Injuries to children who had preinjury cognitive impairment: a 10-year retrospective review

OBJECTIVE: To determine differences between hospitalized injured children who had preinjury cognitive impairments (IMPs) and children who had no preinjury cognitive conditions (NO). DESIGN: Comparative analysis, excluding fatalities, of patients with IMP (n = 371) with patients with NO (n = 58 745), aged from 0 to 19 years. MAIN OUTCOME MEASURES: Demographics, injury characteristics, injury nature and severity, use of resources, disability, and disposition at discharge from acute care. DATA SOURCE: Medical records of children injured between January 1, 1989, and December 31, 1998, submitted to the National Pediatric Trauma Registry, Boston, Mass. RESULTS: Compared with children with NO, children with IMPs were more likely to be boys (72.5% vs 64.3%), to be older (53.1% vs 40.0%, aged 10-19 years), to be victims of child abuse (5.9% vs 1.6%), and to be individuals with self-inflicted injuries (2.2% vs 0.1%). They were more likely to be injured as pedestrians (19.9% vs 13.8%), less likely to be injured in sport activities (2.7% vs 6.9%), and less likely to sustain a penetrating injury (3.8% vs 8.3%). They were more likely to sustain injuries to multiple body regions (57.4% vs 43.7%) and the head (62.0% vs 45.1%), and to be severely injured. They were more likely to be admitted to the intensive care unit (52.6% vs 25.2), and their mean length of stay was twice as long (9.9 vs 4.8 days). They were also more likely to develop impairments from the current injury (46.6% vs 41.0%) and more likely to be discharged to a rehabilitation facility (11.1% vs 2.3%). The IMPs became worse in 75 children. CONCLUSIONS: Preinjury cognitive impairments in a pediatric population had a significant effect on the causes, nature, severity of injury, and outcomes. Targeted prevention programs should consider the characteristics of this population.     

A minimal model for G protein-mediated synaptic facilitation and depression

G protein-coupled receptors are ubiquitous in neurons, as well as other cell types. Activation of receptors by hormones or neurotransmitters splits the G protein heterotrimer into Galpha and Gbetagamma subunits. It is now clear that Gbetagamma directly inhibits Ca2+ channels, putting them into a reluctant state. The effects of Gbetagamma depend on the specific beta and gamma subunits present, as well as the beta subunit isoform of the N-type Ca2+ channel. We describe a minimal mathematical model for the effects of G protein action on the dynamics of synaptic transmission. The model is calibrated by data obtained by transfecting G protein and Ca2+ channel subunits into tsA-201 cells. We demonstrate with numerical simulations that G protein action can provide a mechanism for either short-term synaptic facilitation or depression, depending on the manner in which G protein-coupled receptors are activated. The G protein action performs high-pass filtering of the presynaptic signal, with a filter cutoff that depends on the combination of G protein and Ca2+ channel subunits present. At stimulus frequencies above the cutoff, trains of single spikes are transmitted, while only doublets are transmitted at frequencies below the cutoff. Finally, we demonstrate that relief of G protein inhibition can contribute to paired-pulse facilitation.     

Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and "virtual Northern" hybridization

Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disease of early childhood with both myeloproliferative and myelodysplastic features. We had previously identified the genes for the alpha-chain of the nascent polypeptide-associated complex (NACA) and annexin II (ANX2) as potentially involved in the pathophysiology of JMML. Now we used SMART cDNA synthesis and subsequent "virtual Northern" blot to analyze differential expression of NACA and ANX2 genes in various hematologic cell lines and compared the data to those obtained by standard Northern analyses. The results show that SMART cDNA reproduces the expression profile found in mRNA. Dilution experiments showed that analyses using as little as 0.5 ng of total RNA led to reliable results. After validating the technique, we used virtual Northern blots to analyze expression of NACA and ANX2 in progenitor cultures of nine children with JMML and five healthy individuals. We found no consistent pattern of differential expression between patients and healthy donors. We conclude that aberrant regulation of NACA or ANX2 does not play a relevant role in JMML pathogenesis.     

