tbuckley/cabot-search huggingface dataset:
Abstract 10458: Steroid Hormones Induce Caveolin-1 (cav-1) and Attenuate Vascular Endothelial Growth Factor (VEGF) Responses in Cultured Vascular Endothelial Cells (EC)
Authors: Junsuke Igarashi, Takeshi Hashimoto, Kazuyo Shoji, Kozo Yoneda, Yasuo Kubota, Hiroaki Kosaka
Journal: Circulation (2010)

Steroid hormones play key roles in mediating stress responses in various organs including cardiovascular systems, often associated with attenuated blood vessel responses to extracellular stimuli. However, molecular mechanisms whereby these hormones perturb EC functions remain incompletely understood. We explored whether or not and how steroid hormones may modulate expression of cav-1, a key regulatory protein of cell-surface receptor pathways that thereby determines the degrees of EC responses to growth factors. Western blot and RT-PCR assays of cultured bovine aortic EC (BAEC) revealed that dexamethasone (Dex), a glucocorticoid, augments expression of cav-1 at both levels of protein and mRNA in a time- and dose-dependent manner (7.8 ± 1.2 fold at 1 uM for 48 h in western blots, p<0.05). This cav-1 induction by Dex is mediated by canonical nuclear steroid receptors, since it was sensitive to RU-486 (1 uM), a specific inhibitor of glucocorticoid receptors. Cav-1 serves as a scaffolding protein within plasm...
A Research Agenda for Malaria Eradication: Vector Control
Journal: PLoS Medicine (2011)

Different challenges are presented by the variety of malaria transmission environments present in the world today. In each setting, improved control for reduction of morbidity is a necessary first step towards the long-range goal of malaria eradication and a priority for regions where the disease burden is high. For many geographic areas where transmission rates are low to moderate, sustained and well-managed application of currently available tools may be sufficient to achieve local elimination. The research needs for these areas will be to sustain and perhaps improve the effectiveness of currently available tools. For other low-to-moderate transmission regions, notably areas where the vectors exhibit behaviours such as outdoor feeding and resting that are not well targeted by current strategies, new interventions that target predictable features of the biology/ecologies of the local vectors will be required. To achieve elimination in areas where high levels of transmission are sustained by very efficient vector species, radically new interventions that significantly reduce the vectorial capacity of wild populations will be needed. Ideally, such interventions should be implemented with a one-time application with a long-lasting impact, such as genetic modification of the vectorial capacity of the wild vector population.
Impact of Aortic Regurgitation After Transcatheter Aortic Valve Implantation
Authors: Kibar Yared, Tamara Garcia-Camarero, Leticia Fernandez-Friera, Miguel Llano, Ronen Durst, Anil A. Reddy, William W. O'Neill, Michael H. Picard
Journal: JACC. Cardiovascular imaging (2012)
Abstract 13593: Infarct Tissue Heterogeneity by Contrast-Enhanced MRI is a Novel Predictor of Mortality in Patients with Coronary Artery Disease with Reduced Left Ventricular Systolic Function
Authors: Eri Watanabe, Otavio R Coelho-Filho, Francois-Pierre Mongeon, Michael Jerosch-Herold, Ron Blankstein, Hiroto Hatabu, Yucheng Chen, Damien Mandry, Bobby Heydari, Rob . J van der Geest, Raymond Y Kwong
Journal: Circulation (2011)

