Energy intake and resting metabolic rate in preschool Jamaican children with homozygous sickle cell disease

BACKGROUND: A relative energy deficiency consequent to a high resting metabolic rate (RMR) may contribute to growth impairment in persons with homozygous (SS genotype) sickle cell disease (SCD). The growth deficit in SCD emerges at an early age, but few studies have addressed the adequacy of energy intake relative to RMR in young children. OBJECTIVE: Our objective was to test the hypothesis that energy intake relative to RMR is lower in children with SCD than in control subjects. DESIGN: The dietary intake of 41 children with SCD and 31 control subjects with a normal hemoglobin genotype (AA) aged 3-6 y was assessed by weighing all food consumed during 3 d. RMR was determined with the use of indirect calorimetry. RESULTS: The RMR in the children with SCD ( +/- SD: 5.47 +/- 0.93 MJ/d) was higher than that in the control subjects (5.19 +/- 1.3 MJ/d) after adjustment for sex and weight (P = 0.04). Energy intake did not differ significantly between the 2 genotype groups. The ratio of energy intake to RMR was lower in the children with SCD ( +/- SD: 1.13 +/- 0.33) than in the control subjects (1.35 +/- 0.38) after adjustment for sex and weight (P = 0.005). CONCLUSIONS: Prepubertal children with SCD fail to compensate for their higher RMR by increasing their energy intake. This observation is consistent with a hypothesis of a relative energy deficiency in SCD.     

Effect of reduced dietary protein intake on hepatic and plasma essential fatty acid concentrations in the adult female rat: effect of pregnancy and consequences for accumulation of arachidonic and docosahexaenoic acids in fetal liver and brain

During pregnancy, the accumulation of long-chain polyunsaturated fatty acids (LCPUFA) in fetal tissues places a substantial demand upon maternal lipid metabolism. As lipid metabolism is intimately linked to aspects of protein metabolism, a reduced protein intake in pregnancy may impair activities of enzymes and transport proteins responsible for supplying LCPUFA to the fetus, thereby compromising fetal development. We have investigated the effect of reduced protein intake on LCPUFA status in the non-pregnant rat and in the pregnant rat, and in fetus at day 20 of gestation. Female rats (n 5 per group) were either mated and fed the control diet (180 g protein/kg) or low-protein diet (90 g protein/kg, LPD) diet throughout pregnancy, or fed the control diet or LPD for 20 d (non-pregnant animals). The fatty acid compositions of maternal liver and plasma, and fetal liver and brain were determined by GC. Feeding the LPD did not lead to any gross changes either in adult or fetal growth, or in total lipid concentrations in adult rat liver. However, the LPD was associated specifically with lower liver (42.6 %) and plasma (19.4 %) phosphatidylcholine (PC), and plasma triacylglycerol (28.6 %) docosahexaenoic acid (DHA) concentrations in pregnant rats and reduced fetal brain PC- (26.1 %) and phosphatidylethanolamine- (25.6 %) DHA concentrations. Together, these results show that variations in maternal dietary protein consumption alter DHA status in pregnancy and modify DHA accumulation into the fetal brain. The present results suggest that lower maternal protein intakes reduce delivery of DHA from the mother to the fetus, which may impair development and function of the fetal brain.     

Effect of temperature and pirimiphos methyl on biochemical biomarkers in Chironomus riparius Meigen

Fourth-instar Chironomus riparius Meigen larvae were exposed to the organophosphate (OP) insecticide pirimiphos methyl (0, 0.1, 1.0, and 10 microg/L) for 48, 72, or 96 h at three temperatures (3, 12, or 22 degrees C). Two biochemical biomarkers, acetylcholinesterase (AChE) and glutathione S-transferase (GST), were measured in individual larvae from each treatment. AChE activity was inhibited by the OP in a dose-responsive fashion. This response remained similar at all three temperatures, demonstrating that AChE is a robust and specific biomarker. Exposure duration had little effect on AChE activity. In contrast, GST activity was induced at the highest OP insecticide concentration, but induction was also evident at 3 degrees C. There was a significant effect of exposure duration, with an overall decline in GST activity over time. This result agrees with previous work suggesting that GSTs are not particularly suitable for use as a biomarker of pesticide exposure or effect in Chironomus.     