Effects of ethnicity on treatment attendance,stimulant response/dose,and 14-month outcome in ADHD

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder--a randomized clinical trial of 579 children ages 7-9 years receiving 14 months of medication management, behavioral treatment, combination, or community care--the authors matched each African American and Latino participant with randomly selected Caucasian participants of same sex, treatment group, and site. Although Caucasian children were significantly less symptomatic than African American and Latino children on some ratings, response to treatment did not differ significantly by ethnicity after controlling for public assistance. Ethnic minority families cooperated with and benefited significantly from combination (multimodal) treatment (d = 0.36, compared with medication). This incremental gain withstood statistical control for mother's education, single-parent status, and public assistance. Treatment for lower socioeconomic status minority children, especially if comorbid, should combine medication and behavioral treatment.     

A comparison of clinical variables that predict adverse outcome in term infants with severe respiratory failure randomised to a policy of extracorporeal membrane oxygenation or to conventional neonatal intensive care

OBJECTIVE: To identify clinical variables predicting adverse outcome in a group of infants with severe respiratory failure who were randomized either to referral for extra-corporeal membrane oxygenation (ECMO) or to conventional neonatal intensive care within the United Kingdom. METHODS: Adverse outcome was defined by death or disability by four years of age. Receiver operator characteristic (ROC) plots were constructed for variables with continuous data and relative risk (RR) with 95% confidence intervals (CI) calculated for binominal data. RESULTS: Of variables measurable at trial entry, congenital diaphragmatic hernia and lower birthweight was also associated with increased mortality and morbidity. Seizures or supplementary oxygen at discharge were markers of disease course, which predicted a poorer outcome amongst survivors. These variables behaved similarly in the two trial groups. Those infants in the ECMO group with an episode of sepsis, established full sucking feeds after 14 days of age or a hospital stay over 30 days were at increased risk of disability. CONCLUSIONS: This study has identified clinical variables that predict adverse outcome for term infants with severe respiratory failure. The results may assist clinicians caring for these babies, when counseling their families and in the development of guidelines for neonatal ECMO.     

The group II metabotropic glutamate receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) and clozapine reverse phencyclidine-induced behaviors in monoamine-depleted rats

Recent studies have indicated that the selective group II metabotropic glutamate (mGlu) receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) shares common biochemical and pharmacological effects with the atypical antipsychotic clozapine. The present study aimed to further investigate these similarities (or differences) in monoamine-depleted animals by using the phencyclidine (PCP) model. Animals were pretreated 24 h before PCP administration with (i.p.) vehicle, alpha-methyl-DL-p-tyrosine methyl ester (alpha-MPT; 400 mg/kg), or DL-p-chlorophenyl-alanine methyl ester (PCPA; 300 mg/kg) injections. alpha-MPT and PCPA pretreatment significantly and selectively reduced catecholamine (dopamine and norepinepherine) or 5-hydroxytryptamine (5-HT, serotonin) and 5-hydroxyindoleacetic acid levels, respectively, in whole brain tissue. Both LY379268 and clozapine (s.c.) blocked PCP-evoked ambulatory activity and fine movements in control, alpha-MPT-, and PCPA-treated animals. In contrast, the typical antipsychotic haloperidol (s.c.) attenuated PCP behaviors in control and PCPA-pretreated animals, but was without effect in subjects pretreated with alpha-MPT. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate-selective antagonist (3S,4aR,6R,8aR)-6-[2-(1(2)OH-tetrazole-6-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY293558) attenuated locomotor activity in alpha-MPT-treated animals only, whereas the 5-HT(2A/2C)-selective antagonist ketanserin was effective at reducing ambulations and fine movements in control and alpha-MPT-treated animals. Taken together, these data indicate an important role for glutamatergic and serotonergic mechanisms for PCP-evoked behaviors in catecholamine-depleted animals and suggest that like clozapine, LY379268 is more effective than typical antipsychotics in these models. This study further supports the potential use of group II mGlu agonists as novel therapeutic agents in the treatment of schizophrenia.