prasugrel: Results from a Real World Registry
Authors: Tami L Bair, Heidi T May, Benjamin D Horne, Sterling T Bennett, Brian K Whisenant, Jeffrey L Anderson, Donald L Lappe, Joseph B Muhlestein
Journal: Circulation (2012)

Background:  Dual oral antiplatelet therapy with aspirin and some form of P2Y 12  inhibition is critical for the prevention of future CV events among many pts with CAD. A variety of studies using the VerifyNow™ platelet function assay (as measured by P2Y 12  reaction units [PRU]) have documented significant variability in the levels of P2Y 12  inhibition provided by either clopidogrel or prasugrel and that this variability may be associated with an increased incidence of either ischemic events or bleeding. However, the significance and frequency of such variability in a real world setting is not well known.   Methods:  The Intermountain Healthcare Department of Cardiovascular Medicine has developed guidelines for the use of platelet function testing among pts requiring dual antiplatelet therapy. These guidelines target a PRU of 100-200 and recommend changing medication dosing or type to reach target. Here, we report the results of the initial VerifyNow™ assay performed on 521 patients receiving P2Y 12  inhibitor therapy with either clopidogrel or prasugrel.   Results:  Average age was 68±13 yrs, 66% of pts were male and 87% received drug-eluting stents. Mean (median) PRU levels for those receiving clopidogrel (n=381) and prasugrel (n=140) were 211.5±103.2 (219) and 107.6±92.1 (80) respectively. Of patients receiving clopidogrel, 66(17.3%), 97(25.5%) and 218(57.2%), and of those receiving prasugrel, 78(55.7%), 32(22.9%) and 30(21.4%) had PRU 200 respectively. Therefore, only 24.8% of all pts were initially found to be within target range. Interestingly, none of the baseline clinical variables of age, sex, hypertension, hyperlipidemia, heart failure, renal failure, prior cardiac history or other non-platelet related medications were predictive of PRU results.   Conclusions:  Among pts receiving initial dual antiplatelet therapy and platelet function testing in real world setting, less than a quarter have a PRU within the target range. Pts receiving clopidogrel tend to be under-inhibited, and prasugrel, over-inhibited. Although long-term outcomes remain to be identified, these initial findings demonstrate a large potential for individual targeted dosing of antiplatelet therapy for pts receiving either clopidogrel or prasugrel.
Clinical Strategies and Outcomes in Advanced Heart Failure Patients Older Than 70 Years of Age Receiving the HeartMate II Left Ventricular Assist Device
Authors: Robert M. Adamson, Marcia Stahovich, Suzanne Chillcott, Sam Baradarian, Joseph Chammas, Brian Jaski, Peter Hoagland, Walter Dembitsky
Journal: Journal of the American College of Cardiology (2011)
Emergency room medical clearance: an educational problem
Authors: M P Weissberg
Journal: American Journal of Psychiatry (1979)

The term "medically clear" has a greater capacity to mislead than to inform correctly. The overuse of this term, especially in emergency room settings, may indicate difficulties in medical education and in the consultation/referral process between psychiatry and other specialties; further, it results in poor patient care. Nonpsychiatric physicians may prematurely refer patients as medically clear because of their unfamiliarity or discomfort with clinical psychiatry. Psychiatrists often ask for medical clearance of patients to hide their discomfort with or antipathy toward clinical medicine. The use of emergency room settings for interspecialty collaboration and training helps minimize the underlying difficulties that lead to the use of this term by fostering psychiatric skills in nonpsychiatrists and a sense of medical identity in psychiatrists.
Abstract 1454: Classification of Heart Failure in the Atherosclerosis Risk in Communities (ARIC) Study: A Comparison With Other Diagnostic Criteria
Authors: Wayne D Rosamond, Patricia Chang, Chris Baggett, Alain Bertoni, Eyal Shahar, Anita Deswal, Gerardo Heiss, Lloyd Chambless
Journal: Circulation (2009)

Introduction: Population-based research on heart failure (HF) is hindered by lack of consensus on diagnostic criteria. In addition, established criteria such as Framingham (FRM), National Health an...
The Air Quality Health Index and Asthma Morbidity: A Population-Based Study
Authors: Teresa To, Shixin Shen, Eshetu G. Atenafu, Jun Guan, Susan McLimont, Brian Stocks, Christopher Licskai
Journal: Environmental Health Perspectives (2012)

