tbuckley/cabot-search huggingface dataset:
Abstract 19108: Methylated Arginines and Carotid Artery Intimal-Media Thickness: Results of the Gutenberg Heart Study
Authors: Edzard Schwedhelm, Francisco Ojeda, Philipp Wild, Ralf A Benndorf, Tanja Zeller, Dorothee Atzler, Christine Espinola-Klein, Thomas Munzel, Rainer H Boger, Stefan Blankenberg
Journal: Circulation (2010)

Background: Carotid artery intimal-media thickness (IMT) is a commonly used method to detect subclinical atherosclerotic and has been inversely related to cardiovascular (CV) prognosis. Methylated arginines like asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and monomethyl arginine (NMMA) are markers of CV disease. Methods: We investigated the cross-sectional relations of arginine, ADMA, SDMA, and NMMA plasma concentrations with IMT in 5,000 participants of the Gutenberg Heart Study (GHS, age 56 ±11 years, 51 % male). The IMT was determined in the A. carotis communis. Arginine and methylarginines were analysed by LC-MS/MS. Results: In univariate analysis ADMA (rho=0.161, p<0.001), SDMA (rho=0.145, p<0.001), and NMMA (rho=0.105, p<0.001) were moderately correlated to log IMT whereas arginine was not (rho=0.007, p=0.62). In multivariate linear regression models including age, gender, smoking status, stroke, SBP, CHD, BMI, log creatinine, log CRP, LDL and glucose only ADMA was related...
Abstract 2070: Where do Delays Occur in STEMI Patients Transferred for Primary Percutaneous Coronary Intervention?
Authors: Marc C Newell, Katie M Menssen, Joseph A Browning, David M Larson, Daniel L Lips, Wes R Pedersen, Michael R Mooney, Barbara T Unger, Timothy D Henry
Journal: Circulation (2006)

INTRODUCTION: Recent trials have demonstrated that STEMI patients (pts) benefit from transfer for primary PCI compared to fibrinolysis. AHA/ACC guidelines recommend a door-to-balloon time of 90 min...
Abstract 4781: Rate of Progression and Functional Significance of Aortic Valve and Root Calcification Up To 8 Years Following Total Aortic Root Replacement Using a Homograft Versus Freestyle Prosthesis: Results From a Prospective Randomized Trial
Authors: Ismail El-Hamamsy, Mohamed Zaki, Louis M Stevens, Lucy Clark, Michael Rubens, Magdi H Yacoub
Journal: Circulation (2008)

Introduction - Aortic root calcification is a major limitation following root replacement. The aims of this analysis were to compare the rate of progression of root calcification between homografts and xenografts (Medtronic Freestyle) up to 8 years postoperatively and to determine its functional significance. Methods - Between 1997 and 2003, 161 patients were prospectively randomized to undergo homograft (Group H) or Freestyle (Group F) total aortic root replacement. Of those, 99 patients underwent a total of 248 electron beam computed tomography (EBCT) studies at 0.5, 1, 1.5, 2, 3 and 8 years (n=17 patients at 8 years). Aortic root calcium scores were calculated using Agatston scores. Results - Mean calcium scores in Group H at 1, 2, 3 and 8 years were 550±95, 1026±160, 1440±256 and 3876±604 Hounsfield Units (HU), versus 397±84, 556±125, 683 ±151 and 2518±495 HU in Group F. Mixed effects models show higher calcium scores in Group H at 1, 2 and 3 years, with a trend at 8 years (p=0.11). Group H presents a significantly more rapid early rate of progression (slope from 0 to 3 years; p=0.02) and progress similarly to Group F thereafter (slope from 3 to 8 years; p=0.3) (Figure 1 ). Echocardiographic evaluation of patients at 8 years showed no correlation between EBCT scores and aortic valve dysfunction. Conclusion - Homograft roots have a higher propensity to calcifiy than Freestyle prostheses, which follows a time-dependent progression marked by rapid early calcification. Despite the high calcium scores, no correlation with prosthetic valve function was identified at 8 years.
Telmisartan, Ramipril, or Both in Patients at High Risk of Vascular Events
Authors: Franz H Messerli, Sripal Bangalore, Venkata S Ram
Journal: New England Journal of Medicine (2008)

