Gene expression profile analysis in human T lymphocytes from patients with Down Syndrome.

Down Syndrome (DS) is caused by the presence of three copies of the whole human chromosome 21 (HC21) or of a HC21 restricted region; the phenotype is likely to have originated from the altered expression of genes in the HC21. We apply the cDNA microarray method to the study of gene expression in human T lymphocytes with trisomy 21 in comparison to normal cells. Two patients with DS were investigated, along with two normal subjects as a control, all being tested in independent, duplicated cell culture experiments. The most consistent finding was the overexpression of the superoxide dismutase gene (SOD1), located on 21q, and of MHC DR beta 3 (HLA-DRB3), GABA receptor A gamma 2 (GABRG2), acetyltransferase Coenzyme, A 2 (ACAT2) and ras suppressor protein 1 (RSU1) genes. When the data were clustered according to chromosome localization, the HC21 gene set showed, on average, the highest expression in DS cells in all the experiments. Moreover, separate clustering of patients and controls was obtained when analysis was restricted to HC21 gene expression values. These findings reinforce the specific gene dosage theory for the pathogenesis of the DS phenotype, and show a consistent overexpression of the SOD1 gene on 21q.

Ropivacaine-clonidine combination for caudal blockade in children.

BACKGROUND: Adding clonidine to weak ropivacaine solutions (<0.2%) could potentially enhance analgesia as well as further reduce the risk for unwanted motor blockade. The aim of the present study was to compare the postoperative pain-relieving quality of a ropivacaine 0.1%-clonidine mixture to that of plain ropivacaine 0.2% following caudal administration in children. METHODS: In a prospective, observer-blinded fashion, 40 ASA 1 paediatric patients undergoing subumbilical surgery were randomly allocated to receive a caudal injection of either plain ropivacaine 0.2% (1 ml/kg) (R0.2) or a mixture of ropivacaine 0.1% with clonidine 2 microg/kg (1 ml/kg) (R0.1C). Objective pain scale score and need for supplemental analgesia were used to evaluate analgesia during the first 24 h postoperatively. Residual postoperative sedation was also assessed. RESULTS: A significantly higher number of patients in the R0.1C group (18/20) could be managed without supplemental analgesia during the first 24 h postoperatively compared to the R0.2 group (11/20) (P=0.034). Both the degree and the duration of postoperative sedation was similar in both groups. No signs of postoperative motor blockade were observed. CONCLUSIONS: The combination of clonidine (2 microg/kg) and ropivacaine 0.1% is associated with an improved quality of postoperative analgesia compared to plain 0.2% ropivacaine. The improved analgesic quality of the clonidine-ropivacaine mixture is achieved without causing any significant degree of postoperative sedation.