Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ, for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined.

Causal Evaluation of Acute Recurrent and Chronic Pancreatitis in Children: Consensus From the INSPPIRE Group.

Objectives: Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) have been diagnosed in children at increasing rates during the past decade. As pediatric ARP and CP are still relatively rare conditions, little quality evidence is available on which to base the diagnosis and determination of etiology. The aim of the study was to review the current state of the literature regarding the etiology of these disorders and to developed a consensus among a panel of clinically active specialists caring for children with these disorders to help guide the diagnostic evaluation and identify areas most in need of future research.

Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a severe, typically early onset form of cystic disease that primarily involves the kidneys and biliary tract. Phenotypic expression and age at presentation can be quite variable. The incidence of ARPKD is 1 in 20,000 live births, and its pleotropic manifestations are potentially life-threatening.

Treatment of hepatoblastoma with high-dose chemotherapy and stem cell rescue: the pediatric blood and marrow transplant consortium experience and review of the literature.

Background: Children with high-risk or relapsed hepatoblastoma continue to represent treatment challenges. Multiple case reports have documented the use of high-dose chemotherapy with stem cell rescue (HDC) for this population; however, the efficacy and appropriate use of HDC remains unclear.

Procedure: A literature search was performed to identify cases of hepatoblastoma that were treated with HDC.

Report of the CCFA pediatric bone, growth and muscle health workshop, New York City, November 11-12, 2011, with updates.

Growth retardation, delayed puberty, decreased bone mass, altered bone architecture, hypovitaminosis D and skeletal muscle mass deficits are common in children with inflammatory bowel diseases. The Crohn's and Colitis Foundation of America sponsored a multidisciplinary workshop on the subject of Bone and Skeletal Growth in Pediatric IBD, held in New York City in November 2011. The topic of the workshop was a key recommendation of the Foundation's Pediatric Challenges meeting in 2005.

Shoulder arthroscopy in children and adolescents.

Arthroscopy is increasingly being used to manage a wide range of pathologies in the pediatric population. Knee arthroscopy is an efficacious treatment method for skeletally immature patients, and an increasing number of shoulder conditions can be managed with minimally invasive techniques. Special considerations are needed with regard to anatomy, anesthetic technique, equipment, and patient positioning when performing shoulder arthroscopy in a child or an adolescent.

Expression of estrogen receptor alpha and beta is decreased in hypospadias.

Purpose: Estrogenic endocrine disruptors acting via estrogen receptors α and β have been implicated in the etiology of hypospadias. However, the expression and distribution of estrogen receptors α and β in normal and hypospadiac human foreskins is unknown. We characterized the location and expression of estrogen receptors α and β in normal and hypospadiac foreskins.

New insights on the morphology of adult mouse penis.

The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships.

Morphology of the external genitalia of the adult male and female mice as an endpoint of sex differentiation.

Adult external genitalia (ExG) are the endpoints of normal sex differentiation. Detailed morphometric analysis and comparison of adult mouse ExG has revealed 10 homologous features distinguishing the penis and clitoris that define masculine vs. feminine sex differentiation.

Morphology of mouse external genitalia: implications for a role of estrogen in sexual dimorphism of the mouse genital tubercle.

Purpose: We examined the role of androgens and estrogens in mammalian sexual differentiation by morphological characterization of adult wt and mutant mouse external genitalia. We tested the hypothesis that external genitalia development depends on androgen and estrogen action.

Materials And Methods: We studied serial sections of the external genitalia of the CD-1 and C57BL6 wt strains of adult mice (Charles River Laboratories, Wilmington, Massachusetts).

Safety of the live, attenuated varicella vaccine in pediatric recipients of hematopoietic SCTs.

VZV is an important cause of morbidity and mortality among patients after hematopoietic SCT (HSCT). There is controversy surrounding the use of the live attenuated varicella vaccine (LAVV) in this population due to concerns that the immunization may cause VZ-related disease. The Blood and Marrow Transplant (BMT) group at the University of California, San Francisco (UCSF) Children's Hospital has been recommending the LAVV for immunocompetent HSCT patients since 1995.

Chronic high Epstein-Barr viral load carriage in pediatric small bowel transplant recipients.

The development of EBV infection and PTLD is normally associated with a high EBV load in peripheral blood. Often, children undergoing primary or reactivation of EBV infection subsequent to ITx will have chronically elevated EBV loads. To better understand this phenomenon and its consequences, we retrospectively reviewed the records of children who underwent ITx (either isolated or part of multivisceral transplantation) at our center from 1992 to 2007, to identify chronic high EBV load carriers in this population.

Gender identity in disorders of sex development: review article.

Objectives: Many concerns have been raised regarding the treatment and long-term outcome of infants born with complex genital anomalies. Debate among clinicians, psychologists, ethicists, and patient advocate groups regarding the optimal management of these individuals is ongoing. Although determining the most appropriate gender is a difficult task, this review will help clarify some of the issues at hand.

