tbuckley/cabot-search huggingface dataset:
Abstract 11220: Electrotonic Interactions Contribute to the Genesis of Phase-3 Early Afterdepolarizations and Triggered Activity in Acquired Long QT Syndrome
Authors: Mitsunori Maruyama, Shien-Fong Lin, Yuanfang Xie, Su-Kiat Chua, Boyoung Joung, Seongwook Han, Tetsuji Shinohara, Mark J Shen, Zhilin Qu, James N Weiss, Peng-Sheng Chen
Journal: Circulation (2010)

Introduction: Both phase-2 and phase-3 early afterdepolarizations (EADs) occur in long QT syndromes, with the latter proposed to be generated by spontaneous sarcoplasmic reticulum (SR) Ca release. ...
Megakaryocyte growth and development factor and interleukin-3 induce patterns of protein-tyrosine phosphorylation that correlate with dominant differentiation over proliferation of mpl-transfected 32D cells
Authors: SX Mu, M Xia, G Elliott, J Bogenberger, S Swift, L Bennett, DL Lappinga, R Hecht, R Lee, CJ Saris
Journal: Blood (1995)
Abstract 3843: The Composition and Morphology of the Carotid Artery are Associated with Coronary Artery Disease: A Case-Control High Resolution Magnetic Resonance Imaging Study
Authors: Hunter R Underhill, Chun Yuan, Mark A Espeland, Haiying Chen, James G Terry, Thomas S Hatsukami, Tobias Saam, Baocheng Chu, Norihide Takaya, Rong Tang, Vasily Yarnykh, Jeffrey Carr, Marina Ferguson, John R Crouse
Journal: Circulation (2006)

Background:  To improve the prediction of cardiovascular events in asymptomatic individuals, non-invasive imaging techniques have been increasingly investigated as a potential supplement to the clinically-based risk stratification criteria. We sought to identify structural and compositional differences in the carotid arterial wall via high-resolution magnetic resonance imaging (MRI) between participants with angiographically defined obstructive coronary artery disease (CAD, > 50% stenosis, case) and those with normal coronary arteries (no lumen irregularities, control).   Methods:  Ninety-four participants (56% female; 20% diabetic; 54% smokers; 55% CAD cases) who underwent coronary angiography but were not selected on the basis of carotid disease status were imaged with a multi-sequence, high-resolution carotid MRI protocol on a 1.5T scanner. Two reviewers blinded to CAD status reached a consensus interpretation for each scan. At each axial imaging location, lumen area (LA), total vessel area (TVA), wall area (WA), mean wall thickness (MWT) and normalized wall index (NWI = WA/[LA + WA]) were determined. Area measurements of calcification (CA) and lipid-rich necrotic core (LRNC) were also recorded. Results were compiled after controlling for gender and within-subject correlations among arterial sites.   Results:  In the internal carotid artery (ICA), CAD cases demonstrated a smaller mean LA and TVA, while having a larger MWT, NWI and CA (Table 1). In the distal bulb, CA and LRNC were larger in CAD cases (Table 1). CAD cases also demonstrated a greater prevalence (9.9% vs. 2.9%, p = 0.004) of CA in the ICA. No differences between groups were identified in the common carotid artery.   Conclusions:  Statistically significant structural and compositional differences in the carotid artery exist between subjects with and without CAD. These findings provide compelling evidence that carotid MRI may be an effective screening tool for identifying subjects at risk from CAD.
Abstract 4139: Addition of Omega-3 Fatty Acids to Rosuvastatin Improves Endothelial Function in South Asians with Metabolic Syndrome
Authors: Rakesh P Gupta, Vikas Soma, John Coppola, Mary C DeVoe, Eileen V Hermance, Moses Bachan, Stavros Agorastos, Cezar S Staniloae
Journal: Circulation (2006)

Background Metabolic syndrome is increasing in prevalence and is associated with significant endothelial dysfunction. Omega-3 fatty acids (O3FA) modulate the lipid profile and improve endothelial f...
Abstract 15805: PCSK9 R46L, Lower LDL and Cardiovascular Disease Risk in Familial Hypercholesterolemia
Authors: Alexis Baass
Journal: Circulation (2014)

