tbuckley/cabot-search huggingface dataset:
Abstract 16009: Assessing Blood Flow and Wall Shear Stress of the Ascending Aorta and Aortic Root Using Computational Fluid Dynamics in Patients with Non-Pulsatile and Pulsatile Left Ventricular Assist Devices
Authors: Arjang Ruhparwar, Christoph Karmonik, Matthias Loebe, Bastian Schmack, Matthias Karck, Patrizia Piontek, Klaus Kallenbach, Rawa Arif, George P Noon, Mark R Robbin, Allan B Lumsden, Sasan Partovi
Journal: Circulation (2012)

Background:  Aortic valve insufficiency and atherosclerotic emboli have been described in patients with continuous flow left ventricular assist devices (cf-LVAD). The mechanisms are unknown. We established a novel method for analysis of flow dynamics and aortic wall shear stress (WSS) using computational fluid dynamics (CFD) of computer tomography (CT) studies. Aim of our study was to examine the role of blood flow and WSS in pathologic aortic processes in patients with LVAD.   Methods and Results:  5 patients with cf-LVAD and 2 patients with pulsatile flow (p) LVAD had a CT 9.9±9.2months after device implantation. Transient CFD simulations with turbulent k-a model performing LVAD flow waveforms for pulsatile cases were conducted (time step: 5 msec, 3 cardiac cycles). Flow pattern, dynamic pressure and wall shear stress (WSS) of the aorta were quantified. In cf- LVAD patients, outflow graft position (lateral or anterior) determined hemodynamics in the aorta. Figure 1 representatively depicts the results: Panels A to D refer to continuous flow. In panel A and B lateral outflow graft positioning is associated with a high WSS caused by flow impingement (arrow) indicating contra-lateral focal high pressure (3 -5x higher than in descending aorta) and vertical vortices in the aortic root while no focal pressure and horizontal vortices dominated in panel C and D (anterior outflow graft positioning). For comparison, p-LVAD (panel E), the magnitude of retrograde flow in the ascending aorta varied by one order of magnitude during systole and diastole and WSS of the opposite wall to LVAD outflow varied from 3-4 Pa (diastole) to 31 Pa (systole).   Conclusions:  CFD of CT-scans enables analysis of pathologic aortic processes. Continuous vertical vortex formation in the aortic root may contribute to aortic insufficiency in patients with cf-LVAD support. Outflow graft position determines focal pressure on the aortic wall and shear off of aortic plaques.
Abstract 3994: Pharmacodynamic Assessment of Platelet Inhibition by Prasugrel versus Clopidogrel in the TRITON-TIMI 38 Trial
Authors: Andrew L Frelinger, Alan D Michelson, Eugene Braunwald, William E Downey, Dominick J Angiolillo, Nicholas P Xenopoulos, Joseph A Jakubowski, Youfu Li, Sabina A Murphy, Jie Qin, Carolyn H McCabe, Elliott M Antman, Stephen D Wiviott
Journal: Circulation (2008)

TRITON-TIMI 38 randomized 13,608 ACS patients to prasugrel or standard dose clopidogrel, and demonstrated significantly reduced ischemic events with prasugrel. Prasugrel has been shown to produce h...
Abstract 9327: Depletion of Intracellular Ca2+ Stores Induces Phosphorylation of Stromal Interaction Molecular 1 (STIM1), Which Contributes to the Sustained Phase of Store-operated Ca2+ Influx in Vascular Endothelial Cells
Authors: Katsuya Hirano, Akiko Hanada, Mayumi Hirano
Journal: Circulation (2011)

Store-operated Ca2+ influx (SOC) is a major Ca2+ entry pathway in vascular endothelial cells, thus contributing to the regulation of endothelial barrier function, nitric oxide production, and angio...
Abstract 3727: Beta-1 Adrenergic Antagonism Inhibits Cardiovascular Adaptation to Hemodilution Causing Cerebral Hypoxia
Authors: Gregory M Hare, Tenille E Ragoonanan, C David Mazer, Howard Leong-Poi, David F Wilson, W Scott Beattie
Journal: Circulation (2008)