To the Editor: The investigators of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) (April 10 issue)1 report that telmisartan is equivalent to ramipril in patients with vascular disease or high-risk diabetes. However, the primary composite end point of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure was not lower in the combination-therapy group than in the group receiving ramipril alone, even though blood-pressure levels in the combination-therapy group were 2.4/1.4 mm Hg lower than those in the ramipril group throughout the study period. Still more disturbing was a trend in the combination-therapy group toward even more deaths from cardiovascular and noncardiovascular causes than in the ramipril or telmisartan group (deaths from cardiovascular causes, 620 vs. 603 and 598, respectively; deaths from noncardiovascular causes, 445 vs. 411 and 391, respectively). Given that the number of patients with hyperkalemia was much higher in the combination-therapy group than in the ramipril or telmisartan group (480 vs. 283 and 287, respectively), as was the number of patients with hypotensive symptoms (406 vs. 149 and 229, respectively), we wonder whether a specific cause of death (i.e., sudden death or death from arrhythmia) can be identified in the combination-therapy group. Data from such an analysis should be provided.
Abstract 20393: First Analysis of Relation Between CYP2C19 Genotype and Platelet Function in Ticagrelor versus Clopidogrel Treated Patients: Results from the ONSET/OFFSET and RESPOND Studies
Authors: Paul A Gurbel, Kevin Bliden, Robert F Storey, Cheryl Wei, Martin Armstrong, Kathleen Butler, Udaya S Tantry
Journal: Circulation (2010)

Background: CYP2C19 genotype influences platelet aggregation (PA) and clinical outcomes in patients treated with clopidogrel (C), however its relation to platelet function in ticagrelor (T) treated...
Abstract 4845: Control of Notch Signaling by Reversible Acetylation Through the Antagonistic Activities of p300/PCAF and SIRT1 in Endothelial Cells
Authors: Virginia Guarani, Franck Dequiedt, Mirko H Schmidt, Andreas M Zeiher, Stefanie Dimmeler, Michael Potente
Journal: Circulation (2009)

Signaling by Notch receptors is a key cell-cell communication mechanism essential for development and homeostasis of the cardiovascular system. Several critical steps of angiogenic blood vessel growth are coordinated by the Notch pathway and even subtle perturbations in Notch activity can profoundly influence endothelial cell behavior and blood vessel growth, yet very little is known about the dynamics and intrinsic regulation of endothelial Notch signaling. Here, we show that reversible acetylation regulates the amplitude and duration of Notch responses by altering protein turnover of the Notch1 intracellular domain (NICD) in endothelial cells. We report that the histone acetyltransferases (HATs) p300 and PCAF not only acetylate nucleosomal histones at Notch target promoters, but also the NICD itself. Acetylation of NICD induced by p300 and PCAF results in increased NICD stability and enhanced Notch target gene expression. Likewise, blocking histone deacetylase (HDAC) activity using the class III HDAC inhibitor nicotinamid (NAM) leads to a substantial increase in NICD acetylation while class I/II HDAC inhibition has no significant effect suggesting that class III HDACs primarily target NICD for deacetylation. Among the class III HDACs with deacetylase activity (SIRT1, 2, 3, 5), specifically SIRT1 associates with NICD through its catalytic domain and silencing of SIRT1 enhances NICD acetylation. Wild type SIRT1, but not a catalytically inactive mutant catalyzes the deacetylation of NICD in a nicotinamid-dependent manner indicating that SIRT1 acts as a direct NICD deacetylase, which counteracts HAT-induced NICD acetylation. Inactivation of SIRT1 by NAM or RNAi-mediated knock down results in enhanced NICD protein stability by blocking proteasomal degradation. Consistent with these results, knock down of SIRT1 amplifies Notch target gene expression in endothelial cells in response to NICD overexpression or treatment with the Notch ligand Delta-like 4 (Dll4). Taken together, these findings support a model, in which Notch signaling is dynamically regulated by reversible acetylation and suggest that the antagonistic activities of p300/PCAF and SIRT1 act as rheostat to fine-tune endothelial Notch responses.
Smoking Is Associated With Adverse Clinical Outcomes in Patients Undergoing Revascularization With PCI or CABG
Authors: Yao-Jun Zhang, Javaid Iqbal, David van Klaveren, Carlos M. Campos, David R. Holmes, Arie Pieter Kappetein, Marie-Claude Morice, Adrian P. Banning, Ever D. Grech, Christos V. Bourantas, Yoshinobu Onuma, Hector M. Garcia-Garcia, Michael J. Mack, Antonio Colombo, Friedrich W. Mohr, Ewout W. Steyerberg, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2015)
Oral cavity squamous cell carcinoma in patients aged 80 or older: Risk factors, treatment, and outcome
Authors: C. Ortholan, R. Bensadoun, A. Italiano, S. Teman, O. Dassonville, K. Benezery, A. Lusinchi, J. Thariat, A. Auperin, J. Bourhis
Journal: Journal of Clinical Oncology (2009)

