Christopher W K Lam

Macau University of Science and Technology, Macao, Macau, Macao

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Publications (340)1378.95 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the plasma concentration of the novel regulatory cytokine IL-35 and intracytosolic pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors in granulocytes and explored their potential implication in disease severity monitoring of allergic asthma. The expression of circulating IL-35 and other pro-inflammatory mediators in asthmatic patients or control subjects were evaluated using enzyme-linked immunosorbent assay (ELISA). The intracellular expressions of NOD1 and NOD2 in CCR3+ granulocytes were assessed using flow cytometry. Plasma concentrations of IL-35, IL-17A, basophil activation marker basogranulin, and eosinophilic airway inflammation biomarker periostin were significantly elevated in allergic asthmatic patients compared to non-atopic control subjects (all probability (p) <0.05). Both granulocyte markers exhibited significant and positive correlation with plasma IL-35 concentration in asthmatic patients (all p < 0.05). Significant positive correlation was also identified between plasma concentrations of IL-35 and periostin with disease severity score in asthmatic patients (both p < 0.05). The basophil activation allergenicity test was positive in allergic asthmatic patients but not in control subjects. Despite significantly elevated eosinophil count in allergic asthmatic patients, downregulation of NOD2 in CCR3+ granulocytes was observed in these patients (both p < 0.05). A negative correlation between plasma concentrations of tumor necrosis factor family member LIGHT and soluble herpesvirus entry mediator was observed in patients with elevated plasma concentration of IL-35 (p < 0.05). Aberrant expression of NOD2 in granulocytes may be contributed to the impaired innate immunity predisposing allergic asthma. IL-35 may serve as a potential surrogate biomarker for disease severity of allergic asthma.
    Inflammation 10/2014; · 1.92 Impact Factor
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    ABSTRACT: The role of serum α-fetoprotein (AFP) measurements in the diagnosis of hepatocellular carcinoma (HCC) remains controversial. Some guidelines have advised against the use of AFP in the diagnosis of HCC. This study was conducted to evaluate the performance of AFP in the diagnosis of HCC, and to identify the optimal cut-off value of serum AFP in the diagnosis of HCC in patients with a hepatic mass. Patients who presented during the period from May 1997 to March 2003 with hepatic lesions, for whom paired data on serum AFP values at baseline and lesion histology were available, were reviewed. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. Data for a total of 805 patients were evaluated. The mean AFP value was 26 900 ng/ml (range: 0-1 965 461 ng/ml). The histological diagnosis was HCC in 557 patients. The optimal AFP cut-off value was 10 ng/ml (for sensitivity of 82.6% and specificity of 70.4%). At a cut-off level of 200 ng/ml, sensitivity, specificity, and positive and negative predictive values were 47.7%, 97.1%, 97.5% and 44.4%, respectively. The diagnostic performance of AFP remains similar in patients with chronic hepatitis B virus infection, despite a lower negative predictive value. Common aetiologies of liver lesions associated with elevated AFP include cholangiocarcinoma and neuroendocrine tumours. In Asian patients with suspicious liver lesions, the cut-off AFP level of 200 ng/ml is useful to achieve a diagnosis of HCC with high specificity and reasonable sensitivity. The measurement of serum AFP should not be excluded from guidelines for the diagnosis of HCC.
    HPB 08/2013; · 2.05 Impact Factor
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    ABSTRACT: 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 (β = -0.093, P = 0.003), forced expiratory flow between 25% and 75% of expiration (β = -0.138, P = 0.002) and peak expiratory flow (β = -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. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 06/2013; · 2.38 Impact Factor
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    ABSTRACT: To examine the association between passive smoking and snoring in preschool children using parent-reported questionnaires and urine cotinine levels. This was a population-based cross-sectional survey of 2954 children aged 2-6 years in Hong Kong. Parent-reported questionnaires provided information on snoring and household smoking. One-third of children randomly chosen from the cohort provided urine samples for cotinine analysis. Increased urine cotinine was defined as urinary cotinine concentration ≥30 ng/mg creatinine. Using multivariate logistic regression analysis, we analyzed the association between snoring and passive smoking, controlling for potential confounders including age, sex, body mass index z-score, atopic diseases, recent upper respiratory tract infection, parental allergy, parental education, family income, and bedroom-sharing. A total of 2187 completed questionnaires were included in the final analysis, and 724 children provided urine samples for cotinine measurement. After adjustment for confounding factors, questionnaire-based household smoking (>10 cigarettes/d: OR = 2.22, 95% CI = 1.02-4.81) and increased urine cotinine (OR = 4.37, 95% CI = 1.13-16.95) were significant risk factors for habitual snoring (snoring ≥3 nights per week). For occasional snoring (snoring 1-2 nights per week), reported household smoking (1-10 cigarettes/d: OR = 1.41, 95% CI = 1.14-1.76; >10 cigarettes/d: OR = 1.56, 95% CI = 1.05-2.31), and increased urine cotinine (OR = 1.82, 95% CI = 1.03-3.20) were also identified as significant risk factors. A dose-effect relationship was found for snoring frequency and adjusted natural logarithms of urinary cotinine concentrations (P < .001). Environmental tobacco smoke exposure is an independent risk factor for snoring in preschool children. Parents' smoking cessation should be encouraged in management of childhood snoring.
