Co-occurrence of non-mosaic trisomy 22 and inherited balanced t(4;6)(q33;q23.3) in a liveborn female: case report and review of the literature.

Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non-mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non-mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non-mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non-mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed.

Neonatal resuscitation science, education, and practice: the role of the Neonatal Resuscitation Program.

For almost 25 years, the Neonatal Resuscitation Program of the American Academy of Pediatrics has provided educational tools that are used in the United States and throughout the world to teach neonatal resuscitation. Over that time period, the guidelines for resuscitation have been increasingly evidence-based and a formal system has been established to determine which steps should be updated on the basis of available information. The most recent update occurred in 2010. This article describes the evidence review process and the specific evidence that lead to a number of significant changes in practice that were included in the 2010 guidelines.

A systematic review of retention of adult advanced life support knowledge and skills in healthcare providers.

OBJECTIVE: Advanced life support (ALS) guidelines are widely adopted for healthcare provider training with recommendations for retraining every two years or longer. This systematic review studies the retention of adult ALS knowledge and skills following completion of an ALS course in healthcare providers. METHODS: We retrieved original articles using Medline, CINAHL, Cochrane Library, and PubMed, and reviewed reference citations to identify additional studies. We extracted data from included articles using a structured approach and organized outcomes by evaluation method, and knowledge and skills retention. RESULTS: Among 336 articles retrieved, 11 papers were included. Most studies used multiple-choice questionnaires to evaluate knowledge retention and cardiac arrest simulation or other skills tests to evaluate skills retention. All studies reported variable rates of knowledge or skills deterioration over time, from 6 weeks to 2 years after training. Two studies noted retention of knowledge at 18 months and up to 2 years, and one reported skills retention at 3 months. Clinical experience, either prior to or after the courses, has a positive impact on retention of knowledge and skills. CONCLUSION: There is a lack of large well-designed studies examining the retention of adult ALS knowledge and skills in healthcare providers. The available evidence suggests that ALS knowledge and skills decay by 6 months to 1 year after training and that skills decay faster than knowledge. Additional studies are needed to help provide evidence-based recommendations for assessment of current knowledge and skills and need for refresher training to maximize maintenance of ALS competency.

Glucose management during and after intensive delivery room resuscitation.

Hypoxic-ischemic encephalopathy remains a major cause of morbidity and mortality in preterm and full-term infants. Experimental data from animal studies suggest that interventions that improve survival of injured neurons and prevent delayed neuronal loss may decrease hypoxic ischemic brain injury. Considerable attention has focused on optimizing management of newborns in the period immediately after resuscitation from perinatal asphyxia to minimize delayed neuronal death. The evidence regarding the role of glucose in modifying post-asphyxia brain injury and resuscitation was reviewed to better define optimal glucose management after perinatal asphyxia and resuscitation.

Increased mitochondrial reactive oxygen species production in newborn brain during hypoglycemia.

Hypoglycemia is associated with gray and white matter injury in immature brain, but the specific mechanisms responsible for hypoglycemic brain injury remain poorly defined. We postulated that mitochondrial electron transport chain function is altered during hypoglycemia due to the decreased availability of reducing equivalents, and that altered activity of the electron transport chain would increase mitochondrial production of free radicals and lead to mitochondrial oxidant injury. The present study tests the hypothesis that production of reactive oxygen species (ROS) by cerebral mitochondria is increased during acute hypoglycemia. Studies were performed in an awake, chronically catheterized newborn piglet model. Hypoglycemia (blood glucose 1 mmol/L for 2 h) was induced using a bolus of intravenous lispro insulin, 25 U/kg. Superoxide and hydrogen peroxide production by mitochondria isolated from cerebral cortex of normoglycemic and hypoglycemic newborn piglets was measured using lucigenin- and luminol-derived chemiluminescence. After 2 h of hypoglycemia, superoxide generation was 60% higher and hydrogen peroxide generation was two-fold higher in mitochondria from hypoglycemia animals than in controls (p < 0.005). These data confirm that the ability of the mitochondria to produce ROS is increased after hypoglycemia in immature brain, and are, to our knowledge, the first evidence that ROS may play a role in brain injury due to neonatal hypoglycemia. Increased mitochondrial ROS production could result in alterations in brain structure and function due to oxidant injury to mitochondrial proteins and DNA or changes in oxidant-sensitive signal transduction pathways in brain.

Alterations in cerebral mitochondria during acute hypoglycemia.

To test the hypothesis that acute hypoglycemia leads to free radical induced alterations in cerebral mitochondria, newborn piglets were subjected to 2 h of insulin-induced hypoglycemia (blood glucose 1 mmol/l). The effects of free radicals were determined in cerebral cortical synaptosomes, mitochondria, and neuronal nuclei by measuring membrane lipid peroxidation. Fragmentation of nuclear and mitochondrial DNA was also examined. Lipid peroxidation was significantly increased in hypoglycemic mitochondrial membranes as compared to controls, but no increase in peroxidation in hypoglycemic synaptosomal or nuclear membranes was observed. An increase in low molecular weight DNA fragments was observed only in mitochondrial DNA from hypoglycemic piglets. We speculate that alteration of cerebral mitochondria due to increased free radical production is one of the early events in the pathogenesis of hypoglycemic brain injury.

Modification of glutamate binding sites in newborn brain during hypoglycemia.

We have shown that acute insulin-induced hypoglycemia leads to specific changes in the cerebral NMDA receptor-associated ion channel in the newborn piglet. The present study tests the hypothesis that exposure to acute hypoglycemia in the newborn will alter the glutamate binding site of both NMDA and kainate receptors. Studies were performed in 3-6 days-old piglets randomized to control (n=6) or hypoglycemic (n=6) groups. Hypoglycemia was maintained for 120 min using insulin infusion. Saturation binding assays were performed in cerebral cell membranes using (3)H-glutamate or (3)H-kainate to determine the characteristics of the glutamate binding sites of the NMDA and kainate receptors, respectively. The concentration of glucose in cerebral cortex was 10-fold less in hypoglycemic piglets than in controls (P<0.05). Brain ATP was not significantly decreased during hypoglycemia, but phosphocreatine decreased from control of 6.6 +/- 1.3 micromoles/g brain to 3.2 +/- 1.9 micromoles/g brain in hypoglycemic piglets. The B(max) for NMDA-displaceable (3)H-glutamate binding was 992 +/- 64 fmol/mg protein in hypoglycemic animals, significantly higher than the control value of 746 +/- 42 fmol/mg protein. However, the dissociation constant for glutamate was unchanged during hypoglycemia. The (3)H-kainate binding studies demonstrated no change in B(max) of high-affinity kainate receptors during hypoglycemia. In contrast, the affinity of the kainate receptor glutamate binding site significantly increased compared to control. Thus, acute hypoglycemia in the newborn piglet had specific effects on the glutamate binding sites of the NMDA and kainate receptors that could be due to alterations in cell membrane lipids or modification of receptor proteins.