Christopher Wai-Kei Lam

Queen Mary Hospital, Hong Kong, Hong Kong

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Publications (50)242.83 Total impact

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    ABSTRACT: This study aims to evaluate the relationship between tissue advanced glycation end products, as reflected by skin autofluorescence, and vascular calcification in chronic kidney disease.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2014; · 6.34 Impact Factor
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    Huai Na Qiu, Chun Kwok Wong, Jie Dong, Christopher Wai-Kei Lam, Zhe Cai
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    ABSTRACT: Allergic asthma can cause airway structural remodeling, involving the accumulation of extracellular matrix and thickening of smooth muscle. Tumor necrosis factor (TNF) family ligand LIGHT (TNFSF14) is a cytokine that binds herpesvirus entry mediator (HVEM)/TNFRSF14 and lymphotoxin β receptor (LT β R). LIGHT induces asthmatic cytokine IL-13 and fibrogenic cytokine transforming growth factor- β release from allergic asthma-related eosinophils expressing HVEM and alveolar macrophages expressing LT β R, respectively, thereby playing crucial roles in asthmatic airway remodeling. In this study, we investigated the effects of LIGHT on the coculture of human basophils/eosinophils and bronchial epithelial BEAS-2B cells. The expression of adhesion molecules, cytokines/chemokines, and matrix metalloproteinases (MMP) was measured by flow cytometry, multiplex, assay or ELISA. Results showed that LIGHT could significantly promote intercellular adhesion, cell surface expression of intercellular adhesion molecule-1, release of airway remodeling-related IL-6, CXCL8, and MMP-9 from BEAS-2B cells upon interaction with basophils/eosinophils, probably via the intercellular interaction, cell surface receptors HVEM and LT β R on BEAS-2B cells, and extracellular signal-regulated kinase, p38 mitogen activated protein kinase, and NF- κ B signaling pathways. The above results, therefore, enhance our understanding of the immunopathological roles of LIGHT in allergic asthma and shed light on the potential therapeutic targets for airway remodeling.
    Mediators of Inflammation 01/2014; 2014:136463. · 3.88 Impact Factor
  • Chun-Kwok Wong, Jie Dong, Christopher Wai-Kei Lam
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    ABSTRACT: IL-32 is a proinflammatory cytokine associated with infections, autoimmune diseases, and allergic asthma. In the present study, we elucidated the synergistic effect of IL-32γ and NOD ligand on the activation of human eosinophils, principal effector cells for allergic inflammation, and the underlying mechanisms. Specific IL-32-binding protein, PR3, was found to localize on the cell surface and in the cytoplasm of eosinophils. IL-32γ was more capable of activating eosinophils than its isotype variant IL-32α and exhibited synergistic effect with NOD1 ligand iE-DAP and NOD2 ligand MDP on the induction of allergic inflammation-related IL-1β, TNF-α, and chemokines CXCL8, CCL3, and CCL4 (P<0.05). Moreover, IL-32γ and iE-DAP or MDP induced the significant up-regulation of the cell-surface expression of adhesion molecule CD18 and ICAM-1 on eosinophils. Synergism between IL-32γ and NOD ligands was dependent on the activation of intracellular caspase 1, ERKs, p38 MAPK, and NF-κB pathways in eosinophils. The further-enhanced CD18 and ICAM-1 expression and production of cytokines and chemokines were observed in eosinophils cocultured with human bronchial epithelial BEAS-2B cells. Furthermore, combined treatment of IL-32γ and NOD ligand could activate the release of eosinophil extracellular DNA traps, thereby implying the pathogen-defense mechanisms of eosinophils. Together, the above study provides pivotal immunological mechanisms by which bacterial infection-mediated activation of NOD1,2, together with IL-32γ, can synergize the activation of eosinophils interacting with bronchial epithelial cells.
    Journal of leukocyte biology 12/2013; · 4.99 Impact Factor
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    ABSTRACT: Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 μg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 μg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.
    Journal of the American Society of Nephrology 09/2013; · 8.99 Impact Factor
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    ABSTRACT: Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and NOD2 ligand muramyl dipeptide (MDP). However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule (ICAM)-1 on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system (all P<0.05). Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-κB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 (Th2) cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice (all P<0.05). This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.Cellular & Molecular Immunology advance online publication, 25 March 2013; doi:10.1038/cmi.2012.77.
