Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson disease.

The objectives were to determine the reference intervals of spot urine copper excretion indexes in pre-school children and to evaluate their utility in screening for Wilson disease (WD). With spot urine collected from a control sample of preschool children (aged 3-7 years, n=153), the reference intervals of spot urine copper excretion indexes and their biological variation were defined. In order to investigate their utility performance in screening for WD in this age group, multiple spot urine samples from six WD patients who were diagnosed at presymptomatic stage were also analysed and compared. Cut-off values useful for detection of WD were defined by receiver operator curve (ROC) analysis. Biological (inter-individual) variation of spot urine copper indexes expressed as coefficient of variation (CVg) were around 60% at this age group, which was moderate and similar to other clinically useful urine tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with both urine creatinine and osmolality. Linear regression against both creatinine and osmolality showed that ∼94% of data points in healthy preschool children fell within the prediction interval, suggesting that both were useful normalisation factors. ROC showed that copper to osmolality ratio was the best index with an area under curve (AUC) greater than 0.98. Cut-off values of 0.5 µmol/L, 0.1 µmol/mmol and 0.00085 µmol/mOsmol (32 µg/L, 56 µg/g creatinine and 0.054 µg/mOsmol, respectively, in conventional units) for spot urine copper concentration, copper to creatinine ratio and copper to osmolality ratio, respectively, have potential application in the differentiation of WD patients. Based on the data, a new WD screening strategy targeting preschool children is proposed. Application of a bivariate screening strategy using spot urine copper concentration and urine osmolality may be useful in a population-wide screening program for WD among preschool children.

Relationship between passive smoking exposure and urinary heavy metals and lung functions in preschool children.

Environmental tobacco smoke (ETS) exposure is a risk factor for asthma in school-age children, but there is limited data of ETS exposure on respiratory health in preschool children. This study investigated the relationship between ETS, lead (Pb), and cadmium (Cd) exposures and asthma symptoms and spirometric indices in Chinese preschoolers. Preschool children from 30 nurseries and kindergartens performed spirometry with incentives of animation programs, and their urinary cotinine, Pb and Cd concentrations were measured by immunoassay and inductively coupled plasma-mass spectrometry, respectively. Two thousand seven hundred sixty-three preschoolers participated, and 1,505 and 893 provided valid spirometric data and urine samples, respectively. Current domestic smoking was reported in 37.5% of children, but only 95 (10.6%) had high urinary cotinine-to-creatinine ratio (≥30 ng/mg). Pb was measurable in 3.9% of samples, whereas 406 (45.5%) children had high Cd. Reported ETS exposure was not associated with any spirometric index, whereas cotinine-to-creatinine ratio was inversely associated with forced expiratory volume in 0.5-sec (ß = -0.093, P = 0.003), forced expiratory flow between 25% and 75% of expiration (ß = -0.138, P = 0.002) and peak expiratory flow (ß = -0.106, P = 0.002). Cd exposure was not associated with reported respiratory symptom or spirometric indices. This community study shows that ETS exposure defined by urinary cotinine is a strong risk factor for lung function impairment measured by spirometry in Chinese preschool children. Urinary cotinine is more reliable than questionnaire for assessing ETS exposure in young children. Although high urinary Cd is common in Hong Kong preschoolers, such biomarker is not associated with any clinical or spirometric outcome.

Cadmium and lead in Hong Kong school children.

