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Abdollahpour H Appaswamy G Kotlarz D Diestelhorst J Beier R Schäffer AA Gertz EM Schambach A Kreipe HH Pfeifer D Engelhardt KR Rezaei N Grimbacher B Lohrmann S Sherkat R Klein C 《Blood》2012,119(15):3450-3457
We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome. 相似文献
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Pérez Aisa A Nuevo J López Morante AA González Galilea A Martin de Argila C Aviñoa Arreal D Feu F Borda Celaya F Gisbert JP Pérez Roldan F Gonzalvo Sorribes JM Palazón Azorín JM Ponce Romero M Castro Fernández M Catalina Rodriguez MV Gallego Montañés S Calvet X Rodrigo Saez L Montoro Huguet M González Méndez Y Sierra Hernández A Sánchez Hernández E Dominguez Muñoz E Pérez Cuadrado E Muñoz M Lanas A 《Gastroenterologia y hepatologia》2012,35(7):468-475
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Augustin S González A Badia L Millán L Gelabert A Romero A Segarra A Martell M Esteban R Guardia J Genescà J 《Hepatology (Baltimore, Md.)》2012,56(2):706-714
Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. Conclusions: After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes. 相似文献
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Yedidya I Netzer A Vaduganathan M Solodky A Kornowski R Lev EI 《Journal of thrombosis and thrombolysis》2012,33(1):16-21
Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with
acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug
tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on
platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving
3 months of clopidogrel therapy (75 mg daily) were randomized to either of two discontinuation strategies: (1) Off group–abrupt
drug cessation or (2) Tapering group–receiving clopidogrel 75 mg every other day for 4 weeks duration. Light transmission
aggregometry, induced by ADP (5 and 10 μM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6 weeks
after randomization). In the off group, there was an early rise in platelet reactivity at 2 weeks after abrupt drug cessation
compared to baseline, as measured by ADP 5 μmol/l (39.6 ± 2.8 vs. 67.9 ± 6.0, P < 0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5 μmol/l at 2 weeks (P = 0.001) and 4 weeks (P = 0.001). Similar results were found with ADP 10 μmol/l and collagen agonists. Abrupt cessation of clopidogrel results in
an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration
every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating
clopidogrel tapering strategies and their potential clinical impact are warranted. 相似文献
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