RESUMO
The human phenotype with primarily impaired myelination is represented by hypomyelinating leukodystrophies. The most frequent form is Pelizaeus-Merzbacher disease, which is due to alterations in the PLP1 gene encoding the major myelin protein. Another form, Pelizaeus-Merzbacher-like disease, is partly associated with mutations in the GJA12 gene encoding gap junction protein alpha 12, but seems to be heterogeneous. Olig1 and Olig2 are transcription factors in oligodendrocyte development. We postulated that disturbed oligodendroglial maturation could be associated with primary hypomyelination in humans and analyzed the coding sequence of OLIG1 and OLIG2 in 13 patients from 12 unrelated families which were thoroughly characterized with regard to phenotype and magnetic resonance imaging results. From our findings we conclude that mutations in OLIG1 and OLIG2 are not likely to be associated with this subgroup of hypomyelinating disorders.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas do Tecido Nervoso/genética , Doença de Pelizaeus-Merzbacher/genética , Fenótipo , Família , Ligação Genética , Humanos , Lactente , Proteínas de Membrana/genética , Mutação , Proteína Proteolipídica de Mielina/genética , Fator de Transcrição 2 de OligodendrócitosRESUMO
OBJECTIVE: Ventilation strategies for preterm neonates may influence the severity of pulmonary dysfunction and later development of chronic lung disease. The objective of this report is to compare the effects of high-frequency oscillatory ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV) from the points of views of biochemical and functional variables. DESIGN: Randomized controlled trial. SETTING: Third level NICU. PATIENTS AND PARTICIPANTS: Forty preterm neonates with a gestational age of 24-29 weeks were randomly assigned to one of the two above-mentioned ventilation strategies within 30 min from birth. MEASUREMENTS AND RESULTS: At 1, 3, 5, and 7 days, the babies were monitored by means of ventilator indices, pulmonary function, and eight pro-inflammatory or anti-inflammatory cytokines measured in bronchoalveolar lavage fluid. The neonates assigned to the HFOV procedure benefited from early and sustained improvement in pulmonary mechanics and gas exchange-significantly higher dynamic respiratory compliance values, significantly lower expiratory airway resistance and oxygenation index values-with earlier extubation as compared to the neonates assigned to sIMV treatment, and showed significantly lower transforming growth factor-beta1 concentrations in bronchoalveolar lavage fluid. CONCLUSIONS: The results of this randomized clinical trial support the hypothesis that early and exclusive use of HFOV, combined with optimum volume strategy, has a beneficial effect during the acute phase of lung injury.