A recent clinical study (POISE) demonstrated an increased incidence of stroke in surgical patients treated with a beta-1 adrenergic antagonist. This stroke risk may be attributed to reduced cerebral perfusion in treated patients who are exposed to hemodynamic stress during surgery, including acute blood loss and fluid resuscitation. We tested the hypothesis that acute beta-1 adrenergic antagonism attenuates cardiovascular responses to acute hemodilution causing cerebral tissue hypoxia. After ACC approval, anesthetized rats (1–2% isoflurane) were treated with metoprolol (3 mg kg −1 i.v.) or saline vehicle (n=8/outcome). Acute hemodilution was then performed by exchanging 50% of estimated blood volume (30 ml kg −1 ) with pentastarch (1:1). Experimental outcomes included heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO, echocardiography), carotid and cerebral tissue blood flow (CBF, Doppler), and hippocampal and kidney tissue oxygen tension (P Br O 2 , P Ki O 2 , phosphorescence quenching). Arterial blood gases (ABGs), and hemoglobin concentration (Co- oximetry) were also measured. Data was analyzed by two-way ANOVA (mean ± SD). Acute beta blockade reduced baseline HR (334 ± 31 vs. 291 ± 22 bpm, p&lt;0.05). No differences in ABG and co-oximetry values were observed between groups and a target hemoglobin concentration near 50 g.L −1 was achieved. MAP was maintained near 70 mmHg and was not different between groups at any time. After hemodilution CO and CBF increased, P Br O 2 was maintained and P Ki O 2 decreased in control rats. In beta blocked rats, the CO and CBF responses were greatly attenuated leading to a significant reduction in P Br O 2 (15 ± 4 vs. 30 ± 12 mmHg, p&lt;0.05). P Ki O 2 was reduced comparably to the control group. Acute metoprolol treatment attenuated the cardiovascular response to acute hemodilution resulting in cerebral tissue hypoxia. Acute beta-1 adrenergic blockade may increase the risk of cerebral hypoxia in surgical patients who are exposed to blood loss and fluid resuscitation (CAS and PSI support).
Abstract 3175: Factors Associated with Longer Delays from Symptom Onset to Hospital Presentation in Patients with Acute Myocardial Infarction
Authors: Paul S Chan, Brahmajee K Nallamothu, Henry H Ting, Fengming Tang, Harlan M Krumholz, John A Spertus
Journal: Circulation (2008)

Delayed contact with the medical system may lead to worse patient outcomes in acute myocardial infarction (AMI), particularly ST-elevation myocardial infarction (STEMI). We examined the effect of previously unstudied aspects of patients’ characteristics on delays to presentation, including health status, depressive symptoms, and socioeconomic status. Within the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients’ Health status (TRIUMPH) study, we examined predictors of delays to hospital presentation in 1,476 patients with AMI from 26 sites using multivariable hierarchical ordinal models. Time from symptom onset to hospital presentation was categorized as ≤2 hours, &gt;2 to 6 hours, and &gt;6 hours. Time to hospital presentation was ≤2 hours in 540 (36.6%) patients, between 2– 6 hours in 354 (24.0%) patients, and &gt;6 hours in 582 (39.4%) patients. Factors associated with longer delays to presentation included frequent angina (compared to no angina: daily angina, Odds Ratio [OR] of 3.48 [95% CI: 1.53–7.88]; weekly angina, 2.46 [1.64 –3.67]; and monthly angina, 1.26 [0.96 –1.64]; p for trend&lt;.001), presentation during weekday work hours (8am to 5pm) (compared to weekend: weekday, 1.40 [1.06, 1.85]; weeknight, 1.15 [0.85,1.54]; p for trend = 0.05), cost barriers (1.39 [1.05 to 1.85]; p=0.02), and no healthcare insurance (1.56 [1.15–2.12]; p=0.005). In contrast, patients with STEMI (0.55 [0.43– 0.70]; p&lt;.001), prior coronary revascularization (0.67 [0.48 – 0.92]; p=0.01) and prior AMI (0.68 [0.48 – 0.97]; p=0.03) were more likely to present earlier. No relationship was found for depression, educational level, social support, or marital status. More frequent angina, cost barriers, no healthcare insurance, and time of day are associated with longer delays to hospital presentation, while those with prior AMIs and coronary revascularization were more likely to present earlier. Efforts to reduce delays should address patient issues related to health status (like angina), cost burden, and healthcare access.
Abstract 895: CD47 Activation by Thrombospondin Peptides Enhances Bone Marrow Mononuclear Cell Adhesion, Recruitment during Thrombosis, Endothelial Differentiation and Stimulates Pro-Angiogenic Cell Therapy
Authors: Olivier P Blanc-Brude, Philippe Eren, Arnaud Bonnefoy, Gianfranco Matrone, Philippe Foubert, Micheline Duriez, Chantal Legrand, Jean-Sébastien S Silvestre, Alain Tedgui
Journal: Circulation (2007)