Background:  While LVEF is the robust marker of mortality in patients (pts) with chronic CAD, majority of sudden cardiac death (SCD) occurs in pts with preserved LVEF and current strategies to identify such pts at risk are deficient. Peri-infarct zone (PIZ) assessed by cardiac MRI (CMR), as a marker of infarct tissue heterogeneity, has been linked to arrythmogenic substrates and reduced post-MI survival. However, the prognostic implication of PIZ has not been studied in a large consecutive group of pts with chronic CAD and reduced LVEF. We hypothesized that PIZ provides strong association with mortality in pts with chronic CAD and this association is especially prominent in pts with only mild to moderate reduction of LVEF (>35%).   Methods:  We studied 305 pts with CAD and a LVEF  3SDs and 2 to 3SDs above the remote myocardium, respectively. The PIZ was expressed as a percentage of the total infarct mass (%PIZ).   Results:  Late gadolinium enhancement was present in 231 pts (76%). Mean total infarct mass and %PIZ were 15±21g and 20±18%, respectively. After a median follow-up of 3.9 years, 66 (22%) pts died; with 34 deaths occurred among 198 (65%) pts with LVEF>35%. %PIZ was the strongest univariable predictor of all-cause mortality (HR=1.27, LRχ 2 =15.03, p=0.0001). Adjusted for pt age, LVEF, RVEF, and infarct size, %PIZ maintains a strong association with mortality (HR=1.21, LRχ 2 =8.42, p=0.004). Multivariable regression identified a presence of long QTc and %PIZ as the strongest predictors that form the best overall model for mortality in the entire cohort. In pts with LVEF>35%, %PIZ was the strongest multivariable predictor of mortality (HR=1.34, LRχ 2 =11.53, p=0.0007).   Conclusion:  Infarct heterogeneity characterized by %PIZ demonstrated a strong association with patient mortality independent of pt age, LVEF, RVEF, and infarct size. CMR infarct heterogeneity may provide unique information regarding risk to SCD in CAD pts with LVEF>35% where the role of ICD therapy is currently unclear.
Neuroleptic Malignant Syndrome: A Diagnostic Dilemma
Authors: S M Sagar
Journal: Journal of the Royal Society of Medicine (1991)

3 Vorstman B, Block NL, Politano VA. The management of spermatic cord liposarcomas. J Urol 1984;131:66-9 4 Ishida A, Takeuchi H, Tomoyoshi T. Giant liposarcoma of the spermatic cord: report of a case. Acta Urol Japan 1985;31: 1059-64 5 Hoshino T, Yajima M, Iwasaki A, Hirokawa M, Matsushita K. Liposarcoma of the spermatic cord: a case report. Acta Urol Japan 1987;33:1296-9 6 Mhiri MN, Sellami F, Sellami M, Ben Hamed Y, Smida ML. Malignant paratesticular tumours apropos of three unusual cases. Ann Urol (Paris) 1989;23:23-26 7 Chan YF, Yuen MYP, Tung Ma L, Li MK. Recurrent dedifferentiated liposarcoma of the spermatic cord simulating malignant fibrous histiocytoma. Pathology 1987;19:99-102 8 Rieu JP, Catala F, Boyer JL, Carton M. Liposarcoma of the spermatic cord. Ann Urol (Paris) 1988;22:137-8 9 D'Abrera VS, Burfitt-Williams W. A giant scrotal liposarcoma. Med J Aust 1973;2:854-6 10 Garcia AE, Martin GG, Torrenti H, Monserrat JM. Liposarcoma of the spermatic cord. Rev Argent Urol 1968;37:44-8
Abstract 1682: Nicorandil Prevents Microvascular Dysfunction and Myocardial Damage Resulting from Percutaneous Coronary Intervention
Authors: Atsushi Hirohata, Keizo Yamamoto, Eiki Hirose, Tsunetatsu Namba, Shinji Sato, Hirosuke Yamaji, Makoto Ishizawa, Masaaki Murakami, Kazuyoshi Hina
Journal: Circulation (2007)

Background: Studies suggest that the status of the coronary microvasculature in patients with stable angina pectoris is important in determining long-term outcome. Nicorandil, an ATP sensitive pota...
Abstract 13773: A Bias Corrected Net Reclassification Improvement for Clinical Subgroups
Authors: Nina P Paynter, Nancy R Cook
Journal: Circulation (2011)

