Premature infants are at risk for bilirubin-associated brain damage. In cell cultures bilirubin causes neuronal apoptosis and necrosis. Ibuprofen is used to close the ductus arteriosus, and is often given when hyperbilirubinemia is at its maximum. Ibuprofen is known to interfere with bilirubin-albumin binding. We hypothesized that bilirubin toxicity to cultured rat embryonic cortical neurons is augmented by coincubation with ibuprofen. Incubation with ibuprofen above a concentration of 125 g/mL reduced cell viability, measured by methylthiazole tetrazolium reduction, to 68% of controls (p Ͻ 0.05). Lactate dehydrogenase (LDH) release increased from 29 to 38% (p Ͻ 0.01). The vehicle solution did not affect cell viability. Coincubation with 10 M unconjugated bilirubin (UCB)/human serum albumin in a molar ratio of 3:1 and 250 g/mL ibuprofen caused additional loss of cell viability and increased LDH release (p Ͻ 0.01), DNA fragmentation, and activated caspase-3. Preincubation with the pan-caspase inhibitor z-val-alaasp-fluoromethyl ketone abolished ibuprofen-and UCB-induced DNA fragmentation. The study demonstrates that bilirubin in low concentration of 10 M reduces neuron viability and ibuprofen increases this effect. Apoptosis is the underlying cell death mechanism. (Pediatr Res 65: 392-396, 2009)
Background Group B streptococcus (GBS) is the leading cause of early-onset infections (EOI) in the developed world. Few data are available in Europe about incidence and clinical findings of neonatal disease. We reviewed cases occurred in the last 2 years in Emilia-Romagna (an area with about 4 500 000 million people).Methods Neonatal, pediatric departments and laboratories fulfilled a chart for any case of disease observed during 2003 and 2004. GBS was recovered in blood or cerebrospinal fluid (CSF). Prenatal screening, risk factors, intrapartum chemoprophylaxis (IAP) and clinical findings were analysed.Results: We observed 21 EOI and 13 late onset (LOI). Incidence was 0.56 and 0.38/1.000 live birth in 2003 and 2004 respectively. Mortality was 12,5% (1 EOI and 3 LOI). Among 21 EOI, 7 were bacteraemia, 12 sepsis and 2 meningitis. CSF was not collected in 8/14 symptomatic infants. Six mothers were vaginally colonized; 13/21 were negative and 2 unscreened; 5/21 had one or more risk factors. Only 2 (suspected chorioamnionitis) received a complete IAP, while 19/21 were untreated. Among 13 LOI, 3/13 mothers were colonized and 5/13 had 1 or more risk factors. LOI were: 5 sepsis, 7 meningitis and 1 focal infection. CSF was not collected in 5/13.Conclusion: Incidence of GBS infection was similar to that currently reported in US. Most EOI (90.5%) had no prophylaxis. Risk factors were detected in 23.8 % of EOI (GBS bacteriuria was not routinely screened). Meningitis was diagnosed in 33.3 % symptomatic infants, but CSF analysis was not performed in 48.1% cases. More efforts are needed to improve prophylaxis strategies. PEDIATRIC INTERVENTIONAL CATHETERIZATION: DEVELOPMENT OF A RISK ADJUSTMENT MODEL FOR PREVENTABLE COMPLICATIONS CHILDREN'S HOSPITAL (USA)Background: Development of a risk adjustment method is necessary to account for complexity of case mix in pediatric cardiac catheterization procedures so valid comparisons of outcomes can be determined.Methods: Using a prospective database, we identified patient and procedural characteristics predictive of preventable serious or somewhat serious complications. Creation of 2 diagnosis groups and 5 procedural risk groups allowed classification according to the complexity of the diagnosis and anticipated relative risk of the procedure. Hemodynamic vulnerability was determined by baseline characteristics. Significant variables that increased the area under the receiver operator characteristic (ROC) curve were chosen for the final model. Expected complication rates and standardized complication ratios (SCR) were then determined for individual practitioners.Results: Of 791 procedures, 26 (3.3%) had possibly or definitely preventable, serious or somewhat serious events. Event rates tended to increase as procedural risk category increased (0.5% in 1, 4.4% in 2, 4.2% in 3, 11.1% in 4, 8.0% in 5, p Ͻ0.001). Higher event rates were observed in younger patients (11.4% age Ͻ 1 month vs 2.9% 3 1 month, pϽ0.001) and those with physiologic vulnerability (4.7% vs 2.1%, pϭ0.04). These 3 factor...
Background: Fungal Colonization (FC), mostly by Candida spp., and subsequent invasive fungal infection are increasingly frequent features in preterm neonates in NICUs, and several risk factors have been found associated to them. The objective of this study was to evaluate the role of Early-Onset Neutropenia (EON) in the development of FC in preterm very low birth weight (VLBW) neonates in NICU.Methods:Medical records of all Ͻ1500 g birth weight neonates admitted to our 3rd level Facility between 1997 and 2003 and survived more than 1 week were reviewed. Neonates with baseline fungal colonization were excluded, thus final number of considered neonates was nϭ424. For all neonates we recorded: a) the presence of neutropenia in the first week of life (EON), diagnosed with Manroe (J Pediatr 1979) and Mouzinho (Pediatrics 1994) reference values (nϭ52, 12.2%); b) the presence of FC (at least one site), the number and the type of sites colonized during the first month of life. In 25 on 52 neutropenic infants, a 3-days course of Filgrastim (10 mg/kg/die) was performed during the 1st week of life with normalization of the neutrophil count always before the 8th day of life. In neutropenic not treated neonates neutrophil count became spontaneously normal before the beginning of 3rd week of life. Statistical analysis was performed by Chi-square, ANOVA and T-test using SPSS 8.0 for Windows.Results: Statistical analysis did not show significant differences between neutropenic and not neutropenic neonates as for mean gestational age and birth weight, sex, race, outcome and presence of the most common risk factors associated with FC. Incidence of FC in the 2nd, 3rd and 4th week of life was significantly higher in neutropenic (nϭ32/52, 61.5%) than in not neutropenic patients (nϭ134/372, 36%) (Chi-square 14.288, OR 0.32; pϽ0.001). Intensity (as number of different sites affected) and severity (as number of risk sites affected) of FC were as well higher in the neutropenic patients (pϽ0.002 and pϽ0.001 respectively). Treatment with Filgrastim did not change the relative risk for colonization: FC was present in 60% of neutropenic treated neonates and 64% of not treated (pϽ0.28, NS).Conclusion: EON in VLBW neonates significantly influences the rate of colonization by fungal spp. in the first month of life, causing a higher risk that cannot be corrected by filgrastim therapy. VLBW neonates with EON should be carefully monitored for fungal colonization during their stay in NICU, and should undergo prophylactic measures to prevent it. M Marcinkowski, C Buehrer, M Toennessen, B Gerstner, A Gratopp, M Obladen Charité-Campus Virchow-Klinikum, Otto-Heubner-Center for Pediatric and Adolescent Medicine , Department of Neonatology, Berlin, Germany Background: Apoptosis is an endogenous cell suicide mechanism triggered in response to biological factors and genotoxic stimuli often resulting from oxidative stress. Neuronal apoptosis especially in the developing brain may cause long-term brain dysfunction. Cognitve deficits in the later childhoo...
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