Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment.

BackgroundLeigh syndrome is an early onset, progressive, neurodegenerative disorder with developmental and motor skills regression. Characteristic magnetic resonance imaging abnormalities consist of focal bilateral lesions in the basal ganglia and/or the brainstem. The main cause is a deficiency in oxidative phosphorylation due to mutations in an mtDNA or nuclear oxidative phosphorylation gene.Methods and resultsA consanguineous Moroccan family with Leigh syndrome comprise 11 children, three of which are affected. Marker analysis revealed a homozygous region of 11.5 Mb on chromosome 20, containing 111 genes. Eight possible mitochondrial candidate genes were sequenced. Patients were homozygous for an unclassified variant (p.P193L) in the cardiolipin synthase gene (CRLS1). As this variant was present in 20% of a Moroccan control population and enzyme activity was only reduced to 50%, this could not explain the rare clinical phenotype in our family. Patients were also homozygous for an amino acid substitution (p.L159F) in C20orf7, a new complex I assembly factor. Parents were heterozygous and unaffected sibs heterozygous or homozygous wild type. The mutation affects the predicted S-adenosylmethionine (SAM) dependent methyltransferase domain of C20orf7, possibly involved in methylation of NDUFB3 during the assembly process. Blue native gel electrophoresis showed an altered complex I assembly with only 30–40% of mature complex I present in patients and 70–90% in carriers.ConclusionsA new cause of Leigh syndrome can be a defect in early complex I assembly due to C20orf7 mutations.

Chronic kidney disease (CKD) is associated with a sharp increase in the risk for cardiovascular disease, which can only be partially explained by known classical risk factors. However, there is a well-established association with increased systemic inflammation. In the last decade, an unique cytotoxic CD4(+) T cell population has been identified, which can be recognized by the loss of the costimulatory cell surface marker CD28, hence their name CD4(+)CD28null T cells. These cells are highly proinflammatory, have the functional features of professional killer lymphocytes and can expand from less than 1% to over 50% of the total CD4(+) T cell population. In this review, we show that these cells probably play an important role in destabilizing atherosclerotic plaques and could explain, at least in part, the association of cardiovascular disease with an increased inflammatory milieu in CKD patients.

Tacrolimus is a critical dose drug and to avoid under-and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug-related toxicity occur despite whole-blood tacrolimus pre-dose concentrations ([Tac] blood) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac] cells) may better correlate with drug-efficacy. The aim of this study was to (1) investigate the relationship between [Tac] blood and [Tac] cells , (2) identify factors affecting the tacrolimus distribution in cells and whole-blood, and (3) study the relationship between [Tac] cells and clinical outcomes after kidney transplantation. Methods: A total of 175 renal transplant recipients were prospectively followed. [Tac] blood and [Tac] cells were determined at Months 3, 6 and 12 post-transplantation. Patients were genotyped for ABCB1 1199G>A and 3435C>T, CYP3A4 15389C>T, and CYP3A5 6986G>A. Data on rejection and tacrolimus-related nephrotoxicity and post-transplant diabetes mellitus were collected. Results: Correlations between [Tac] blood and [Tac] cells were moderate to poor