Comparing prediction models using reclassification within subgroups at intermediate risk is often of clinical interest and has been used extensively in the cardiovascular literature. We found the current method to be substantially biased towards false positive results. Consequently, we propose a method for obtaining an unbiased estimate for the Net Reclassification Improvement (NRI) evaluated only on a subset, or clinical NRI. To do this we derived the expected value of the clinical NRI under the null hypothesis of no improvement in prediction using the same principles as the overall NRI. Our bias-corrected estimate is shown, unlike the naive estimate commonly used in the literature, to be unbiased with a reasonable type 1 error. We applied our method to data from the Women9s Health Study, a prospective cohort of 24,171 female health professionals, comparing models for 10-year cardiovascular risk with and without high-density lipoprotein cholesterol using cut points at 5%, 10% and 20%, with risk between 5% and 20% as the subset of interest. The naive clinical NRI was 17.0% (95% CI 10.4 to 23.7) and the naive p-value was less than 0.001. However, the bias-corrected clinical NRI was 4.0%, with a p-value of 0.24 (95% CI -2.7 to 10.7). Our proposed method is an improvement over currently used methods of calculating the clinical NRI and is recommended to reduce overly optimistic results.
Abstract 16398: Prognostic Utility of the Hemoglobin/Hematocrit Equation for Estimating Plasma Volume Changes Over Time in Chronic Heart Failure
Authors: Francesco Papalia, Nay Aung, Hua Zen Ling, Suneil Aggarwal, Julia Flint, Alistair Connell, Susanne Weissert, Jamil Mayet, Darrel Francis, Martin Thomas, Simon Woldman, Darlington O Okonko
Journal: Circulation (2011)

Background: Plasma volume (PV) expansion is a hallmark feature of worsening heart failure that is notoriously underestimated by clinical examination. Whilst radioisotope assays optimally quantify P...
Abstract 5881: Influence Of Cardiac Inflammation And Extracellular Matrix Regulation On Diastolic Dysfunction In Patients With Heart Failure With Normal Ejection Fraction
Authors: Dirk Westermann, Mario Kasner, Olga Lettau, Micheal Noutsias, Heinz-Peter Schultheiss, Carsten Tschöpe
Journal: Circulation (2008)

Aims: One of the hemodynamic mechanisms underlying heart failure with normal EF (HFNEF) is increased LV stiffness. In order to clarify the pathological changes leading to increased stiffness we investigated the left ventricular (LV) function using pressure-volume loops under basal conditions and during atrial pacing and investigated endomyocardial biopsies of patients with HFNEF. Methods: In 36 patients with HFNEF and 8 controls pressure volume loops were measured under basal conditions and during atrial pacing. Furthermore, endomyocardial biopsies were analyzed for changes in the extracellular matrix regulation, cardiac inflammation and changes in the titin isoforms. Results: Patients with HFNEF had an increased LV diastolic stiffness (+350%) compared to controls. During atrial pacing, stroke volume decreased (−35%) due to a leftward shift of the PV loops. This was associated with increased collagen content in cardiac biopsies (+380%), which blunted their cardiac output response to enhanced cardiac demand. This may explain the exercise intolerance in HFNEF patients. The total collagen correlated with cardiac stiffness in the HFNEF group (r2=0.69). This was associated with increased mRNA levels of the pro fibrotic TGF-b. Furthermore, the collagenase matrix metalloproteinases (MMP) 1 was not changed while TIMP-1 was increased (+150%), which supposes a decrease in collagen degradation in HFNEF. Nevertheless, MMP 2 was increased (+160%). This MMP is also associated with inflammation, and coherently, we investigated cardiac inflammation. We documented increased cardiac inflammation by an increment of adhesion molecules (ICAM +55%) and invading cells (CD11b cells +250%) in the cardiac tissue of HFNEF patients compared to controls. Interestingly, there was no change in titin isoforms between both groups. Conclusion: Patients with HFNEF have increased diastolic stiffness leading to an impairment of the Frank-Starling mechanism during atrial pacing. Since increased stiffness correlated with the cardiac collagen content, changes in the ECM regulation might be important for the development of HFNEF and invading cells triggering cardiac inflammation might further participate in this pathophysiology.
The Cost-Effectiveness of a Telaprevir-Inclusive Regimen as Initial Therapy for Genotype 1 Hepatitis C Infection in Individuals with the Cc Il-28B Polymorphism
Authors: Ziad F. Gellad, Susanna Naggie, Shelby D. Reed, Paul J. Clark, Alex J. Thompson, Kevin A. Schulman, Andrew J. Muir
Journal: Hepatology (2011)
The pharmacokinetics of azacitidine following subcutaneous treatment in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML)
Authors: E. Laille, R. Ward, A. Nasser, M. Stoltz, C. Cogle, S. Gore, B. S. Skikne, G. Garcia-Manero
Journal: Journal of Clinical Oncology (2009)