Bone marrow-mononuclear cells (BMC) contain endothelial progenitor cells (EPC) useful in cell therapy to enhance ischemic neovascularization. There is growing interest in the role of thrombosis in EPC engraftment and function. We hypothesized that activation of CD47 on the surface of BMC by platelet thrombospondin-1 (TSP1) and derived peptides modulates their proliferation, survival, EPC differentiation and pro-angiogenic potential. Culture of BMC with peptide 4N1–1 that recapitulates the CD47-binding site of TSP1 (1 to 100 μM) stimulated changes in cell shape by FACS within 90 seconds and cytoskeletal rearrangement within minutes (Phalloidin-stained actin stress fibers). 4N1–1 stimulated a striking increase in adhesion to fibrin (8 fold increase above control; p < 0.05), increased EPC differentiation (50% above BSA; p < 0.05), but did not modulate proliferation or apoptosis. In a model of FeCl3-induced intravascular thrombosis combined with systemic injection of fluorescent BMC and intra-vital microscopy, we showed specific BMC recruitment to sites of intra-vascular thrombosis, with increased BMC-to-vessel wall interactions (4 fold increase; p < 0.05) and decreased rolling speeds. BMC recruitment was strongly stimulated by 4N1–1 treatment for 1h prior to injection, with further decreased local rolling speeds (−90% vs BSA-treatment; p < 0.05) and the emergence of permanent cell engraftment (12 fold increase; p < 0.05). In a mouse model of hindlimb ischemia after femoral artery ligation, systemic injection of BMC promoted neovascularization significantly compared to saline (+51.5%, p < 0.05). BMC pretreatment with 4N1–1 for 1h promoted neovascularization beyond BSA-treated cells (+94.4%, p < 0.05), by cutaneous flow, capillary density and microangiographic score assessment 14d after ligation. In summary, we showed that CD47 activation stimulates strong BMC adhesion, specific recruitment to sites of thrombosis in vivo and ischemic neovascularization. CD47 activation and TSP1-derived peptides may thus play a critical role in EPC engraftment to sites of vascular injury and in the onset of vasculogenesis. We suggest that 4N1–1 could be useful in the clinic to stimulate progenitor cell preparations, and to enhance pro-angiogenic cell therapy.
Positron Emission Tomography (PET) Guided Therapy of Aggressive Lymphomas – a Randomized Controlled Trial Comparing Different Treatment Approaches Based on Interim PET Results (PETAL Trial)
Authors: Ulrich Duehrsen, Andreas Hüttmann, Stefan Müller, Bernd Hertenstein, Jörg Kotzerke, Rolf Mesters, Christiane Franzius, Frank Kroschinsky, Matthias Weckesser, Anke Franzke, Frank Bengel, Jan Dürig, Johannes Matschke, Thorsten Pöppel, Jan Rekowski, Claudia Ose, Marcus Brinkmann, Paul LaRosée, Martin Freesmeyer, Andreas Hertel, Heinz-Gert Hoeffkes, Dirk Behringer, Gabriele Prange-Krex, Stefan Wilop, Thomas Krohn, Eva Fricke, Martin Griesshammer, Aristoteles Giagounidis, Aruna Raghavachar, Georg Maschmeyer, Ingo Brink, Arne Brecht, Uwe Haberkorn, Tobias Gaska, Wolfram Klapper, Dieter Hoelzer, Karl-Heinz Jöckel, André Scherag, Andreas Bockisch
Journal: Blood (2014)
Birth weight and blood pressure No evidence for a U shaped relation
Authors: P M Fayer, M De Swiet, L J Launer, A Hofman, D E Grobbee
Journal: BMJ (1994)

