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https://www.readbyqxmd.com/read/27913272/the-northeast-regional-sps-meeting-update-safety-pharmacology-innovations-and-applications
#1
REVIEW
Malar Pannirselvam, Tiffini Brabham, Alfred W Botchway, Donald B Hodges, Martin Traebert, Michael K Pugsley
The Safety Pharmacology Society (SPS) held a Northeast (NE) regional meeting in Boston, MA on May 13, 2016 at the Vertex Pharmaceuticals Incorporated site. There were 103 attendees from the pharmaceutical industry, contract research organizations (CROs), academia, and global regulatory agencies. An assortment of scientific topics were presented by 7 speakers that included broad topics in the cardiovascular (organ on chip, statistical power and translation of rat cardiovascular telemetry data and dual inhibition of IKr and IKs on QT interval prolongation) and central nervous system (in vitro platform for neurotoxicity, an integrated risk assessment of suicidal ideation and behavior, and EEG advances in safety pharmacology) and a novel topic discussing preclinical challenges faced in the development of a novel gene therapy...
November 29, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27904744/qt-interval-prolongation-and-torsades-de-pointes-with-oxaliplatin
#2
Jules C Hancox, Rachel E Caves, Stéphanie C M Choisy, Andrew F James
No abstract text is available yet for this article.
December 2016: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/27904611/selective-serotonin-reuptake-inhibitors-and-cardiovascular-events-a-systematic-review
#3
REVIEW
Mohammad Hassan Nezafati, Ali Eshraghi, Mohammad Vojdanparast, Saeed Abtahi, Pouya Nezafati
BACKGROUND: Given the importance of the role of depression in predicting the outcome of cardiovascular disorders, current medications for treating depression, particularly selective serotonin reuptake inhibitors (SSRIs), are taken into consideration. This study aimed to systematically review the published findings in the use of SSRIs and the risk for cardiac events. MATERIALS AND METHODS: An independent review of the Web of Science, PubMed, Scopus, Cochrane, CINAHL, index Copernicus, and Google Scholar, up to 2014, was performed...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27903879/the-analysis-of-qt-interval-and-repolarization-morphology-of-the-heart-in-chronic-exposure-to-lead
#4
J Kiełtucki, M Dobrakowski, N Pawlas, B Średniawa, M Boroń, S Kasperczyk
There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbBmean) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbBmean = 20...
November 30, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27903458/cardiac-arrest-among-patients-with-infections-causes-clinical-practice-and-research-implications
#5
REVIEW
Davide Leoni, Jordi Rello
The incidence of sepsis is increasing, and the condition is now the leading cause of death in general intensive care units (ICUs). Our review failed to identify studies of the causes of cardiac arrest among infected patients, even though non-cardiac causes represent 15% of out-of-hospital cardiac arrests and though one-third of events have positive blood cultures. Sudden cardiac arrest is the result of local damage to the heart and of the impact of systemic and pulmonary conditions on cardiac performance, and its danger is underestimated...
November 26, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27902493/intravenous-amisulpride-for-the-prevention-of-postoperative-nausea-and-vomiting-two-concurrent-randomized-double-blind-placebo-controlled-trials
#6
Tong J Gan, Peter Kranke, Harold S Minkowitz, Sergio D Bergese, Johann Motsch, Leopold Eberhart, David G Leiman, Timothy I Melson, Dominique Chassard, Anthony L Kovac, Keith A Candiotti, Gabriel Fox, Pierre Diemunsch
BACKGROUND: Two essentially identical, randomized, double-blind, placebo-controlled, parallel-group phase III studies evaluated the efficacy of intravenous amisulpride, a dopamine D2/D3 antagonist, in the prevention of postoperative nausea and vomiting in adult surgical patients. METHODS: Adult inpatients undergoing elective surgery during general anesthesia and having at least two of the four Apfel risk factors for postoperative nausea and vomiting were enrolled at 9 U...
November 30, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27899938/detailed-analysis-of-the-impact-of-age-on-the-qt-interval
#7
Simon W Rabkin, Xin-Bo Justin Cheng, Darby Js Thompson
OBJECTIVE: To analyze the effect of age on the ECG QT interval, an important predictor of cardiovascular mortality and drug-induced cardiac arrhythmias, and determine whether QT-heart rate correction formulae (QTc) have differential relationships with age and sex. METHODS: Data were examined from the US National Health and Nutrition Examination Survey (NHANES) II and III, civilian population aged 25 to 90 years. QT weighted means and standard deviations were calculated for all ages...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27899087/paradoxical-physiological-responses-to-propranolol-in-a-rett-syndrome-patient-a-case-report
#8
P J Santosh, L Bell, K Lievesley, J Singh, F Fiori
BACKGROUND: Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT...