7087 Background: 5-azacitidine (AZA), through its effects on DNA metabolism, gene expression, and cell differentiation, has proven beneficial in treatment of MDS and AML and AZA therapy significantly increases survival in higher-risk MDS and AML compared to conventional care. Few studies have evaluated the pharmacokinetics (PK) of AZA and the renal elimination of AZA has not been previously published to our knowledge. Plasma PK of AZA are herein reported in patients receiving SC doses of 75 mg/m 2 . This study was designed to also assess the contribution of renal elimination to the overall clearance of AZA. Methods: Adult patients with MDS or AML and ECOG status 0–2 were treated with 7 consecutive daily SC doses of 75 mg/m 2 AZA during their first treatment cycle. PK parameters of AZA were derived from drug concentrations in plasma and urine collected after the first and last dose (day 7) of AZA. Safety was evaluated by adverse event reporting (NCI-CTC). Results: Currently, 18 patients have been treated with SC AZA. AZA was rapidly absorbed and reached peak plasma concentrations (concs) within 0.5 hr post dosing. The AUC inf after SC doses was 1170 hr*ng/mL. The AZA concs declined in a pseudo bi-phasic manner with an elimination half-life of 1.25 hours. The plasma PK profiles after the first and last dose were superimposable. The apparent total clearance (CL/F) and volume of distribution (Vd/F) were 143 L/hr and 318 L, respectively. AZA recovery in urine was very small relative to dose (&lt;2%). AZA was well tolerated and no unexpected toxicities were observed. Conclusions: The AZA AUC inf after SC doses is similar to the published AUC value (1044 hr*ng/mL) after 75 mg/m 2 IV doses indicating approximating 100% systemic bioavailability. After SC dosing, CL/F exceeded hepatic blood flow indicating extra-hepatic metabolism. Vd/F was 4–5 fold greater than total body water suggesting extensive AZA tissue distribution. Renal elimination appears to play a minor role in the overall clearance of AZA. [Table: see text]
Abstract 5508: PSGL-1-expressing CD4 T Cells Induce Endothelial Injury in Perimenopausal Women with Low Estrogen Levels
Authors: Keiko Gomita, Kayoko Sato, Kazutaka Kitamura, Masayuki Yoshida, Nobuhisa Hagiwara
Journal: Circulation (2008)