6064 Background: We have recently reported a large series of patients aged ≥ 80 years showing that in this population about half of head and neck squamous cell carcinomas (SCC) are located in the oral cavity. There are no specific data on this cancer location outcome in elderly patients. Therefore, we report here the experience of two French cancer centers in the treatment of oral cavity SCC in patients aged ≥ 80 years. Methods: Two hundred sixty patients aged ≥ 80 years with a primary oral cavity SCC were included in this retrospective analysis. Results: Sex ratio was near to 1. The risk factor distribution was significantly different between men and women: tobacco/alcohol consumption (66.3% vs 15.8%, p &lt; 0.001), history of leukoplakia/lichen planus/oral traumatism (10.8% vs 55.3%, p = 0.002). Two hundred patients received a loco regional (LR) treatment with a curative intent (surgery and/or radiotherapy), 29 with a palliative intent and 31 did not receive a LR treatment. Curative treatments were delivered according to the institution policy in 56 patients (28%).The median disease specific survival (DSS) was 16.9 months. In multivariate analysis, independent prognostic factors were stage (HR = 0.45 [0.29–0.69], p &lt; 0.001), and curative intent of treatment (HR = 0.28 [0.17–0.45], p &lt; 0.001). Median overall survival (OS) was 13.9 months. In multivariate analysis, the independent prognostic factors for OS were age (HR = 0.63 [0.33–0.76], p &lt; 0.001), stage (HR = 0.61 [0.40–0.91], p = 0,016), and curative intent of treatment (HR = 0.41 [0.23–0.71], p &lt; 0.001. In patients treated with a curative intent, the standard treatment was not associated with improved overall survival or disease specific survival as compared with those treated with an adapted treatment. However, prophylactic lymph node treatment in early stage cancer decreased the rate of nodal recurrence from 38% to 6% (p = 0.01). Conclusions: This study emphasizes the need for prospective evaluation of standard and adapted schedules in elderly patients with oral cavity cancer. No significant financial relationships to disclose.
A controlled clinical trial of alprazolam for the treatment of anxiety
Authors: K Rickels, I Csanalosi, P Greisman, D Cohen, J Werblowsky, H A Ross, H Harris
Journal: American Journal of Psychiatry (1983)

The authors report the results of a large-scale double-blind study comparing the anxiolytic effects of alprazolam, a triazolobenzodiazepine; diazepam, a 1,4-benzodiazepine; and placebo in 151 anxious outpatients. Alprazolam and diazepam produced similar clinical improvement, which was significantly larger than improvement produced by placebo and was clearly evident after only 1 week of treatment. The incidence of sedation was lower with alprazolam than with diazepam.
Abstract 4609: Evidence of Need for a More Comprehensive Approach to Dietary Self-Management for Patients with Heart Failure and Diabetes
Authors: Heather Payne-Emerson, Eun Kyeung Song, Seongkum Heo, Debra K Moser, Misook L Chung, Sandra B Dunbar, Susan J Pressler, Terry A Lennie
Journal: Circulation (2008)

