The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On ...two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CV of less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10 6 Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.
Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and ...not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk.
The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for association between disease status and individual common variants, screened for rare variants exclusive to either affected or unaffected subjects, and tested the combined association of variants across gene loci. Pathway analysis was performed and disease-related expression patterns were assessed. Marginal association with BPD was observed for numerous common and rare variants. We identified 345 genes with variants unique to BPD-affected preterm subjects, and 292 genes with variants unique to our unaffected preterm subjects. Of these unique variants, 28 (19 in the affected cohort and 9 in unaffected cohort) replicate a prior WES study of BPD-associated variants. Pathway analysis of sets of variants, informed by disease-related gene expression, implicated protein kinase A, MAPK and Neuregulin/epidermal growth factor receptor signaling.
We identified novel genes and associated pathways that may play an important role in susceptibility/resilience for the development of lung disease in preterm infants.
The World Health Organization has implemented an international program of antibiotic resistance survey, called WHONET, with the participation of 121 laboratories from 41 countries around the world. ...Argentina joined WHONET program in 1989. Five hospitals from Buenos Aires are taking part, under the coordination of the National Institute of Microbiology ‘Dr. C. Malbran’. From the results obtained between 1991 and 1994, the low level of susceptibility to aminopenicillins, cephalosporins and aminoglycosides is remarkable. On the other hand, vancomycin-resistant
Enterococcus spp. and
Staphylococcus spp. have not been detected and imipenem resistance in
Pseudomonas aeruginosa, and
Acinetobacter spp. isolates has not overcome 7% and 11%, respectively. Analytical programs utilizing these data aid in the understanding of the epidemiology of antibiotic resistance and in the development of rational antibiotic prescription practices and infection control procedures.
A 10% soybean oil emulsion (Intralipid 10%), used extensively in Europe for intravenous alimentation, has now been clinically evaluated in the United States. Controlled studies have shown that the ...soybean oil emulsion can be substituted for glucose to supply one-third to two-thirds of the total calories, and can be administered peripherally without significant vein irritation. Essential fatty acid deficiencies, frequently encountered in patients dependent on parenteral alimentation with fat-free solutions, are prevented and corrected by use of this preparation. Data on long-term tolerance to Intralipid 10% infusions are presented for 292 patients treated for more than 6,000 patient days. The soybean oil emulsion was usually well tolerated. Side effects were reported in two of 133 adults and 12 of 159 pediatric patients.