    Cellular & molecular immunology 03/2013; · 3.42 Impact Factor
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    ABSTRACT: BACKGROUND: Heart failure is one of the most frequent complications in dialysis patients. However, little is known of the significance of the entity "heart failure with preserved ejection fraction" (HFPEF) in this population. This study aimed to determine the prevalence, clinical profiles, and long-term outcomes of peritoneal dialysis patients with HFPEF. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 220 patients treated with peritoneal dialysis were recruited from a university teaching hospital in Hong Kong. PREDICTOR: Heart failure was defined clinically based on the presence of: (1) symptoms and signs, including dyspnea, increased jugular venous pressure, and basal crepitations; (2) radiographic evidence of pulmonary venous congestion or interstitial edema; and (3) resolution of symptoms, signs, and radiographic changes with hypertonic peritoneal dialysis exchanges. Based on a combination of clinical history of heart failure and echocardiography-derived ejection fraction, patients were classified as having no heart failure, HFPEF, and heart failure with reduced ejection fraction (HFREF). OUTCOMES: All-cause mortality, cardiac death, heart failure, and fatal or nonfatal cardiovascular events. MEASUREMENTS: All patients underwent 2-dimensional echocardiography and tissue Doppler imaging at baseline and were followed up prospectively for clinical events for 4 years. RESULTS: 86 (39%) patients had heart failure, of whom 54.7% had preserved ejection fraction ≥50% and 45.3% had reduced ejection fraction <50%. Patients with HFPEF were intermediate between those with no heart failure and those with HFREF in terms of blood pressure, prevalence of coronary artery disease, diabetes, cardiac biomarkers, left ventricular mass, volume, and ratio of early mitral inflow velocity to peak mitral annulus velocity. In the multivariable Cox regression analysis, patients with HFPEF showed an increased adjusted HR for cardiac death (2.57; 95% CI, 1.20-5.50), heart failure (HR, 2.25; 95% CI, 1.28-3.96), and fatal or nonfatal cardiovascular event (HR, 2.01; 95% CI, 1.26-3.21) compared with those with no heart failure, but the risk was lower compared with those with HFREF. LIMITATIONS: The study included prevalent peritoneal dialysis patients and may introduce survival bias. CONCLUSIONS: HFPEF is common in peritoneal dialysis patients (∼55% of all heart failure) and is associated with increased risk of mortality and adverse cardiovascular outcomes compared with those with no heart failure, although the risk was lower than in patients with HFREF. This entity needs to be more recognized in peritoneal dialysis patients.
    American Journal of Kidney Diseases 03/2013; · 5.29 Impact Factor
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    ABSTRACT: Background Left atrial enlargement (LAE) reflects diastolic dysfunction and predicts mortality in end-stage renal disease patients. However, little is known of its prevalence and factors associated with subclinical LAE in earlier stages of chronic kidney disease (CKD).Methods We conducted a prospective, cross-sectional study in 261 Stage 3-5 non-dialysis CKD patients without symptomatic cardiovascular disease with two-dimensional echocardiography performed to estimate left atrial volume index and other cardiac parameters.ResultsOne hundred and nine (41.8%) patients had LAE. Mild and moderate/severe LAEs were observed in 22.9 and 41.3% of patients with left ventricular (LV) hypertrophy (n = 109) versus 13.2 and 12.5% of patients with no LV hypertrophy (n = 152), respectively (P < 0.001). On univariate analysis, plasma sodium concentration showed a significant association with LAE [odds ratio (OR) 1.22, 95% confidence interval (95% CI) 1.09-1.37; P = 0.001]. In the stepwise multiple logistic regression, plasma sodium concentration emerged as one of the most significant factors associated with LAE (adjusted OR 1.29, 95% CI 1.14-1.47; P < 0.001]. Its significance was well maintained (adjusted OR 1.23, 95% CI 1.07-1.43; P = 0.005) when including LV mass and volume index and N-terminal pro-brain natriuretic peptide in the model, while blood haemoglobin and systolic blood pressure were displaced.Conclusions This study for the first time alerted to a very high prevalence of subclinical LAE and reported a strong novel, independent relationship between plasma sodium concentration and subclinical LAE in Stage 3-5 CKD patients. Longitudinal studies are needed to establish causality between high plasma sodium concentration and LAE and their usefulness as therapeutic targets in CKD.
