Prenatal methylmercury exposure is associated with decrease heart rate variability in children.

BACKGROUND: Although several epidemiological studies have suggested mercury (Hg) might be associated with cardiotoxicity, the impact of Hg exposure on cardiac autonomic activity and blood pressure in children has not been investigated at Hg exposure levels equivalent to the Environmental Protection Agency (EPA) reference dose. OBJECTIVE: To investigate the association between low dose prenatal and recent methylmercury (MeHg) exposures and cardiac autonomic function and blood pressure with adjustment for factors such as fish consumption among children from a high fish consumption coastal city. METHODS: Children aged 7-8 years were recruited from the birth cohort of our previous study. Heart rate variability (HRV), resting heart rate (RHR) and blood pressure were measured as surrogate markers of cardiac autonomic function. Cord blood and current whole blood Hg concentration were used as biomarkers of prenatal and recent MeHg exposure, respectively. Recent fish consumption information was estimated with a food frequency questionnaire. RESULTS: Among 604 children, median cord blood and whole blood Hg concentrations were 45.9 nmol/L (IQR: 32.8-65.03 nmol/L) and 13.57 nmol/L (IQR: 9.29-19.72 nmol/L), respectively. Our results demonstrated that prenatal MeHg exposure was associated with decreased HRV (i.e. low CVRR, SDRR, and RMSSD), reflecting reduced parasympathetic activity (i.e. low CCVHF and HF), and a sympathovagal balance shift toward sympathetic predominance (i.e. high %LF and LF/HF ratio). Adjustment of recent fish consumption further increased the significance and magnitude of the adverse associations of MeHg. CONCLUSION: The results of this study suggest that prenatal MeHg exposure is associated with decreased parasympathetic modulation of cardiac autonomic function in children.

Impact of fetal and childhood mercury exposure on immune status in children.

BACKGROUND: Mercury exposure have been shown to affect immune status in animals as reflected by cytokine expression. It is unclear whether low levels of exposure during fetal and/or childhood periods could impact on immune status in humans. OBJECTIVES: To test the hypothesis that fetal and childhood mercury exposure is associated with childhood cytokine profiles and to investigate whether childhood selenium levels interact with any of the associations found. METHODS: Children were recruited from a previously established birth cohort between the ages of 6-9 years for assessment and measurement of blood mercury, selenium and cytokine profile (interleukin (IL)-4, IL-6, IL-8, IL-10, IL-13 and TNF-alpha). Multivariable linear regression models were used to assess the adjusted association of cord blood mercury concentration and current mercury concentrations with levels of the cytokine levels. We tested whether the association with current mercury level varied by current selenium level and cord blood mercury level. RESULTS: IL-10 was negatively associated with current blood mercury concentration. The effect was greatest in cases with low cord blood mercury and low current selenium concentrations. None of the other cytokine levels were associated with either cord blood or current blood mercury concentrations, except that cord blood mercury was negatively associated with IL-6. CONCLUSIONS: Childhood mercury exposure was negatively associated with childhood IL-10 levels. It is postulated that while selenium is protective, low levels of fetal mercury exposure may increase the degree of this negative association during childhood. Further studies into the clinical significance of these findings are required.

Development of a novel mouse model of severe glucose-6-phosphate dehydrogenase (G6PD)-deficiency for in vitro and in vivo assessment of hemolytic toxicity to red blood cells.

Studies of hemolytic agents on G6PD-deficient subjects have been extensively performed on red blood cells obtained from donors, only using in vitro methods. However, there has been no adequate G6PD-deficient animal model for in vivo assessment of potentially hemolytic agents. The objective of this study is to establish a novel mouse model of severe G6PD-deficiency, with high susceptibility to hemolytic damage upon oxidative agents. To create this model, G6PD mutant Gpdx allele was introduced into the C57L/J mouse strain background by breeding program. The hemolytic toxicity of naphthalene and its metabolite α-naphthol on G6PD-deficient red blood cells was evaluated. Our data showed that the F2 homozygous Gpdx mutant with C57L/J background exhibiting the G6PD activity was 0.9±0.1 U/g Hb, level similar to those of G6PD deficiency in human. A significantly negative correlation was demonstrated between GSH percentage reduction and G6PD activity (r=-0.51, p<0.001) upon challenge of the red blood cells with alpha-naphthol in vitro. Similar correlation was also found between GSSG elevation and G6PD activity. Our in vivo studies showed that the administration of naphthalene at 250 mg/kg inflicted significant oxidative damage to the G6PD-deficient mice, as illustrated by the decrease of the GSH-to-GSSG ratio (by 34.2%, p=0.005) and the increase of the methemoglobin level (by 1.9 fold, p<0.001). Hemolytic anemia was also found in G6PD-deficient mice at this dosage of naphthalene. In summary, this novel mouse model could be utilized as a screening platform to more accurately determine the hemolytic toxicity of pharmacological agents on G6PD-deficient subjects.

