Utility of bronchodilator response for asthma diagnosis in Latino preschoolers

BACKGROUND: Asthma diagnosis in preschoolers is mostly based on clinical evidence, but a bronchodilator response could be used to help confirm the diagnosis. The objective of this study is to evaluate the utility of bronchodilator response for asthma diagnosis in preschoolers by using spirometry standardised for this specific age group. METHODS: A standardised spirometry was performed before and after 200 mcg of salbutamol in 64 asthmatics and 32 healthy control preschoolers in a case-control design study. RESULTS: The mean age of the population was 4.1 years (3-5.9 years) and 60% were females. Almost 95% of asthmatics and controls could perform an acceptable spirometry, but more asthmatics than controls reached forced expiratory volume in one second (FEV1) (57% vs. 23%, p = 0.033), independent of age. Basal flows and FEV1 were significantly lower in asthmatics than in controls, but no difference was found between groups in forced vital capacity (FVC) and FEV in 0.5 s (FEV0.5). Using receiver operating characteristic (ROC) curves, the variable with higher power to discriminate asthmatics from healthy controls was a bronchodilator response (% of change from basal above the coefficient of repeatability) of 25% in forced expiratory flow between 25% and 75% (FEF25-75) with 41% sensitivity, 80% specificity. The higher positive likelihood ratio for asthma equalled three for a bronchodilator response of 11% in FEV0.5 (sensitivity 30%, specificity 90%). CONCLUSIONS: In this sample of Chilean preschoolers, spirometry had a very high performance and bronchodilator response was very specific but had low sensitivity to confirm asthma diagnosis

No disponible

Utility of bronchodilator response for asthma diagnosis in Latino preschoolers.

BACKGROUND: Asthma diagnosis in preschoolers is mostly based on clinical evidence, but a bronchodilator response could be used to help confirm the diagnosis. The objective of this study is to evaluate the utility of bronchodilator response for asthma diagnosis in preschoolers by using spirometry standardised for this specific age group. METHODS: A standardised spirometry was performed before and after 200 mcg of salbutamol in 64 asthmatics and 32 healthy control preschoolers in a case-control design study. RESULTS: The mean age of the population was 4.1 years (3-5.9 years) and 60% were females. Almost 95% of asthmatics and controls could perform an acceptable spirometry, but more asthmatics than controls reached forced expiratory volume in one second (FEV1) (57% vs. 23%, p=0.033), independent of age. Basal flows and FEV1 were significantly lower in asthmatics than in controls, but no difference was found between groups in forced vital capacity (FVC) and FEV in 0.5s (FEV0.5). Using receiver operating characteristic (ROC) curves, the variable with higher power to discriminate asthmatics from healthy controls was a bronchodilator response (% of change from basal above the coefficient of repeatability) of 25% in forced expiratory flow between 25% and 75% (FEF25₋75) with 41% sensitivity, 80% specificity. The higher positive likelihood ratio for asthma equalled three for a bronchodilator response of 11% in FEV0.5 (sensitivity 30%, specificity 90%). CONCLUSIONS: In this sample of Chilean preschoolers, spirometry had a very high performance and bronchodilator response was very specific but had low sensitivity to confirm asthma diagnosis.

The transcription factor Sox10 is a key regulator of peripheral glial development.

The molecular mechanisms that determine glial cell fate in the vertebrate nervous system have not been elucidated. Peripheral glial cells differentiate from pluripotent neural crest cells. We show here that the transcription factor Sox10 is a key regulator in differentiation of peripheral glial cells. In mice that carry a spontaneous or a targeted mutation of Sox10, neuronal cells form in dorsal root ganglia, but Schwann cells or satellite cells are not generated. At later developmental stages, this lack of peripheral glial cells results in a severe degeneration of sensory and motor neurons. Moreover, we show that Sox10 controls expression of ErbB3 in neural crest cells. ErbB3 encodes a Neuregulin receptor, and down-regulation of ErbB3 accounts for many changes in development of neural crest cells observed in Sox10 mutant mice. Sox10 also has functions not mediated by ErbB3, for instance in the melanocyte lineage. Phenotypes observed in heterozygous mice that carry a targeted Sox10 null allele reproduce those observed in heterozygous Sox10(Dom) mice. Haploinsufficiency of Sox10 can thus cause pigmentation and megacolon defects, which are also observed in Sox10(Dom)/+ mice and in patients with Waardenburg-Hirschsprung disease caused by heterozygous SOX10 mutations.

The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences.

Sox10 is an important transcriptional regulator in the neural crest and various neural-crest derived lineages, such as the Schwann cells of the peripheral nervous system. Recently, we identified the gene for myelin Protein zero (P(0)) as a transcriptional target of Sox10 in Schwann cells, allowing for the first time a detailed analysis of Sox10 responsive elements and their functional interaction with Sox10. Here we show that Sox10 functions through two different types of DNA response elements, one that allows binding of monomers, and a second that favors cooperative binding of two molecules. This dimeric binding required the presence of two heptameric Sox binding sites in a specific orientation and spacing, and was mediated by an N-terminal region of Sox10 with high conservation in the related Sox9, which also exhibited dimeric binding. This argues that the conserved region has the capacity to function as a DNA-dependent dimerization domain. The interaction between Sox10 dimers and DNA differed dramatically from that of Sox10 monomers, as it drastically reduced the protein's off-rate and increased the protein-induced angle of DNA bending. These results indicate that functionally relevant interactions between Sox10 and DNA occur through completely different modes of binding.

Protein zero gene expression is regulated by the glial transcription factor Sox10.

Myelinating glia express high levels of a unique set of genes which code for structural proteins of the myelin sheath. Few transcription factors have so far been implicated in the regulation of any myelin gene. Here we show that the protein zero (P(0)) gene, a myelin gene exclusively expressed in the Schwann cell lineage of the peripheral nervous system, is controlled in its expression by the high-mobility-group domain protein Sox10 both in tissue culture and in vivo. Induction of wild-type Sox10, but not of other transcription factors or Sox10 mutants, strongly increased endogenous P(0) expression in tissue culture. This activation was mediated by the P(0) promoter, which was stimulated by Sox10 in transient transfections. Detailed analyses revealed the involvement of a proximal and a distal promoter region. The distal region functioned only in conjunction with the proximal one and contained a single Sox consensus binding site, which accounted for most of its activity. In contrast, the proximal region mediated Sox10 responsiveness on its own. It contained multiple binding sites for Sox proteins, with two high-affinity sites being the most significant. P(0) expression also depended on Sox10 in vivo, as evident from the analysis of Schwann cell precursors in mouse embryos with Sox10 mutation at day 12.5 of embryogenesis. To our knowledge this is the most conclusive link to date between a glial transcription factor and cell-specific activation of myelin gene expression.

Complicaciones quirúrgicas del transplante renal / Surgical complications of renal transplant

Se presentan las complicaciones quirúrgicas de 172 transplantes renales efectuados por el equipo quirúrgico del Servicio de Urología del Hospital G. Fricke de Viña del Mar, la mayor parte en el propio Servicio. Encontramos 32 complicaciones (18 por ciento) en total. En 9 casos se perdió el injerto (5,2 por ciento), presentando 3 óbitos atribuibles a la cirugía (1.74 por ciento). 2 pacientes mueren a raíz de un linfocele infectado y uno por sepsis urinaria tardía. Se analizan las causas y oportunidades en que se presentaron las complicaciones, comprobando que la mayoría aparecen en los primeros casos de cirugía del transplante