    Nephrology Dialysis Transplantation 01/2013; · 3.37 Impact Factor
  • Angela Yee-Moon Wang, Christopher Wai-Kei Lam
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    ABSTRACT: Mortality in dialysis patients remains high due to excessive cardiovascular disease burden from coronary artery disease, left ventricular hypertrophy, and heart failure. Thus, cardiovascular risk stratification is an important aspect in managing dialysis patients; it may enable early identification of high-risk patients to optimize therapeutic interventions that may ultimately lower their cardiovascular morbidity and mortality. In particular, serum cardiac biomarkers that are readily measured, inexpensive, reproducible with high sensitivity and specificity, may have potential for cardiovascular risk prediction and stratification. Cardiac troponin represents a highly sensitive and specific marker of myocardial damage and is a current gold standard test for diagnosing acute myocardial infarction in the general population. On the other hand, natriuretic peptides, released from the heart secondary to increased left ventricular wall stress, have emerged as a diagnostic marker for heart failure in the general population. These two biomarkers reflect unique pathology of the myocardium and are powerful prognostic markers in the dialysis population. This article reviews the diagnostic potentials of these two cardiac biomarkers and their clinical application in the dialysis population.
    Seminars in Dialysis 07/2012; 25(4):388-96. · 2.25 Impact Factor
  • Journal of Investigative Dermatology 03/2012; 132(7):1930-2. · 6.19 Impact Factor
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    ABSTRACT: IL-31 is a pruritogenic cytokine, and IL-33 is an alarmin for damaging inflammation. They together relate to the pathogenesis of atopic dermatitis (AD). Eosinophil infiltration into the inner dermal compartment is a predominant pathological feature of AD. We herein investigated the in vitro inflammatory effects of IL-31 and IL-33 on the activation of human eosinophils and dermal fibroblasts. Receptors, adhesion molecules and signaling molecules were assessed by Western blot or flow cytometry. Chemokines and cytokine were quantitated by multiplex assay. Functional IL-31 receptor component IL-31RA, OSMR-β and IL-33 receptor component ST2 were constitutively expressed on the surface of eosinophils. Co-culture of eosinophils and fibroblasts significantly induced pro-inflammatory cytokine IL-6 and AD-related chemokines CXCL1, CXCL10, CCL2 and CCL5. Such inductions were further enhanced with IL-31 and IL-33 stimulation. IL-31 and IL-33 could significantly provoke the release of CXCL8 from eosinophils and fibroblasts, respectively, which was further enhanced upon co-culture. In co-culture, eosinophils and fibroblasts were the main source for the release of CCL5, and IL-6, CXCL1, CXCL8, CXCL10 and CCL2, respectively. Direct interaction between eosinophils and fibroblasts was required for CXCL1, CXCL10, CXCL8 and CCL5 release. Cell surface expression of intercellular adhesion molecule-1 on eosinophils and fibroblasts was up-regulated in co-culture upon IL-31 and IL-33 stimulation. The interaction between eosinophils and fibroblasts under IL-31 and IL-33 stimulation differentially activated extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, nuclear factor-κB and phosphatidylinositol 3-kinase-Akt pathways. Using specific signaling molecule inhibitors, the differential induction of IL-31 and IL-33-mediated release of cytokines and chemokines such as IL-6 and CXCL8 from co-culture should be related to their distinct activation profile of intracellular signaling pathways. The above findings suggest a crucial immunopathological role of IL-31 and IL-33 in AD through the activation of eosinophils-fibroblasts interaction via differential intracellular signaling mechanisms.