Novel mutations in PHKA2 gene in glycogen storage disease type IX patients from Hong Kong, China.

The diagnosis of glycogen storage disease (GSD) type IX is often complicated by the complexity of the phosphorylase kinase enzyme (PHK), and molecular analysis is the preferred way to provide definitive diagnosis. Here we reported two novel mutations found in two GSD type IX patients with different residual enzyme activities from Hong Kong, China using genetic analysis and, provided the molecular interpretation of the deficient PHK activity. These two newly described mutations would be useful for the study of future GSD patients.

Brain-derived neurotrophic factor rescues and prevents chronic intermittent hypoxia-induced impairment of hippocampal long-term synaptic plasticity.

Obstructive sleep apnea (OSA) is a common sleep and breathing disorder characterized by repeated episodes of hypoxemia. OSA causes neurocognitive deficits including perception and memory impairment but the underlying mechanisms are unknown. Here we show that in a mouse model of OSA, chronic intermittent hypoxia treatment impairs both early- and late-phase long-term potentiation (LTP) in the hippocampus. In intermittent hypoxia-treated mice the excitability of CA1 neurons was reduced and hippocampal brain-derived neurotrophic factor (BDNF) was down-regulated. We further showed that exogenous application of BDNF restored the magnitude of LTP in hippocampal slices from hypoxia-treated mice. In addition, microinjection of BDNF into the brain of the hypoxic mice prevented the impairment in LTP. These data suggest that intermittent hypoxia impairs hippocampal neuronal excitability and reduces the expression of BDNF leading to deficits in LTP and memory formation. Thus, BDNF level may be a novel therapeutic target for alleviating OSA-induced neurocognitive deficits.

Roles of parental sleep/wake patterns, socioeconomic status, and daytime activities in the sleep/wake patterns of children.

OBJECTIVES: To determine sleep/wake patterns of primary school children and their correlates. STUDY DESIGN: A total of 4470 sets of mother-father-child community-based trios were recruited in this study. We constructed 3 integrated models with structural equation modeling to predict sleep/wake patterns of children (bedtime, wakeup time, and time in bed [TIB]). RESULTS: Our best-fitting models explained 40% to 71% variances of various sleep/wake patterns of the children, which were influenced by a web of interactive factors including school start time, parental sleep/wake patterns, sociodemographics, and daytime activities. The strongest predictor of various sleep/wake patterns was school start time. Higher socioeconomic status would shorten TIB of both children and parents, but through different pathways (by advancing wakeup time and delaying bedtime in children but by delaying bedtime in parents). Media use and homework shortened TIB of children, while leisure extracurricular activities and later school start time lengthened it. The age and sex effects on sleep/wake patterns, at least in part, were mediated by daytime activities. Daytime activities of children also influenced their parental sleep/wake patterns, especially their maternal one. A consistent pattern of stronger mother-child than father-child associations were found in various sleep/wake patterns. CONCLUSIONS: There was a complex and interactive relationship among school schedule, parental sleep/wake patterns, socioeconomic status, and daytime activities in determining the sleep/wake patterns of children. These findings have important clinical implications for the management of childhood sleep/wake habits and problems.

Serum levels of heavy metals in childhood eczema and skin diseases: friends or foes.