Background: Type 2 diabetes (DM) is a common comorbidity in patients with heart failure (HF). Nutritional management is a key strategy in achieving blood glucose control and decreasing the risk of microvascular complications. The ability of patients with HF to nutritionally self-manage multiple comorbidities is unknown. Purpose: To compare nutritional intake of a group of patients with HF and DM with a group without DM. Methods: A total of 174 patients (66 with DM, age 60± 12 yrs, 35% female, 57% NYHA class III/IV) recruited from HF clinics completed detailed 4-day food diaries that were reviewed by a registered dietitian. Nutrition Data System software was used to determine carbohydrate (total and subtype), protein, fat, cholesterol, and sodium intake. Fasting blood glucose was obtained on a subset of 123 patients. Between-group comparisons were made using independent sample t-tests. Results: Patients with DM consumed a lower percentage of calories from carbohydrate (44% vs. 49%, p=.003) and a greater percentage of calories from protein (19% vs. 16%, p&lt;.001) and fat (38% vs. 35%, p=.049) compared to patients without DM. With respect to carbohydrate subtypes, patients with DM consumed 30% less sucrose (29g vs. 42g, p&lt;.001) and 39% less fructose (14g vs. 23g, p&lt;.001) than patients without DM, but a similar amount of starch (93g vs. 95g). There were no differences in sodium (3472mg vs. 3209mg), cholesterol (321mg vs. 285mg) or saturated fat (12% vs. 11% of kcal) intake between groups with and without DM. A total of 60% of patients with DM had fasting blood glucose levels &gt;120mg/dl and 40% had a fasting levels &gt; 140mg/dl. Conclusions: Patients with HF and DM primarily limited dietary sugar intake, with only moderate success. Nutritional management of HF has focused on the single nutrient sodium with limited success; these data suggest that teaching for DM may be similarly focused on the single nutrient sugar. This indicates that new, more comprehensive, approaches are needed to help patients meet the challenge of nutritionally managing multiple comorbidities. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania &amp; West Virginia).
Abstract 1235: Molecular Basis for Sympathetic Remodeling in the Left Atrium in the Ventricular Tachypacing Canine Model of Congestive Heart Failure
Authors: Rashad J Belin, Steve Mottl, Jacob Goldstein, Abigail Angulo, Ashima Salwan, Roger Villuendas, Gary Aistrup, Jeffrey Goldberger, Alan Kadish, Rishi Arora
Journal: Circulation (2007)

Background: The sympathetic nervous system (SNS) is thought to play an important role in promoting atrial fibrillation (AF) initiation and maintenance, especially in the setting of congestive heart failure (CHF). However, it is unclear as to which components of the SNS are altered in atria isolated from failing hearts. These studies are essential, as they will delineate potential molecular targets that may be probed for therapeutic intervention in order to reduce AF pathogenesis. Methods : CHF was induced by ventricular tachypacing (240 beats/minute) for 4 weeks in hound dogs. A total of 4 CHF and 5 control dogs were used. Immunoblot analysis was performed on left atrial appendage (LAA) homogenates to examine the protein expression of Gsα, Gi2α, and the catalytic subunit of protein kinase A (PKA). Catalytic activities of PKA and protein phosphatase type 2a (PP2a) were determined using non-radioactive enzyme activity assay systems. Cyclic AMP (cAMP) accumulation was assessed by an enzyme linked immunoabsorbant assay and phosphorylation of cardiac troponin I (cTnI) was determined using a phosphospecific antibody against cTnI. Results: Gsαconcentrations were increased approximately 4-fold in failing left atrial preparations relative to control. In contrast, expression of Gi2αwas modestly increased ~1-fold in failing LAA relative to non-failing atrial muscles. PKA activity was significantly increased in failing LAA preparations compared to control (124.7 vs. 42.1 pmole phosphate/minute, P &lt;0.05); while, PP2a activity was substantially decreased in failing LAA (4.60 vs. 7.06 pmole phosphate/μg protein/minute, P &lt;0.05). cAMP concentrations were increased and expression of the catalytic subunit of PKA was upregulated (~1.5-fold increase) in failing LAA. Lastly, phosphorylation of cardiac troponin I (cTnI) was enhanced in failing LAA preparations. Conclusions: Our data are the first to characterize sympathetic remodeling in left atrial muscles isolated from an experimental model of CHF. Additionally, our results support the hypothesis that augmented sympathetic signaling and activation may contribute to the AF substrate in a canine model of CHF characterized by increased AF susceptibility.
Abstract 1928: Effects of a Selective Inhibitor of Secretory Phospholipase A2 on Low Density and Very Low Density Lipoprotein Subclasses in Stable Coronary Heart Disease Patients
Authors: Robert S Rosenson, Colin Hislop, Michael Elliott, Yuri Stasiv
Journal: Circulation (2008)

Secretory phospholipase A2 (sPLA2) represents a family of pro-inflammatory enzymes that contribute to the development of atherosclerosis in part through adverse modification of lipoproteins that re...
Salt--overwhelming evidence but still no action: can a consensus be reached with the food industry?
Authors: G. A MacGregor, P. S Sever
Journal: BMJ (1996)

Evidence that our current high salt intake plays an important role in blood pressure regulation comes from many sources, chiefly epidemiological studies, intervention studies, migration studies, studies of salt restriction, and evidence in mammals.

