RESUMO
PURPOSE: To identify the relationship between specific genes and phenotypic features of Williams syndrome. METHODS: Subjects were selected based on their deletion status determined by fluorescence in situ hybridization using a panel of 24 BACs and cosmids spanning the region commonly deleted and single gene analysis using Southern blotting. From the cohort of subjects, three had atypical deletions. Physical examinations and cognitive tests were administered to the three subjects and the results were compared to those from a cohort of typical WS subjects. RESULTS: The molecular results indicate smaller deletions for each subject. In all three cases, typical Williams facies were absent and visual spatial abilities were above that of full deletion WS subjects, particularly in the qualitative aspects of visual spatial processing. CONCLUSIONS: Combining the molecular analysis with the cognitive results suggest that the genes GTF2IRD1 and GTF2I contribute to deficits on visual spatial functioning.
Assuntos
Cromossomos Humanos Par 7 , Proteínas Musculares/genética , Proteínas Nucleares/genética , Transativadores/genética , Fatores de Transcrição TFII/genética , Síndrome de Williams/diagnóstico , Síndrome de Williams/genética , Adolescente , Adulto , Criança , Mapeamento Cromossômico , Estudos de Coortes , Cosmídeos , Feminino , Deleção de Genes , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Testes de Inteligência , Modelos Genéticos , Fenótipo , Mapeamento Físico do Cromossomo , Síndrome de Williams/patologiaRESUMO
Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.