Exposure to air pollution has been linked to the exacerbation of respiratory diseases. The Air Quality Health Index (AQHI), developed in Canada, is a new health risk scale for reporting air quality and advising risk reduction actions.
Abstract 1735: The Relationship of the Ventricular Septum and Right Ventricular Outflow Tract to the Right and Non-coronary Sinuses: Implications for Ablation of Ventricular Tachycardias
Authors: Marmar Vaseghi, Chi Lai, Alarice Huang, Michael C Fishbein, Kalyanam Shivkumar
Journal: Circulation (2007)

Background: Outflow tract ventricular tachycardias (VT’s) have been successfully ablated from the aortic sinuses. However, detailed anatomy of the interventricular septum (IVS) in this region is no...
Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Proteasome Inhibitors
Authors: Barbara Muz, Feda Azab, Pilar De La Puente, Scott A Rollins, Richard Alvarez, Ziad Kawar, Abdel Kareem Azab
Journal: Blood (2014)
Enhanced efficiency of genetic programming toward cardiomyocyte creation through topographical cues
Authors: Constant Morez, Michela Noseda, Marta Abreu Paiva, Elisa Belian, Michael D. Schneider, Molly M. Stevens
Journal: Biomaterials (2015)

Generation of de novo cardiomyocytes through viral over-expression of key transcription factors represents a highly promising strategy for cardiac muscle tissue regeneration. Although the feasibility of cell reprogramming has been proven possible both in vitro and in vivo, the efficiency of the process remains extremely low. Here, we report a chemical-free technique in which topographical cues, more specifically parallel microgrooves, enhance the directed differentiation of cardiac progenitors into cardiomyocyte-like cells. Using a lentivirus-mediated direct reprogramming strategy for expression of Myocardin, Tbx5, and Mef2c, we showed that the microgrooved substrate provokes an increase in histone H3 acetylation (AcH3), known to be a permissive environment for reprogramming by “stemness” factors, as well as stimulation of myocardin sumoylation, a post-translational modification essential to the transcriptional function of this key co-activator. These biochemical effects mimicked those of a pharmacological histone deacetylase inhibitor, valproic acid (VPA), and like VPA markedly augmented the expression of cardiomyocyte-specific proteins by the genetically engineered cells. No instructive effect was seen in cells unresponsive to VPA. In addition, the anisotropy resulting from parallel microgrooves induced cellular alignment, mimicking the native ventricular myocardium and augmenting sarcomere organization.
Abstract 511: Mrp8 And Mrp14,Endogenous Activators of Toll-lLke Receptor4, are Associated with Rupture-Prone Human Atherosclerotic Plaques
Authors: Mihaela G Ionita, Gerard Pasterkamp, Dominique deKleijn
Journal: Circulation (2008)

Objectives : Atherosclerosis is a chronic, complex inflammatory process and is the underlying cause of stroke and myocardial infarction due to rupture of the atherosclerotic plaque leading to acute occlusion of the artery in the brain or heart. Macrophages, infiltrating atherosclerotic lesions, abundantly express Mrp8 and Mrp14. Recently Mrp8, Mrp14 and the complex Mrp8/14 have been identified as endogenous ligands of Tlr-4.The role of Tlr-4 in the development and progression of the atherosclerotic plaque is well recognized and it is associated with a rupture-prone plaque phenotype. Expression of Mrps in human plaques and its relation to plaque phenotype is unknown. For this, we investigated the levels of Mrp8, Mrp14 and Mrp8/14 complex in a large number of human atherosclerotic plaques. Methods and results : Mrp8, Mrp14 and Mrp8/14 were quantified by ELISAs in human carotid endarterectomy specimens (186 patients) and plaque phenotype was determined by immunohistochemistry. Mrp levels were higher in the unstable (58 fibro-atheromatous, 64 atheromatous) compared to the stable (64 fibrous) plaques: Mrp8 p = 0.001 ; Mrp14 p = 0.001 ; Mrp8/14 p = 0.01 . Concomitantly, Mrp8, Mrp14 and Mrp8/14 were associated with characteristics of unstable plaques: more macrophages ( p = 0.024; p = 0.002; p = 0.076 ), less smooth muscle cells ( p = 0.041; p = 0.001; p = 0.074 ), larger lipid core ( p = 0.001; p = 0.001; p=0.004 ), less collagen ( p = 0.440; p = 0.011; p = 0.372 ). Furthermore, Mrp plaque levels were positively correlated with the pro-inflammatory cytokines (IL-6 and IL-8) and matrix metalloproteinsases (MMP2, MMP8 and MMP9) plaque levels. EDA, marker of stable plaques, was negatively associated with Mrps plaque levels. Histological analysis revealed that Mrps are expressed by a subgroup of plaque macrophages localized in the plaque cap and shoulder, the most rupture-prone sites of an atherosclerotic plaque. Conclusions: We show that Mrp8, Mrp14 and Mrp8/14 are strongly associated with the histological characteristics and inflammatory status of human rupture-prone plaques and identify Mrps as a potential marker for rupture-prone plaques.
Active management of labour
Authors: P. Boylan, R. Buist
Journal: BMJ (1997)