AIM: Cadmium (Cd) and lead (Pb) are toxic elements in our environment. This study is to determine the reference intervals of Cd and Pb in blood and urine from Hong Kong school children and to identify their determinants. METHODS: A total of 2209 secondary school children and 893 preschool children were recruited. Cd and Pb in blood and urine were measured by inductively-coupled plasma mass spectrometry. RESULTS: Blood Cd was affected by age, smoking and residential district, while urine Cd was influenced by age and blood Cd. Blood Cd was positively correlated with smoking as confirmed by urinary cotinine (rho  = 0.183, p  <  0.001, n = 2074). Blood Pb was dependent on gender and residential district, while urinary Pb was dependent on gender and blood Pb. Students from schools of lower academic grading had higher blood Cd and Pb than those from higher academic grading schools (p < 0.001, respectively). Urinary albumin was positively associated with urinary Cd and Pb. CONCLUSIONS: Using a non-occupationally exposed population, the reference ranges are: blood Cd < 21.9  nmol/L for smokers and < 8.8  nmol/L for non-smokers, and blood Pb < 203.8  nmol/L. Reference intervals for urinary Cd and Pb are also reported.

Asthma and bronchodilator responsiveness are associated with polymorphic markers of ARG1, CRHR2 and chromosome 17q21.

OBJECTIVE: Asthma is caused by complex interactions between multiple genes. ß2-Agonist is the standard rescue treatment to relieve asthma symptoms and bronchoconstriction. A genetic study for spirometric parameters helps to predict the responses to this antiasthma treatment. This study investigated the relationship between asthma and bronchodilator responsiveness (BDR) and eight asthma genes. METHODS: Fifteen single-nucleotide polymorphisms in these genes were genotyped in 345 Chinese asthmatics and 464 controls. Gene-gene interactions were analysed by generalized multifactor dimensionality reduction (GMDR). RESULTS: The diagnosis of asthma was associated with rs7216389 in ORMDL3 [odds ratio (OR) 0.74 and 95% confidence interval (95% CI) 0.56-0.99] and rs3756780 in ARG1 (OR 0.67, 95% CI 0.51-0.89) and BDR with rs2749935 in ARG1. However, none of these associations remained significant at 5% when adjusted for multiple testing by the Bonferroni correction or a false discovery rate. GMDR analyses revealed that rs7216389 in ORMDL3 and rs3756780 in ARG1 might interact for a risk of asthma. Individuals with high-risk genotypes had OR 1.66 (95% CI 1.24-2.23) for asthma when compared with those with low-risk genotypes. GMDR suggested a two-locus model with rs2749935 in ARG1 and rs2190242 in CRHR2 to be associated with BDR. Specifically, reversibility of forced expiratory volume in 1 s was higher in high-risk than that in low-risk patients [mean (95% CI): 10.7 (8.6-12.9) vs. 6.8 (5.9-7.6)%]; with the latter group showing higher forced expiratory volume in 1 s reversibility compared with high-risk controls [2.8 (1.4-4.3)%]. CONCLUSION: ARG1 and ORMDL3 may interact to determine the risk of asthma and ARG1 and CRHR2 to alter BDR in asthmatics. Nonetheless, this study is only hypothesis-generating as none of the single marker comparisons is significant when adjusted for multiple testing. These findings need to be confirmed in independent populations.

A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products.

OBJECTIVE: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. METHODS: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. RESULTS: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. CONCLUSIONS: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

Domestic exposure to aeroallergens in Hong Kong families with asthmatic children.

Indoor aeroallergen exposures increased asthma symptoms in Caucasians, but their determinants and relationship to asthma and allergy in Asians are unclear. This study investigated exposures to cat, cockroach, and Blomia tropicalis allergens in 115 Hong Kong families with asthmatic children. Patients underwent exhaled nitric oxide and spirometric measurements. Home visits were made within 2 weeks during which parents completed a standardized questionnaire. Fel d 1, Bla g 2, and Blo t 5 in dust samples collected from patients' mattresses, bedroom floors, and living room floors were measured by immunoassays. These aeroallergens were only detectable in some homes (38-55% for Fel d 1; 9-21% for Bla g 2, and 7-14% for Blo t 5). The presence of cat and/or dog was a strong determinant for Fel d 1 in all indoor sites. The timing and frequency of bedding change was associated with Bla g 2 levels, whereas the timing of bedroom floor cleaning was a consistent factor for Blo t 5 levels. Asthmatic children in families with high allergen exposure were more likely to have ≥4 wheezing attacks in preceding 12 months and exercise-induced wheezing than those with normal allergen exposure (P = 0.051 and 0.030, respectively). Mattress levels of all three allergens were also associated with severity of several allergy symptoms (P = 0.025-0.005). None of these aeroallergens correlated with exhaled nitric oxide and spirometric parameters. This study identifies determinants for cat, cockroach, and B. tropicalis levels in Hong Kong families with asthmatic children. These exposures are associated with severity of allergy symptoms.

