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https://www.readbyqxmd.com/read/29449639/a-herg-mutation-e1039x-produced-a-synergistic-lesion-on-i-ks-together-with-kcnq1-r174c-mutation-in-a-lqts-family-with-three-compound-mutations
#1
Jie Wu, Yuka Mizusawa, Seiko Ohno, Wei-Guang Ding, Takashi Higaki, Qi Wang, Hirohiko Kohjitani, Takeru Makiyama, Hideki Itoh, Futoshi Toyoda, Andrew F James, Jules C Hancox, Hiroshi Matsuura, Minoru Horie
Congenital long QT syndrome (LQTS) caused by compound mutations is usually associated with more severe clinical phenotypes. We identified a LQTS family harboring three compound mutations in different genes (KCNQ1-R174C, hERG-E1039X and SCN5A-E428K). KCNQ1-R174C, hERG-E1039X and SCN5A-E428K mutations and/or relevant wild-type (WT) cDNAs were respectively expressed in mammalian cells. I Ks -like, I Kr -like, I Na -like currents and the functional interaction between KCNQ1-R174C and hERG-E1039X channels were studied using patch-clamp and immunocytochemistry techniques...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29445055/an-inappropriate-shock-case-early-after-implantation-of-a-subcutaneous-cardiac-defibrillator-by-subcutaneous-entrapped-air
#2
Yuka Taguchi, Toshiyuki Ishikawa, Katsumi Matsumoto, Yutaka Ogino, Hirooki Matsushita, Kohei Iguchi, Junya Hosoda
A 17-year-old woman was resuscitated from cardiac arrest due to ventricular fibrillation and was diagnosed with concealed long QT syndrome. She underwent subcutaneous implantable cardiac defibrillator (S-ICD) implantation at our hospital. The device electrogram immediately after implantation was normal. Four days after implantation, she received an inappropriate shock. The device interrogation revealed a continuous baseline shift and frequent oversensing for low amplitude signals, followed by a shock. A chest radiograph in the orthogonal view showed entrapped subcutaneous air surrounding the distal electrode...
February 14, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29444807/hypoxic-challenge-testing-fitness-to-fly-in-children-with-complex-congenital-heart-disease
#3
Nitha N Naqvi, Victoria L Doughty, Luke Starling, Rodney C Franklin, Simon Ward, Piers E F Daubeney, Ian M Balfour-Lynn
OBJECTIVE: Commercial airplanes fly with an equivalent cabin fraction of inspired oxygen of 0.15, leading to reduced oxygen saturation (SpO 2 ) in passengers. How this affects children with complex congenital heart disease (CHD) is unknown. We conducted Hypoxic Challenge Testing (HCT) to assess need for inflight supplemental oxygen. METHODS: Children aged <16 years had a standard HCT. They were grouped as (A) normal versus abnormal baseline SpO 2 (≥95% vs <95%) and (B) absence versus presence of an actual/potential right-to-left (R-L) shunt...
February 14, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29444113/effects-of-protein-protein-interactions-and-ligand-binding-on-the-ion-permeation-in-kcnq1-potassium-channel
#4
Horia Jalily Hasani, Aravindhan Ganesan, Marawan Ahmed, Khaled H Barakat
The voltage-gated KCNQ1 potassium ion channel interacts with the type I transmembrane protein minK (KCNE1) to generate the slow delayed rectifier (IKs) current in the heart. Mutations in these transmembrane proteins have been linked with several heart-related issues, including long QT syndromes (LQTS), congenital atrial fibrillation, and short QT syndrome. Off-target interactions of several drugs with that of KCNQ1/KCNE1 ion channel complex have been known to cause fatal cardiac irregularities. Thus, KCNQ1/KCNE1 remains an important avenue for drug-design and discovery research...
2018: PloS One
https://www.readbyqxmd.com/read/29441683/cardiovascular-safety-of-prokinetic-agents-a-focus-on-drug-induced-arrhythmias
#5
REVIEW
J R Giudicessi, M J Ackerman, M Camilleri
BACKGROUND: Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use...
February 14, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29440923/managing-hyperparathyroidism-in-hemodialysis-role-of-etelcalcetide
#6
REVIEW
Keith E Eidman, James B Wetmore
Secondary hyperparathyroidism (SHPT) is common in patients receiving maintenance hemodialysis and is associated with adverse outcomes. Currently, SHPT is managed by reducing circulating levels of phosphate with oral binders and parathyroid hormone (PTH) with vitamin D analogs and/or the calcimimetic cinacalcet. Etelcalcetide, a novel calcimimetic administered intravenously (IV) at the end of a hemodialysis treatment session, effectively reduces PTH in clinical trials when given thrice weekly. Additional clinical effects include reductions in circulating levels of phosphate and FGF-23 and an improved profile of markers of bone turnover...