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a down-regulator of the low density lipoprotein receptor (LDLR). Familial hypercholesterolemia (FH) is a autosomal monogenic disease associated with high LDL-C concentration and cardiovascular risk. Hypothesis: This study aimed to examine whether the PCSK9 R46L loss of function mutation found in a cohort of FH patients will be associated with lower LDL-C and cardiovascular risk. Methods: We studied FH patients attending the IRCM Lipid Clinic and whose DNA genotyping was positive for LDLR mutations. The presence of the PCSK9 loss of function R46L missense mutation was determined among a cohort of 582 FH patients by sequencing. Results: Frequency of the R46L variant was 3%. Comparison of their lipid profile showed that carriers had significantly reduced LDL-C (11%, p&lt;0.001), TC (9%, p&lt;0.01), ApoB (10%, p&lt;0.01) and non-HDL (12%, p&lt;0.001) concentrations compared to non-carriers. The analysis of physical xanthomata among both groups, showed a decreased average number of xanthoma per individual in R46L carriers (0.33 and 0.76 respectively, p&lt;0.001). Importantly, the R46L mutation was associated with a significant 66% (p=0.05) lower risk of cardiovascular events compared to non-carriers. Conclusion: Our study showed that the presence of the PCSK9 loss of function R46L mutation in the genotype of FH patients is beneficial for the lipid homeostasis and down-regulate the effect of the LDLR mutation in terms of accumulation of LDL-C, ApoB , total cholesterol, non-HDL and thereby, lowers the coronary heart disease risk of PCSK9 LOF mutation carriers. It is therefore very likely that anti-PCSK9 therapy will be useful in reducing cardiovascular risk in FH patients.
Treatment of Refractory and Relapsed Acute Myelogenous Leukemia With Combination Chemotherapy Plus the Multidrug Resistance Modulator PSC 833 (Valspodar)
Authors: Ranjana Advani, Hussain I. Saba, Martin S. Tallman, Jacob M. Rowe, Peter H. Wiernik, Joseph Ramek, Kathleen Dugan, Bert Lum, Jenny Villena, Eric Davis, Elisabeth Paietta, Manuel Litchman, Branimir I. Sikic, Peter L. Greenberg
Journal: Blood (1999)
Mumps outbreak in the former Yugoslav Republic of Macedonia, January 2008 – June 2009: epidemiology and control measures
Authors: G Kuzmanovska, A Polozhani, V Mikik, K Stavridis, B Aleksoski, Z Cvetanovska, R Binnendijk, G Bosevska
Journal: Eurosurveillance (2010)

Between January 2008 and June 2009, the Institute of Public Health received 16,352 notifications of mumps cases through routine surveillance: young people aged 15-19 years were most affected.
External Validation Of The HIT Expert Probability (HEP) Score, a Novel Pre-Test Probability Model For Heparin-Induced Thrombocytopenia Based On Broad Expert Opinion
Authors: Lee Joseph, Marcelo P.V. Gomes, Firas Al Solaiman, Julie St John, Asuka Ozaki, Manjunath Raju, Manoj Dhariwal, Esther S.H. Kim
Journal: Blood (2013)
Abstract 9984: Concomitant Sleep-Disordered Breathing Increases the Recurrence of Atrial Fibrillation Following Radiofrequency Catheter Ablation of Atrial Fibrillation: Efficacy of CPAP Therapy
Authors: Yoshihisa Naruse, Hiroshi Tada, Makoto Satoh, Mariko Yanagihara, Hidekazu Tsuneoka, Yumi Hirata, Takeshi Machino, Hiro Yamasaki, Miyako Igarashi, Kenji Kuroki, Yoko Ito, Kentaro Yoshida, Yukio Sekiguchi, Kazutaka Aonuma
Journal: Circulation (2011)

Background: Recent studies have suggested an emerging link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). Patients with OSA are reported to be less likely to maintain sinus rhythm after radiofrequency (RF) catheter ablation of AF. Continuous positive airway pressure (CPAP) is a well-established treatment for OSA. However, the effect of the CPAP on AF recurrences following ablation has not been clarified. Methods: This study prospectively included 133 patients (20 women; 57±11 years) who underwent RF catheter ablation for drug-refractory AF. At 1 week after the ablation, a standard overnight polysomnographic evaluation was performed, and the total duration and number of episodes of central or obstructive sleep apnea or hypopnea were examined. The primary endpoint was the recurrence of AF after the RF catheter ablation of AF. Results: The overnight polysomnography revealed no sleep-disordered breathing in 30 patients (23%; No-OSA-Gr). However, 103 (77%) patients were identified as having OSA by the overnight polysomnography. Sixty-one (59%) of those 103 patients received CPAP therapy (CPAP-Gr), and the remaining 42 (41%) did not (No-CPAP-Gr). After a mean follow-up period of 12.3±4.1 months, the prevalence of AF recurrences was 36% in the No-CPAP-Gr patients, which was greater than that in the CPAP-Gr (11%) and No-OSA-Gr (10%; p=0.003) patients. A multivariate analysis revealed that the OSA (hazard ratio [HR]= 4.082, 95% confidence interval [CI]= 1.083-15.388, P=0.038), usage of CPAP (HR= 0.236, 95% CI= 0.091-0.614, P=0.003), total duration of the AF history (HR= 1.084, 95% CI 1.024-1.144, P=0.011), and left atrial volume (HR=1.120, 95% CI=1.010-1.239, P=0.029) were independent predictors of AF recurrences. An AHI of &gt; 10 by PSG identified an AF recurrence after the RF catheter ablation of AF with a sensitivity of 67% and specificity of 83% (area under the curve= 0.752, P=0.003). Conclusions: Patients with untreated OSA have a higher recurrence of AF after ablation. The CPAP treatment is effective for AF recurrences as well as for OSA patients, and should be performed after AF ablation.
The Impact of For-Profit Hospital Status on the Care and Outcomes of Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Bimal R. Shah, Seth W. Glickman, Li Liang, W. Brian Gibler, E. Magnus Ohman, Charles V. Pollack, Matthew T. Roe, Eric D. Peterson
Journal: Journal of the American College of Cardiology (2007)
History: Two hundred years since Malthus
Authors: J. A Black
Journal: BMJ (1997)