    PLoS ONE 01/2012; 7(1):e29815. · 3.53 Impact Factor
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    ABSTRACT: The progression to type 2 diabetes mellitus (DM) and other long-term cardiometabolic risks in Chinese women with prior history of gestational diabetes (GD) was studied at 15 years postpartum. 139 Chinese women (45 with GD and 94 with normal glucose tolerance (NGT) at the index pregnancy) who had their insulin sensitivity and β-cell functions examined at 8 years postpartum were again followed up at 15 years for the investigation of the rate of type 2 DM, hypertension and metabolic syndrome. Women with prior history of GD had a significantly higher rate of hypertension (35.6% vs. 16.0%, p = 0.01), type 2 DM (24.4% vs. 5.3%, p < 0.001) and impaired glucose regulation (26.6% vs. 14.9%, p < 0.001) than women with NGT during the index pregnancy. The Matsuda insulin sensitivity index and the quantitative insulin sensitivity check index at 8 years postpartum were independent predictors of both DM and metabolic syndrome at 15 years postpartum. The conversion rate of type 2 DM increased at an average rate of 1.6% per year after a pregnancy affected by GD. Insulin resistance at 8 years postpartum could refine a future diabetic risk in women with prior history of GD.
    Gynecologic and Obstetric Investigation 12/2011; 73(2):168-76. · 1.10 Impact Factor
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    ABSTRACT: Sinomenine, an alkaloid isolated from the root of Sinomenium acutum, has been used to alleviate the symptoms of rheumatic diseases. Liang Miao San (LMS), composed of the herbs Rhizoma Atractylodis (Cangzhu) and Cotex Phellodendri (Huangbai), is another traditional Chinese medicine formula for rheumatoid arthritis (RA) treatment. Although numerous studies have demonstrated the potential anti-inflammatory activities of sinomenine and LMS, the underlying intracellular mechanisms regulating the anti-inflammatory activities of sinomenine and LMS on human primary fibroblast-like synoviocytes (FLS) from RA patients and normal control subjects have not been elucidated. We investigated the in vitro anti-inflammatory activity of sinomenine and LMS on inflammatory cytokine tumor necrosis factor (TNF)-α-mediated activation of human normal and RA-FLS. The underlying intracellular signaling molecules were analyzed quantitatively using flow cytometry. Sinomenine was found to significantly inhibit TNF-α induced cell surface expression of vascular cell adhesion molecule (VCAM)-1 and release of inflammatory cytokine and chemokine IL-6, CCL2 and CXCL8 from both normal and RA-FLS (all p<0.05). Moreover, the suppression of sinomenine on TNF-α induced VCAM-1 expression and IL-6 release of RA-FLS was significantly higher than that of normal FLS (p<0.05). LMS significantly inhibited TNF-α-induced inflammatory chemokines CXCL10 and CCL5 release from both normal and RA-FLS, with significantly higher suppression on CXCL10 secretion in RA-FLS than that of normal FLS (all p<0.05). Further investigations showed that sinomenine and LMS could significantly suppress TNF-α-induced phosphorylation of inhibitor κBα and extracellular signal-regulated protein kinase, the central signaling molecules mediating TNF-α-induced VCAM-1 expression and chemokine production. Our results therefore provide a new insight into the differential anti-inflammatory activities of sinomenine and LMS through the suppression of TNF-α-activated FLS by modulating distinct intracellular signaling pathways in RA.
    Journal of ethnopharmacology 06/2011; 137(1):457-68. · 2.32 Impact Factor
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    ABSTRACT: Heart failure occurs frequently in end-stage renal disease patients. However, there are no prospective, longitudinal follow-up data on its prevalence, severity, and risk factors in long-term peritoneal dialysis (PD) patients. A prospective observational study was conducted in 220 long-term PD patients followed up for 4 years or until death. Echocardiography was obtained at baseline. Primary study end points were heart failure and mortality. Eighty-six patients had a previous history of heart failure at study entry. The cumulative 4-year survival probability was 37.4% and 64.7% for patients with and without previous heart failure, respectively (P<0.0001). During follow-up, 87 patients (40.9%) developed heart failure, of which 53 were recurrence and 34 were new-onset heart failure. Diabetes, background atherosclerotic vascular disease, systolic hypertension, left ventricular (LV) mass index, systolic dysfunction, and hypoalbuminemia were significant risk factors predicting heart failure in the entire cohort. Diabetes and LV mass and volume index were significant predictors of new-onset heart failure. Systolic hypertension, LV volume index, and hypoalbuminemia were significant predictors of recurrent heart failure. Heart failure is a highly prevalent complication in long-term PD patients and predicts adverse clinical outcomes. More attention should be focused on improving BP and volume control and identifying treatment strategies that effectively lower atherosclerotic burden and reverse LV hypertrophy, remodeling, and systolic dysfunction in PD patients.