November 29, 2016: BMC Pediatrics
https://www.readbyqxmd.com/read/27896662/investigating-the-additive-interaction-of-qt-prolonging-drugs-in-older-people-using-claims-data
#9
Andreas D Meid, Anna von Medem, Dirk Heider, Jürgen-Bernhard Adler, Christian Günster, Hanna M Seidling, Renate Quinzler, Hans-Helmut König, Walter E Haefeli
INTRODUCTION: Drugs that potentially prolong the QT interval carry the risk of life-threatening Torsades de pointes (TdP) ventricular arrhythmia. OBJECTIVE: The objective of this study was to investigate the potential additive risk for ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs. METHODS: Claims data for persons aged ≥65 years between 2010 and 2012 in Germany were analyzed and all cases hospitalized for ventricular arrhythmia were selected...
November 29, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/27890073/switching-to-nilotinib-versus-imatinib-dose-escalation-in-patients-with-chronic-myeloid-leukaemia-in-chronic-phase-with-suboptimal-response-to-imatinib-lasor-a-randomised-open-label-trial
#10
Jorge E Cortes, Carmino Antonio De Souza, Manuel Ayala, Jose Luis Lopez, Eduardo Bullorsky, Sandip Shah, Xiaojun Huang, K Govind Babu, Kudrat Abdulkadyrov, José Salvador Rodrigues de Oliveira, Zhi-Xiang Shen, Tomasz Sacha, Israel Bendit, Zhizhou Liang, Tina Owugah, Tomasz Szczudlo, Sadhvi Khanna, Rafik Fellague-Chebra, Philipp D le Coutre
BACKGROUND: Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. METHODS: We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries)...
December 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27886373/clemizole-hydrochloride-blocks-cardiac-potassium-currents-stably-expressed-in-hek-293-cells
#11
Ling-Jun Jie, Wei-Yin Wu, Gang Li, Guo-Sheng Xiao, Shetuan Zhang, Gui-Rong Li, Yan Wang
BACKGROUND AND PURPOSE: Recent studies showed that clemizole has a potential therapeutic effect for hepatitis C infection and also potently inhibits TRPC5 channels. The aim of the present study was to investigate whether clemizole blocks cardiac K(+) currents and affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch technique was employed to examine the effects of clemizole on hERG channel current, IKs and Kv1.5 current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts...
November 25, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27878411/reckless-administration-of-qt-interval-prolonging-agents-in-elderly-patients-with-drug-induced-torsade-de-pointes
#12
Galia Jackobson, Narin Nard Carmel, Dor Lotan, Anjelika Kremer, Dan Justo
A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome, female gender and congestive heart failure), modifiable risk factors (e.g. hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless administration of a QT interval-prolonging agent (e...
November 22, 2016: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/27875726/the-association-of-uncoupling-protein-2-ucp2-exon-8-insertion-deletion-polymorphism-and-ecg-derived-qrs-duration-a-cross-sectional-study-in-an-australian-rural-population
#13
Yvonne Yin Leng Lee, Yuling Zhou, Herbert F Jelinek, Brett D Hambly, Craig S McLachlan
BACKGROUND: Associations between inherited mitochondrial disease and cardiac conduction have been previously described. However, there are no available studies exploring the mitochondrial uncoupling protein 2 gene (UCP2) insertion/deletion (I/D) polymorphisms interaction on cardiac electrical conduction. Our aim was to determine if ECG-derived QRS duration is associated with UCP2 DD genotype in a cross-sectional Australian aging rural population. METHODS: A retrospective study design utilizing a rural health diabetic screening clinic data-base containing observational data from September 2011 to September 2014...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27871843/considerations-when-using-next-generation-sequencing-for-genetic-diagnosis-of-long-qt-syndrome-in-the-clinical-testing-laboratory
#14
Hyojin Chae, Jiyeon Kim, Gun Dong Lee, Woori Jang, Joonhong Park, Dong Wook Jekarl, Yong Seog Oh, Myungshin Kim, Yonggoo Kim
BACKGROUND: Congenital long-QT syndrome (LQTS) is a potentially lethal cardiac electrophysiologic disorder characterized by QT interval prolongation and T-wave abnormalities. At least 13 LQTS-associated genes have been reported, but the high cost and low throughput of conventional Sanger sequencing has hampered the multi-gene-based LQTS diagnosis in clinical laboratories. METHODS: We developed an NGS (next-generation sequencing)-based targeted gene panel for 13 LQTS genes using the Ion PGM platform, and a cohort of 36 LQTS patients were studied for characterization of analytical performance specifications...
