38 research outputs found
PCN114 DEVELOPING A FAMILIAL CANCER RISK ASSESSMENT TOOL FOR USE IN UNDERSERVED COMMUNITIES
Renal relapse in antineutrophil cytoplasmic autoantibody-associated vasculitis: unpredictable, but predictive of renal outcome
Objectives. To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis.Methods. Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate.Results. The number of patients participating was 535; mean serum creatinine (+/- S.D.) at entry was 341 +/- 321 mu mol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing >= 1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found.Conclusion. In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome.Pathophysiology and treatment of rheumatic disease
Antioxidant Systems in Tumour Cells: The Levels of Antioxidant Enzymes, Ferritin, and Total Iron in a Human Hepatoma Cell Line
Hydraulic efficiency and safety of branch xylem increases with height in Sequoia sempervirens (D. Don) crowns
Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.
Telomere maintenance 2 (TELO2), Tel2 interacting protein 2 (TTI2), and Tel2 interacting protein 1 (TTI1) are the three components of the conserved Triple T (TTT) complex that modulates activity of phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including mTOR, ATM, and ATR, by regulating the assembly of mTOR complex 1 (mTORC1). The TTT complex is essential for the expression, maturation, and stability of ATM and ATR in response to DNA damage. TELO2- and TTI2-related bi-allelic autosomal-recessive (AR) encephalopathies have been described in individuals with moderate to severe intellectual disability (ID), short stature, postnatal microcephaly, and a movement disorder (in the case of variants within TELO2). We present clinical, genomic, and functional data from 11 individuals in 9 unrelated families with bi-allelic variants in TTI1. All present with ID, and most with microcephaly, short stature, and a movement disorder. Functional studies performed in HEK293T cell lines and fibroblasts and lymphoblastoid cells derived from 4 unrelated individuals showed impairment of the TTT complex and of mTOR pathway activity which is improved by treatment with Rapamycin. Our data delineate a TTI1-related neurodevelopmental disorder and expand the group of disorders related to the TTT complex