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.

Long term neurocognitive impact of low dose prenatal methylmercury exposure in Hong Kong.

BACKGROUND: International studies suggest that low dose prenatal methylmercury exposure (>29 nmol/L) has long-term adverse neurocognitive effects. There is evidence that the majority of children in Hong Kong exceed this level as a result of high fish consumption of mothers during pregnancy. OBJECTIVE: To study whether there are any associations between low-dose prenatal methylmercury exposure and neurocognitive outcomes in Hong Kong children. MATERIALS AND METHODS: All 1057 children from the original birth cohort were eligible for entry into the study, except children with conditions that would affect neurocognitive development, but were unrelated to methylmercury exposure. Subjects were assessed by a wide panel of tests covering a broad range of neurocognitive functions: Hong Kong Wechsler Intelligence Scale for Children (HK-WISC), Hong Kong List Learning Test (HKLLT), Tests of Everyday Attention for Children (TEACH), Boston Naming Test, and Grooved Pegboard Test. RESULTS: 608 subjects were recruited (median age 8.2 years, IQR 7.3, 8.8; 53.9% boys). After correction by confounders including child age and sex, multivariate analysis showed that cord blood mercury concentration was significantly associated with three subtests: Picture Arrangement of HK-WISC (coefficient -0.944, P=0.049) and Short and Long Delay Recall Difference of the HKLLT (coefficient -1.087, P=0.007 and coefficient -1.161, P=0.005, respectively), i.e., performance worsened with increasing prenatal methylmercury exposure in these subtests. CONCLUSIONS: Small, but statistically significant adverse associations between prenatal methylmercury exposure and long-term neurocognitive effects (a visual sequencing task and retention ability of verbal memory) were found in our study. These effects are compatible with findings of studies with higher prenatal methylmercury exposure levels and suggest that safe strategies to further reduce exposure levels in Hong Kong are desirable.

Psychometric properties of the Chinese version of the Pediatric Quality Of Life Inventory 4.0 Generic Core scales among pediatric cancer patients.

BACKGROUND: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales are commonly used to assess health-related quality of life of healthy children and pediatric patients. Validation of the Generic Core Scales among Chinese pediatric cancer patients has not been reported in the literature. The scales can serve to measure different quality-of-life domains that are not captured by the PedsQL Cancer Module. OBJECTIVE: Psychometric properties of the Chinese version of the PedsQL 4.0 among pediatric cancer patients and their caretakers were examined. METHODS: The Generic Core Scales were administered to 335 pairs of pediatric cancer patients (aged 8-18 years) and their caretakers in Hong Kong. RESULTS: A 5-factor structure (physical, emotional, social, school-related cognitive function, and missed school) was identified in the patient and proxy versions of the scales using confirmatory factor analysis. Both versions of the total scale reported Cronbach α's of .90 or greater, with almost all subscales reporting α's of .70 or greater. Test-retest reliability at 2 weeks was acceptable (intraclass correlations ≥0.60) for a majority of subscales. Agreement between patients' and caretakers' ratings was medium. CONCLUSIONS: The scales demonstrated acceptable psychometric properties and construct validity. IMPLICATIONS FOR PRACTICE: This study validated the Chinese version of the Generic Core Scales among pediatric cancer patients and their caretakers, which supports the future use of the scales in clinical settings. The Generic Core Scales can also be supplementary to the PedsQL Cancer Module for measuring multiple domains of quality of life in cancer population.

Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants.

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

Prospective self-controlled trial of the efficacy and tolerability of a herbal syrup for young children with eczema.

OBJECTIVES: Traditional Chinese medicine (TCM) is popular as an alternative medicine in children with atopic dermatitis (AD). A concoction of five herbs in a capsular preparation has been confirmed to be efficacious in improving the quality of life and sparing topical corticosteroid usage. We evaluated the clinical efficacy and tolerability of the same concoction in syrup form. METHODS: This was a prospective self-controlled trial set in the pediatric dermatology clinic of a teaching hospital. Children aged 4-7 years with moderate-to-severe AD received 20 ml of TCM syrup daily. Clinical parameters and laboratory markers were measured before and at 2 weeks, 7 weeks and 12 weeks of treatment, and at 4 weeks after completion. Disease severity was evaluated by the SCORing Atopic Dermatitis (SCORAD) index and quality of life by the Children's Dermatology Life Quality Index (CDLQI). Blood was obtained for a complete blood count, total IgE, eosinophil count, and biochemical studies prior to and after 3 months of TCM usage. RESULTS: Twenty-two patients participated in the study. There were significant improvements in the objective SCORAD, pruritus and CDLQI scores 4 weeks after study completion. There was no change in sleep score or amount of topical steroid consumption. No biochemical evidence of any adverse drug reaction was observed during the study period. The TCM syrup was generally palatable and well tolerated by the children. Adverse effects were generally mild but two patients with rash withdrew during the study. CONCLUSION: The palatability means that further evaluations and dosage studies of the concoction will be possible in young children.

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.