Reduction in the minimum candidate interval in the dominant-intermediate form of Charcot-Marie-Tooth neuropathy to D19S586 to D19S432

As part of an on-going genomic screen of unlinked Charcot-Marie-Tooth disease type 2 (CMT2) families, we identified 11 regions in the genome with lod scores ≥1.0. One of these regions was near the recently identified CMTDI1 locus on 19q. We show evidence of linkage of DUK 1118 to this region and our data reduce the minimum candidate interval for CMTDI1 to the 9-cM interval spanned by D19S586 and D19S432.We also demonstrate that five additional CMT2 families are unlinked to 19q markers, providing further evidence of CMT2 heterogeneity. Electronic Publication     

Childhood cerebellar hemangioblastoma does not predict germline or somatic mutations in the von Hippel-Lindau tumor suppressor gene

Tumor suppressor gene "knockout" models would predict that children who present with hemangioblastoma are likely to harbor germline mutation of the von Hippel-Lindau gene. We screened 6 pediatric patients with cerebellar hemangioblastoma for germline or somatic mutations of the von Hippel-Lindau gene. Two had prior clinical manifestations of von Hippel-Lindau disease and, as expected, had germline von Hippel-Lindau gene mutations. Four children with solitary hemangioblastoma did not have a detectable germline deletion, rearrangement, or point mutation in their von Hippel-Lindau gene, and tumor specimens in 3 of these 4 showed no somatic von Hippel-Lindau allelic loss. Solitary cerebellar hemangioblastoma in children does not predict a germline or somatic mutation in the von Hippel-Lindau tumor suppressor gene. The tumorigenesis of hemangioblastoma in younger patients may differ from that in adults, and may involve a molecular process unrelated to the von Hippel-Lindau tumor suppressor pathway.     

Age does not influence DNA fragmentation in the hippocampus after fatal traumatic brain injury in young and aged humans compared with controls

Paraffin sections from the hippocampus of 12 head-injured patients (Group A, aged between 4 and 12 years n = 6 and Group B, aged between 64 and 89 years n = 6) and associated age-matched controls were stained by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique for evidence of in-situ DNA fragmentation. TUNEL+ cells were of 2 Types: I (non-apoptotic) and II (apoptotic). In addition sections stained H&E, combined Luxol Fast Blue/Cresyl Violet and by immunohistochemistry for astrocytes (GFAP) and macrophages (CD68) were used to characterize the lesions. Small numbers of Type I TUNEL+ cells were seen in all sectors of the hippocampus except CA2 of both Groups A and B. Type II TUNEL+ cells were mainly found in the white matter. They constituted less than 1% of all TUNEL+ cells. There were similar or fewer TUNEL+ cells in the corresponding areas in the controls compared with the head-injured patients. However, in the dentate fascia and the CA4 sector of the Group B cases, larger numbers of TUNEL+ cells were seen in controls than after trauma. In the grey matter most TUNEL+ cells had the morphology ofnecrosis that corresponded with foci of selective neuronal damage. Only a few TUNEL+ cells were seen in white matter. The occasional Type I TUNEL+ cells were seen in grey matter. It is concluded that the amount and distribution of DNA fragmentation in children and adults is similar and therefore at least in the hippocampus does not provide an explanation for age as an independent variable of outcome after traumatic brain injury in childhood.     

Comparison of five point-of-care prothrombin and activated partial thromboplastin time devices based on age of blood sample

Delays in processing statium (STAT) blood samples have led to the production of an increasing number of point-of-care tests. Product inserts recommend measuring blood samples immediately after procurement, suggesting that delays may invalidate the test results. We studied the effect of the age of blood samples on point-of-care (POC) prothrombin time (PT) and an activated partial thromboplastin time (aPTT) result. Informed consent was obtained from 11 patients undergoing cardiopulmonary bypass (CPB). Blood samples (40 mL) were taken from each patient. Each blood sample was used to perform five PT tests and six aPTT tests on five POC devices (Gem PCL, Hemochron 801, Hemochron Jr. Signature, Hemochron Response, Rapidpoint Coag) at three different sample ages [< 60 s (fresh blood), 10 and 18 min after sample collection]. Blood samples were procured in a plastic syringe devoid of air bubbles, which was left undisturbed between tests but was gently agitated before initiating the 10- and 18-min tests. For tests requiring citrated whole blood, a fraction of each sample was anticoagulated (3.8% citrate) at each age. Statistical analysis was used for comparison of test results for fresh blood to aged samples (10 and 18 min). Test values were recorded as International Normalized Ratio (INR) and seconds for PT and aPTT, respectively. Two devices, the Hemochron 801 and Hemochron response showed statistically, although not clinically, significant variation in PT test results when the samples were aged to 10 and 18 minutes. As for aPTT results, Hemochron 801, Hemochron response, Hemochron Jr. signature, and Gem PCL showed statistically significant variation at 18 minutes. One device (Hemochron 801) reported results with 10-min aged blood that were statistically different from fresh blood. None of the aPTT tests results from any device produced results with aged blood that were clinically different from fresh blood. This study suggests that, in the tests evaluated, blood samples that have aged 10 or 18 min will produce clinically relevant aPTT and PT results, respectively.