Interferon beta in multiple sclerosis Reducing frequency and severity of relapses will be of great clinical benefitEditor-Richard G Richards's editorial on interferon beta in multiple sclerosis deals with the "clinical cost effectiveness" of the drug in the disease, but it lacks a fair balance, emphasising the cost effectiveness and minimising the clinical effectiveness of the drug. 1 Richards states that "the studies showed no evidence of any reduction in the more clinically relevant endpoint-the progression of disability, which should be the goal of treatment."This is his personal judgment and does not reflect the needs and wishes of patients with multiple sclerosis and their families.Multiple sclerosis is a distressing, humiliating, and often long drawn out disease with no cure.For this reason, quality of life, for the patients and their families, is paramount.A drug that can reduce the frequency and severity of relapses, whether or not it diminishes the progression of the disease, will be of great clinical benefit to many patients, improving their situation physically, psychologically, and socially.Surely happiness, feeling better, and increased health have great value.This is what many of us believe that the practice of our profession is about.
Abstract 3659: Prognostic Simple Test of Short Memory and Physical Function in Aged 80 and Older Outpatients
Authors: Satoshi Hoshide, Joji Ishikawa, Kazuo Eguchi, Kazuyuki Shimada, Kazuomi Kario
Journal: Circulation (2007)

Background: Cognitive and physical dysfunction is reported increase mortality in very elderly patients. We evaluated the impact of cognitive and physical dysfunction on future total and cardiovascu...
Identification and characterization of a human CD40 agonist antibody with efficacy against human tumors in SCID mice.
Authors: R. P. Gladue, V. Bedian
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

SS02-01 

CD40, a member of TNF receptor superfamily, is expressed on antigen-presenting cells, including B cells and dendritic cells, as well many tumors. Its role in the generation of an effective immune response has been suggested by several studies which have demonstrated that stimulation of this receptor with its ligand and/or agonist antibodies leads to the upregulation of several co-stimulatory molecules, including B7.1 and B7.2 on antigen presenting cells, whereas blockade of this receptor inhibits the generation of an effective T cell response. These studies suggest that a CD40 agonist might have therapeutic potential to enhance immune responses. In support of this concept, in vivo studies have shown that CD40 agonist antibodies have the ability to break immune tolerance, bypass the need for T-cell helper cytokines, and upregulate cell surface markers on CD40pos tumors potentially making them more immunogenic. CD40 agonist antibodies have also shown therapeutic activity in several murine tumor models. These data prompted the identification of the fully human CD40 agonist antibody, CP-870,893. CP-870,893 was identified as a CD40 agonist antibody by screening lead molecules generated through the Abgenix Xenomouse® platform. It binds human CD40 at a site distinct from its natural ligand at low nM potency, increases costimulatory molecule expression on antigen-presenting cells, and primes dendritic cells to release IL-12. Using SCID mice repopulated with human cells, CP-870,893 also demonstrated anti-tumor efficacy against several CD40pos and CD40neg human tumors. These studies demonstrate the immune enhancing activity of CP-870,893 and suggest its potential utility for the therapy of cancer. CP-870,893 is currently in early clinical trials in cancer patients.
Abstract 14857: Hepatic Insulin Signaling Posttranscriptionally Regulates Ldl Receptor via Pcsk9
Authors: Ding Ai, Seongah Han, Chien-Ping Liang, Minako Ishibashi, Rebecca Haeusler, Domenico Accili, Alan Tall
Journal: Circulation (2010)

The levels of hepatic LDLRs play a key role in the regulation of LDL levels and atherogenesis. Recently, we proposed that the increased VLDL, normal LDL levels typically associated with Type 2 diab...
Abstract 2735: Effects of Carvedilol and Metoprolol on Plasma advanced Glycation End Products (AGE) and Advanced Oxidation Protein Products (AOPP) in Patients with Chronic Heart Failure
Authors: Ding-Li Xu, Hua He, Ping Zeng, Wenyan Lai, Hao Ren
Journal: Circulation (2006)