A prospective longitudinal study to estimate the "adjusted cortisol percentile" in preterm infants.

The normal range of serum cortisol concentrations and the appropriate levels of circulating cortisol in different clinical situations in preterm infants are not well defined. This study aimed to evaluate the impact of perinatal factors on circulating cortisol levels in preterm infants and to create a quantitative model that could estimate the "adjusted cortisol percentile." Serial serum cortisol concentrations were measured in 209 infants ≤ 32 wk gestation on d 1, 4, 7, 14, and 21 of life. Seven perinatal factors or conditions that could affect circulating cortisol level were identified. Serum cortisol levels were higher on d 4 (p = 0.007) and d 7 (p = 0.007) but lower on d 21 (p = 0.001) compared with d 1. Serum cortisol was also higher in infants on nasal continuous positive airway pressure (p = 0.003); requiring a second vasopressor (p < 0.001); with intraventricular hemorrhage (≥ grade 3; p < 0.001); with histologic chorioamnionitis (p = 0.007); with severe lung disease (p = 0.046); and with decreasing GA (p < 0.001). A mathematical equation was proposed based on factors derived in this preliminary study for estimating the adjusted cortisol percentile. Frontline neonatologists could now access the equation on our Web site (http://www.sta.cuhk.edu.hk/pswong/ACortP.html) to calculate the adjusted cortisol percentile, which could potentially improve the interpretation of circulating cortisol in different clinical situations.

Haplotype effect in the IGF1 promoter accounts for the association between microsatellite and serum IGF1 concentration.

OBJECTIVE: Systemic insulin-like growth factor 1 (IGF1) level is an important risk factor for various diseases. The inter-individual variation of serum IGF1 is determined by environmental and genetic factors, which are attributed to a microsatellite in IGF1 promoter. However, the exact nature of the underlying regulatory elements accounting for this association has not been characterized. Here, we defined the haplotype patterns, including both SNPs and the microsatellite, in the Chinese population, and investigated their regulatory effect on serum IGF1 level. This is the first study in which haplotype patterns of the microsatellite and SNPs in the IGF1 promoter are examined together. METHODS: The linkage disequilibrium (LD) patterns of IGF1 were examined using tagSNPs of the IGF1 regulatory region. The microsatellite, three tagSNPs and haplotypes were correlated with serum IGF1 concentration in 450 normal premenopausal Chinese women. RESULTS: Common alleles of the microsatellite were in strong LD with the three tagSNPs and were associated with particular haplotypes composed of SNPs. Neither the CA repeat number nor SNPs alone showed a robust association with serum IGF1 concentration. On the other hand, the haplotype T-19-A-T was significantly associated with serum IGF1 level. CONCLUSION: No association was found between SNPs and microsatellite alone. However, the haplotype showed better correlation with serum IGF1 level. The results indicate that the previously observed correlation with microsatellite was because of a haplotype effect in the IGF1 promoter. Microsatellite or tagSNPs alone are not the primary regulatory elements of IGF1 expression. The exact regulatory genetic variant needs to be defined by functional genetic studies.

Specific IgE of common foods in Chinese children with eczema.