EDITOR, - Lenore J Launer and colleagues claim “a distinct U shaped relation between birth weight and blood pressure.”1 We have re-examined data from the Brompton study of 2000 children followed up until the age of 10.2,3 We found no evidence for a U shaped relation; that birth weight seems to be weakly associated with blood pressure at age 4 years and later; and that the main influence of birth weight seems to be indirect.

We believe that the statistical analysis of Launer and colleagues are misleading. Firstly, they imply that a U shape has been established despite observing a P value of only 0.06. They declare in the methods section that P<0.05 will be interpreted as significant. Thus it is curious to assume proof of a U shape after obtaining P<0.06 at 4 years of age. Their claims for a U shaped …
直接督导下短程药物治疗的疑惑提出“直接督导下的短程药物治疗结核失败”还为时尚早
Authors: Davies(specialist), registrar, Squire(consultant), 陶梅梅
Journal: BMJ (2008)

1993年世界卫生组织宣布结核病可能在世界范围大流行，为此提出加强结核病控制的新方案，即直接督导下短程药物治疗（DOTS）^1。DOTS的5个目标中有两个旨在促进使用以利福平为基础的短程药物治疗，同时提高直接监督下的治疗依从性。该策略的关键目标之一是提高6个月治疗成功率到85％。
Abstract 1747: Post-Conditioning Reduces Infarct Size and Improves LV function During Acute Myocardial Infarction
Authors: Jay H Traverse, Yale L Wang, Ivan J Chavez, John R Lesser, Wesley R Pedersen, Hossein Mirheydar, Timothy D Henry
Journal: Circulation (2006)

The modification of reperfusion by Post-Conditioning (PC) following coronary occlusion in animals significantly reduces myocardial necrosis and improves left-ventricular function (LVEF). To see if ...
Germ-Cell Tumors
Authors: Jonathan Shamash, Justin Stebbing, Thomas Powles
Journal: New England Journal of Medicine (2007)

Testicular cancer is rare, accounting for 1% to 2% of all male malignancies. Nearly 90% to 95% of tumors arising in testis are germ cell in origin. Other sites of malignant germ cell tumors include the retroperitoneum, mediastinum, sacrococcygeal region, and pineal gland. The highest incidence is seen in Scandinavian countries, particularly Denmark (1). There has been a significant disparity in the incidence of testicular cancer among the white and black populations in the United States, with higher incidence rates in the white population. Recent studies, however, show that this is changing, with an increased incidence of testicular germ cell tumors (TGCTs) among black men (2). Though these are one of the most frequent malignancies in the 15 to 50 age group, they are still relatively rare, with the incidence in that age group being 2 to 9/100,000 per year (1).
Abstract 16575: Diaphragmatic Dysfunction After Repair of Congenital Heart Defects: Return of Diaphragm Function Occurs in a Significant Proportion of Patients
Authors: Brendan M Smith, Alaina K Kipps, Jeffery Meadows
Journal: Circulation (2011)

Objective: Hemi-diaphragm dysfunction from phrenic nerve injury is a known complication of congenital cardiac surgery. Return of diaphragm function can occur; however, most estimates of its prevale...
Safety, tolerability and pharmacokinetics of QAV680, an oral CRTh2 antagonist, in healthy subjects
Authors: Veit J. Erpenbeck, Rainard Fuhr, Gerald Dubois, Sheryl Perry
Journal: European Respiratory Journal (2014)

