Children's Memorial Hospital

About: Children's Memorial Hospital is a based out in . It is known for research contribution in the topics: Population & Transplantation. The organization has 5652 authors who have published 8967 publications receiving 283837 citations.

Prevalence of Low Birth Weight among Hispanic Infants with United States-born and Foreign-born Mothers: The Effect of Urban Poverty

Abstract: Although Hispanics are a poorly educated and medically underserved minority, the incidence of low birth weight (less than 2,500 g) Hispanic infants is similar to that of non-Hispanic whites. The authors used 1982-1983 Illinois vital records and 1980 US census income data to determine the contribution of maternal nativity and place of residence to this epidemiologic paradox. The proportion of low birth weight Hispanic (n = 22,892) infants ranged from 4.3% for Mexicans to 9.1% for Puerto Ricans. Maternal age, education, trimester of prenatal care initiation, and place of residence were associated with the prevalence of low birth weight infants among Puerto Rican but not foreign-born Mexican or Central-South American mothers. In very low-income (less than $10,000/year) census tracts, Mexican and other Hispanic infants with US-born mothers had low birth weight rates of 14 and 15%, respectively. In contrast, Mexican and other Hispanic infants with foreign-born mothers who resided in these areas had low birth weight rates of 3 and 7%, respectively. In a logistic model that included only impoverished infants, the adjusted odds ratio of low birth weight for those with US-born mothers equalled 6.3 (95 percent confidence interval 2.3-16.9). The authors conclude that urban poverty is negatively associated with Hispanic birth weight only when the mother is Puerto Rican or a US-born member of another subgroup.

Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development

Abstract: Denys-Drash syndrome is a rare human developmental disorder affecting the urogenital system and leading to renal failure, intersex disorders and Wilms' tumour. In this report, four individuals with this syndrome are described carrying germline point mutations in the Wilms' tumour suppressor gene, WT1. Three of these mutations were in the zinc finger domains of WT1. The fourth occurred within intron 9, preventing splicing at one of the alternatively chosen splice donor sites of exon 9 when assayed in vitro. These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development.

Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study

Abstract: Purpose: To investigate the safety, dose-limiting toxicities, and pharmacokinetics of the smoothened inhibitor vismodegib in children with refractory or relapsed medulloblastoma. Experimental design: Initially, vismodegib was administered daily at 85 mg/m 2 and escalated to 170 mg/m 2 . The study was then revised to investigate a flat-dosing schedule of 150 mg for patients with small body surface area (BSA, 0.67–1.32 m 2 ) or 300 mg for those who were larger (BSA, 1.33–2.20 m 2 ). Pharmacokinetics were performed during the first course of therapy, and the right knees of all patients were imaged to monitor bone toxicity. Immunohistochemical analysis was done to identify patients with Sonic Hedgehog (SHH)-subtype medulloblastoma. Results: Thirteen eligible patients were enrolled in the initial study: 6 received 85 mg/m 2 vismodegib, and 7 received 170 mg/m 2 . Twenty eligible patients were enrolled in the flat-dosing part of the study: 10 at each dosage level. Three dose-limiting toxicities were observed, but no drug-related bone toxicity was documented. The median (range) vismodegib penetration in the cerebrospinal fluid (CSF) was 0.53 (0.26–0.78), when expressed as a ratio of the concentration of vismodegib in the CSF to that of the unbound drug in plasma. Antitumor activity was seen in 1 of 3 patients with SHH-subtype disease whose tumors were evaluable, and in none of the patients in the other subgroups. Conclusions: Vismodegib was well tolerated in children with recurrent or refractory medulloblastoma; only two dose-limiting toxicities were observed with flat dosing. The recommended phase II study dose is 150 or 300 mg, depending on the patient9s BSA. Clin Cancer Res; 19(22); 6305–12. ©2013 AACR .

Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system.

Abstract: HIV-1 infection of the brain results in chronic inflammation, contributing to the neuropathogenesis of HIV-1 associated neurologic disease. HIV-1-infected mononuclear phagocytes (MP) present in inflammatory infiltrates produce neurotoxins that mediate inflammation, dysfunction, and neuronal apoptosis. Neurologic disease is correlated with the relative number of MP in and around inflammatory infiltrates and not viral burden. It is unclear whether these cells also play a neuroprotective role. We show that the chemokine, fractalkine (FKN), is markedly up-regulated in neurons and neuropil in brain tissue from pediatric patients with HIV-1 encephalitis (HIVE) compared with those without HIVE, or that were HIV-1 seronegative. FKN receptors are expressed on both neurons and microglia in patients with HIVE. These receptors are localized to cytoplasmic structures which are characterized by a vesicular appearance in neurons which may be in cell-to-cell contact with MPs. FKN colocalizes with glutamate in these neurons. Similar findings are observed in brain tissue from an adult patient with HIVE. FKN is able to potently induce the migration of primary human monocytes across an endothelial cell/primary human fetal astrocyte trans-well bilayer, and is neuroprotective to cultured neurons when coadministered with either the HIV-1 neurotoxin platelet activating factor (PAF) or the regulatory HIV-1 gene product Tat. Thus focal inflammation in brain tissue with HIVE may up-regulate neuronal FKN levels, which in turn may be a neuroimmune modulator recruiting peripheral macrophages into the brain, and in a paracrine fashion protecting glutamatergic neurons.