Epidemiological studies illustrate that salt intake may be a major factor in determining differences in blood pressure between and within communities as well as being closely associated with the rise in blood pressure with age in communities with a high salt intake. But these studies can only suggest relationships. Attempts to derive from epidemiological evidence simple relationships between a rather crude index of sodium intake and blood pressure will inevitably be confounded by the variable expression of other environmental and genetic factors, which may modulate the blood pressure response to sodium.1 Further analyses of results from large epidemiological studies such as Intersalt are unlikely to shed further light on this complex issue. It is therefore necessary to look at different types of evidence that more clearly show the effect of salt on blood pressure.

Stronger evidence comes from intervention studies such as a carefully controlled six month double blind study in newborn babies.2 Those receiving a modestly restricted salt intake had a significantly lower blood pressure (2.1 mm Hg) than those with a normal sodium intake. As the sodium restriction was discontinued at six months it is not known whether this difference would have increased, but a reduction of even 2.0 mm Hg in population blood pressure would have immense benefits in reducing cardiovascular morbidity and mortality. In another study, a village in Portugal reduced salt intake by reducing salt in cooking and also in processed food, including bread. At the end of the observation period blood pressure was significantly lower than in a control …
Perifusion of Isolated Rat Adipose Cells
Authors: B. Paul Turpin, William C. Duckworth, Solomon S. Solomon
Journal: Journal of Clinical Investigation (1977)

Incubation of isolated rat epididymal fat cells is associated with the accumulation of adenosine in the incubation medium. To more clearly define the effect of adenosine on lipolysis, isolated rat epididymal adipocytes were studied with the perifusion system.
Abstract 4201: Benefit of Thrombus Aspiration for Myocardial Infarction With ST-Segment Elevation: Analysis by Biomarkers of Thrombosis and Inflammation
Authors: Tetsuo Yamasaki, Tomomi Koizumi, Shinichiro Iida, Shuhei Funada, Keiki Sugi, Mayuko Yamaguchi, Tohru Tamaki, Atsushi Sakamoto, Toshihiko Kikutani, Eiji Takagi, Shigeyuki Nishimura, Nobuyuki Komiyama
Journal: Circulation (2009)
Mechanisms of Killing of Newborn Larvae of Trichinella spiralis by Neutrophils and Eosinophils
Authors: David A. Bass, Pamela Szejda
Journal: Journal of Clinical Investigation (1979)

Eosinophil and/or neutrophil leukocytes appear to have important roles in host defense against invasive, migratory helminth infestations, but the mechanisms of larval killing by leukocytes are uncertain. This study examines killing of newborn (migratory phase) larvae of Trichinella spiralis during incubation with granule preparations of human eosinophils or neutrophils and generators of hydrogen peroxide (glucose-glucose oxidase) (G-GO) or superoxide and hydrogen peroxide (xanthine-xanthine oxidase). Larvae were killed by either hydrogen peroxide-generating system in a concentration-dependent manner. Direct enumeration of surviving larvae after incubation in microtiter wells containing the appropriate reagents was used in assess larval killing. Verification of the microplate assay was demonstrated by complete loss of larval ability to incorporate [(3)H]deoxyglucose and loss of infectivity after incubation in comparable concentrations of G-GO. Larvae were highly sensitive to oxidative products; significant killing occurred after incubation with 0.12 mU glucose oxidase and complete killing occurred with 0.5 mU. Comparable killing of bacteria required over 60 mU glucose oxidase. At 5 mU glucose oxidase, killing was complete after 6 h of incubation. Killing by G-GO was inhibited by catalase but not by boiled catalase or superoxide dismutase and was enhanced by azide. Addition of peroxidase in granule pellet preparations of eosinophils or neutrophils did not enhance killing by G-GO. These data indicate a remarkable susceptibility of newborn larvae of T. spiralis to the hydrogen peroxide generated by neutrophil and eosinophil leukocytes.