Malthus was by training a mathematician and by profession a teacher of political economy, but his work was greatly influenced by his Christian convictions. In the first edition of his Essay , published in 1798, he put forward the hypothesis that population, if unchecked, would increase by geometrical ratio, doubling itself every 25 years, while food supply could increase by only arithmetical ratio. He suggested that population was controlled by “positive checks” such as war, famine, and disease.

He campaigned unsuccessfully for the gradual abolition of the old poor laws which, he thought, encouraged the working class to marry young and to have large families. In his second edition he introduced the concept of the “preventive checks” by moral restraint—late marriage and restraint within marriage. The reduction in fertility which Malthus advocated was achieved by the acceptance of birth control, to which he was violently opposed. He was attacked during his lifetime and has been misinterpreted and misunderstood ever since.

Thomas Robert Malthus (known as Robert) (fig 1) was born on 14 February 1766 near Dorking, Surrey. He was born with a cleft lip and palate, but this does not seem to have hindered his academic career. In 1785 he entered Jesus College, Cambridge, where he read mathematics, obtaining a first class degree. He was elected fellow of the college in 1797, and four years later took Holy Orders. In 1805 he was appointed professor of history and political economy at the newly founded College of the East India Company, at Haileybury, in Hertfordshire (now Haileybury and Imperial Service College). He held this post until his death in 1834 from “disease of the heart” in Bath (fig 2). He married at the age of 38 and had three children.



Fig 1 
John Linnell's portrait of Malthus in 1833, aged 67. (Reproduced with …
A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant chronic phase chronic myeloid leukemia (CML): Results from CA180002
Authors: M. Talpaz, H. M. Kantarjian, R. Paquette, N. Shah, J. Cortes, J. Nicoll, S. A. Bai, F. Huang, A. P. Decillis, C. L. Sawyers
Journal: Journal of Clinical Oncology (2005)

6519 Background: Resistance to imatinib in CML patients is often associated with Bcr-Abl point mutations which interfere with imatinib binding. BMS-354825 is a novel, orally available, dual SRC/ABL kinase inhibitor with more than 300-fold greater potency than imatinib and has preclinical activity against 14 of 15 imatinib resistant Bcr-Abl mutants (Shah et al, Science, 305:399, 2004). Methods: CA180002 is a phase I, dose-escalation study of BMS-354825 in CML patients with hematologic resistance or intolerance to imatinib. Intrapatient dose escalation is permitted. Patient samples are analyzed for pharmacokinetics (PK), Bcr-Abl kinase domain mutations, and CRKL, HCK, and LYN phosphorylation. Results: 36 chronic phase CML patients have been treated (31 resistant, 5 intolerant) with total daily doses ranging from 15 - 180 mg (given as single or divided doses). Mutations associated with imatinib resistance were identified in 27 patients. Thirty-one patients (86%) have had complete hematologic response (CHR). Only 2 patients have had progression of their disease. Thirteen of 29 patients had cytogenetic improvement including 5 complete and 4 partial cytogenetic responses (i.e. major cytogenetic responses (MCyR) in 9 of 29 patients. MCyR rate = 31%). Hematologic and cytogenetic responses have occurred regardless of mutation status, or whether the mutation was in the P-loop, catalytic or activation region, with the exception of one patient who progressed with T315I. Responses are durable, and 33 of 36 patients remain on study for 1+ to 13+ months. BMS-354825 has been well tolerated. Three patients had grade 4 thrombocytopenia and 2 patients had grade 4 neutropenia, all of which were reversible and easily managed with dose modification. One patient developed a duodenal ulcer possibly related to BMS-354825. Mild QTc prolongation has been noted. Conclusions: BMS-345825 appears to be safe and effective therapy for patients with imatinib-resistant and imatinib-intolerant CML producing hematologic and cytogenetic responses. The phase I study continues to accrue patients to determine the maximally tolerated dose. No significant financial relationships to disclose.
Abstract 19718: Incidence of Atrial Fibrillation and Associated Mortality among Medicare Beneficiaries from 1993 to 2007
Authors: Jonathan P Piccini, Bradley G Hammill, Moritz F Sinner, Paul N Jensen, Adrian F Hernandez, Susan R Heckbert, Emelia J Benjamin, Lesley H Curtis
Journal: Circulation (2010)

