Hematopoietic lineage cell-specific protein 1 is recruited to the immunological synapse by IL-2-inducible T cell kinase and regulates phospholipase Cgamma1 Microcluster dynamics during T cell spreading.

Productive T cell activation requires efficient reorganization of the actin cytoskeleton. We showed previously that the actin-regulatory protein, hematopoietic lineage cell-specific protein 1 (HS1), is required for the stabilization of F-actin and Vav1 at the immunological synapse and for efficient calcium responses. The Tec family kinase IL-2-inducible T cell kinase (Itk) regulates similar aspects of T cell activation, suggesting that these proteins act in the same pathway.

Psychosocial adjustment of siblings of children with cancer: a systematic review.

Objectives: To promote a broader understanding of the psychosocial impact of childhood cancer on siblings, a systematic review was undertaken. Directions for future research are proposed and clinical strategies are suggested for addressing the needs of these children.

Methods: Searches of Medline, PsycINFO and CINAHL revealed 65 relevant qualitative, quantitative, or mixed methods' papers published between 1997 and 2008.

Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption.

To learn more about how the step of cholesterol uptake into the brush border membrane (BBM) of enterocytes influences overall cholesterol absorption, we measured cholesterol absorption 4 and 24 h after administration of an intragastric bolus of radioactive cholesterol in mice with scavenger receptor class B, type 1 (SR-BI) and/or cluster determinant 36 (CD36) deleted. The cholesterol absorption efficiency is unaltered by deletion of either one or both of the receptors. In vitro determinations of the cholesterol uptake specific activity of the BBM from the mice reveal that the scavenger receptors facilitate cholesterol uptake into the proximal BBM.

The efficacy of the Storz Miller 1 video laryngoscope in a simulated infant difficult intubation.

Background: Several studies have shown video laryngoscopy to be a useful technique in the management of patients in whom glottic exposure by direct laryngoscopy is difficult. We conducted this study as a preliminary investigation comparing the Storz DCI Miller 1 video laryngoscope (VL, Karl Storz GmbH, Tuttlingen, Germany) and direct laryngoscopy with a Miller 1 laryngoscope (DL) in an infant manikin model simulating difficult direct laryngoscopy. We hypothesized that compared with DL, VL would provide a better glottic view but would be associated with a longer time to intubation because of the different skill set required when using video intubation.

Venom factor V from the common brown snake escapes hemostatic regulation through procoagulant adaptations.

Venomous snakes produce an array of toxic compounds, including procoagulants to defend themselves and incapacitate prey. The Australian snake Pseudonaja textilis has a venom-derived prothrombin activator homologous to coagulation factors V (FV) and Xa (FXa). Here we show that the FV component (pt-FV) has unique biologic properties that subvert the normal regulatory restraints intended to restrict an unregulated procoagulant response.

Treatment with oseltamivir in children hospitalized with community-acquired, laboratory-confirmed influenza: review of five seasons and evaluation of an electronic reminder.

Background: When initiated within 48 hours of the onset of symptoms, oseltamivir has been shown to reduce severity and length of influenza illness. Few studies have evaluated the use of oseltamivir in patients hospitalized with influenza.

Objective: To describe the prescribing practices for oseltamivir in children hospitalized with influenza and to evaluate a mechanism to improve the rate of appropriate prescription.

Lower extremity neuromotor function and short-term ambulatory potential following in utero myelomeningocele surgery.

Objective: To evaluate lower extremity neuromotor function (LENF) and short-term ambulatory potential following fetal myelomeningocele (fMMC) closure.

Methods: Retrospective chart review of 54 children that underwent fMMC closure at our institution prior to the NIHCD-MOMS trial. Neonatal LENF was compared to predicted function based on spinal lesion level assigned by prenatal ultrasound.

SNP array mapping of chromosome 20p deletions: genotypes, phenotypes, and copy number variation.