Food atopy is important but inadequately studied among children with atopic dermatitis (AD). We evaluated whether any association existed between AD severity, quality of life, total IgE, eosinophil counts, and the number of food items sensitized. Specific IgE of ten common food items was measured for a group of consecutive AD patients (n=85) enrolled during a randomized trial and correlated the findings with eczema severity. Twenty-four patients (28%) were negative for any of the ten common food items. The most commonly sensitized foods were shrimp (54%), egg white (43%), wheat (42%), and peanut (41%). Atopy to beef as a protein and orange as a fruit were least common among the food items studied, even among patients positive for 8-9 IgE items. Patients with severe AD (objective SCORAD>40) were more likely to be positive for at least one of the food items (Yates corrected p=0.024 for ≥1 food-specific IgE in severe vs. moderate AD, OR 3.42 and 95% CI 1.15-10.32); and for at least seven of the food items (p=0.001 for ≥7 food-specific IgE vs. nil with OR 11.67 and 95% CI 2.29-67.77), respectively. The Spearman coefficients between the number of positive food-specific IgE and total SCORAD, objective SCORAD, area of AD involvement, Children's Dermatology Life Quality Index (CDLQI), total IgE levels, and eosinophil counts were 0.42 (p<0.001), 0.45 (p<0.001), 0.50 (p<0.001), 0.17 (p=0.116), 0.80 (p<0.001), and 0.22 (p=0.043), respectively. Specific IgE levels for beef correlated with all the other food-specific IgE levels, including cow's milk (ρ=0.061, p<0.001) and soy (ρ=0.70, p<0.001). The number of common food items sensitized correlated with disease severity, extent, and total IgE levels. IgE sensitization to beef protein is unlikely in the majority of children with AD, but its serum IgE level is associated with disease severity and risk of sensitization to other foods.

PHF11 is not a major candidate gene for asthma or eczema in Chinese children.

SUMMARY: Positional cloning and candidate gene studies in different Caucasian populations identified the gene encoding plant homeodomain zinc finger protein 11 (PHF11) to be associated with asthma and eczema. Microarray analysis also confirmed increased PHF11 expression in type 1 T-helper lymphocytes. However, such disease associations are unclear in Asian subjects. This case-control genetic association study investigated the relationship between asthma and eczema phenotypes and tagging single-nucleotide polymorphisms (SNPs) of PHF11 in Hong Kong Chinese children. Three hundred and nineteen asthmatic children and 236 children with eczema were recruited from hospital clinics and 445 children without any history of allergic disease were recruited as controls from local schools and hospitals. Atopy was defined by the presence of allergen-specific IgE in plasma or positive skin prick tests with wheal >or=3 mm larger than negative control. Lung function of asthmatics was evaluated by pre-bronchodilator spirometry. Ten PHF11 SNPs were genotyped by multiplex SNaPshot assay. Genotyping call rates were 100% for all SNPs, which also followed Hardy-Weinberg equilibrium. These SNPs were tightly linked in one haplotype block (D' >or= 0.95 for nearly all SNP pairs). Physician-diagnosed asthma was weakly associated with PHF11 +20860 and +22818 (P = 0.032 for both). Atopy was also associated with PHF11 +22398 (P = 0.029). However, none of the PHF11 SNPs was associated with eczema diagnosis and plasma total IgE and spirometric parameters in our patients. Our findings do not support PHF11 to be a major candidate gene for asthma, eczema and aeroallergen sensitization in Chinese children.

Indoor determinants of endotoxin and dust mite exposures in Hong Kong homes with asthmatic children.

