Acute chest syndrome in children with sickle cell disease. A retrospective analysis of 100 hospitalized cases

We reviewed the clinical features of 100 cases of the sickle cell chest syndrome in 57 pediatric patients hospitalized with radiographic findings of pulmonary or pleural disease. Pulmonary infiltration was more common in the lower lobes (86%) than in the upper (25%) or middle lobes (22%). Pleural effusions were present in 38% of cases. Chest syndrome was recognized on presentation in 79% of cases, but was recognized only later in 21% of patients admitted for other indications. Patients recognized initially were more often febrile on admission (68%) than were subsequently recognized patients (33%) (p less than 0.01), but fever eventually occurred in 99 of 100 cases. Pain was an antecedent or coincident problem in 67% of cases. Median hospital stay was 7 days in those 58 cases in which narcotics were given, but only 4 days in those 42 cases in which narcotics were not administered (p less than 0.001). Polyvalent pneumococcal vaccine had been administered to 44 of our 57 patients at some time before their hospitalizations, and 18 patients had been on oral penicillin prophylaxis. Blood was cultured in 93 cases and in only two instances grew Streptococcus pneumoniae. Serologic evidence of Hemophilus influenzae type b infection was found in two additional patients. We conclude that the sickle cell chest syndrome is an acute febrile pulmonary disease frequently associated with pain and/or narcotic analgesic therapy but infrequently associated with proven bacterial infection.     

Social status and the comorbidity of child depression and conduct disorder

This study examined the overlap between child depression and conduct disorder (D&CD) as a function of peer social status (i.e., popular, rejected, neglected, controversial, average) in a sample of 1,464 nonreferred 4th graders. Both D&CD were measured by self-report, peer nomination, and teacher ratings. Social status was assessed by peer nomination. A strong correlation (.73) was found between D&CD, even after accounting for shared method variance by confirmatory factor analysis. Furthermore, the number of Ss who scored high on both D&CD was greater than would be expected by chance alone. Multivariate tests revealed that rejected Ss scored higher than average Ss on measures of D&CD. Controversial boys also scored higher on measures of CD. However, analyses also revealed that the association between depression and rejected social status might be due to a subgroup of depressed children who also manifested symptoms of CD. Implications for assessment and treatment of child disorders are discussed.     

Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression

Neuroblastoma is a heterogeneous neoplasm that has served as a paradigm for the clinical utility of somatically acquired genomic aberrations. DNA copy number alterations (CNA) are currently used to predict prognosis, including MYCN amplification and deletions at chromosome bands 1p36 and 11q23. We predicted that genome-wide assessment of DNA aberrations in neuroblastoma tumors would provide a more precise estimation of clinical phenotype, and could be used to predict outcome. We measured CNAs in a representative set of 82 diagnostic tumors on a customized high-resolution BAC array-based CGH platform supplemented with additional clones across 1p36, 2p24, 3p21-22, 11q14-24, and 16p12-13, and integrated these data with RNA expression data. We used an unbiased statistical method to define a set of minimal common regions (MCRs) of aberration. Unsupervised hierarchical clustering identified four distinct genomic subclasses. First, a subset of tumors with a clinically benign phenotype showed predominantly whole chromosome gains and losses. Second, tumors with MYCN amplification had a unique genomic signature of 1p deletion and 17q gain, but few other rearrangements. Third, tumors with an aggressive clinical phenotype without MYCN amplification, showed multiple structural rearrangements. Most notable were deletions of 3p, 4p, and 11q and gain of 1q, 2p, 12q, and 17q. Lastly, there was a subset of tumors with an aggressive clinical phenotype and no detectable DNA CNAs. The genomic subsets were highly correlated with patient outcome, and individual MCRs remained prognostic in a multivariable model. DNA signature patterns embed important prognostic information in diagnostic neuroblastoma samples, and can identify candidate cancer-related genes.     