2018: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/29439887/a-challenge-for-mutation-specific-risk-stratification-in-long-qt-syndrome-type-1
#7
Noriaki Yagi, Hideki Itoh, Takashi Hisamatsu, Yukinori Tomita, Hiromi Kimura, Yusuke Fujii, Takeru Makiyama, Minoru Horie, Seiko Ohno
BACKGROUND: The relationship between mutation locations in KCNQ1 which is a major gene in long QT syndrome (LQTS) and phenotype has been analyzed and used for risk stratification. Mutations in the transmembrane region (TM) or cytoplasmic-loop (C-loop) are associated with more frequent cardiac events than those in other regions. However, accumulation of LQTS type 1 (LQT1) patients poses the question of whether the location specific risk stratification is really effective. METHODS: The study cohort consisted of 67 KCNQ1 mutation carriers and 13 family members who were suspected as having LQTS due to sudden cardiac death or syncope from 36 unrelated families...
February 10, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29436197/the-role-of-serotonin-in-ventricular-repolarization-in-pregnant-mice
#8
Shanyu Cui, Hyewon Park, Hyelim Park, Dasom Mun, Seung Hyun Lee, Hyoeun Kim, Nuri Yun, Hail Kim, Michael Kim, Hui Nam Pak, Moon Hyoung Lee, Boyoung Joung
PURPOSE: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. MATERIALS AND METHODS: We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP)...
March 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29434624/improvement-of-increased-cqtd-is-associated-with-heart-function-in-patients-with-ischemic-heart-failure
#9
Hui Guo, Miao Wang, Juan Zhao, Jing Liu, Jie-Mei Yang
Background: Chronic heart failure (CHF) is life-threatening without timely or effective intervention. In this study, we investigated the association between QT dispersion corrected for heart rate (cQTd) and heart function in patients with CHF. Methods: From January 2013 to December 2015, we continuously enrolled 240 patients categorized as New York Heart Association functional class (NYHA) III-IV with a left ventricular ejection fraction (LVEF) < 40%. Based on the etiology, the patients were divided into a dilated cardiomyopathy (DCM) group ( n = 120) and an ischemic cardiomyopathy (ICM) group ( n = 120)...
January 2018: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/29434162/bradycardia-is-a-specific-phenotype-of-catecholaminergic-polymorphic-ventricular-tachycardia-induced-by-ryr2-mutations
#10
Kazuaki Miyata, Seiko Ohno, Hideki Itoh, Minoru Horie
Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited disease characterized by ventricular arrhythmias induced by physical exercise or emotional stress. The major cause of CPVT is mutations in RYR2, which encodes the cardiac ryanodine receptor channel. Recent advances in sequencing technology have yielded incidental findings of RYR2 variants in other cardiac diseases. Analyzing the characteristics of RYR2 variants related to CPVT will be useful for differentiation from those related to other cardiac diseases...
February 9, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29433934/evidence-based-review-of-pharmacotherapy-for-acute-agitation-part-2-safety
#11
Leslie S Zun
BACKGROUND: The management of acute agitation in the emergency department often requires the administration of rapid-acting antipsychotic agents. However, there are few comparative studies and little guidance regarding the risks associated with use of such drugs in the acute setting. OBJECTIVE: This structured evidence-based review compared the safety of antipsychotic pharmacotherapies for acute agitation using data from randomized controlled trials identified by a literature search of the PubMed database...
February 9, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29431731/physiological-genomics-identifies-genetic-modifiers-of-long-qt-syndrome-type-2-severity
#12
Sam Chai, Xiaoping Wan, Angelina Ramirez-Navarro, Paul J Tesar, Elizabeth S Kaufman, Eckhard Ficker, Alfred L George, Isabelle Deschênes
Congenital long QT syndrome (LQTS) is an inherited channelopathy associated with life-threatening arrhythmias. LQTS type 2 (LQT2) is caused by mutations in KCNH2, which encodes the potassium channel hERG. We hypothesized that modifier genes are partly responsible for the variable phenotype severity observed in some LQT2 families. Here, we identified contributors to variable expressivity in an LQT2 family by using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and whole exome sequencing in a synergistic manner...
February 12, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29431662/classification-and-reporting-of-potentially-proarrhythmic-common-genetic-variation-in-long-qt-syndrome-genetic-testing
#13
REVIEW
John R Giudicessi, Dan M Roden, Arthur A M Wilde, Michael J Ackerman
The acquired and congenital forms of long QT syndrome represent 2 distinct but clinically and genetically intertwined disorders of cardiac repolarization characterized by the shared final common pathway of QT interval prolongation and risk of potentially life-threatening arrhythmias. Over the past 2 decades, our understanding of the spectrum of genetic variation that (1) perturbs the function of cardiac ion channel macromolecular complexes and intracellular calcium-handling proteins, (2) underlies acquired/congenital long QT syndrome susceptibility, and (3) serves as a determinant of QT interval duration in the general population has grown exponentially...
February 6, 2018: Circulation
https://www.readbyqxmd.com/read/29431613/mhra-quinine-qt-prolonging-effects-and-drug-interactions
#14
(no author information available yet)
No abstract text is available yet for this article.
February 5, 2018: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/29430560/epilepsy-is-associated-with-ventricular-alterations-following-convulsive-status-epilepticus-in-children
#15
Wail Ali, Beth A Bubolz, Linh Nguyen, Danny Castro, Jorge Coss-Bu, Michael M Quach, Curtis E Kennedy, Anne E Anderson, Yi-Chen Lai
Objective: Convulsive status epilepticus can exert profound cardiovascular effects in adults including ventricular depolarization-repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus. Methods: We conducted a 2-year retrospective, case-control study...