    The Journal of pediatrics 06/2013; · 4.02 Impact Factor
  • H N Qiu, C K Wong, I M T Chu, S Hu, C W K Lam
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    ABSTRACT: Respiratory tract bacterial infection can amplify and sustain airway inflammation. Intracytosolic nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is one member of the nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) family, which senses the conserved structural peptidoglycan component muramyl dipeptide (MDP) in almost all bacteria. In the present study, activation of the NOD2 ligand MDP on primary human bronchial epithelial cells (HBE) co-cultured with human basophils was investigated. Cytokines, NOD2, adhesion molecules and intracellular signalling molecules were assayed by enzyme-linked immunosorbent assay or flow cytometry. The protein expression of NOD2 was confirmed in basophils/KU812 cells and HBE/human bronchial epithelial cell line (BEAS-2B) cells. MDP was found to up-regulate significantly the cell surface expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 on basophils and HBE in the co-culture system with or without basophil priming by interleukin (IL)-33 (all P < 0·05). MDP could further enhance the release of inflammatory cytokine IL-6 and chemokine CXCL8, and epithelium-derived anti-microbial peptide β-defensin 2 in the co-culture. HBE cells were the major source for the release of IL-6, CXCL8 and β-defensin2 upon stimulation by MDP in the co-culture system. The expression of ICAM-1 and VCAM-1 and release of IL-6 and CXCL8 were suppressed by various signalling molecule inhibitors, implying that the interaction between basophils and primary human bronchial epithelial cells could be regulated differentially by the mitogen-activated protein kinase pathways and nuclear transcription factors. The results therefore provide a new insight into the functional role of basophils in innate immunity, and the link between respiratory bacteria-mediated innate immunity and subsequent amplification of allergic inflammation in the airway.
    Clinical & Experimental Immunology 04/2013; 172(1):81-94. · 3.28 Impact Factor
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    ABSTRACT: Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 μg/mL) and GA (10 μg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-kB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects.
    Molecules 03/2013; 18(3):2483-500. · 2.10 Impact Factor
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    ABSTRACT: 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.
    Pathology 10/2012; · 2.62 Impact Factor
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    ABSTRACT: This study is a direct assessment of blood heavy metal concentrations of frequent users of Chinese medicines (CM), who had been taking prescribed CM at least 6 days per week for not less than 3 months, to determine whether their intake of CM could cause an increased load of toxic heavy metals in the body. From November 2009 to June 2010, 85 subjects were recruited with informed consent, and their blood samples were collected for measurement of arsenic, cadmium, lead and mercury concentrations. Results showed that blood concentrations of four heavy metals of nearly all 85 subjects were within reference ranges. Only one subject who had consumed plentiful seafood was found to have transiently increased blood arsenic concentration (29% higher than the upper limit of the reference range). However, after refraining from eating seafood for 1 month, his blood arsenic concentration returned to normal. Eighty commonly prescribed CM in both raw medicine and powder concentrate supplied by local distributors were also tested for the four heavy metals. Twelve out of the 80 raw medicines were found to contain one or more of the heavy metals that exceeded the respective maximum permitted content. Cadmium was most frequently found in the contaminated samples. None of the powder concentrates had heavy metal content exceeding their respective maximum permitted level. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 08/2012; 27(6). · 2.40 Impact Factor
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    ABSTRACT: Aims:  To study the prediction of abnormal glucose tolerance (AGT), diabetes mellitus (DM), hypertension (HT) and metabolic syndrome (MetS) among Chinese women using glycemic indices in the mid-trimester of pregnancy. Methods:  A cohort of Chinese women who had had either normal glucose tolerance or gestational diabetes mellitus (GDM) during a pregnancy were assessed at a median of 8 and 15 years post-delivery. All women underwent a 50-g glucose challenge test (GCT) and a 75-g oral glucose tolerance test in the mid-trimester of the index pregnancy. A receiver operating characteristic curve was used to assess the prediction of AGT, DM, HT and MetS. Results:  All glycemic indices were significant predictors of AGT and DM, and the 2-h plasma glucose (PG) and GCT were predictive of HT, at both 8 and 15 years post-delivery. MetS can only be predicted by the fasting plasma glucose (FPG) and was confined to 15 years post-delivery. After adjustment for confounding variables, all glycemic indices were still independent predictors of AGT and DM at both 8 and 15 years post-delivery, except for FPG in predicting DM at 8 years, while only the 2-h PG remains an independent predictor of HT at 15 years. The optimal cut-off values for FPG, 2-h PG and GCT are 4.2 mmol/L, 7.2 mmol/L and 7.7 mmol/L, respectively; all are lower than the current cut-off thresholds for the screening and diagnosis of GDM. Conclusions:  Women who had a glycemic level below the criteria for a positive screening test and below the diagnostic threshold for GDM still have a significant cardiometabolic risk.