November 18, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27866063/anticancer-therapy-induced-vascular-toxicity-vegf-inhibition-and-beyond
#15
REVIEW
Daniela Di Lisi, Rosalinda Madonna, Concetta Zito, Enrico Bronte, Giuseppe Badalamenti, Paolo Parrella, Ines Monte, Carlo Gabriele Tocchetti, Antonio Russo, Giuseppina Novo
Cardiotoxicity induced by chemotherapeutic agents and radiotherapy is a growing problem. In recent years, an increasing number of new drugs with targeted action have been designed. These molecules, such as monoclonal antibodies and tyrosine kinase inhibitors, can cause different type of toxicities compared to traditional chemotherapy. However, they can also cause cardiac complications such as heart failure, arterial hypertension, QT interval prolongation and arrhythmias. Currently, a field of intense research is the vascular toxicity induced by new biologic drugs, particularly those which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and other tyrosine kinases...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27863364/interactions-of-digitalis-and-class-iii-antiarrhythmic-drugs-amiodarone-versus-dronedarone
#16
Gerrit Frommeyer, Dirk Puckhaber, Christian Ellermann, Dirk G Dechering, Simon Kochhäuser, Patrick Leitz, Florian Reinke, Lars Eckardt
BACKGROUND: A post hoc analysis of the PALLAS trial suggested possible interactions of dronedarone and digitalis glycosides. The aim of the present study was to compare the effects dronedarone or amiodarone in combination with digitalis glycosides. METHODS AND RESULTS: Eleven female rabbits underwent chronic oral treatment with amiodarone (50mg/kg/d for 6weeks). Ten rabbits were treated with dronedarone (50mg/kg/d for 6weeks). Ten rabbits were used as controls. Hearts were isolated and Langendorff-perfused...
November 7, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27862484/%C3%AE-1-adrenoceptor-autoantibodies-increase-the-susceptibility-of-ventricular-arrhythmias-involving-abnormal-repolarization-in-guinea-pigs
#17
Yu-Hui Zhao, Hai-Xia Huang, Ping Liu, Yun-Hui Du, Peng Wang, Wen Wang, Ye Wu, Li Wang, Chang-Sheng Ma, Hui-Rong Liu
High titers of autoantibodies against the second extracellular loop of β1 -adrenergic receptors (β1 -AA) can be detected in the sera from patients with ventricular arrhythmias, but a causal relationship between β1 -AAs and ventricular arrhythmias has not been established. In this work, electrocardiograms of guinea pigs and isolated guinea pig hearts were recorded. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were evoked by programmed electrical stimulation of the left ventricular epicardium of isolated guinea pig hearts...
November 11, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27861123/tecrl-a-new-life-threatening-inherited-arrhythmia-gene-associated-with-overlapping-clinical-features-of-both-lqts-and-cpvt
#18
Harsha D Devalla, Roselle Gélinas, Elhadi H Aburawi, Abdelaziz Beqqali, Philippe Goyette, Christian Freund, Marie-A Chaix, Rafik Tadros, Hui Jiang, Antony Le Béchec, Jantine J Monshouwer-Kloots, Tom Zwetsloot, Georgios Kosmidis, Frédéric Latour, Azadeh Alikashani, Maaike Hoekstra, Jurg Schlaepfer, Christine L Mummery, Brian Stevenson, Zoltan Kutalik, Antoine Af de Vries, Léna Rivard, Arthur Am Wilde, Mario Talajic, Arie O Verkerk, Lihadh Al-Gazali, John D Rioux, Zahurul A Bhuiyan, Robert Passier
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation...
December 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27856406/efficacy-and-safety-of-high-dose-ivermectin-for-reducing-malaria-transmission-ivermal-protocol-for-a-double-blind-randomized-placebo-controlled-dose-finding-trial-in-western-kenya
#19
Menno R Smit, Eric Ochomo, Ghaith Aljayyoussi, Titus Kwambai, Bernard Abong'o, Nabie Bayoh, John Gimnig, Aaron Samuels, Meghna Desai, Penelope A Phillips-Howard, Simon Kariuki, Duolao Wang, Steve Ward, Feiko O Ter Kuile
BACKGROUND: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150 to 200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150 to 200 mcg/kg oral dose is short-lived (6 to 11 days). Modeling suggests higher doses, which prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination...
November 17, 2016: JMIR Research Protocols
https://www.readbyqxmd.com/read/27826330/management-of-patients-with-long-qt-syndrome
#20
REVIEW
Yongkeun Cho
Long QT syndrome (LQTS) is a rare cardiac channelopathy associated with syncope and sudden death due to torsades de pointes and ventricular fibrillation. Syncope and sudden death are frequently associated with physical and emotional stress. Management of patients with LQTS consists of life-style modification, β-blockers, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD) implantation. Prohibition of competitive exercise and avoidance of QT-prolonging drugs are important issues in life-style modification...
November 2016: Korean Circulation Journal
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