Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Effect of HECNU in malignant supratentorial gliomas - a phase II study

Forty adults with recurring brain gliomas were treated with HECNU 130 mg/m2, given i v. every 5 to 6 weeks (mean 5.4) and corticosteroids. According to the response to treatment, patients were divided in 3 groups: 1. Group 1 included 8 pts (20%) with objective remission, defined as a clear-cut clinical improvement persisting at least 4 weeks after the complete discontinuation of corticosteroids. 2. Group 2 included 14 patients (35%) who improved or remained stable yet stayed corticosteroid-dependent. 3. The 18 patients (45%) of group 3 failed to respond. There was a fair correlation between clinical and radiological response. Thus sequential CT scans showed a 50 to 100% tumour reduction in all patients of group 1, and in 5 of group 2. CT-scans remained unchanged in 8 patients of group 2 and in one of group 3, and showed tumour progression in 10 patients of group 3. Drug toxicity appeared mild, reversible and was not cumulative. The better tolerence of HECNU could represent a real advantage of this drug over the commonly used nitrosourea derivatives such as BCNU and CCNU. © 1988 Kluwer Academic Publishers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The contribution of automatic anatomical matching of sequential brain MRI scans in the monitoring of multiple sclerosis lesions

in FrenchInternational audienceINTRODUCTION: Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. The exact contribution of brain MRI remains a subject of debate, but it is generally considered to provide a more specific and more sensitive outcome measure for monitoring purposes and for testing new therapies. The choice of MRI techniques, and measurement reproducibility for multiple sclerosis brain lesions are not defined with precision for routine practice. There are many sources of error when comparing successive images which can be overcome to some extent with repositioning and image processing techniques. METHODS: We evaluated the impact of image repositioning on treatment decision-making for twelve relapsing remitting patients. Brain MRIs were performed every three months for a one-year period. Two neurologists interpreted the non-repositioned and repositioned images giving their analysis of changes in the lesions visualized on the T2 sequences and their therapeutic decisions. RESULTS: For the first neurologist, analysis of the non-repositioned images yielded six patients whose lesions had worsened while for the repositioned images there were only three. For the second neurologist, four patients had more lesions with the non-repositioned images and only three with repositioning. The subjective interpretations were the same for the two neurologists when they used repositioned images. CONCLUSIONS: Comparison by two neurologists of non-repositioned and repositioned MRI, with no other image processing, affected the analysis and in certain cases propositions for treatment

SPM Analysis Applied to MIBI-SPECT for the Diagnosis of Recurrent Oligodendrogliomas

European Journal of Nuclear Medecine 27(8):1144International audienceno abstrac