Background: Atrial fibrillation (AF) is a common and costly problem in the elderly. The frequency of AF increases with age, but representative national data about incidence and associated mortality...
Abstract 9164: Low Doses of Ranolazine and Dronedarone in Combination Exert Potent Protection against Atrial Fibrillation and Vulnerability to Ventricular Arrhythmias during Acute Myocardial Ischemia
Authors: Richard L Verrier, Vitor P Pagotto, Alexandre F Kanas, Marcel F Sobrado, Bruce D Nearing, Dewan Zeng, Luiz Belardinelli
Journal: Circulation (2012)

Background: Coronary artery disease carries dual risk for atrial fibrillation (AF) and sudden cardiac death. We examined whether low-dose ranolazine and/or dronedarone can protect against AF and vulnerability to ventricular tachyarrhythmias. Methods, Results: In chloralose-anesthetized, open-chest Yorkshire pigs (N=19), proximal segment of left circumflex (LCx) coronary artery was occluded to reduce flow by 75%. Electrode catheter was positioned on left atrial appendage to measure AF threshold (AFT) before and during LCx coronary artery stenosis prior to and at one hour after dronedarone (0.5 mg/kg i.v. bolus over 5 min) and/or ranolazine (0.6 mg/kg, i.v. bolus, followed by 0.035 mg/kg/min). Without drugs, LCx coronary artery stenosis lowered AFT from 25.2±1.7 control (mean±SEM) to 4.9±1.0 mA baseline (p&lt;0.01). At these low doses, neither ranolazine (plasma concentration: 2.4±0.6 μ M) nor dronedarone (plasma concentration: 20.9±3.5 nM) alone blunted ischemia-induced reduction in AFT, but combination was effective (from 25.2±1.7 control to 22.0±3.0 mA, NS). Combined but not separate administration blunted ischemia-induced surge in T-wave heterogeneity (TWH), a marker of risk for ventricular tachyarrhythmias. Without drug, TWH increased from 43.1±11.1 control to 149.7±15.1 μ V baseline during stenosis (p&lt;0.001); with both agents, TWH increased only from 61.7±13.7 control to 83.7±15.8 μ V during stenosis (NS) (Fig.). Conclusions: Combined administration of low doses of ranolazine and dronedarone exerts a potent, antiarrhythmic action consistent with synergy due to direct effects on myocardial electrical properties not on coronary flow, which was controlled.
Abstract 15017: Decreased Incidence of Supravalvar Pulmonary Stenosis Following Modified Technique of Arterial Switch Operation
Authors: Michael F Swartz, Ariel Senna, Nader Atallah-Yunes, Cecilia Meagher, Jill Cholette, Francisco Gensini, George M Alfieris
Journal: Circulation (2011)

Objective: Supravalvar pulmonary stenosis (SVPS) is frequently observed after arterial switch. Traditionally, the ascending aorta is transected at the level of the sinotubular junction and the coro...
Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning on Children Undergoing Cardiac Surgery
Authors: Michael M.H. Cheung, Rajesh K. Kharbanda, Igor E. Konstantinov, Mikiko Shimizu, Helena Frndova, Jia Li, Helen M. Holtby, Peter N. Cox, Jeffrey F. Smallhorn, Glen S. Van Arsdell, Andrew N. Redington
Journal: Journal of the American College of Cardiology (2006)
Prognostic relevance of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy: The German SUCCESS-Trial
Authors: B. K. Rack, C. Schindlbeck, A. Schneeweiss, J. Hilfrich, R. Lorenz, M. W. Beckmann, K. Pantel, W. Lichtenegger, H. L. Sommer, W. J. Janni
Journal: Journal of Clinical Oncology (2008)