A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity.

ZAP-70 is critical for T cell receptor (TCR) signaling. Tyrosine to phenylalanine mutations of Y315 and Y319 in ZAP-70 suggest these residues function to recruit downstream effector molecules, but mutagenesis and crystallization studies reveal that these residues also play an important role in autoinhibition ZAP-70. To address the importance of the scaffolding function, we generated a zap70 mutant mouse (YYAA mouse) with Y315 and Y319 both mutated to alanines.

Characterization of regulatory T cells in urban newborns.

Background: In the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers.

Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery.

Children undergoing congenital heart surgery are at risk for prolonged mechanical ventilation and length of hospital stay. We investigated the prognostic value of pulmonary dead space fraction as a non-invasive, physiologic marker in this population. In a prospective, cross-sectional study, we measured pulmonary dead space fraction in 52 intubated, pediatric patients within 24 hr postoperative from congenital heart surgery.

A non-leaky Artemis-deficient mouse that accurately models the human severe combined immune deficiency phenotype, including resistance to hematopoietic stem cell transplantation.

Two Artemis-deficient (mArt(-/-)) mouse models, generated independently on 129/SvJ backgrounds, have the expected T(-)B(-)NK(+) severe combined immune deficiency (SCID) phenotype but fail to mimic the human disease because of CD4(+) T cell leakiness. Moreover, immune reconstitution after hematopoietic stem cell transplantation is achieved more readily in these leaky mouse models than in Artemis-deficient humans. To develop a more clinically relevant animal model, we backcrossed the mArt(-/-) mutation onto the C57Bl/6 (B6) background (99.

Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976: follow-up of a Children's Oncology Group cohort.

Background: The growing number of individuals surviving childhood cancer has increased the awareness of adverse long-term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs).

Methods: The authors describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors who were treated on legacy Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005.

Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation.

To determine whether T cell engraftment and recovery of B cell immunity could be improved, we prospectively treated 15 children with severe combined immunodeficiency disease (SCID) with megadoses of haplocompatible CD34(+) cells and a fixed number of CD3(+) cells without previous myeloablative chemotherapy. Evidence of T cell engraftment was seen in 73% of patients (95% confidence interval [CI] = 48%-90%). Engraftment was more likely in patients with X-linked SCID and in those with evidence of maternal engraftment at the time of diagnosis.

A novel missense RAG-1 mutation results in T-B-NK+ SCID in Athabascan-speaking Dine Indians from the Canadian Northwest Territories.

DNA double-strand repair factors in the non-homologous end joining (NHEJ) pathway resolve DNA double-strand breaks introduced by the recombination-activating gene (RAG) proteins during V(D)J recombination of T and B lymphocyte receptor genes. Defective NHEJ and subsequent failure of V(D)J recombination leads to severe combined immunodeficiency disease (SCID). We originally linked T(-)B(-)NK(+) SCID in Athabascan-speaking Native Americans in the Southwestern US and Northwest Territories of Canada to chromosome 10.

Neonatal mitral and tricuspid valve repair for in utero papillary muscle rupture.

Background: Papillary muscle rupture in the fetus and neonate is a rare event that leads to severe mitral or tricuspid insufficiency and is associated with high perinatal mortality. We undertook surgical repair of this lesion in the neonatal period and report on our midterm results.

Methods: Three neonates with tricuspid insufficiency and 1 infant with mitral insufficiency, all due to papillary muscle or chordal rupture, underwent surgical repair with artificial chordal replacement and a modification of the de Vega annuloplasty technique that allowed external adjustment of the annulus size under transesophageal echocardiographic guidance after separation from cardiopulmonary bypass.

Pulmonary valve cusp augmentation with autologous pericardium may improve early outcome for tetralogy of Fallot.

Objectives: The transannular patch used to relieve right ventricular outflow tract obstruction in children with tetralogy of Fallot may result in pulmonary insufficiency. We hypothesized that pulmonary valve cusp augmentation with pericardium would decrease pulmonary insufficiency and improve the early outcome for transatrial-transpulmonary tetralogy of Fallot repair requiring transannular patch.

Methods: Since November 2001, 41 patients with tetralogy of Fallot and 2 patients with isolated pulmonary valve stenosis had relief of right ventricular outflow tract obstruction with either a transannular patch plus pulmonary valve cusp augmentation (n = 18) or a transannular patch alone (n = 25).

Prone positioning can be safely performed in critically ill infants and children.

Objective: To describe the effects of prone positioning on airway management, mechanical ventilation, enteral nutrition, pain and sedation management, and staff utilization in infants and children with acute lung injury.

Design: Secondary analysis of data collected in a multiple-center, randomized, controlled clinical trial of supine vs. prone positioning.