    Clinical Journal of the American Society of Nephrology 01/2011; 6(4):805-12. · 5.07 Impact Factor
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    ABSTRACT: Myeloperoxidase (MPO) has been suggested to have a role in atherosclerosis through its strong oxidative capacity. We hypothesized that MPO level may predict clinical outcomes in patients with end-stage renal disease receiving long-term peritoneal dialysis (PD) therapy. Prospective cohort study. 236 long-term PD patients were recruited from a single regional dialysis unit in Hong Kong between April 1999 and February 2001. Level of plasma MPO, analyzed using a sandwich enzyme-linked immunosorbent assay. Mortality and fatal or nonfatal cardiovascular events at 3 years. The distribution of MPO levels was skewed with a median of 31.8 μg/L (25th-75th percentiles, 24.4-42.7). There were 69 deaths and 81 cardiovascular events. Adjusting for traditional and nontraditional risk factors and C-reactive protein, cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels, a doubling in plasma MPO level was associated independently with a 46% (95% CI, 1.02-2.08; P = 0.04) and 60% (95% CI, 1.17-2.18; P = 0.003) increase in risks of mortality and cardiovascular events, respectively. Log(2)MPO showed significant additional predictive value for mortality (P = 0.04) and cardiovascular events (P = 0.005) when included in Cox regression models consisting of clinical, demographic, dialysis, echocardiographic, and biochemical parameters, as well as C-reactive protein, cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels. MPO was measured at a single time and did not reflect changes over time. These data suggest that plasma MPO level has significant independent and additional prognostic value beyond the standard clinical, biochemical, and echocardiographic parameters and is useful for outcome stratification in long-term PD patients. MPO may be an important mediator of increased cardiovascular risk in patients with end-stage renal disease and warrants further investigation.
    American Journal of Kidney Diseases 11/2010; 56(5):937-46. · 5.29 Impact Factor
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    ABSTRACT: Handgrip strength (HGS) is a marker of lean muscle mass. This study aims to test the hypothesis that a low HGS reflects a diseased cardiac status and predicts future risk of circulatory congestion in chronic peritoneal dialysis (PD) patients. Two hundred and eighteen chronic PD patients were prospectively recruited from a single regional dialysis unit in Hong Kong. HGS, serum albumin, lean body mass (LBM) by creatinine kinetics (CK) and subjective global assessment (SGA) were assessed at study entry and examined in relation to the risk of developing circulatory congestion over a 4-year follow-up. Adjusting for age, gender and height, HGS showed significant correlations with LBM by CK, SGA, serum albumin, atherosclerotic vascular disease, left ventricular (LV) mass index and early mitral inflow velocity to peak mitral annulus velocity (E/Em ratio). In the multivariable Cox regression analysis, HGS (P = 0.004) and ejection fraction (P = 0.004) were both second to LV mass index (P < 0.001) as the most significant factors in predicting circulatory congestion at 4 years. Serum albumin, LBM by CK and SGA were not independently predictive of circulatory congestion. Patients with systolic dysfunction and HGS < gender-specific median had an adjusted hazard ratio of 2.77 [95% confidence interval (CI), 1.46-5.28; P = 0.002] in developing circulatory congestion than those with normal systolic function and HGS ≥ gender-specific median. A low HGS reflects a diseased cardiac status and predicts future risk of circulatory congestion independent of other nutritional, echocardiographic and clinical parameters in PD patients. The important link between skeletal myopathy and myocardial disease in uraemic patients warrants further investigation.
