Search

Background: There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42)., Methods/principal Findings: The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups., Conclusions/significance: As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS.

Objective: All cases of neonatal septicemia among neonates admitted to the neonatal unit in the pediatric department (CHUS) in Santiago de Compostela between 1992 and 1995 were studied. Our aims were: 1) To assess the incidence and microbial epidemiology. 2) To study the incidence of coagulase-negative staphylococci (CONS) sepsis stratified according to birth weight and gestational age. 3) To assess the incidence density of sepsis (IDS) and 4) To analyze the associated mortality., Patients and Methods: One hundred eighteen episodes of sepsis in 103 neonates which fulfilled clinical and laboratory criteria with positive blood cultures were included in this study. Between the years of 1992 and 1995 there were 318 neonates suspect of having sepsis among the 2,083 who were admitted to the unit during this period and which came from our own maternity department, as well as other centers., Results: In this period there were 10,457 live births in our maternity department. The annual incidence of sepsis was 6/1000 live births. Early onset sepsis was observed in 2.5/1000 live births (26 cases) and the occurrence of late onset increased to 3.5/1000 live births (36 cases). Neonatal sepsis was confirmed in 103 neonates (4.9%) corresponding to 118 episodes of sepsis. S. epidermidis was the most frequent agent isolated in blood cultures (38.1%). The highest incidence of sepsis caused by S. epidermidis was observed in neonates below 1500 g (12.1%) and less than 32 weeks gestational age (13.4%). The incidence was lower in those whose birth weights were more than 2500 g (1.9%) and > 37 weeks of gestational age (1.6%), p < 0.001. Overall mortality due to sepsis was 0.7% and increased to 5.0% among hospitalized newborns with birth weights below 1500 g. The average IDS stratified in three groups of birth weight and gestational age was 18 sepsis work-ups per 1000 patient-days of hospitalization, the lowest IDS 12.9/1000 was found in neonates whose birth weights were between 1501 g and 2500 g in comparison with neonates who weighted more than 2500 g (21.5/1000), p < 0.05, and very similar to the IDS found in the intermediate group of gestational age (13.1/1000)., Conclusions: S. epidermidis and other CONS are the main agents causing sepsis in hospitalized neonates, although there is a decreasing trend of incidence (-71.1%) between the years 1992 and 1995 (5.0% vs 1.5%). Gram-negative organisms and S. agalactiae played a minor role as agents causing sepsis even though S. agalactiae is the most important agent in early onset sepsis. Overall mortality associated with sepsis (7/1000 live births) is in or under the average range of international statistics. Indexes of IDS are more valuable as epidemiological tools in assessing septicemia than the simple attack rate because they have taken into consideration the length of stay, number of hospitalized newborns, as well as the number of positive sepsis work-ups in the calculating process.

We have studied the clinical usefulness of Flumazenil to reverse the sedative action of Midazolam in 12 children admitted in a Pediatric Intensive Care Unit. Two groups were established, one treated with individual dose and the other treated with continuous infusion. In four cases the indication of Flumazenil was the reversion of secondary effects and in 8 cases it was elective. The average reversion time was 1.22 +/- 0.42 minutes. Flumazenil is able to reverse immediately the effects of Midazolam.