The incidence of eczema has been increasing in developed countries. Environmental and hygiene factors have been incriminated. Although air and food pollution with heavy metals have been considered as possible culprits, these factors have never been investigated in Hong Kong. To evaluate if quality of life and eczema severity are associated with abnormal serum levels of six common heavy metals, namely, cadmium, lead, mercury, selenium, copper and zinc. Serum or whole blood was taken for measurement of six heavy metals from patients referred to the pediatric dermatology clinic. Eczema severity (SCORAD and NESS) and quality of life (CDLQI) were recorded. A total of 110 patients with eczema and 41 patients with miscellaneous skin conditions were recruited. Serum levels of the six heavy metals were generally within the upper limits of local reference ranges. Zinc levels were below the lower reference limit of 9.4 mum in 66 patients with eczema (60%) and 22 non-eczema patients (53%). Forty-four patients with eczema (40%) and 24 (58%) in non-eczema group had low copper levels. In eczema patients, lead levels were generally within normal limits but their levels were positively correlated with poor quality of life (CDLQI: r = 0.22 and p < 0.05), disease severity (objective SCORAD: r = 0.33 and p < 0.005; NESS: 0.20, p < 0.05), eosinophil count and log-transformed IgE. Copper/zinc ratio also correlated with NESS and CDLQI and was generally higher than non-eczema skin diseases. Our findings help reassure parents that levels of heavy metals generally do not exceed the local reference ranges for toxicity. However, lead levels have significant correlations with disease severity, quality of life and atopy. Low zinc and copper levels are commonly found in pediatric skin diseases and their significance needs to be determined.

Validation of the Chinese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module.

OBJECTIVE: The psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module were investigated. METHODS: This instrument and the Generic Core Scales were administered to 359 pediatric patients with cancer (5-18 years) and 413 parents of such patients (2-18 years old). RESULTS: Seven and eight factors were, respectively, identified for the patient and parent versions. The Cronbach's alpha coefficients were respectively .89 and .92 for the total scale, and respectively .75-.90 and .76-.93 for the subscales of the patient and parent versions. Test-retest reliability coefficients exceeded .60 for most cases. The total/subscale scores of the Cancer Module significantly correlated with those of the Generic Core Scales. Some of the subscales could distinguish between on-treatment and off-treatment patients. CONCLUSIONS: The psychometric properties of the patient and parent versions of the Chinese PedsQL Cancer Module were found acceptable.

Sodium tanshinone IIA sulfonate increased intestinal hemodynamics without systemic circulatory changes in healthy newborn piglets.

In traditional Chinese medicine, tanshinone IIA is a lipid-soluble component of Danshen that has been widely used for various cardiovascular and cerebrovascular disorders, including neonatal asphyxia. Despite promising effects, little is known regarding the hemodynamic effects of tanshinone IIA in newborn subjects. To examine the dose-response effects of sodium tanshinone IIA sulfonate (STS) on systemic and regional hemodynamics and oxygen transport, 12 newborn piglets were anesthetized and acutely instrumented for the placement of femoral arterial and venous, pulmonary arterial catheters to measure mean arterial, central venous, and pulmonary arterial pressures, respectively. The blood flow at the common carotid, renal, pulmonary, and superior mesenteric (SMA) arteries were continuously monitored after treating the piglets with either STS (0.1-30 mg/kg iv) or saline treatment (n = 6/group). To further delineate the underlying mechanisms for vasorelaxant effects of STS, in vitro vascular myography was carried out to compare its effect on rat mesenteric and carotid arteries (n = 4-5/group). STS dose-dependently increased the SMA blood flow and the corresponding oxygen delivery with no significant effect on systemic and pulmonary, carotid and renal hemodynamic parameters. In vitro studies also demonstrated that STS selectively dilated rat mesenteric but not carotid arteries. Vasodilation in mesenteric arteries was inhibited by apamin and TRAM-34 (calcium-activated potassium channel inhibitors) but not by meclofenamate (cyclooxygenase inhibitor) or N-nitro-l-arginine methyl ester hydrochloride (nitric oxide synthase inhibitor). In summary, without significant hemodynamic effects on newborn piglets, intravenous infusion of STS selectively increased mesenteric perfusion in a dose-dependent manner, possibly via an endothelium-derived hyperpolarizing factor vasodilating pathway.

Adjunctive pharmacotherapy in neonates with respiratory failure.

Whereas oxygen, continuous positive airway pressure (CPAP) and mechanical ventilation are the mainstays of treatment of pulmonary conditions in newborns, there are a number of adjunctive therapies that may improve the pulmonary function of these infants. These include the use of bronchodilators and diuretics given either systemically or through the inhaled route, mucolytic agents, and anti-inflammatory agents. This chapter gives an overview of the use of the most-studied agents including aerosolized bronchodilators, systemic and inhaled diuretics, and systemic and inhaled corticosteroids in the treatment and prevention of, where appropriate, respiratory distress syndrome, bronchopulmonary dysplasia, and meconium aspiration syndrome. Evidence on the use of mucolytic agents including acetylcysteine and deoxyribonuclease, and the anti-inflammatory agents including the macrolide antibiotics, cromolyn, pentoxyfylline, and recombinant human Clara cell protein are also reviewed.