    Nephrology Dialysis Transplantation 10/2010; 25(10):3372-9. · 3.37 Impact Factor
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    ABSTRACT: End-stage renal disease patients experience a high incidence of sudden cardiac death. We performed a 5-year prospective study in 230 end-stage renal disease patients, aiming to determine the role of echocardiography and the additional value of serum biomarkers in predicting sudden cardiac death. During follow-up, 24% of all deaths were attributed to sudden cardiac death. In the multivariable Cox regression analysis considering clinical, biochemical, dialysis, and echocardiographic parameters, left ventricular systolic dysfunction emerged as the most significant predictor of sudden cardiac death, followed by a high systolic and a low diastolic blood pressure. An ejection fraction cutoff </=48.0% is associated with a specificity of 78.6% and a sensitivity of 57.7% in predicting sudden cardiac death. In biomarker-based multivariable Cox regression analysis, N-terminal probrain natriuretic peptide displays an independent association with sudden cardiac death and is more significantly associated with sudden cardiac death than cardiac troponin T. In the combined echocardiography and biomarker-based multivariable Cox regression model, N-terminal probrain natriuretic peptide loses significance to left ventricular ejection fraction, whereas cardiac troponin T retains a significant association with sudden cardiac death independent of echocardiographic parameters. In conclusion, systolic dysfunction is the most significant predictor of sudden cardiac death followed by a high systolic and a low diastolic blood pressure. Our data suggest additional value in measuring cardiac troponin T for sudden cardiac death risk stratification. N-terminal probrain natriuretic peptide may be used in place of echocardiography to identify patients at risk of sudden cardiac death but had no added value over echocardiography in predicting sudden cardiac death.
    Hypertension 08/2010; 56(2):210-6. · 6.87 Impact Factor
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    ABSTRACT: IL-31 is a novel T(h) type 2 cytokine that can induce pruritus and dermatitis in mice resembling human atopic dermatitis (AD). Eosinophil infiltration in skin lesions is a predominant pathological feature of AD. In the present study, we investigated the effects of IL-31 on the activation of human eosinophils and epidermal keratinocytes. Eosinophils and keratinocytes were cultured either together or separately in the presence or absence of IL-31 stimulation. IL-31 could significantly induce the release of pro-inflammatory cytokines IL-1beta, IL-6 and AD-related chemokines CXCL1, CXCL8, CCL2 and CCL18 from eosinophils, via functional cell surface IL-31 receptor. Such induction was further enhanced upon the co-culture of eosinophils and keratinocytes, in which eosinophils were the main source for releasing pro-inflammatory cytokines and chemokines. The presence of transwell inserts in co-culture system demonstrated that the direct interaction between eosinophils and keratinocytes was required for IL-31-induced cytokine and chemokine release. Cell surface expression of adhesion molecule CD18 on eosinophils and intercellular adhesion molecule-1 on keratinocytes was up-regulated in the co-culture, and levels were further enhanced upon IL-31 stimulation. The interaction between eosinophils and keratinocytes under IL-31 stimulation was differentially mediated through intracellular mitogen-activated protein kinases, nuclear factor-kappaB and phosphatidylinositol 3-kinase-Akt pathways. The above findings suggest a crucial immunopathological role of IL-31 in AD through activation of eosinophils-keratinocytes system.
    International Immunology 06/2010; 22(6):453-67. · 3.14 Impact Factor
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    ABSTRACT: Circulatory congestion is an adverse predictor of mortality in peritoneal dialysis (PD) patients. This study evaluated the nutritional status, energy intake, and expenditure profile of PD patients with and without previous circulatory congestion. We conducted a cross-sectional study in 244 PD patients, of whom 92 had previous circulatory congestion. We estimated dietary energy intake by using a locally validated 7-d food-frequency questionnaire and by assessing resting energy expenditure (REE) and total energy expenditure (TEE) with indirect calorimetry and a locally validated physical activity questionnaire, respectively. In comparison with those without circulatory congestion, patients with previous circulatory congestion were more malnourished by subjective global assessment (59% compared with 36%; P < 0.001), had lower handgrip strength, had lower midarm muscle circumference, had lower dietary protein (0.98 +/- 0.45 compared with 1.19 +/- 0.44 g x kg(-1) x d(-1); P < 0.001), and had lower energy intake (92.5 +/- 37.0 compared with 110.9 +/- 35.7 kJ x kg(-1) x d(-1); P < 0.001) but had higher C-reactive protein (P = 0.025) and higher REE (P < 0.001). However, no difference in TEE was noted between the 2 groups, which indicated lower activity energy expenditure among patients with previous circulatory congestion. The resulting energy balance was significantly more negative for patients with previous circulatory congestion than for those without previous circulatory congestion (P = 0.050). Furthermore, the prevalence of malnutrition increased with increasing episodes of circulatory congestion (P = 0.017). Patients with previous circulatory congestion had significantly more inflammation, more muscle wasting, and higher REE but lower activity energy expenditure and energy and protein intakes in keeping with an anorexia-cachexia syndrome. The mechanisms of increased REE and reduced energy intake among patients with previous circulatory congestion warrant further investigation.
