University of Milan

About: University of Milan is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 58413 authors who have published 139784 publications receiving 4636354 citations. The organization is also known as: Università degli Studi di Milano & Statale.

Diagnostic criteria for the long QT syndrome. An update.

Abstract: T he idiopathic long QT syndrome (LQTS) is a congenital disease with frequent familial transmission, characterized primarily by prolongation of the QT interval and by the occurrence of life-threatening tachyarrhythmias, particularly in association with emotional or physical stress.1-5 Among untreated symptomatic patients, lethality is high, with 20% mortality in the first year after the initial syncope and approximately 50% within 10 years3; however, the risk of death varies among different families. This poor prognosis has been significantly improved by the use of pharmacological or surgical antiadrenergic therapy or both, which has reduced long-term mortality to <5%.3,4,6 The availability of effective therapy for this often lethal disease emphasizes the importance of early and accurate diagnosis. Unfortunately, there is frequently a delay in the diagnosis of LQTS, and patients with syncope are often misdiagnosed, most commonly as affected by a seizure disorder. In its most characteristic presentation, with obvious QT prolongation and stress-induced syncope, the diagnosis of LQTS is quite straightforward for physicians aware of the disease. In cases of borderline QT prolongation and/or absence of symptoms, however, a correct diagnosis may be more difficult. It was for this reason that a first set of diagnostic criteria (Table 1) was proposed in 1985.3 The major merit of that proposal was that it provided a logical and quantitative approach to the clinical diagnosis of LQTS by giving a different weight to major and minor criteria. Its major limitation was that it used the traditional, but untested for diagnostic purposes, cutoff value of QT, >440 msec '2. This also resulted in a rather black-and-white situation in which patients were judged to have an entirely normal or abnormal duration of ventricular repolarization on the basis of a difference of a few milliseconds in a measurement fraught with difficulties, such as interobserver variability.7

Genome-wide meta-analyses identify multiple loci associated with smoking behavior

Abstract: Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.