The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients and five relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to: 1) more accurately determine the deletion sizes; 2) identify and compare breakpoints; 3) establish genotype/phenotype correlations; and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95 kb to 14.

Evaluation of ultrasound-guided radial artery cannulation in children.

Objective: To compare ultrasound (US)-guided radial artery cannulation with the traditional palpation technique.

Design: : Prospective randomized study.

Setting: Operating room in a tertiary care pediatric center.

Loss of INI1 expression defines a unique subset of pediatric undifferentiated soft tissue sarcomas.

Malignant rhabdoid tumor has traditionally been defined by its histologic phenotype. However, genetic investigations of malignant rhabdoid tumor have revealed a characteristic loss of or mutation in the INI1 gene on chromosome 22q. The occurrence and significance of soft tissue tumors meeting genetic criteria for malignant rhabdoid tumor but with an undifferentiated non-rhabdoid histology is poorly characterized.

Efficacy of addition of fentanyl to epidural bupivacaine on postoperative analgesia after thoracotomy for lung resection in infants.

Background: The authors evaluated the efficacy of adding fentanyl to epidural bupivacaine in infants up to 6 months of age after a thoracotomy in a prospective, randomized, double-blind study. The primary outcome was the total amount of rescue doses of intravenous nalbuphine in the first 24 h after surgery. Secondary outcomes included (1) time to first rescue dose of nalbuphine, (2) pain scores, and (3) behavior scores.

Prenatal course and postnatal management of peripheral bronchial atresia: association with congenital cystic adenomatoid malformation of the lung.

Objective: Peripheral bronchial atresia (PBA), a newly identified fetal lung lesion, is often asymptomatic and managed nonoperatively. However, recent studies suggest that bronchial atresia plays a role in the etiology of microcystic maldevelopment present in congenital cystic adenomatoid malformations (CCAM) which require resection to decrease the risk of infection, pneumothorax and malignant degeneration. The purpose of this study was to evaluate the prenatal radiographic and postnatal computed tomography (CT) scan/pathology findings with attention to the pathologic diagnosis of microcystic maldevelopment in infants with the presumptive diagnosis of PBA.

Risk factors for interstage death after stage 1 reconstruction of hypoplastic left heart syndrome and variants.

Objective: The risk of death during the interstage period remains high after stage 1 reconstruction for single ventricle lesions, despite improved surgical results. The purpose of this study is to identify risk factors for interstage death and to describe the events leading to interstage death.

Methods: A nested case-control study was conducted of 368 patients who underwent stage 1 reconstruction at a single center between January 1998 and April 2005.

Integrins put the brakes on microcluster dynamics at the immunological synapse.

Integrin engagement costimulates T cell receptor signaling, but the underlying mechanisms are poorly understood. In this issue of Immunity, Nguyen et al. (2008) show that engagement of VLA-4 promotes sustained signaling by altering the dynamics of actin filaments and signaling molecules at the immunological synapse.

Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance.

Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two related conditions of differing severity. BM is a relatively mild dominantly inherited disorder characterized by proximal weakness and distal joint contractures. UCMD was originally regarded as an exclusively autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity.

Neurodevelopmental outcomes after staged palliation for hypoplastic left heart syndrome.

Objective: The goal was to determine the relative effects of underlying genetic factors and current management strategies on neurodevelopmental disabilities among one-year old survivors of palliation for hypoplastic left heart syndrome.

Methods: Children who underwent staged reconstruction for hypoplastic left heart syndrome and variants were assessed at 1 year of age by using a neuromuscular examination and the Bayley Scales of Infant Development II, which provide the Mental Development Index and the Psychomotor Development Index. The effects of perioperative, operative, and genetic variables on developmental scores were evaluated.

Effects of continuity of care in infancy on receipt of lead, anemia, and tuberculosis screening.

Objectives: The goals were (1) to examine the influence of continuity of care on delivery of lead, anemia, and tuberculosis screening in a cohort of Medicaid-enrolled children, (2) to determine whether well-child care continuity had a greater effect than continuity for all ambulatory visits, and (3) to investigate which aspects of continuity were most associated with receipt of these screening services.