    Journal of Obstetrics and Gynaecology Research 08/2012; · 0.84 Impact Factor
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    ABSTRACT: Eosinophils are the principal effector cells of allergic inflammation, and hematopoietic cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) is the primary cytokine that activates and prolongs the survival of eosinophils in local inflammatory sites by mediating anti-apoptotic activity in allergic inflammation. To investigate the immunopathological role of microRNA (miRNA) in allergic inflammation, we elucidated the regulatory mechanisms of miRNA on the GM-CSF-mediated in vitro survival in eosinophils. Eosinophils were purified from fresh human peripheral blood buffy coat fraction obtained from adult volunteer using microbead magnetic cell sorting. The apoptosis, viability and phosphorylation of extracellular signal-regulated kinase (ERK) were assessed by flow cytometry, and the expression of miRNA was analyzed using Agilent Human miRNA Microarray with Human miRNA Microarray Version 3 and real time RT-PCR. We have confirmed the increased in vitro viability of GM-CSF-treated eosinophils and upregulated expression of miRNA-21* (miR-21*), a complementary miRNA of miR-21, in GM-CSF-treated eosinophils. The transfection of pre-miR miR-21* precursor molecule could up-regulate the miR-21* expression, subsequently enhance the GM-CSF-activated ERK pathway and reverse the apoptosis of eosinophils, while anti-miR-21* inhibitor could down-regulate the miR-21* expression, suppress the GM-CSF-activated ERK pathway and enhance the apoptosis. Our results should shed light on the potential immunopathological role of miRNA-21* regulating the in vitro apoptosis of eosinophils and development of novel molecular treatment of allergic inflammation.
    Immunobiology 05/2012; · 2.81 Impact Factor
  • S H Chui, Y T Szeto, C W K Lam
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    ABSTRACT: To investigate the prevalence and genotypes of human papillomavirus (HPV) infection in Macau women. Female patients presenting for a medical consultation or medical check-up were recruited with informed consent. Cytology and HPV-DNA genotyping were performed on 402 cervical specimens that were collected from Macau women. Of the specimens, 29.9% were found to be HPV-DNA positive; 26.4% were infected with one HPV genotype, while 3.0% and 0.5% were infected with two and three HPV genotypes, respectively. The most prevalent HPV genotype was type 52 (11.1%), followed by type 16 (9.7%). Both types 51 and 62 ranked third (9.0%). The HPV infection rate in Macau appears to be higher than that in the neighbouring city of Hong Kong. The most prevalent genotypes were similar to those in South-west and Southern China.
    Public health 05/2012; 126(7):600-4. · 1.26 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
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    ABSTRACT: Traditional Chinese medicine (TCM) has been used for prevention and treatment of severe acute respiratory syndrome (SARS) in Hong Kong during the outbreak in spring 2003. We investigated the immunomodulating effects of an innovative TCM regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for treating febrile diseases. Thirty-seven healthy volunteers were given the oral TCM regimen daily for 14 days. Peripheral venous blood samples were taken on days 0, 15 and 29 for hematology, biochemistry and immunology tests, including the measurement of blood lymphocyte subsets and plasma T-helper lymphocyte types 1 and 2 cytokines and receptor. After 3 months, 23 of the volunteers participated in a control study without TCM treatment for the same time course of blood tests. Two volunteers withdrew on day 2, due to headache and dizziness. All others remained well without any side effects. No participants showed significant changes in their blood test results, except that the T-lymphocyte CD4/CD8 ratio increased significantly from 1.31 ± 0.50 (mean ± SD) on day 0 to 1.41 ± 0.63 on day 15 (p < 0.02), and reduced to 1.32 ± 0.47 on day 29 (p < 0.05). In the control study, there were no changes in the CD4/CD8 ratio. The transient increase in CD4/CD8 ratio was likely due to the TCM intake. We postulate that the administration of the innovative TCM may have beneficial immunomodulatory effects for preventing viral infections including SARS.
