RESUMO
Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. NBS for the proximal UCDs involves the detection in NBS spots of low citrulline values, a finding which is often overlooked because it is considered to be inadequate. We retrospectively analyzed NBS blood spots from known UCD patients comparing the utility of the Region 4 Stork (R4S) interpretive tools to conventional cutoff based interpretation. This study shows the utility of R4S tools in detecting all UCDs, and provides evidence to support the nomination to add proximal UCDs to the recommended uniform screening panel.
Assuntos
Citrulina/sangue , Teste em Amostras de Sangue Seco/métodos , Triagem Neonatal/normas , Guias de Prática Clínica como Assunto/normas , Distúrbios Congênitos do Ciclo da Ureia/sangue , Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Feminino , Humanos , Recém-Nascido , Masculino , Projetos Piloto , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The replication initiation pattern of the murine beta-globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine beta-globin locus were detected in a region extending from the embryonic Ey gene to the adult betaminor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5' hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion.
Assuntos
Replicação do DNA , Globinas/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Diferenciação Celular , Linhagem Celular , DNA/genética , Regulação da Expressão Gênica , Humanos , Camundongos , Fase S , Deleção de SequênciaRESUMO
OBJECTIVES: South Africa has among the highest levels of HIV prevalence in the world. Our objectives are to describe the distribution of South African infant and child mortality by age at fine resolution, to identify any trends over recent time and to examine these trends for HIV-associated and non HIV-associated causes of mortality. METHODS: A retrospective review of vital registration data was conducted. All registered postneonatal deaths under 1 year of age in South Africa for the period 1997-2002 were analysed by age in months using a generalized linear model with a log link and Poisson family. RESULTS: Postneonatal mortality increased each year over the period 1997-2002. A peak in HIV-related deaths was observed, centred at 2-3 months of age, rising monotonically over time. CONCLUSION: We interpret the peak in mortality at 2-3 months as an indicator for paediatric AIDS in a South African population with high HIV prevalence and where other causes of death are not sufficiently high to mask HIV effects. Intrauterine and intrapartum infection may contribute to this peak. It is potentially a useful surveillance tool, not requiring an exact cause of death. The findings also illustrate the need for early treatment of mother and child in settings with very high HIV prevalence.