Gestational and lactational transfer of melamine following gavage administration of a single dose to rats.

Melamine contamination in an infant formula manufactured by a firm in China was reported in September 2008. Maternal transfer of melamine during pregnancy and through breast-feeding are possible ways of introduction. This study aims to evaluate the maternal transfer of melamine into amniotic fluid and breast milk through oral intake by pregnant and lactating rats, respectively. The quantity of melamine in the dam's sera, amniotic fluid, breast milk as well as in fetal whole body extract was measured. Our results showed that, after administration of single dose of 21.4 mg/kg per body weight of melamine to pregnant rats (16-18 days of gestation) by gavage, about 80% of melamine was found in dam's serum in 0.5 h. Melamine further reached the fetuses through placental transfer as it was found that peak melamine level of 7.15 ppm (∼30%) was detected in the fetuses after 2h and 4.36 ppm (∼20%) was shown in amniotic fluid after 3h of maternal intake. In the lactating rats, about 40% of maternal intake of melamine was transferred to breast milk and peaked at 3h. The results of this study confirmed the maternal transfer of melamine to fetuses in utero and infants through breast feeding.

Early diagnosis of intra-abdominal inflammation and sepsis by neutrophil CD64 expression in newborns.

BACKGROUND: Newborn infants with intra-abdominal inflammation/sepsis often present with nonspecific signs in the early stages of the disease, but can rapidly develop life-threatening complications. A reliable 'early' biomarker would be invaluable. OBJECTIVE: To evaluate the effectiveness of neutrophil CD64 as an 'early' biomarker of intra-abdominal inflammation/sepsis. METHODS: Blood was collected from newborns with suspected intra-abdominal pathology for neutrophil CD64 and C-reactive protein (CRP) determination at the onset of clinical presentation and 24 h later. They were classified into three groups: intra-abdominal inflammation/sepsis (group 1), extra-abdominal sepsis (group 2) and nonsepsis (group 3). Between-group comparisons were made by Kruskal-Wallis and χ(2) tests. Receiver-operating characteristic curves and diagnostic utilities for single and combination of tests were determined. RESULTS: 310 infants were recruited (102, 34 and 174 in groups 1, 2 and 3, respectively). CD64 (conventional cutoff = 6,010 antibody-PE molecules bound/cell) had substantially better sensitivity (0.81 vs. 0.56) and negative predictive value (0.90 vs. 0.79) for diagnosing intra-abdominal sepsis than CRP, at presentation. Pairing CD64 with routine abdominal radiograph (AXR) substantially increased the sensitivity and negative predictive value for group 1 to 0.99 and 0.99, respectively. By adjusting the CD64 cutoff to 12,500 units, a substantial improvement in specificity could be achieved (0.62 to 0.80) without significantly compromising sensitivity (0.99 to 0.97). CONCLUSIONS: CD64 is a sensitive and 'early' biomarker for diagnosing intra-abdominal inflammation/sepsis. Intra-abdominal catastrophes, including necrotizing enterocolitis, intestinal necrosis, perforation and peritonitis can confidently be excluded using CD64 and AXR early in the course of the disease.

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.

Transition care for adolescents and families with chronic illnesses.

OBJECTIVES: To explore the attitudes of adolescents and parents toward transition care and to identify factors and barriers associated with transition decision. METHODS: The study was conducted at a pediatric out-patient clinic using a self-administered questionnaire to evaluate the perspective of adolescent chronic patients on transition care for common chronic diseases. Despite its importance as emphasized in medical literature, transition care for adolescent patients with chronic illnesses is under-developed in Hong Kong. RESULTS: A total of 137 adolescents aged 16-19 years, and 67 parents completed the survey; 85.3% of adolescents and 82.5% of parents were willing to transfer to adult care. "Adolescent's perception of his/her own responsibility towards chronic illness" was positively associated with willingness to transfer to adult care (OR = 3.84; 95% CI, 1.41-10.45; p = .008), whereas "Detailed explanation by doctors" encouraged transition decision for adolescents (OR = 12.20; 95% CI, 1.22-122.33; p = .033). "Do not want to change" was the only significant barrier for transition for both adolescents (OR = .08; 95% CI, .01-.50; p = .007) and parents (OR = .07; 95% CI, .02-.36; p = .001). However, less than 10% of subjects had ever received any transition information from doctors or other healthcare workers. CONCLUSIONS: This is the first study in Asia region evaluating attitudes of adolescents and parents on transition care. The majority of adolescents and parents accept transition care from pediatrics to adult service, but only a small proportion has ever received transition information from doctors. Our findings should be useful to healthcare providers in planning transition care programmes for adolescent patients with chronic illnesses.

Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants.

Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.

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.

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.

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.

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.

Severe childhood injuries and poisoning in a densely populated city: where do they occur and what type?