BACKGROUND: Domestic endotoxin enhances airway inflammation and increases asthma severity in Caucasian children, but little data are published on indoor endotoxin exposure in Asian countries. This study investigated house dust endotoxin and Der p 1 levels in Hong Kong families with asthmatic children, and their effects on asthma severity. METHODS: 115 asthmatics from a pediatric clinic underwent fractional exhaled nitric oxide (FeNO) and spirometric measurements. Home visits were then made within 2 weeks, during which parents completed the International Study of Asthma and Allergies in Childhood questionnaire. Settled dust was collected from patients' mattresses, bedroom floors and living room floors. Endotoxin and Der p 1 were measured by limulus amebocyte lysate and immunoassay, respectively. RESULTS: Endotoxin was detectable in all locations from all families, whereas Der p 1 was detectable in 58-70% of indoor sites. Floors of both bedroom and living rooms had higher endotoxin but lower Der p 1 levels than mattresses (p < 0.001 for both). Mattress endotoxin level correlated inversely with Der p 1 level (r = -0.308, p = 0.001). Household smoker, feather bedding and vacuum cleaning were independent determinants of indoor endotoxin. Timing of last bedding change was associated with Der p 1 levels at all sites. Mattress endotoxin level was associated with frequency of wheezing episodes (p = 0.044), but neither endotoxin nor Der p 1 was associated with FeNO and spirometric parameters. CONCLUSIONS: Domestic endotoxin levels are associated with frequency of wheezing episodes in asthmatic children but not their FeNO or spirometric measurements.

High-level expression of early growth response-1 and association of polymorphism with total IgE and atopy in allergic rhinitis adults.

BACKGROUND: Early growth response-1 (Egr-1) is expressed in human airways and its polymorphisms have been associated with total IgE and atopy in asthmatic patients. We investigated the effects of Chinese-tagging single nucleotide polymorphism (SNP) of Egr-1 and its mRNA expression on allergic rhinitis (AR) traits. METHODS: Among 214 Chinese AR adults and 259 controls, tag SNP -4071 A-->G was genotyped and mRNA expression in peripheral blood was quantified by real-time PCR. RESULTS: Egr-1 mRNA expression was significantly higher in patients than controls (median of 0.23 vs 0.15 fold GAPDH expression; p<0.001). Its expression was not associated with -4071 polymorphism. However, significant correlations were found between -4071 A-->G with increased plasma total IgE (p=0.028) and atopy (p=0.030) in patients. Logistic regression confirmed the association (p=0.034) with age and gender adjusted. Patients homozygous for the A allele had a 2.3-fold and 1.9-fold risks, respectively of having increased plasma total IgE and atopy than those G allele carriers. CONCLUSIONS: We showed high levels of Egr-1 mRNA expression and demonstrated a significant association of polymorphism with increased plasma total IgE and atopy in AR patients. It may be useful to explore the pharmacogenetics of Egr-1 inhibitors.

Association of plasma soluble CTLA-4 with lung function and gene polymorphism in Chinese asthmatic children.

BACKGROUND: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is known to downregulate the T(H)2 immune response. Recent studies have suggested an association of CTLA-4 polymorphisms with allergic diseases. We investigated the effects of single nucleotide polymorphisms (SNPs) of CTLA-4 on asthma traits and plasma sCTLA-4 in 298 Chinese asthmatic children and 175 controls. METHODS: Plasma sCTLA-4, total and allergen-specific IgE concentrations were measured by enzyme immunoassay. Six SNPs, namely -1147CT, +49AG, CT60, JO31, JO30 and JO27_1, in CTLA-4 were genotyped by restriction fragment length polymorphism. RESULTS: Plasma sCTLA-4 was negatively associated with FEV(1)/FVC (r = -0.146, p = 0.036) among our asthmatic patients. Analysis of locus-locus interaction by generalized multifactor dimensionality reduction showed that -1147CT was the best model for plasma sCTLA-4 with a cross-validation consistency of 10 out of 10 and a prediction error of 40.9% (p < 0.001). Multivariate regression analysis confirmed the association between plasma sCTLA-4 concentration with -1147CT among the 6 SNPs tested (p = 0.002) after adjustment for gender and age. The plasma sCTLA-4 concentration was significantly lower in patients homozygous for the C allele than in T allele carriers (p = 0.001). There was also a significant association between the most common haplotypes with low sCTLA-4 in asthmatics. We could not find any significant association between plasma total IgE, atopy and lung function with the 6 SNPs after Bonferroni correction. CONCLUSIONS: Plasma sCTLA-4 is associated with lung function and -1147CT polymorphism in Chinese asthmatic children. This may help to identify CTLA-4 signaling as a potential therapeutic target in asthma.

Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese.

BACKGROUND: Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. METHODS: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. RESULTS: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. CONCLUSION: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits.

Cold-vapour atomic absorption spectrometry underestimates total mercury in blood and urine compared to inductively-coupled plasma mass spectrometry: an important factor for determining mercury reference intervals.

AIM: In recent years, the application of inductively-coupled plasma mass spectrometry (ICP-MS) has been used increasingly in clinical laboratories for the measurement of various trace elements and heavy metals. However, full evaluation of this technique has not been conducted to ensure the transfer of comparable results from conventional cold-vapour atomic absorption spectrophotometry (CVAAS) for blood and urine total mercury (Hg) analysis. METHODS: A total of 131 blood and 223 urine samples from both patients and normal healthy subjects were collected from a university-based trace element laboratory and a population survey of healthy school adolescents. Correlation study was conducted for total Hg concentration measured by the traditional on-line digestion with flow injection CVAAS and the newly installed ICP-MS. Reference materials were used for method validation and quality control. Standard addition of fixed amounts of inorganic and methyl Hg standards into blood and urine were performed for recovery study. Bias in total Hg measurement was investigated by re-calibrating both instruments using methyl Hg standards. RESULTS: The intra- and inter-assay coefficients of variation in the ICP-MS were <6% in the range of 14-259 nmol/L for Hg in blood and urine samples assayed. The detection limit was 1.1 nmol/L and linearity was up to 186 nmol/L. The results from analyses of a range of whole blood and urine reference materials agreed well with the certified values. The correlation study showed a significant correlation between ICP-MS and CVAAS with: [ICP-MS] = 7.36 + 1.69*[CVAAS] in blood samples (r = 0.84, p < 0.0001) and [ICP-MS] = 1.90 + 1.14*[CVAAS] in urine samples (r = 0.93, p < 0.0001) for total Hg. Recovery study showed that the % recovery of inorganic Hg in blood for ICP-MS and CVAAS ranged from 83 to 95% and 77 to 84%, respectively, while that of inorganic Hg in urine for ICP-MS and CVAAS ranged from 92 to 126% and 43 to 93%, respectively. For methyl Hg, the % recovery in blood for ICP-MS and CVAAS ranged from 72 to 89% and 37 to 75%, respectively, while that in urine for ICP-MS and CVAAS ranged from 65 to 85% and 29 to 42%, respectively. When both instruments were re-calibrated using methyl Hg standards, the blood and urinary total Hg results in ICP-MS were corrected at 24% and -11% of CVAAS, respectively. CONCLUSIONS: Analysis of total Hg was underestimated at about 69% in blood and 14% in urine using the traditional CVAAS method compared to ICP-MS, plausibly due to incomplete oxidation and reduction of methyl Hg species in CVAAS method. The normal limit of blood total Hg concentration has been targeted at <50 nmol/L based on the traditional CVAAS method, and the in vivo proportion of methyl Hg of individuals mainly depends on the dietary intake of seafood. Therefore, for clinical laboratories preparing to change over to ICP-MS method for total Hg analysis, the local reference interval for blood total Hg should be re-determined using a non-occupationally exposed population. Otherwise, over-diagnosis of Hg intoxication can result. We have found that by using ICP-MS for total Hg analysis, the local reference range in blood was <77 nmol/L while in spot urine was <15 nmol/L or 1.2 nmol/mmol of creatinine.

Leukotriene receptor antagonist in the treatment of childhood allergic rhinitis--a randomized placebo-controlled study.

