Health disparities in infants with hypertrophic pyloric stenosis.

BACKGROUND: This study investigates whether health disparities exist in infants with hypertrophic pyloric stenosis (HPS), to identify factors affecting definitive treatment, and if more morbidity occurs. METHODS: A 6-year retrospective analysis was performed on infants with HPS. Analysis of variance was used to evaluate the impact of socioeconomic factors on disease severity and hospitalization. General linear models were used to assess the impact of risk factors on the outcomes. RESULTS: There were a total of 584 infants. African-American's had lower serum chloride (P < .001), higher bicarbonate (P = .001), and sodium levels (P = .006), adding to longer hospitalization than whites (P = .03). Uninsured infants had lower sodium and chloride (P < .001) and higher bicarbonate (P < .001), resulting in a longer time to operation (P = .05) than privately insured infants. In multivariable analyses, African-American's were associated with chloride (P = .002) and higher bicarbonate (P = .009), and uninsured status remained significantly associated with all electrolyte abnormalities. CONCLUSIONS: African-American and poorly insured infants with HPS had greater risk of metabolic derangements. This required more time to correct dehydration and electrolytes, adding to longer hospitalizations.

Midkine Mediates Intercellular Crosstalk between Drug-Resistant and Drug-Sensitive Neuroblastoma Cells In Vitro and In Vivo.

Resistance to cytotoxic agents has long been known to be a major limitation in the treatment of human cancers. Although many mechanisms of drug resistance have been identified, chemotherapies targeting known mechanisms have failed to lead to effective reversal of drug resistance, suggesting that alternative mechanisms remain undiscovered. Previous work identified midkine (MK) as a novel putative survival molecule responsible for cytoprotective signaling between drug-resistant and drug-sensitive neuroblastoma, osteosarcoma and breast carcinoma cells in vitro. In the present study, we provide further in vitro and in vivo studies supporting the role of MK in neuroblastoma cytoprotection. MK overexpressing wild type neuroblastoma cells exhibit a cytoprotective effect on wild type cells when grown in a co-culture system, similar to that seen with doxorubicin resistant cells. siRNA knockdown of MK expression in doxorubicin resistant neuroblastoma and osteosarcoma cells ameliorates this protective effect. Overexpression of MK in wild type neuroblastoma cells leads to acquired drug resistance to doxorubicin and to the related drug etoposide. Mouse studies injecting various ratios of doxorubicin resistant or MK transfected cells with GFP transfected wild type cells confirm this cytoprotective effect in vivo. These findings provide additional evidence for the existence of intercellular cytoprotective signals mediated by MK which contribute to chemotherapy resistance in neuroblastoma.

The role of nerve growth factor in caspase-dependent apoptosis in human BE(2)C neuroblastoma.

PURPOSE: The purpose of the study was to determine if nerve growth factor (NGF) stimulation induces apoptosis in the BE(2)C neuroblastoma cell line in vitro. METHODS: The LPCX retroviral vector was used to achieve stable transduction of NGF complementary DNA into BE(2)C neuroblastoma cells. Wild-type and NGF-transduced cells were then incubated with varying concentrations of NGF for varying periods. A laddering assay was performed to determine the presence of DNA fragments characteristic of apoptosis. The expression of various cleaved and total caspases was determined by Western immunoblotting. RESULTS: p75 receptor expression in the NGF-transduced cell line was equivalent to that in the wild-type cell line, but Trk A receptor expression was significantly decreased in BE(2)C-NGF cells. DNA laddering assay demonstrated that only BE(2)C-NGF cells underwent apoptosis after stimulation with exogenous NGF. BE(2)C-NGF cells have increased expression of cleaved caspase-3 when compared with wild-type cells. Cleaved caspase-3 expression is further increased with exogenous NGF stimulation in the transduced cells. CONCLUSION: This study confirms that NGF stimulation of BE(2)C neuroblastoma cells can induce apoptosis through activation of the caspase cascade in vitro. The differential expression of the receptors Trk A and p75 between the wild-type and NGF-transduced cell lines may explain the differing effects observed.