Methods: A prospective birth cohort of 1564 Medicaid-enrolled infants was studied. Continuity of care scores for the first 6 months of life were calculated for total ambulatory visits and well-child care visits.

In utero Repair of Myelomeningocele: Rationale, Initial Clinical Experience and a Randomized Controlled Prospective Clinical Trial.

Myelomeningocele (MMC), one of the most common congenital malformations, can result in severe lifelong disabilities, including paraplegia, hydrocephalus, Arnold-Chiari II malformation, incontinence, sexual dysfunction, skeletal deformations, and mental impairment. MMC was the first nonlethal anomaly to be treated by fetal surgery. Studies in animals provide compelling evidence that the primary cause of the neurological deficit associated with MMC is not simply incomplete neurulation but rather chronic mechanical injury and amniotic-fluid-induced chemical trauma that progressively damage the exposed neural tissue during gestation.

Evaluation of the VIA Blood Chemistry Monitor for Glucose in Healthy and Diabetic Volunteers.

Background: Manual methods of blood glucose monitoring are labor-intensive, costly, prone to error, and expose the caregiver to blood. The VIA(R) blood chemistry monitor for glucose can automatically measure plasma glucose (PG) every 5 minutes for 72 hours using blood sampled from a peripheral vein/artery or a central vein.

Methods: VIA performance was evaluated in eight normal and five type 1 diabetic (T1DM) subjects in 15 separate experiments.

Macrophage activation syndrome in rheumatic disease: what is the role of the antigen presenting cell?

Macrophage Activation Syndrome (MAS), alternatively referred to as secondary hemophagocytic lymphohistiocytosis (HLH), is a complication of many rheumatic diseases, most commonly Systemic Juvenile Idiopathic Arthritis (SJIA). MAS consists of a fulminant picture of pan-cytopenia, hectic high fevers, hepatosplenomegaly, lymphadenopathy, rash, and central nervous systemic inflammation. It can arise from genetic defects in the cytotoxic effector response of CD8+ T-cells, resulting in an inability to terminate antigen presentation, which in turn leads to uncontrolled immune activation.

An autosomal dominant genetically heterogeneous variant of rolandic epilepsy and speech disorder.

We report a three generation pedigree with 11 of 22 affected with a variant form of rolandic epilepsy, speech impairment, oromotor apraxia, and cognitive deficit. The core features comprised nocturnal rolandic seizures, interictal centrotemporal spike waves with early age of onset and late age of offset. The transmission of the phenotype was consistent with autosomal dominant inheritance, with variable expressivity but no evidence of anticipation.

The relationship between current intensity for nerve stimulation and success of peripheral nerve blocks performed in pediatric patients under general anesthesia.

Background: We evaluated the relationship between the lowest current amperage used to obtain a motor response, the success rate and the incidence of neurological complications with peripheral nerve blocks (PNB) in pediatric patients under general anesthesia.

Methods: We reviewed the regional anesthesia database at The Children's Hospital of Philadelphia and included all pediatric patients who received a single-injection PNB under general anesthesia with the aid of a peripheral nerve stimulator between October 2002 and July 2006. Data analyzed included age, sex, type of block, stimulation threshold, presence of sensory and motor blockade, and neurological complications.

Familial perinatal liver disease and fetal thrombotic vasculopathy.

The association between placental fetal thrombotic vasculopathy (FTV) and perinatal liver disease was not recognized until 2002, when Dahms and colleagues reported a series of 3 patients in whom severe liver disease developed in the first 2 days of life. All had abnormal liver histology and showed a variety of abnormalities, including Budd-Chiari syndrome, changes mimicking extrahepatic obstruction, lobular fibrosis, cholestasis, and hepatocyte giant cell transformation. We report recurrent significant perinatal liver disease in a family, associated with proven FTV in at least 1 pregnancy.