    American Journal of Clinical Nutrition 09/2009; 90(5):1179-84. · 6.50 Impact Factor
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    ABSTRACT: Residual renal function (RRF) predicts survival and shows an important inverse relation with cardiac hypertrophy in peritoneal dialysis (PD) patients. We hypothesized that valvular calcification and the calcification milieu may be part of the process linking loss of RRF and cardiac hypertrophy. A cross-sectional study was conducted by performing two-dimensional echocardiography on 230 PD patients to assess valvular calcification and left ventricular (LV) mass and collecting 24-h urine for estimation of RRF. Patients having valvular calcification had lower RRF than those without. Patients with no RRF showed higher calcium-phosphorus product (Ca x P) and C-reactive protein (CRP). Using multiple logistic regression analysis, every 1-ml/min per 1.73 m(2) increase in residual GFR was associated with a 28% reduction in the risk for valvular calcification. The association was lost after additional adjustment for Ca x P and CRP. Using multiple linear regression analysis, loss of RRF showed significant association with increased LV mass index, but this association was lost after additional adjustment for CRP, Ca x P, and valvular calcification. Patients with all three calcification risk factors, namely inflammation, high CaxP, and no RRF, showed the highest prevalence of valvular calcification and had the most severe cardiac hypertrophy. The association among loss of RRF, valvular calcification, and cardiac hypertrophy was closely linked to increased inflammation and high Ca x P in PD patients. These data suggest that valvular calcification and the calcification milieu are part of the processes linking loss of RRF and worsening cardiac hypertrophy in PD.
    Clinical Journal of the American Society of Nephrology 09/2009; 4(10):1629-36. · 5.07 Impact Factor
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    ABSTRACT: It remains unknown whether a composite of inflammation and calcification markers provides better mortality and cardiovascular risk stratification in chronic peritoneal dialysis (PD) patients. We performed a 4-year prospective follow-up study in 231 chronic PD patients from a single regional dialysis centre in Hong Kong. Valvular calcification was detected using echocardiography, and fasting venous blood was collected to measure a panel of inflammation markers. The patients were stratified into five groups on the basis of 0, 1, 2, 3 and all 4 inflammation and calcification risk markers, namely high C-reactive protein (CRP) (CRP in upper tertile), high interleukin-6 (IL-6) (IL-6 in upper tertile), low fetuin-A (fetuin-A in lower tertile) and valvular calcification. Study outcomes included all-cause and cardiovascular mortality and fatal or non-fatal cardiovascular events (CVEs). The patients with 4, 3, 2 and 1 markers had an adjusted hazard ratio (HR) of 5.17 (95% CI, 1.81-14.77, P = 0.002), 3.38 (95% CI, 1.50-7.60; P = 0.003), 2.17 (95% CI, 0.98-4.77; P = 0.056) and 2.42 (95% CI, 1.18-4.96; P = 0.016), respectively, for mortality at 4 years than those with 0 risk marker. The adjusted HRs for fatal or non-fatal CVEs were 4.33 (95% CI, 1.70-11.03; P = 0.002), 1.60 (95% CI, 0.73-3.52; P = 0.24), 1.92 (95% CI, 0.95-3.90; P = 0.07) and 1.33 (95% CI, 0.67-2.62; P = 0.42), respectively, for patients with 4, 3, 2 and 1 markers than those with 0 risk markers. A composite of inflammation and calcification markers provides long-term prognostication and identifies the sickest PD patients with the worst clinical outcomes. Since these parameters can all be obtained quite readily, our data support the adoption of a multiinflammation and calcification risk marker approach for mortality and cardiovascular risk stratification in PD patients.
    Nephrology Dialysis Transplantation 08/2009; 24(12):3826-33. · 3.37 Impact Factor

Publication Stats

1k Citations
242.83 Total Impact Points

Institutions

  • 2013
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 2002–2013
    • The Chinese University of Hong Kong
      • • Department of Medicine and Therapeutics
      • • Department of Chemical Pathology
      • • Prince of Wales Hospital
      • • Faculty of Medicine
      Hong Kong, Hong Kong
  • 2010
    • The University of Hong Kong
      • Department of Medicine
      Hong Kong, Hong Kong