Growth in children with cystic fibrosis-related diabetes.

Cystic fibrosis-related diabetes (CFRD) is associated with a shortened life expectancy and greater deterioration in lung function than in CF patients with normal glucose metabolism. There are few published data on how CFRD affects growth in childhood. We carried out a retrospective case controlled study of growth and lung function in 34 children with CFRD attending three specialist centers in London. We found that for the 2 years leading to CFRD diagnosis (at a mean age of 13.1 years), the mean height velocity was significantly less compared to controls: 4.9 (standard deviation-SD 1.6) cm/year vs. 6.0 (SD 1.9) cm/year (P = 0.005). For the 2 years following diagnosis, height velocity remained significantly lower (3.4 (SD 2.2) cm/year vs. 4.4 (SD 2.2) cm/year, P = 0.02). Mean FEV(1) was reduced prior to diagnosis and at diagnosis, but was similar to controls 2 years after diagnosis. This study highlights the compromise in height velocity and lung function that occurs prior to diagnosis of CFRD in children with CF, and a reduction in height velocity should be considered an indicator of impaired glucose metabolism. It would be useful to know whether early treatment with insulin can help promote catch up growth.

Implication of maternal-cell contamination in the clinical banking of umbilical cord blood.

BACKGROUND: The increasing utilization of human UC blood (UCB) in transplantation has drawn attention to the need for rationalization of selection, collection, processing, testing, banking and release of UCB. However, the issue of maternal blood contamination has not been well addressed. There are concerns that maternal T cells might elicit GvHD post-UCB transplant. METHODS: Maternal T cells in 58 male UCB allografts were enumerated using fluorescent in situ hybridization and flow cytometry. Obstetric factors, preceding labor, multi-parity and gestational age, were also analyzed. RESULTS: Levels of maternal cells of 0.75-5.25% were found in 15.5% (9/58) UCB. There was no association of maternal-cell contamination with preceding labor [25% (2/8) with previous delivery versus 35.4% (17/48) first born, P = 0.702], nor any correlation with multi-parity [37.5% (3/8) para > or = 3 versus 16.7% (8/48) para < 3, P = 0.181]. Gestation age of newborns also exhibited no association with maternal-cell contamination (39.47 weeks in newborn UCB with maternal cells, versus 39.58 weeks without: P = 0.674). The extrapolated maternal T cells/kg in nine UCB transplants were 1.05 x 10(5) +/- 1.12 x 10(5) (3.40 x 10(4) - 3.18 x 10(5)). DISCUSSION: In relation to the arbitrary threshold of 1 x 10(5) T cells/kg in HLA-mismatched transplants utilizing T-cell depleted BM, 22.2% (2/9) of UCB transplants having maternal-cell contamination might be at risk of GvHD. Data support the need for testing for maternal blood in UCB, and evaluating the clinical relevance of GvHD in patients post-UCB transplant. The establishment of guidelines and standards for release of such UCB collections would be advisable in evidence-based UCB transplantation.

6-Nitrobenzo[a]pyrene can be denitrated during mammalian metabolism.

Nitropolycyclic aromatic hydrocarbons (nitroarenes), including 6-nitrobenzo[a]pyrene (6-NBap), occur in our environment and are mutagenic in bacterial mutagenesis assays. The mutagenicity of 6-NBaP is enhanced when rat liver S9 is added. To investigate the cause of this increased activity, the metabolism of 6-NBaP was carried out with a total rat liver homogenate obtained from 3-methylcholanthrene- (MC-) induced rats, a 9000 X g supernatant enzyme, and with both unwashed and washed microsomes. Ring-hydroxylated 6-NBaP was detected. On the basis of retention times for known standards in a high-performance liquid chromatographic system, benzo[a]pyrene (BaP) and 6-acetoxy-BaP (6-OAcBaP) were isolated as products. BaP was further characterized via ultraviolet (UV) and mass spectra and 6-OAcBaP by UV, mass, and nuclear magnetic resonance (NMR) spectra. 6-HydroxyBaP (6-OHBaP) was also detected by UV and mass spectra. It is suggested that BaP is formed via a nitroanion radical of 6-NBaP and undergoes metabolism, while the 6-OHBaP is acetylated to form 6-OAcBaP. The acetyl donor remains to be identified.