Boston Children's Hospital

About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.

Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents.

Abstract: Objective. Lead is a confirmed neurotoxicant, but the lowest blood lead concentration associated with deficits in cognitive functioning anc academic achievement is poorly definec. The purpose of the present study was to examine the relationship of relatively low blood lead concentrations-especially concentrations <10 micrograms per deciliter (μg/dL) with performance on tests of cognitive function ng in a representative sample of US children and adolescents, Methods. The authors used data from the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994, to assess the relationship between blood lead concentration and performance on tests of arithmetic skills, reading skil s. nonverbal reasoning, and short-term memory among 4,853 children ages 6-16 years. Results. The geometric mean blood lead concentration for child en in the study sample was 1.9 μg/dL: 172 (2.1%) had blood lead concentrations ≥10 μg/dL. After adjustment for gender, race/ethn city, poverty, region of the country, parent or caregiver's educational level, parent or caregiver's marital status parent, serum ferritin level, and serum cotinine leve, the data showed an inverse relationship between blood lead concentration and scores on four measures of cognitive functioning. For every! μg/dL increase in blooc lead concentration, there was a 0.7-point decrement in mean arithmetic scores, an approximately I-point decrement n mean reading scores, a 0.1-point decrement in mean scores on a measure of nonverbal reasoring, and a 0.5-point decrement in mean scores on a measure of short-term memory, An inverse relationship between blood lead concentration and arithmetic and reading scores was observed for children with blood lead concentrations lower than 5.0 μg/dL Conclusion. Deficits n cognitive and academic skills associated with lead exposure occur at blood lead concentrations lower than 5 μg/dL.

Epidemiology and Natural History of Acute Patellar Dislocation

Abstract: BackgroundThe goals of this study were to (1) define the epidemiology of acute patellar dislocation, (2) determine the risk of subsequent patellar instability episodes (subluxation and/or redislocation) during the study period, and (3) identify risk factors for subsequent instability episodes.Study DesignProspective cohort study.MethodsThe authors prospectively followed 189 patients for a period of 2 to 5 years. Historical data, injury mechanisms, and physical and radiographic measurements were recorded to identify potential risk factors for poor outcomes.ResultsRisk was highest among females 10 to 17 years old. Patients presenting with a prior history of instability were more likely to be female (P < .05) and were older than first-time dislocation patients (P < .05). Fewer first-time dislocators (17%) had episodes of instability during follow-up than patients with a previous history of instability (49%) (P < .01). After adjusting for demographics, patients with a prior history had 7 times higher odds of ...

Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using 'real-time' quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) - a Europe against cancer program

Abstract: Real-time quantitative RT-PCR (RQ-PCR) is a sensitive tool to monitor minimal residual disease (MRD) in leukemic patients through the amplification of a fusion gene (FG) transcript. In order to correct variations in RNA quality and quantity and to calculate the sensitivity of each measurement, a control gene (CG) transcript should be amplified in parallel to the FG transcript. To identify suitable CGs, a study group within the Europe Against Cancer (EAC) program initially focused on 14 potential CGs using a standardized RQ-PCR protocol. Based on the absence of pseudogenes and the level and stability of the CG expression, three genes were finally selected: Abelson (ABL), beta-2-microglobulin (B2M), and beta-glucuronidase (GUS). A multicenter prospective study on normal (n=126) and diagnostic leukemic (n=184) samples processed the same day has established reference values for the CG expression. A multicenter retrospective study on over 250 acute and chronic leukemia samples obtained at diagnosis and with an identified FG transcript confirmed that the three CGs had a stable expression in the different types of samples. However, only ABL gene transcript expression did not differ significantly between normal and leukemic samples at diagnosis. We therefore propose to use the ABL gene as CG for RQ-PCR-based diagnosis and MRD detection in leukemic patients. Overall, these data are not only eligible for quantification of fusion gene transcripts, but also for the quantification of aberrantly expressed genes.

Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome.

Abstract: Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.