OBJECTIVE: This study was designed to assess the hypothesis that leukotriene receptor antagonists (LTRAs) would provide additional symptom relief in asthmatic children with persistent AR already taking regular antihistamine. The effects of 16-week treatment of LTRA in addition to fexofenadine (FEX) on persistent AR in asthmatic children were examined. STUDY DESIGN: Consecutive children with stable asthma and persistent AR were invited in this randomized, double-blind, placebo-controlled study. After a 2-week run-in period in which subjects were given FEX alone, they were randomly assigned to take LTRA or placebo in addition to FEX for 16 weeks, followed by 8 weeks of follow-up phase with FEX taken alone. Symptom scoring, rhinoscopy, acoustic rhinometry, spirometry, nasal secretion extraction and blood taking for IL-4 and IL-13 analysis were performed after a 2-week run-in and at the end of treatment. RESULTS: Forty-four subjects with a median (IQR) age of 12.2 (10.1-14.1) years were recruited. At week 4 of treatment, the between-group differences in the mean changes of daytime sneezing score (mean difference (95% CI) = -0.35 (-0.59, -0.12), P = 0.004), nighttime sneezing score (mean difference (95% CI) = -0.37 (-0.62, -0.11), P = 0.007) and daytime composite score (mean difference (95% CI) = -1.08 (-1.92, -0.25), P = 0.013) were significant. Acoustic rhinometry also demonstrated a nearly significant difference in nasal volume change between groups at 16 weeks of treatment (mean difference (95% CI) = 0.572 (0.090-1.054), P = 0.021). IL-4 and IL-13 were not detected in the majority of nasal secretion or serum samples. CONCLUSIONS: Additional LTRA provided a more rapid relief on sneezing at the 4-week time point. This combination therapy also maintained a greater nasal volume and this might translate to lesser nasal congestion.

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.

Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: a prospective randomized study.

Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia and hyperandrogenism in women. Few prospective data are available. We evaluated the reproductive endocrine and insulin-related metabolic parameters in men and women with untreated epilepsy randomized to valproate (n=44) or lamotrigine (n=37) monotherapy for 12 months. On treatment, there was no significant difference in fasting serum insulin concentrations between the two groups. In women (n=40), there was no significant difference between the two groups in change from baseline in serum total testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, or follicle-stimulating hormone. In men (n=41), follicle-stimulating hormone concentration significantly decreased in patients taking valproate compared with those on lamotrigine as early as 3 months after treatment. Greater attention should be paid to investigate the potential impact of valproate on reproductive function in men.

PTGDR is not a major candidate gene for asthma and atopy in Chinese children.

Airway sensitization requires the expression of prostanoid DP receptor in mice. Recent studies reported that polymorphisms in the gene encoding prostanoid DP receptor (PTGDR) were associated with asthma in White people and Black people, but this association could not be replicated among Latinos and Koreans. This study investigated the association between asthma-related traits and six single nucleotide polymorphisms (SNPs) of PTGDR in Chinese children, consisted of 308 asthmatics and 368 non-allergic controls. Plasma total and aeroallergen-specific immunoglobulin E were measured by immunoassays. PTGDR SNPs were determined by multiplex SNaPshot genotyping. All polymorphic markers followed Hardy-Weinberg equilibrium except G1044A in the controls (p = 0.021). The linkage disequilibrium (LD) scores for these SNPs were moderate to high, and in particular, T-549C and C-441T were in strong LD. Significant interethnic variations in PTGDR alleles and haplotypes (up to 41%) were found in our subjects when compared with White people or Latinos. Asthma diagnosis, atopy and aeroallergen sensitization did not differ among children with different PTGDR genotypes (p > 0.15 for all). Linear regression showed weakly significant associations between T-197C and G1044A of PTGDR and spirometric variables. PTGDR haplotypes were not associated with asthma and atopy phenotypes (p > 0.09 for all). Our results do not support PTGDR to be a major candidate gene for asthma traits in Chinese children.