December 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29428463/cardiac-repolarization-evolves-differently-during-the-course-of-benign-and-disabling-multiple-sclerosis
#16
Alma Mikkola, Aku Ojanen, Juha Ek Hartikainen, Anne M Remes, Sakari Simula
BACKGROUND: Cardiac repolarization is modulated by the autonomic nervous system. Even though multiple sclerosis associates with prolonged cardiac repolarization the physiology responsible for the phenomenon remains unknown. OBJECTIVE: To study in longitudinal setting whether the patients with confirmed benign and disabling outcome of relapsing-remitting multiple sclerosis (RRMS) differ in regard to changes of cardiac repolarization. METHODS: Total of 43 patients, 26% with benign (EDSS ≤2 at least 10y after onset symptom) and 74% with disabling (EDSS >2 at least 10y after onset symptom) RRMS, having 12-lead electrocardiogram (ECG) recorded at the time of onset symptom (ECG1) and for follow-up (ECG2), were studied...
February 1, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29427819/significance-of-t-wave-inversion-triggered-by-spontaneous-atrial-premature-beats-in-patients-with-long-qt-syndrome
#17
Nobuhiro Takasugi, Mieko Takasugi, Hiroko Goto, Takashi Kuwahara, Takashi Nakashima, Tomoki Kubota, Hiromitsu Kanamori, Masanori Kawasaki, Kazuhiko Nishigaki, Shinya Minatoguchi, Richard L Verrier
BACKGROUND: In patients with long QT syndrome (LQTS), a sudden increase in heart rate can cause T-wave alternans (TWA) with beat-to-beat alternating polarity of T wave. We hypothesized that LQTS patients at a high risk of Torsade de Pointes (TdP) may exhibit momentary atrial or sinoatrial premature beat-induced T-wave inversion (APB-TWI). OBJECTIVE: To assess the association of APB-TWI with TdP history and with microvolt TWA. METHODS: 24-h continuous 12-lead electrocardiograms (ECGs) were recorded in 18 healthy subjects and 39 consecutive patients with LQTS types 1 (n=21), 2 (n=4), 3 (n=4), and unidentified (n=10)...
February 7, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29426220/comprehensive-assessment-of-drought-risk-in-the-arid-region-of-northwest-china-based-on-the-global-palmer-drought-severity-index-gridded-data
#18
Peng Yang, Jun Xia, Yongyong Zhang, Chesheng Zhan, Yunfeng Qiao
Droughts are extremely widespread natural disasters, which cause the most severe losses among natural disasters. The comprehensive drought risk in Northwest China (NWC) was evaluated based on the self-calibrating (SC) Palmer Drought Severity Index (PDSI) and copula method. The major conclusions are the following: (1) based on the rotated empirical orthogonal function (REOF), a significant consistency in the spatial distribution of the monthly averaged SC-PDSI was observed in NWC, especially in the subregions Inner Mongolia Plateau (IM), Hexi Corridor (HX), and Qiangtang Plateau (QT); (2) the largest frequency was obtained for slight drought and slight wet conditions, while extreme drought and extreme wet showed the lowest values; (3) with respect to the PDSI-th, the Clayton, Arch12, Arch12, Arch12, Arch12, and Frank played the major roles in the copula weight in the subregions IM, HX, Qinghai River Basin (QH), QT, North Xinjiang (NXJ), and South Xinjiang (SXJ), respectively...
February 2, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29425340/clinical-review-of-delafloxacin-a-novel-anionic-fluoroquinolone
#19
Bryan T Mogle, Jeffrey M Steele, Stephen J Thomas, KarenBeth H Bohan, Wesley D Kufel
Delafloxacin is a novel anionic fluoroquinolone (FQ) approved for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by a number of Gram-positive and Gram-negative organisms including MRSA and Pseudomonas aeruginosa. The unique chemical structure of delafloxacin renders it a weak acid and results in increased potency in acidic environments. In Phase III studies, delafloxacin had similar outcomes to comparator regimens for treatment of ABSSSIs, and was well tolerated overall. Similar to other FQs, delafloxacin is available in both intravenous and oral formulations, but differs in that delafloxacin exerts a minimal effect on cytochrome P450 enzymes and on the corrected QT interval...
February 7, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29424967/predicting-drug-induced-arrhythmias-by-multiscale-modeling
#20
F Sahli Costabal, J Yao, E Kuhl
Drugs often have undesired side effects. In the heart, they can induce lethal arrhythmias such as torsades de pointes. The risk evaluation of a new compound is costly and can take a long time, which often hinders the development of new drugs. Here we establish a high resolution, multiscale computational model to quickly assess the cardiac toxicity of new and existing drugs. The input of the model is the drug-specific current block from single cell electrophysiology; the output is the spatio-temporal activation profile and the associated electrocardiogram...
February 9, 2018: International Journal for Numerical Methods in Biomedical Engineering
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