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.

Wohlfahrtseinrichtungen für Israeliten in Frankfurt a. M. : gewidmet der am 7. u. 8. Juli 1902 in Frankfurt a. M. ... Generalversammlung des Rabbiner-Verbandes in Deutschland

von A. Freimann

Die rumänischen Juden unter dem Fürsten und König Karl

von Julius Plotke

Jüdische Charaktere bei Grillparzer, Hebbel und Otto Ludwig : litterar. Studien

von S. Lublinski

Einladung zur Akademischen Feier des Geburtsfestes seiner Majestät des Königs Karl von Württemberg auf den 6. März 1881

Tübingen, Univ., Universitätsprogramm, 1881

Ludwig Philippson : eine Biographie

von M. Kayserling

Ludwig Philippson : 18. Dez. 1811 - 28. Dez. 1911 ; Vortrag

geh. ... von I[smar] Elbogen

Ludwig Philippson : sein Leben u. sein Werk ; ein Buch f. jung u. alt

von Jos. Feiner

Studien zum althebräischen Buchwesen und zur biblischen Litteraturgeschichte

von Ludwig Blau

Jubelklänge : zur allerhöchsten Vermählungsfeier Seiner Majestät Ludwig des Zweiten König von Bayern mit Ihrer kgl. Hoheit der Prinzessin Sofie Charlotte Auguste Herzogin von Bayern

Text u. Musik von Maximilian G. Loewenstamm

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease.

BACKGROUND Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER NCT02164604 ; Date of registration: 13.06.2014.