Background: Chronic heart failure (CHF) is characterized by abnormal neurohormonal activation. Advanced glycation end products (AGE) and advanced oxidation protein products (AOPP) maybe represent n...
Low Prevalence of Risk Markers in Cases of Sudden Death Due to Brugada Syndrome
Authors: Hariharan Raju, Michael Papadakis, Malini Govindan, Rachel Bastiaenen, Navin Chandra, Ann O'Sullivan, Georgina Baines, Sanjay Sharma, Elijah R. Behr
Journal: Journal of the American College of Cardiology (2011)
Identification of conserved gene expression features across human and murine mammary tumors
Authors: Jason I. Herschkowitz, Karl Simin, Victor J. Weigman, Igor Mikaelian, Zhiyuan Hu, Karen E. Rasmussen, Laundette P. Jones, Shahin Assefnia, Subhashini Chandrasekharan, Michael G. Backlund, Yuzhi Yin, Robert I. Glazer, Powel H. Brown, Jeffrey E. Green, Levy Kopelovich, Priscilla A. Furth, Juan P. Palazzo, Olufunmilayo I. Olopade, Philip S. Bernard, Gary A. Churchill, Terry Van Dyke, Charles M. Perou
Journal: Cancer Research (2006)

4841   Breast cancer has been shown to consist of not just a single disease but several distinct diseases or subtypes identified by microarray analysis. To study breast cancer, researchers have spent the last couple of decades developing a number of mouse models to mimic human breast cancer. How well these models represent human breast tumor phenotypes is still unclear. We have used gene expression analysis with DNA microarrays to address this question. We have characterized more than 13 different murine mammary models and compared these data to the expression patterns from primary human breast tumors. Hierarchical clustering analysis of the murine samples showed that the WAP- myc , MMTV- neu , MMTV- PyMT , WAP- In t3, WAP- Tag  and C3(1)- Tag  tumors were highly correlated within each model. Other models, including the WAP- T 121  , MMTV- Wnt1 ,  Brca1  conditional, and DMBA-induced tumor model, did not show this consistency and gave rise to tumors with expression profiles consistent with the expansion of multiple cell types or different cell types of origin. A combined clustering analysis of the murine tumors with 184 human breast tumors showed many shared expression features. These features included a proliferation signature, an interferon-regulated pattern, and patterns reflective of the presence of immune cells, adipocytes and fibroblasts. Like human breast tumors, murine tumors could be categorized according to their presumed cellular origins; the C3(1)- Tag , two independent  Brca1  deficient models, and DMBA-treated models displayed expression characteristics of human basal-like breast tumors. In contrast, the MMTV- neu , MMTV- PyMT , and WAP- myc  models shared features with human luminal breast tumors including the high expression of  GATA3  and  XBP1 . Single mouse models did not reproduce the entire expression pattern seen in a specific human subtype; rather portions of a subtype’s expression profile were captured/represented by different murine models. The shared patterns of expression present between mice and humans provides a common framework for the direct comparison and integration of animal models with human breast tumors.
Hungarian cancer patients are reluctant to seek pain relief.
Authors: Carl Kovac
Journal: BMJ (2001)

The majority of the estimated 200000 people with cancer in Hungary are unaware that their pain can be effectively controlled or are reluctant to seek relief, according to a survey of 142 patients across the country which was conducted by the Hungarian Anticancer League.

Dr Arturne Vasvary, secretary general of the league, said that 83% of the country's patients with cancer “constantly suffer pain and don't think there is any relief [available].”

The survey used international data to emphasise that pain can be alleviated in 95% of cases of cancer; 80% of the time it can be controlled by drug treatment and 15% of the time by invasive means, such as epidural and intrathecal anaesthesia and nerve and ganglion blocks.