Background: Atherosclerosis develops rapidly in postmenopausal women, and plaque erosion induces acute coronary syndromes (ACS) in perimenopausal women (PMW). However, the causal relationship between low estrogen levels and the mechanism of plaque erosion in PMW is not fully resolved. We examined whether PWM have historical T cell dysfunction related to adhesion molecules, and whether they experience accelerated plaque erosion as a result. Methods and Results: Fresh CD4 T cells were isolated from 62 PMW (mean age 54.0±5.0 years) and 69 women with regular menstruation cycles (NC, mean age 33.0±8.0 years). Estrogen levels were lower in PMW than in NC (P&lt;0.0001). Measurements of DAPI-binding nuclear protein fragmentations showed that CD4 T cells from PMW induced significant human umbilical vein endothelial cells (HUVEC) apoptosis compared to CD4 T cells from NC (P&lt;0.002). Furthermore, CD4 T cells from PMW had high T cell activation marker CD69 (P&lt;0.001) and expressed strong p-selectin glycoprotein ligand-1(PSGL-1) and integrinβ 2 but not L-selectin and integrin α M by FACS (P&lt;0.0001, P&lt;0.04, respectively). Estrogen levels correlated negatively with PSGL-1 (R=0.448, P&lt;0.02) and integrinβ 2 (R=0.442, P&lt;0.03), and negatively with CD4 T cell-induced HUVEC apoptosis (R=0.524, P&lt;0.03). Rolling and adhesion of CD4 T cells to activated HUVEC under laminar flow showed strong correlation with HUVEC apoptosis (R=0.717, P&lt;0.03 and R=0.562, P&lt;0.03, respectively). Anti-PSGL-1 Ab inhibited both CD4 T cell-rolling and CD4 T cell-adhesion to activated HUVEC (P&lt;0.05, P&lt;0.009, respectively), but anti-CD18 Ab only affected cell-adhesion (P&lt;0.006). Finally, we included anti-PSGL-1 Ab and anti-CD18 Ab in the apoptosis assay due to investigate whether the CD4 T cell-mediated apoptosis of endothelial cells was dependent on PSGL-1. Anti PSGL-1Ab treatment reduced CD4 T cell-induced apoptosis of endothelial cells (P=0.001) while anti integlinβ 2 Ab did not. Conclusions: From these results, we concluded that PSGL-1-expressing CD4 T cells in PMW with low estrogen levels is a factor that contributes to the acceleration of atherosclerosis and plaque erosion.
Abstract 3269: Increased Aortic Stiffness is a Risk of Left Ventricular Diastolic Dysfunction Even in Normotensive Subjects
Authors: Mika Maeda, Takuya Hasewawa, Hideaki Kanzaki, Jiyoong Kim, Takahiro Ohara, Masanori Asakura, Hiroshi Asanuma, Hiroyuki Takahama, Makoto Amaki, Kazuhiro Hashimura, Masafumi Kitakaze
Journal: Circulation (2009)
A phase II study of radiation and docetaxel and cisplatin in the treatment of locally advanced pancreatic carcinoma. FNCLCC-ACCORD 09 /0201 trial
Authors: F. Viret, M. Ychou, C. Baey, J. Bennouna, A. Adenis, D. Peiffert, F. Mornex, P. Celier, C. Montoto-Grillot, M. Ducreux
Journal: Journal of Clinical Oncology (2009)

4625 Background: Locally advanced pancreatic carcinoma remains a challenging tumor with no clear standard of care in terms of radio-chemotherapy. The purpose of this phase II trial was to determine the efficacy and the toxicity of radiotherapy and docetaxel and cisplatin in histologically proven adenocarcinoma of the pancreas. Methods: Patients (pts) received external beam radiotherapy (54 Gy in 1.8 Gy fractions, six weeks) and weekly chemotherapy regimen of association docetaxel and cisplatine (20 mg/m 2 /weeks each) for six weeks. Results: 51 pts (20 women and 31 men, with median age of 62 years) with disease considered to be unresectable but confined to pancreas area and celiac nodes were included between 06/10/2003 and 15/02/2008. Location of the tumor: head (33 pts), body (13 pts), and tail (5 pts). The median dose of radiotherapy received by the patients was 54 Gy. The median dose of docetaxel and cisplatin administered was 19.8 mg/m 2 /w (relative dose intensity 97%). Radiotherapy has to be interrupted in 7 pts. 30 pts experienced at least one episode of grade 3 or 4 toxicity (asthenia 12 pts, anorexia 11 pts, vomiting 10 pts, nausea 9 pts, abdominal pain 5 pts). No toxic death was observed. 6 pts underwent secondary pancreatic resection (4 compete resection and 1 pt with histological complete remission). The objective response rate (CR 5 pts, PR 3 pts), was 16% with a median duration of 7.6 months. At 6 months, 30 pts had progressed. Median progression free survival was 5.8 months. With a 21 months median follow up, median overall survival was 9.6 months and 18 months survival rate of 31%. Conclusions: The association docetaxel+cisplatin+radiotherapy has limited effect in patients with locally advanced pancreatic carcinoma but major objective responses have been observed allowing secondary resections. Grant by sanofi-aventis, Amgen, and Ligue Nationale Contre Le Cancer. No significant financial relationships to disclose.
Abstract 283: Oxidant and Antioxidant Levels During Brain Hypothermia Therapy After Cardiopulmonary Resuscitation
Authors: Kenji Dohi, Kazuyuki Miyamoto, Kazue Satoh, Shunsuke Nakamura, Hirokazu Ohtaki, Seiji Shioda, Tohru Aruga
Journal: Circulation (2010)