    The American Journal of Chinese Medicine 04/2012; 34(01). · 2.63 Impact Factor
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    ABSTRACT: At the peak of the SARS epidemic in Hong Kong, hospital workers were under high risks of contraction of the infection. Herbal preparations had been used historically in China to treat influenza-like diseases. During the SARS outbreak, herbal preparations had been used jointly with standard modern treatment in China. As a means to protect the at-risk hospital workers, an innovative herbal formula was created and consumed by 3160 of them in two weeks. During the two weeks, symptoms and adverse effects were close monitored; 37 of them had their serum checked for immunological responses. The results showed that none of the herb consumers contracted the infection, compared to 0.4% among the non-consumers. Adverse effects had been infrequent and mild. There were hardly any influenza-like symptoms and the quality of life improved. In the group who volunteered to have their immunological state checked, significant boosting effects were found. It was concluded that there might be a good indication for using suitable herbal preparations as a means of preventing influenza-like infection. The mode of preventive effect could be treatment of the infection at its very early stage instead of producing a period of higher immunological ability, as in the case of vaccination.
    The American Journal of Chinese Medicine 04/2012; 33(03). · 2.63 Impact Factor
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    ABSTRACT: BACKGROUND: Earlier studies reported that Chinese subjects with heterozygous familial hypercholesterolemia (heFH) living in Mainland China or in Western countries had lower plasma low-density lipoprotein cholesterol (LDL-C) levels and lower prevalence of xanthomata or coronary heart disease (CHD) than Caucasians with heFH and a greater proportion went unrecognized. We characterized the features of Hong Kong Chinese with heFH identified by cascade screening. METHODS: Potential probands with primary hypercholesterolemia manifesting total cholesterol (TC) greater than 7.5mmol/L or LDL-C greater than 4.9mmol/L were selected from a lipid clinic in a public hospital in Hong Kong. After screening of 132 unrelated potential probands and their relatives, 252 subjects from 87 pedigrees were clinically diagnosed as heFH. RESULTS: In 252 heFH patients (mean age 37±17 years, 100 males), the plasma TC and LDL-C were 9.1±1.5mmol/L and 7.2±1.5mmol/L, respectively. In subjects aged ≥18years, the prevalence of xanthomata and corneal arcus was 40.6% and 81.2% in males, and 54.8% and 66.9% in females respectively. The overall incidence of CHD was 9.9% in males and 8.5% in females in patients aged over 18years with CHD history available. Multiple logistic regression analysis showed that advanced age and presence of xanthelasmata were significantly associated with increased risk of CHD. CONCLUSIONS: This study is the first to characterize the epidemiologic features of heFH in Hong Kong Chinese, which provides new population-specific information on this genetic disorder. This may presage how this condition will manifest in China in the near future.
    International journal of cardiology 03/2012; · 6.18 Impact Factor
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    ABSTRACT: Cardiovascular disease (CVD) is the principal cause of mortality in chronic kidney disease (CKD) patients. Dyslipoproteinaemia is a common metabolic derangement in CKD and a traditional risk factor for CVD. This study investigates serum lipoprotein, especially small-dense low-density lipoprotein (sd-LDL), abnormalities in CKD patients. A total of 131 CKD patients (age: 59 +/- 12 years, male = 64) diagnosed according to Kidney Disease: Improving Global Outcomes, 2004 (KDIGO) and 121 age- and gender-matched control subjects (age: 58 +/- 6 years, male = 62) were recruited from Hong Kong and Macau. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and direct LDL-C were assayed enzymatically. In addition, sd-LDL, together with very low density and intermediate-density lipoproteins (VLDL and IDL) were measured by US Food and Drug Administration (FDA)-approved polyacrylamide gradient gel electrophoresis. Compared to controls, CKD patients showed significantly decreased TC, LDL-C, normal-size LDL and HDL-C with increased TG, VLDL, IDL and sd-LDL (all P < 0.01). The increased sd-LDL and decreased normal-size LDL fractions resulted in a significantly elevated sd-LDL:LDL ratio in CKD (P < 0.005). In contrast to the low TC and LDL-C, sd-LDL and sd-LDL:LDL ratio were significantly elevated in CKD. Thus, sd-LDL will be used increasingly for CVD risk assessment in CKD and other diseases that show lipoprotein derangement.