Introduction   We report the safety, tolerability and pharmacokinetics (PK) data of QAV680, an oral CRTh2 antagonist, from two phase I dose-escalation studies.   Methods   Doses of between 10 and 1000 mg QAV680 were tested in two double-blind, placebo (PBO)-controlled studies with healthy subjects. In the first study, 19 subjects received oral single escalating doses of QAV680 or PBO in 4 sequences within each of two cohorts. In the second study, 40 subjects received multiple ascending oral doses of either QAV680 or PBO (3:1) in each of 4 cohorts at doses of 100, 300, 500 mg b.i.d. and 1000 mg o.d. for 7 days and QAV680 1000 mg b.i.d or PBO (3:1) in a fifth cohort (extension phase). Safety and tolerability (including clinical and laboratory data) and PK were evaluated.   Results   Single doses of QAV680 up to 1000 mg were well tolerated with adverse events (AEs) [n=3] being mild in severity and unrelated to study drug. Multiple doses of QAV680 up to 1000 mg b.i.d. were also well tolerated with 43.3% of subjects reporting AEs in the QAV680 groups versus 30.0% in the PBO group. AEs were mild to moderate in severity and the most common AEs were dizziness, fatigue and headache. In both studies, no deaths, serious AEs or clinically relevant changes in clinical or laboratory parameters were noted. Oral QAV680 was rapidly absorbed with median Tmax occurring between 0.5-1.5 h. Mean half-life ranged between 11.5 to 20.4 h and systemic exposure increased in an approximately dose proportional manner. A maximum tolerated dose was not established.   Conclusion   QAV680 was well tolerated with no serious AEs or imbalances in AEs compared to placebo and exhibited linear pharmacokinetics.
Abstract 13761: Vitamin D Deficiency is Associated with Increased Cardiovascular Events: A Meta - Analysis of Prospective Studies
Authors: Pansy Tsang, Vikas Aggarwal, VS Srinivas, Seth I Sokol
Journal: Circulation (2010)

Background: Accumulating evidence suggests that vitamin D (VitD) deficiency is associated with worse cardiovascular outcomes. Hence, we conducted a meta-analysis of prospective studies assessing th...
Abstract 16434: Prevalence, Distribution, and Risk Factor Correlates of High Thoracic Periaortic Fat in the Framingham Heart Study
Authors: Kathryn Britton, Alison Pedley, Joseph Massaro, Erin Corsini, Joanne Murabito, Caroline Fox
Journal: Circulation (2011)

Background:  Thoracic periaortic adipose tissue (TAT) is associated with cardiovascular disease (CVD) risk factors, and may play a role in obesity-mediated vascular disease. We sought to determine the prevalence and risk factor correlates of high TAT.   Methods:  Participants from the Framingham Heart Study (n=3246, 50% women, mean age 51 years) underwent multidetector computed tomography. TAT was measured using a semi-automatic technique which identified characteristic pixels of adipose tissue surrounding the thoracic aorta on 27 non-overlapping 2.5 mm slices. High TAT (Males ≥ 18.98; Females ≥ 10.19) and VAT (Males ≥ 2323; Females ≥ 1359) were defined as volumes ≥ sex-specific 90 th  percentiles in a healthy referent subsample. Sex-specific regression models were used to compare risk factors between individuals with different patterns of high TAT and high VAT.   Results:  The prevalence of high TAT was 38.1% in women, 35.7% in men, and increased with age into the 7 th  decade. Among individuals discordant for high TAT and high VAT, high VAT was associated with a more adverse cardiometabolic profile after adjusting for age. Among individuals without high VAT, 10.1% had high TAT. After adjustment for age and VAT, high TAT, even in the absence of high VAT, was associated with a higher prevalence of CVD (p    Conclusion:  In the absence of high VAT, individuals with high TAT were characterized by a higher prevalence of CVD and differences in certain risk factors compared with those without high TAT. This adipose phenotype may identify individuals with distinct cardiometabolic characteristics that may not be recognized by clinical adiposity measures alone.
Abstract 477: Selective Heart Rate Reduction Via Inhibition Of The <i>I</i> <sub>F</sub> -current Prevents Atherosclerosis And Improves Endothelial And Erectile Function In Apoe −/− Mice
Authors: Florian Custodis, Magnus Baumhaekel, Nils Schlimmer, Franka List, Christoph Gensch, Michael Boehm, Ulrich Laufs
Journal: Circulation (2007)

