170,118 research outputs found
Diagnostic and genetic aspects of the Brugada and other inherited arrhythmias syndromes
No full textDoctor Wilde, presenting on behalf of himself and Dr Eckardt, discussed the role of invasive and noninvasive tests for risk stratification of Brugada syndrome. Doctor Hiraoka, presenting on behalf of Y. Yokoyama, M. Takagi, N. Aihara, K. Aonuma, and the Japan Idiopathic Ventricular Fibrillation Study Investigators, further discussed the diagnostic criteria for the Brugada syndrome. Doctor Antzelevitch examined the hypothesis that amplification of spatial dispersion of repolarization in the form of transmural dispersion of repolarization underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies including the long QT, short QT, and Brugada syndromes. Doctor Corrado discussed the relationship between channelopathies and heart muscle diseases. (c) 2007 Elsevier Inc. All rights reserve
Ion channels and beating heart: the players and the music
No full textSoft gentle music accompanies us throughout our lifetime; it is the music of our heart beating. Although at times it is questionable as to who serves as conductor of the orchestra, there is little doubt that our ion channels are the main players. Whenever one of them plays too loudly, too softly or simply off key, disharmony results, sometimes leading to total disruption of the rate and rhythm. Ion channels can disrupt the music of our heart by different mechanisms. Sometimes their function is correct, but their expression is altered by underlying cardiac diseases (i.e. heart failure); sometimes the defect is in their structure, because of an underlying genetic defect, and in this case a channelopathy is present
Inherited arrhythmogenic diseases
No full textThis chapter will examine the clinical, molecular and cellular aspects of inherited arrhythmogenic disease with specific focus on clinical mangemen
How to prevent sudden death in patients with inherited arrhythmia syndromes or cardiomyopathies
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
New approaches to antiarrhythmic therapy, Part I. Emerging therapeutic applications of the cell biology of cardiac arrhythmias.
No full textDispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Molecular basis of cardiac arrhythmias: genetics of natural variants and electrophysiological investigation of mutant proteins
No full textChannelopathies are diseases caused by deranged functioning of ion channel subunits or the proteins that regulate them. Long QT and Brugada syndrome are included in this group. In particular, long QT syndrome (LQTS) is a familial autosomal dominant disease characterized by prolongation of the QT interval on the surface ECG, syncope, torsade de pointes and sudden cardiac death in young patients. Each type of heritable LQTS (LQTS 1-12) is linked to mutations in a specific gene. Mutations occur more frequently in the cardiac ion channel coding genes (SCN5A, KCNH2,KCNQ1) and ancillary β-subunits (KCNE1 and KCNE2). Differently, BrS is an inherited cardiac disease characterized by ST segment elevation in the right precordial leads (V1 to V3), susceptibility to ventricular tachyarrhythmia and sudden cardiac death, typically during rest or sleep. BrS is inherited as an autosomal dominant trait and its prevalence in Caucasians is 5/1000. The disorder is linked to mutations in the SCN5A gene. Our project was designed to functionally characterize the novel mutations found in genes related to LQTS and BrS to better understand the pathogenesis of pathological phenotypes .
To this aim, we firs amplified by PCR all coding exons, 5’ and 3’ UTR of the SCN5A, KCNQ1, KCNH2, KCNE1 and KCNE2 genes and analyzed them by dHPLC and automatic sequencing. The mutants were generated by QuickChange site-directed mutagenesis. Mutants were transiently transfected in mammalian cells for in vitro analysis.
We characterized the LQT3 associated p.ΔN1472 mutation that we found in SCN5A gene. The electrophysiological studies demonstrated that the hH1 mutation had a shift in the voltage-dependence of inactivation, a positive shift in the voltage dependence of activation and a slower recovery from inactivation compared to WT channel. Moreover, the persistent current levels were much higher in SCN5A-p.ΔN1472 than in the WT channel.
We also studied mutations KCNH2-p.C108Y and KCNQ1-p.R583H. Interestingly, only subjects carrying both mutations manifested severe LQTS. The biophysical studies showed that in the homozygous condition, KCNH2-p.C108Y, led to a non-functional KCNH2 channel, whereas, in the heterozygous condition, mutant KCNH2 had a significantly reduced current density and a negative shift in the voltage dependence of activation compared to the WT. Furthermore, mutant KCNQ1-p.R583H had a significantly reduced tail current density compared to the WT channel, but no significant changes in activating current density and in voltage-dependence of activation. In conclusion, we demonstrate that the SCN5A-p.ΔN1472 and KCNH2-p.C108Y mutants exhibit characteristic biophysical properties causing LQTS; whereas KCNQ1-p.R583H, in combination with KCNE1-WT, does not exhibit striking biophysical defects, but in combination with mutant KCNH2 it results in a more severe phenotype. Our results allow to better understand the pathogenesis of LQTS phenotype and to increase the knowledge of ion channel behavior in the pathological conditions
A Molecular Link between the Sudden Infant Death Syndrome and the Long-QT Syndrome.
No full textThe ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups.
METHODS AND RESULTS:
Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%).
CONCLUSIONS:
At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management
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