503 Background: The prognostic significance of CTCs in metastatic breast cancer has been demonstrated. If the presence of CTCs in early breast cancer would also predict an increased risk for relapse, this method might be used as an early marker for treatment efficacy and risk for disease recurrence. Methods: As part of the translational research project of the German SUCCESS-trial, we analyzed 23ml of peripheral blood from 1,500 N+ and high risk N- breast cancer pts before and after adjuvant taxane-based chemotherapy. The presence of CTCs was assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Results: In 10% of pts (n=143) >1 CTC was detected before the start of systemic treatment (mean 14, range 2–827). While we found 2 CTCs in 4% of pts, 3% had 3–5 CTCs and 1% 6–10 and >10 CTCs respectively. The presence of CTCs did not correlate with tumor size (p=0.32), grading (p=0.36), hormonal status (p=0.28) or HER2/neu status of the primary tumor (p=0.82), but with the presence of lymph node metastases (p=0.003). Three of 74 individuals without malignant disease (4%) showed more than 1 CTC. After completion of chemotherapy, 9% of pts (n=130) presented with >1 CTC (mean 6, range 2–124). Of those initially CTC positive, 10% remained positive (n=15), whereas of those initially CTC negative, 8% returned with a positive test (n=115, p=0.42). 21 recurrences occurred during a median follow-up of 12 months and 7 pts died of their disease. While the presence of CTCs before systemic treatment did not show prognostic relevance for DFS (p=0.89) and OAS (p=0.71), persistence of CTCs after chemotherapy was a significant predictor for both reduced DFS (p=0.04) and OAS (p=0.03). Conclusions: In a considerable number of pts CTCs in peripheral blood can be detected after the completion of chemotherapy. Preliminary results demonstrate a prognostic relevance of persisting CTCs after chemotherapy, thus indicating a potential role for treatment monitoring in early breast cancer. Longer follow-up of the SUCCESS-trial will have to be awaited to confirm these findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Veridex Veridex Veridex Veridex
Quality improvement reports: a new kind of article
Authors: R. Smith
Journal: BMJ (2000)

Cariprazine is an approved antipsychotic and antidepressant which is a dopamine (DA) D<sub>3</sub>-preferring D<sub>3</sub>/D<sub>2</sub> receptor partial agonist, serotonin (5-HT) 5-HT<sub>1A</sub> receptor partial agonist, and 5-HT<sub>2B</sub> and 5-HT<sub>2A</sub> receptor antagonist, a profile unique for atypical antipsychotic drugs. The purpose of this study was to clarify the effects of cariprazine and selective D<sub>3</sub> receptor ligands on neurotransmitter efflux in the rat nucleus accumbens (NAC) and ventral hippocampus (HIP), brain regions important for reality testing, rewarded behavior, and cognition. In vivo microdialysis was performed in awake, freely moving rats after administration of cariprazine; (+)-PD-128907 [(4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], a D<sub>3</sub> receptor–preferring agonist; and SB-277011A [trans-<i>N</i>-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide hydrochloride], a selective D<sub>3</sub> receptor antagonist, alone or combined, and extracellular levels of multiple neurotransmitters and metabolites were measured in the NAC and HIP by ultraperformance liquid chromatography with tandem mass spectrometry. Cariprazine increased DA, norepinephrine (NE), and 5-HT efflux in both regions, whereas it increased glycine (Gly) and glutamate efflux only in the NAC and efflux of DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) only in the HIP. Similarly, SB-277011A increased DA, NE, DOPAC, and HVA, but not 5-HT, efflux in the NAC and HIP, and acetylcholine efflux in the HIP. Most of these effects of cariprazine and SB-277011A were fully or partially attenuated by the D<sub>3</sub> receptor agonist (+)-PD-128907, suggesting these effects of cariprazine are related to its D<sub>3</sub> receptor partial agonism, and that this mechanism, leading to diminished stimulation of D<sub>3</sub> receptors, may contribute to its efficacy in both schizophrenia and bipolar disorder. The possible role of Gly in the action of cariprazine is discussed. <h3>SIGNIFICANCE STATEMENT</h3> The novel atypical antipsychotic drug cariprazine increased nucleus accumbens and hippocampal neurotransmitter efflux, similar to the actions of the D<sub>3</sub> receptor antagonist SB-277011A [trans-<i>N</i>-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide hydrochloride]. The D<sub>3</sub> receptor–preferring agonist (+)-PD-128907 [(4aR, 10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], diminished the effects of both compounds on neurotransmitter efflux in both regions. These results suggested D3 receptor partial agonist activity of cariprazine, producing functional antagonism, may contribute to its efficacy in schizophrenia and bipolar disorder.