Validation of a Sulfuric Acid Digestion Method for Inductively Coupled Plasma Mass Spectrometry Quantification of TiO<Subscript>2</Subscript> Nanoparticles

A consistent analytical method incorporating sulfuric acid (H₂SO₄) digestion and ICP-MS quantification has been developed for TiO₂ quantification in biotic and abiotic environmentally relevant matrices. Sample digestion in H₂SO₄ at 110°C provided consistent results without using hydrofluoric acid or microwave digestion. Analysis of seven replicate samples for four matrices on each of 3 days produced Ti recoveries of 97%?±?2.5%, 91?% ±?4.0%, 94%?±?1.8%, and 73?% ±?2.6% (mean?±?standard deviation) from water, fish tissue, periphyton, and sediment, respectively. The method demonstrated consistent performance in analysis of water collected over a 1 month.     

High-performance liquid chromatography separation of aminopterin-polyglutamates within red blood cells of children treated for acute lymphoblastic leukemia

Aminopterin (AMT), like the related compound methotrexate (MTX), is a drug with anticancer and antiinflammatory efficacy that works by interfering with synthetic reactions dependent on the vitamin folic acid. Red blood cell (RBC) precursors will accumulate antifolates like AMT and MTX through the same mechanism by which they take up folate. Intracellular folate and antifolates are then metabolized to polyglutamates that remain within the mature RBCs. RBC MTX has been correlated with toxicity and/or treatment efficacy among patients with acute lymphoblastic leukemia (ALL) or rheumatoid arthritis. Because AMT may offer clinically relevant advantages over MTX, we are testing whether it can be administered safely in multiagent therapy to children with ALL. Total RBC AMT was measured to monitor compliance with this oral, outpatient regimen, and to estimate AMT exposure to the bone marrow. Here we describe methods for quantifying each AMT-polyglutamate species within the RBCs of patients. The assay was linear over a concentration range of 62.5-500 nmol/L. Recovery of individual AMT-polyglutamates ranged from 85% to 92%, and the intraday coefficients of variation were 1.3% to 3.6%. Long-chain AMT-polyglutamates (triglutamate and tetraglutamate forms) accounted for over 40% of intracellular AMT within the RBCs of patients. Patients with long-chain AMT polyglutamate concentrations above the median tended to have lower mean neutrophil counts during weekly AMT therapy, which suggests that RBC AMT polyglutamate accumulation may correlate with hematologic toxicity. As AMT continues to be tested in clinical trials, the methods described here will be useful to define relationships between clinical response to AMT and RBC accumulation of AMT-polyglutamates.     

Ultrasound effect on osteoblast precursor cells in trabecular calcium phosphate scaffolds

This study investigated the in vitro effect of low-intensity pulsed ultrasound (LIPUS) on human embryonic palatal mesenchyme cells (HEPM, CRL-1486, ATCC, Manassas, VA), an osteoblast precursor cell line, during early adhesion to calcium phosphate scaffolds. Hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) ceramic scaffolds were produced by a template coating method. Phospho-specific antibody cell-based ELISA (PACE) technique was utilized on stress activation proteins, including the extracellular signal-regulated kinase (ERK1/2), P38, c-Jun N-terminal kinase (JNK) and the anti-apoptosis mediator protein kinase B (PKB/AKT). Cell-based ELISAs were also performed on the membrane anchoring protein vinculin and alpha6beta4 integrin. LIPUS stimulated activation of PERK 1/2, PJNK, PP38 and vinculin in traditional two-dimensional (2-D) culture. Calcium release from the scaffolds was partially involved in the activation of PERK 1/2 when cell response was compared between culture on 2-D surfaces and three-dimensional (3-D) HA and TCP scaffolds. Effects of calcium extracted media from scaffolds alone could not account for the full activation of PJNK, PP38, PAKT, vinculin and alpha6beta4 integrin. LIPUS stimulation further increased PERK activity on TCP scaffolds corresponding with an increase in both vinculin and alpha6beta4 integrin levels. It was concluded from this study that LIPUS treatment can significantly affect stress signaling mediators and adhesion proteins in osteoblast precursor cells during the early cell-attachment phase to trabecular patterned scaffolds.