The plant mannose-binding lectin NTL preserves cord blood haematopoietic stem/progenitor cells in long-term culture and enhances their ex vivo expansion.

Ex vivo expansion of haematopoietic stem and progenitor cells in cytokine combinations is effective in promoting differentiation and proliferation of multilineage progenitor cells, but often results in reduction of self-renewable stem cells. This study investigated the effect of a mannose-binding lectin, NTL, purified from Narcissus tazetta var. chinensis, on prolonged maintenance and expansion of cord blood CD34+ cells. Our results showed that the presence of NTL or Flt-3 ligand (FL) significantly preserved a population of early stem/progenitor cells in a serum- and cytokine-free culture for 35 d. The effect of NTL on the ex vivo expansion of CD34+ cells in the presence of stem cell factor, thrombopoietin (TPO) and FL was also investigated. NTL-enhanced expansion of early progenitors (CD34+, CD34+CD38-, mixed colony-forming units and CFU-GEMM) and committed progenitor cells (granulocyte CFU, erythroid burst-forming units/CFU and megakayocyte CFU) after 8 and 12 d of culture. Six weeks after transplanting 12 d-expanded cells to non-obese diabetic severe combined immunodeficient mice, increased engraftment of human CD45+ cells was observed in the bone marrow of animals that received NTL-treated cells. The dual functions of NTL on long-term preservation and expansion of early stem/multilineage progenitor cells could be developed for applications in various cell therapy strategies, such as the clinical expansion of CD34+ cells for transplantation.

Oscillometrically measured blood pressure in Hong Kong Chinese children and associations with anthropometric parameters.

BACKGROUND: Oscillometric devices are increasingly used to measure blood pressure (BP). Reference data are limited and have not used devices validated against sphygmomanometric measurements on which current standards are based. BP standards for Chinese children have been based on sphygmomanometry and have not provided height-related or weight-related BP percentiles. METHODS: BP was measured in 14842 Hong Kong Chinese schoolchildren aged 6-18 years randomly selected from 36 schools in the 18 Hong Kong districts, using a validated oscillometric device (Datascope Accutorr Plus). Height, weight, heart rate and waist circumference were measured. Percentiles for systolic BP and diastolic BP by sex, age, height and weight were generated. Features associated with systolic BP and diastolic BP in 12680 children were analysed by univariate and multivariate analysis. RESULTS: Reference BP standards by sex, age, weight and height are presented. BP was associated (in descending order of strength) with weight > height > age > waist circumference > body mass index, and weakly with heart rate (which added considerable influence on multivariate analysis). BP increases similarly with age, height (which can normalize for variations in growth) and weight (which is associated most strongly with BP). BP was associated also with family history of high BP and (inversely) with sleep duration. CONCLUSIONS: The study provides oscillometrically measured BP standards for Chinese children, with age-related and sex-related height-specific and weight-specific percentiles. Implications of the findings are discussed. Screening by sex-specific BP-height percentile charts, and then if high, reference to the BP-sex-age-weight table, is suggested.

A longitudinal study to establish the normative value and to evaluate perinatal factors affecting intraocular pressure in preterm infants.

PURPOSE: To establish a normative range of intraocular pressure (IOP) in preterm infants and to identify important perinatal factors that could affect the IOP during the early weeks of neonatal life. METHODS: The IOP of 104 preterm infants, with a median (interquartile range) gestational age of 29.8 (28.7-30.9) weeks and birth weight of 1208 (1049-1370) g, were assessed in a university-affiliated tertiary neonatal center. These infants had IOP measured by a handheld tonometer at 1, 4, 6, 8, and 10 weeks of postnatal age. The mixed-effects models were used to evaluate the longitudinal IOP measurements and to identify critical perinatal factors that would significantly affect the ocular pressure. RESULTS: A percentile chart of IOP in preterm infants was constructed, and the median (10th-90th percentile) IOP ranged from 16.9 (12.3-21.5) to 14.6 (10.1-19.2) mm Hg at 26.1 and 46.4 weeks of postconceptional age, respectively. The IOP was significantly and negatively associated with postconceptional age (P < 0.001), mean blood pressure (P = 0.01), Apgar score at 1 minute (P = 0.04), and use of inhaled corticosteroids (P = 0.03), but was positively correlated with the commencement of high-frequency oscillatory ventilation (P = 0.01). CONCLUSIONS: A quantitative statistical model has been developed and a percentile chart of IOP constructed for preterm infants that could be used for future reference. Pediatric ophthalmologists and neonatal clinicians can compare the IOP of preterm infants against this chart and make relevant quantitative adjustments for critical perinatal factors so that the IOP may be properly evaluated, both in healthy and ill infants.