Introduction : Elevated resting heart rate (HR) is associated with increased risk for cardiovascular morbidity and mortality. Erectile dysfunction is associated with endothelial dysfunction and atherosclerosis due to similar risk factors. We hypothesized that HR reduction may influence endothelial- and erectile function and tested the effects of the I f -current inhibitor ivabradine in ApoE−/− mice. Methods and Results: Male ApoE−/− mice fed a high-cholesterol diet were treated with ivabradine (iva) (10 mg/kg/d p.o.) or vehicle (n=10 per group) for 6 weeks. Treatment with ivabradine reduced HR by 13.4% (iva 472±9 bpm vs vehicle 545±11 bpm, p&lt;0.01). High cholesterol feeding led to severe atherosclerosis in the aortic sinus and the aorta. Ivabradine reduced atherosclerotic plaque size in the aortic root from 32±4% to 18±2% and in the ascending aorta from 26±4% to 7±1% (p&lt;0,05). Endothelium dependent relaxation of aortic rings and corpora cavernosa to carbachol was significantly improved in ivabradine fed ApoE−/− mice compared to controls (p&lt;0.01). Aortic eNOS mRNA expression, quantified by real time PCR with the TaqMan system was upregulated to 156±11% (p&lt;0.05) in aortic rings after treatment with ivabradine. HR reduction led to attenuation of NADPH oxidase activity to 48±6% as measured by a lucigenin-enhanced chemiluminescence assay and decreased L-012 chemiluminescence to 24±9% (both p&lt;0.05). Lipidperoxidation was reduced to 65±8% in the vasculature of the iva group compared to vehicle treatment (p&lt;0.05). DHE fluorescence microscopy in aortic sections detected reduction of ROS release to 62±4% in ivabradine treated mice (p&lt;0.01). Conclusions : Selective HR reduction improves endothelial as well as erectile function and reduces atherosclerotic plaque formation in ApoE−/− mice. Those functional effects are mediated by decreased oxidative stress and upregulation of endothelial NOS (eNOS). These results identify HR as a risk factor for vascular disease and support the importance of heart rate reduction in vascular prevention.
Abstract 20663: The Effect of Insulin and Insulin-induced Hypoglycemia on Myocardial Blood Flow Reserve in Patients with Complicated Type 1 Diabetes Mellitus
Authors: Omar Rana, David Kerr, Soha Zouwail, David V Coppini, Joe Begley, Christopher D Byrne, Roxy Senior, Kim Greaves
Journal: Circulation (2010)

Background and Purpose:  Hypoglycemia is a frequent complication of insulin therapy in patients with diabetes mellitus (DM) and is associated with increased cardiovascular mortality. This study assessed the effect of insulin-induced hypoglycemia on myocardial perfusion in Type 1 DM patients with microvascular complications.   Methods:  Eight (44.5±4 years) Type 1 DM patients with microvascular disease (two of the following: retinopathy, nephropathy and neuropathy) and normal exercise stress echocardiograms participated. Hyperinsulinemic euglycemia (HE) was maintained for 60 minutes followed by hyperinsulinemic hypoglycemia (HH) for a further 60 minutes. Real-time myocardial contrast echocardiography (MCE) with flash impulse imaging was used to assess the myocardial blood flow (MBF) and myocardial blood flow reserve (MBFR) before and after dipyridamole administration at baseline, HE and HH.   Results:  MBFR was 1.72±0.16 at baseline and increased by 17% with insulin during HE to 2.02±0.31 (p=0.018). This was due to an increase in the baseline MBF from 36.6±4.8 dB 2 .s −1  to peak stress HE 43.7±3.5 dB 2 .s −1  (p=0.02). During HH, MBFR decreased significantly to 1.57±0.12 (vs. HE, p=0.001). This was due to a lower peak stress HH MBF of 39.8±6.0 dB 2 .s −1  (p = 0.06). Baseline endothelin-1 levels were 3-fold elevated in comparison to healthy subjects (p   Conclusion:  This study has shown that insulin-induced hypoglycemia leads to a reduction in MBFR in subjects with complicated Type 1 DM. In the presence of flow limiting coronary disease this may worsen coronary ischemia.