    British journal of biomedical science 01/2012; 69(3):99-102. · 0.83 Impact Factor
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    ABSTRACT: 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. 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. 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. It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 11/2011; 32(3):280-91.
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    Da P Chen, Chun K Wong, Lai S Tam, Edmund K Li, Christopher W K Lam
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    ABSTRACT: Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses. However, the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) have not been elucidated. Therefore, we investigated the in vitro effects of monosodium urate crystals, alone or in combination with the inflammatory cytokines tumor-necrosis factor (TNF)-α or interleukin (IL)-1β, on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals. Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6, the chemokine CXCL8 and the matrix metalloproteinase (MMP)-1 from both normal and RA-FLS (all P<0.05). Moreover, the additive or synergistic effect on the release of IL-6, CXCL8 and MMP-1 from both normal and RA-FLS was observed following the combined treatment with monosodium urate crystals and TNF-α or IL-1β. Further experiments showed that the release of the measured inflammatory cytokine, chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase pathway. Our results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA.
    Cellular & molecular immunology 09/2011; 8(6):469-78. · 4.19 Impact Factor
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    ABSTRACT: Previous studies have suggested that Lingzhi (Ganoderma lucidum) has antioxidant effects and possibly beneficial effects on blood pressure, plasma lipids and glucose, but these have not been confirmed in subjects with mild hypertension or hyperlipidaemia. The objective of the present study was to assess the cardiovascular, metabolic, antioxidant and immunomodulatory responses to therapy with Lingzhi in patients with borderline elevations of blood pressure and/or cholesterol in a controlled cross-over trial. A total of twenty-six patients received 1·44 g Lingzhi daily or matching placebo for 12 weeks in a randomised, double-blind, cross-over study with placebo-controlled run-in and cross-over periods. Body weight, blood pressure, metabolic parameters, urine catecholamines and cortisol, antioxidant status and lymphocyte subsets were measured after each period. Lingzhi was well tolerated and data from twenty-three evaluable subjects showed no changes in BMI or blood pressure when treated with Lingzhi or placebo. Plasma insulin and homeostasis model assessment-insulin resistance were lower after treatment with Lingzhi than after placebo. TAG decreased and HDL-cholesterol increased with Lingzhi but not with placebo in the first treatment period, but significant carry-over effects prevented complete analysis of these parameters. Urine catecholamines and cortisol, plasma antioxidant status and blood lymphocyte subsets showed no significant differences across treatments. Results indicate that Lingzhi might have mild antidiabetic effects and potentially improve the dyslipidaemia of diabetes, as shown previously in some animal studies. Further studies are desirable in patients with hyperglycaemia.
    The British journal of nutrition 08/2011; 107(7):1017-27. · 3.45 Impact Factor
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    ABSTRACT: 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.
    Pediatric Pulmonology 07/2011; 46(7):632-9. · 2.38 Impact Factor

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8k Citations
1,378.95 Total Impact Points


  • 2010–2012
    • Macau University of Science and Technology
      • Macau Institute for Applied Research in Medicine and Health
      Macao, Macau, Macao
  • 1987–2012
    • The Chinese University of Hong Kong
      • • Department of Chemical Pathology
      • • Department of Paediatrics
      • • Department of Medicine and Therapeutics
      • • Prince of Wales Hospital
      Hong Kong, Hong Kong
  • 1997–2008
    • The University of Hong Kong
      • Department of Medicine
      Hong Kong, Hong Kong
  • 2003–2006
    • Hong Kong Hospital Authority
      Hong Kong, Hong Kong
  • 2005
    • Caritas Medical Centre
      Hong Kong, Hong Kong
  • 2004
    • Hong Kong SAR Government
      Hong Kong, Hong Kong
  • 1993–2004
    • Royal Prince Alfred Hospital
      Camperdown, New South Wales, Australia
  • 1987–2004
    • Prince of Wales Hospital, Hong Kong
      Chiu-lung, Kowloon City, Hong Kong
  • 1998–2001
    • Queen Mary Hospital
      Hong Kong, Hong Kong