Oxidative stress has important roles in global brain ischemia. The control of free radical production is one of the targets in the treatment for prevention from brain damage. Therapeutic brain hypo...
Abstract 2832: Papillary Muscle Infarction is a Predictor of Ischemic Mitral Regurgitation: Novel Insights from Cardiac Magnetic Resonance Study
Authors: Thananya Boonyasirinant, Adisai Buakhamsri, Ronan Curtin, Randolph M Setser, Scott D Flamm
Journal: Circulation (2008)

Introduction Ischemic mitral regurgitation (MR) bodes worsened prognosis and increased mortality in patients with ischemic cardiomyopathy. Various mechanisms of ischemic MR have been purposed, resulting in a spectrum of surgical strategies with varying success rates. Papillary muscle infarction may contribute to ischemic MR, but could not be identified non-invasively until the recent development of chronic infarction specific imaging (delayed-enhancement, or DE-MRI). Hypothesis We hypothesized that papillary muscle infarction, determined by DE-MRI, was correlated with the presence of ischemic MR. Methods Contrast-enhanced cardiac MRI for viability assessment was performed in 100 patients with ischemic cardiomyopathy (67 male, mean age 65 years). Papillary muscle infarction was determined from DE-MRI, and left ventricular (LV) functional parameters were calculated from contiguous short-axis cine-MRI images using the disc-summation technique. Results MR by echocardiography was present in 67%: 30% with mild MR (1+), 27% moderate MR (2+), and 10% severe MR (3– 4+). In patients with no, mild, moderate, and severe MR, there was a positive correlation with the prevalence of posterior papillary muscle infarction (15%, 40%, 52%, and 70%, respectively), but there was no association with anterior papillary muscle infarction (p=NS). There was a significant inverse relationship with LV ejection fraction (LVEF) (29%, 26%, 24%, and 20%, respectively). Both LVEF (p=0.013) and posterior papillary muscle infarction (p=0.006) were significantly associated with ischemic MR on univariate analysis. Using multiple logistic regression analysis, both posterior papillary muscle infarction and LVEF remained independent determinants of MR presence and severity (p&lt;0.001 for both). Conclusions Patients with ischemic cardiomyopathy demonstrate a significant and positive correlation between the severity of MR and prevalence of posterior, but not anterior papillary muscle infarction identified by DE-MRI, and an inverse relationship with LVEF. The identification of papillary muscle infarction may provide insights into alternative approaches for repair of ischemic MR.
Abstract 2995: Impact of Atenolol versus Losartan-Based Treatment on Aortic Root Dilatation in Hypertension: The LIFE Study
Authors: Jonathan N Bella, Mary J Roman, Eva Gerdts, Kristian Wachtell, Markku Nieminen, Kurt Boman, Bjorn Dahlof, Richard B Devereux
Journal: Circulation (2006)