Pro-oxidative effects of Chinese herbal medicine on G6PD-deficient erythrocytes in vitro.

Glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects are susceptible to chemical-induced oxidative haemolysis. Little is known concerning the haemolytic properties of Chinese herbal medicine on G6PD-deficient subjects. Our objective was to investigate the pro-oxidative effect of 18 commonly used Chinese herbal medicine (CHM) on human G6PD-deficient red blood cells. G6PD-deficient (n=10) and normal (n=10) whole blood samples were incubated with water extracts of CHM. The resulting levels of reduced glutathione (GSH) and methaemoglobin (MetHb) were determined by biochemical assays. Rhizoma Coptidis significantly reduced GSH level by 48.9+/-5.4% (at 1 mg/mL) in the G6PD-deficient erythrocytes (P<0.001) compared with the respective control group without challenge. Similar dose-dependent responses were observed at higher concentrations of Cortex Moutan, Radix Rehmanniae, Radix Bupleuri, Rhizoma Polygoni Cuspidati and Flos Chimonanthi (P<0.01, 5-10 mg/mL). In addition, the levels of MetHb were elevated significantly when challenged with Rhizoma Coptidis (2.8 fold at 5 mg/mL) and Cortex Moutan (3.4 fold at 10 mg/mL). This is the first report on the pro-oxidative action of CHM on G6PD-deficient blood samples in vitro as demonstrated by the decrease of GSH and increase of MetHb. G6PD-deficient subjects should restrain from excessive consumption of these pro-oxidative herbs.

Secular changes in height, weight and body mass index in Hong Kong Children.

BACKGROUND: Large population growth surveys of children and adolescents aged 6 to 18 y were undertaken in Hong Kong in 1963 and 1993. The global epidemic of obesity is a major public health concern. To monitor the impact of this epidemic in Hong Kong children and to identify secular changes in growth, a further growth survey was undertaken in 2005/6. METHODS: Cross-sectional height and weight measurements of 14,842 children and adolescents aged 6 to 18 y from Hong Kong's 18 districts were obtained during the 2005/6 school year. Percentile curves were constructed using LMS method and sex-specific percentile values of weight-for-age, height-for-age, and BMI-for-age were compared with those data from 1963 and 1993. RESULTS: Secular changes in height, weight and BMI were noted between 1963 and 1993 and between 1993 and 2005/6. In the latter period, greater changes were observed at younger ages, and particularly in boys. On an annual basis, the 1993-2005/6 changes were less than those during 1963-1993. Using the International Obesity Task Force cut-offs, 16.7% of children were overweight or obese in 2005/6, which was a 5.1% increase since 1993. CONCLUSION: These data provide policy-makers with further evidence of the secular changes in child growth and the increasing obesity epidemic among Hong Kong children.

Waist circumference and waist-to-height ratio of Hong Kong Chinese children.

BACKGROUND: Central body fat is a better predictor than overall body fat for cardiovascular (CV) risk factors in both adults and children. Waist circumference (WC) has been used as a proxy measure of central body fat. Children at high CV risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been proposed as an alternative, conveniently age-independent measure of CV risk although WHTR percentiles have not been reported. We aim to provide age- and sex-specific reference values for WC and WHTR in Hong Kong Chinese children. METHODS: Cross sectional study in a large representative sample of 14,842 children aged 6 to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age groups and smoothed percentile curves of WC and WHTR were derived and presented. RESULTS: WC increased with age, although less after age 14 years in girls. WHTR decreased with age (particularly up to age 14). WHTR correlated less closely than WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively). CONCLUSION: Reference values and percentile curves for WC and WHRT of Chinese children and adolescents are provided. Both WC and WHTR are age dependent. Since the use of WHRT does not obviate the need for age-related reference standards, simple WC measurement is a more convenient method for central fat estimation than WHRT.

Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin.