AIM: The aim of this study was to review the patterns of severe childhood injuries and poisoning necessitating pediatric intensive care in a regional trauma center. METHODS: We reviewed discharge data of all children who were hospitalized for severe injuries and poisoning at the pediatric intensive care unit of a teaching hospital between October 2002 and December 2008. RESULTS: There were 86 patients (males/females, 2:1). Road traffic injuries (n = 19), falls (n = 17), and scalds (n = 13) were the 3 leading categories and accounted for 57% of these pediatric intensive care unit admissions. Injuries more commonly occurred indoor (63%), and victims of indoor accidents were younger (median age, 2.6 vs 8.4 years; P < .0001), with scalds, poisoning, and foreign body aspiration being predominant, whereas road traffic accidents predominated in outdoor accidents. As a risk factor, premorbid neurodevelopmental conditions such as mental retardation, convulsion disorder, or cerebral palsy were only present in indoor accidents. Children in outdoor injuries were generally healthy. Both groups were associated with significant morbidity (mechanical ventilation in 60%, inotrope use in 20%, anticonvulsants in 24%, and neurological/neurosurgical supports in 49%). Comparing the 3 most common categories of patients, there were significant differences in the median age, requirement of neurological/neurosurgical supports, and median hospital stay. Although not requiring neurological/neurosurgical supports, scalds injuries involved the youngest age group and required the longest hospital stay. CONCLUSIONS: The causes of severe childhood injuries are heterogeneous. Cardiopulmonary or neurological/neurosurgical supports are often required. These injuries more commonly occur indoor and involve toddlers with underlying neurodevelopmental conditions. These findings have important implications and serve to heighten public awareness especially on home safety measures in the prevention of childhood accidents.

Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma.

OBJECTIVES: The purpose of this trial was to evaluate whether the herbal formula of CUF2 used as complementary therapy improves the clinical symptoms and biochemical markers in children with asthma using inhaled corticosteroids. PATIENTS AND METHODS: In a double-blind, placebo-controlled prospective trial, 85 children with asthma aged 7-15 years were randomly assigned to receive either a daily oral herbal formula of 0.619-g CUF2 capsule of dried aqueous extract with an equal weight of five herbs (Astragalus mongholius Bunge, Cordyceps sinensis Sacc., Radix stemonae, Bulbus fritillariae cirrhosae, and Radix scutellariae) or placebo for 6 months. RESULTS: The primary endpoint was the change in steroids dosage; the secondary outcomes included the disease severity score, lung function test, and biochemical markers in blood. Eighty-five (85) children (42 on active treatment and 43 on placebo) completed the 6-month clinical trial. Children randomized to the herbal formula of CUF2 and the placebo showed a similar improvement in clinical symptoms and biomedical markers. The comparison between the CUF2 group and the placebo group showed no significant difference on the dosage of steroids (-2.3 versus -3.1 mg, p = 0.915), disease severity score (-2.3 versus -3.1, p = 0.215), and lung function test of forced expiratory volume in 1 second/forced vital capacity percent (0.1 versus 0.6%, p = 0.809) and peak expiratory flow rate (-7.3 versus -0.6 l/minutes, p = 0.118). No significant difference was found between the two study groups in the biochemical outcomes measured. The intervention effect of CUF2 was smaller than the placebo effect. CONCLUSIONS: This study provides no evidence to support the use of the herbal formula of CUF2 in children with asthma. Parents are thus advised to discuss with health professionals before choosing an herbal formula in preference to conventional treatment modes.

Validation of prediction equations for estimating resting energy expenditure in obese Chinese children.

OBJECTIVES: (1) To examine the validity of existing prediction equations (PREE) for estimating resting energy expenditure (REE) in obese Chinese children, (2) to correlate the measured REE (MREE) with anthropometric and biochemical parameters and (3) to derive a new PREE for local use. DESIGN: Cross-sectional study. SUBJECTS: 100 obese children (71 boys) were studied. MEASUREMENTS: All subjects underwent physical examination and anthropometric measurement. Upper and central body fat distribution was signified by centrality and conicity index respectively, and REE was measured by indirect calorimetry. Fat free mass (FFM) were measured by DEXA scan. Thirteen existing prediction equations for estimating REE were compared with MREE among these obese children. Fasting blood for glucose, lipid profile and insulin were obtained. RESULTS: The overall, male and female median MREEs were 7.1 mJ/d (IR 6.2-8.4), 7.3 mJ/d (IR 6.3-9.7) and 6.9 mJ/d (IR 5.6-8.1) respectively. No sex difference was noted in MREE (p=0.203). Most of the equations except Schofield equation underestimated REE of our children. By multiple linear regression, MREE was positively correlated with FFM (p<0.0001), conicity index (p<0.001) and centrality index (p=0.001). A new equation for estimating REE for local use was derived as: REE=(17.4*logFFM)+(11.4*conicity index)-(2.4*centrality index)-31.3. The mean difference of new PREE-MREE was -0.011 mJ/d (SD 1.51) with an interclass correlation coefficient of 0.91. CONCLUSION: None of the existing prediction equations were accurate in their estimation of REE, when applied to obese Chinese children. A new prediction equation has been derived for local use.

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.