About 3% of patients surveyed said that they did not report their pain to their doctors, and about 3% said that they had told their doctors about their pain within a few months. About 7% complained to their doctor after several months, and about 15% informed their doctors within a few weeks. Almost 72% reported their pain immediately.
Europe’s initial experience with pandemic (H1N1) 2009 - mitigation and delaying policies and practices
Authors: A Nicoll, D Coulombier
Journal: Eurosurveillance (2009)

Europe has experienced more than two months of the first transmissions and outbreak of the 2009 pandemic of A(H1N1)v. This article summarises some of the experience to date and looks towards the expected autumn increases of influenza activity that will affect every country. To date the distribution of transmission has been highly heterogenous between and within countries, with one country the United Kingdom (UK) experiencing the most cases and the highest transmission rates. Most infections are mild but there are steadily increasing numbers of people needing hospital care and more deaths are being reported. An initial difference in practice between Europe and North America was over case-finding and treatment with some authorities in Europe using active case-finding, contact tracing and treatment/prophylaxis with antivirals to try and delay transmission. This article details the history of this practice in the past two months and explains how and why countries are moving to mitigation, especially treating with antivirals those at higher risk of experiencing severe disease.
Abstract P159: Coronary Artery Calcium Score Improves the Net Reclassification Index of Prevalent Cardiovascular Disease In African Americans: The Jackson Heart Study
Authors: Joseph Yeboah, Che L Smith, Mario Sims, Ervin Fox, Yaorong Ge, James G Wilson, J G Terry, Herman A Taylor, J J Carr
Journal: Circulation (2012)

Background: Prior studies suggest that African Americans (AA) have lower prevalence of coronary artery calcium (CAC) compared to whites, yet CAC has similar ability to predict coronary heart disease (CHD) events. The role of CAC as a screening tool for CHD risk in AA is unclear. We compared the diagnostic accuracy for CHD prevalence using the CAC score and the Framingham Risk Score (FRS) in an adult population of AA. Methods: CAC was measured in 2944 participants in the Jackson Heart Study, an NHLBI funded study of AA based in Jackson, MS. Approximately 8% of this cohort had known cardiovascular disease (CVD) defined as prior MI, angina, stroke, PTCA, CABG or PVD. Logistic regression, ROC and net reclassification index (NRI) analysis were used adjusting for age, gender, SBP, total and HDL cholesterol, smoking status, DM and BMI. FRS was calculated and those with DM were classified as high risk. Results: The mean age was 60, 65% were females, 26% had DM, 50% were obese and 30% were current or former smokers. Prevalent CVD was associated with older age, higher SBP, lower HDL and total cholesterol, and higher CAC. CAC was independently associated with prevalent CVD in our multivariable model [OR (95% CI): 1.26 (1.17, 1.35), p&lt; 0.0001]. In ROC analysis, CAC improved the diagnostic accuracy (c statistic) of the FRS from 0.617 to 0.757 (p &lt; 0.0001) for prevalent CVD. The FRS classified 30% of the cohort as high risk, 38.5% as intermediate risk and 31.5% as low risk. FRS classfied 51% of subjects with prevalent CVD as high risk. Addition of CAC to FRS resulted in net reclassification improvement of 4% for subjects with known CVD and 28.5% in those without CVD (see figure). Conclusion: In AA, the CAC is independently associated with prevalent CVD and improves the diagnostic accuracy of FRS for prevalent CVD by 14%. Addition of CAC improves the NRI of those with prevalent CVD by 4% and the NRI of individuals without CVD by 28.5%. Determination of CAC in AA may be useful in identifying individuals at risk of CVD and reclassifying individuals with low and intermediate FRS.
Tobacco War: Inside the California Battles
Authors: Stan Shatenstein
Journal: BMJ (2000)

Stanton A Glantz, Edith D Balbach 

University of California Press, £12.50, pp 496

ISBN 0 520 22286 5

Rating: ![Graphic][1]  ![Graphic][2]  ![Graphic][3] 

Karl von Clausewitz wrote: “War is nothing more than the continuation of politics by other means” ( On War ). The dictum is faultless, but its application can be problematic. The devil, as always, is in the detail.

Normally, a war's protagonists are well identified, and the combatants carve their bloody path from the political chambers to the battlefield. The usual presumptions do not always apply, however, a point that is forcefully argued in Tobacco War by Stanton Glantz, lead author of The Cigarette Papers and a professor of medicine at the University of California, San Francisco, and Edith …

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Recent review has similar findings
Authors: A. Kessel
Journal: BMJ (1995)

referrals may well have reversed since 1991 because of the NHS reforms, which have seen so many radical changes in both general practice and the hospital sector.Until more up to date national data are available, Armstrong and Nicoll's argument, which is based on historical trends, may not be applicable.In addition, our figures show a small decrease in the number of patients followed up during the period.This is contrary to Armstrong and Nicoll's suggestion that the problem of recycling patients has become worse in recent years and has resulted in access for new outpatient referrals being blocked.