BACKGROUND: Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. METHODS AND RESULTS: In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 microg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. CONCLUSIONS: These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

A novel functional assay for simultaneous determination of total fatty acid beta-oxidation flux and acylcarnitine profiling in human skin fibroblasts using (2)H(31)-palmitate by isotope ratio mass spectrometry and electrospray tandem mass spectrometry.

BACKGROUND: Two separate and complementary assays, total mitochondrial fatty acid beta-oxidation (FAO) flux rate and acylcarnitine profiling, have been used to establish a definitive diagnosis of FAO defects (FAOD) in cultured cells. We developed a novel functional assay for total FAO rate assay by measurement of deuterated water enrichment and to combine it with the conventional acylcarnitine profiling method into a single tracer incubation experiment. METHODS: Skin fibroblasts were incubated in a medium containing universal deuterium-labeled palmitate ((2)H(31)-palmitate) and l-carnitine without glucose supplementation for 96 h. The culture medium was assayed for deuterated water enrichment using isotope ratio mass spectrometry (IRMS) and acylcarnitine profiling by electrospray-ionization tandem mass spectrometry (ESI/MS/MS). RESULTS: The medians of (2)H(2)O enrichment after 96 h of incubation of (2)H(31)-palmitate of the control, other inherited metabolic diseases and FAOD cell lines were 109.9, 102 and 23.1 ppm/mg protein/96 h, respectively. All fibroblasts with FAOD except carnitine uptake defective, multiple acyl-CoA dehydrogenase and short-chain 3-hydroxyacyl-CoA dehydrogenase deficient cells were well separated from the control (<60% control median, p<0.05) and could be identified by IRMS assay. Accumulations of disease-specific acylcarnitines due to blockage in the carnitine cycle and FAO spiral were also demonstrated by acylcarnitine profiling. CONCLUSIONS: This novel functional assay is less time consuming and relatively simple by comparison to other published methods and can be used to investigate patients suspected to have FAO defects.

Eczema exacerbation and food atopy beyond infancy: how should we advise Chinese parents about dietary history, eczema severity, and skin prick testing?

Issues related to empirical dietary restriction are important, but they have been inadequately studied among children with atopic dermatitis (AD). To evaluate whether any association exists between food atopy, food avoidance, and AD severity, investigators in the present study reviewed all skin prick tests (SPTs) performed between January 2005 and April 2006 at a pediatric dermatology clinic and correlated findings with history of food avoidance and eczema severity. Only 13% of 114 children with AD had a positive SPT for beef. The most commonly sensitized foods were egg yolk (53%), egg white (42%), shrimp (35%), peanuts (31%), and crab (29%). Disease severity was not associated with prevalence of sensitization to these foods. The investigators concluded that immediate immunoglobulin E reaction to beef, as suggested by positive SPT findings, is unlikely to occur in most children with AD. SPT information may be useful in reassuring parents about the unlikelihood of a severe and immediate reaction to beef. As for other foods, it is sensible to advise parents about specific avoidance strategies only in more severely affected children with a definite history of eczema exacerbation by specific food allergens.

Metabolomic and bioinformatic analyses in asphyxiated neonates.

OBJECTIVES: We tested the application of bioinformatic algorithms in studying the metabolomic profiles of neonatal urine samples with clinical evidence of severe asphyxia at birth and subsequent neurodevelopmental handicap. DESIGN AND METHODS: The clinical outcomes of 256 newborns that required direct admission to neonatal intensive care unit for respiratory support or did not require direct admission were studied. Urinary metabolite profiles were measured by high throughput mass spectrometry and analyzed by bioinformatic methods. RESULTS: We found a positive relationship between suppressed biochemical networks involved in macromolecular synthesis and birth asphyxia associated with significant neonatal oxidative stress and morbidity. The metabolomic discriminators between good neonatal outcome and poor neonatal outcome were established using hierarchical clustering analysis. Concentrations of eight urinary organic acids in distinct biochemical pathways were elevated and significantly associated with the prognosis of neurodevelopmental handicap with high sensitivity and specificity: ethylmalonate, 3-hydroxy-3-methylglutarate, 2-hydroxy-glutarate and 2-oxo-glutarate were associated with good neonatal outcome, whereas glutarate, methylmalonate, 3-hydroxy-butyrate and orotate were associated with poor outcome. CONCLUSIONS: The data demonstrated the potential application of bioinformatics methods in this metabolomic study and proved its clinical relevance.