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Biomedical subjects

L S Tam

Publications and source records attributed to L S Tam.

At least 19 recordsLinked to original sources
PubMed2006

Urine protein-to-creatinine ratio in an untimed urine collection is a reliable measure of proteinuria in lupus nephritis.

OBJECTIVE: To evaluate the accuracy of urine protein-to-creatinine (P/C) ratio in an untimed urine specimen as compared with 24 h total protein excretion for measurement of proteinuria in patients with lupus nephritis. METHODS: Proteinuria in patients with lupus nephritis was assessed by 24 h total protein excretion and spot urine P/C ratio. Correlation and limits of agreement between the two methods were evaluated. The discriminant cutoff values for spot urine P/C ratio in predicting 24 h protein 'threshold' excretion of > or =0.3, > or =0.5, > or =1.0 and > or =3.5 g/day were determined using receiver operating characteristic curves. RESULTS: A total of 165 samples were available for assessment with 21.8% excluded due to inadequate collection. A strong correlation (r = 0.91, P < 0.0001) was found between spot urine P/C ratio and 24 h urine protein excretion. Bland-Altman plot showed the two tests had acceptable limits of agreement in low level of protein excretion (-0.86 to +0.92 g/day when protein excretion was <2.0 g/day). The limits became wider as the protein excretion increased. The spot urine P/C ratios of 0.45 (sensitivity 0.92; specificity 0.88), 0.7 (0.92; 0.89) and 1.84 (1.0; 0.86) mg/mg reliably predicted 24 h urine total protein equivalent 'thresholds' at > or =0.5, 1.0 and 3.5 g/day. CONCLUSION: This study supports the recommendation of using spot urine P/C ratio in screening and monitoring proteinuria in patients with lupus nephritis. However, in assessing the exact amount of proteinuria, the urine P/C ratio may have unacceptably wide limits of agreement in high protein excretion range.

Adult↗
PubMed2006

Urinary mononuclear cell and disease activity of systemic lupus erythematosus.

Mononuclear cells play a cardinal role in the pathogenesis of systemic lupus erythematosus (SLE). A high urine cytology score has been reported to be associated with lupus nephritis in relapse. The objective of this study was to examine the urinary mononuclear cell population of patients with lupus nephritis, and explore its correlation with lupus disease activity. We studied 12 patients with active lupus nephritis, 17 patients with lupus nephritis in remission, 12 SLE patients with no history of renal disease and 13 healthy subjects. Clinical disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Mononuclear cell species in the urinary sediment were examined by immunocytochemistry. Patients with active lupus nephritis had significantly more mononuclear cells in the urinary sediment. The number of CD3+ cell was significantly elevated in the active lupus nephritis than the others (P < 0.001), while there was no significant difference in the number of CD20+ and CD56+ cell among patient groups. The total urinary mononuclear cell correlated significantly with the overall SLEDAI score (r = 0.58, P < 0.001) as well as the renal score (r = 0.57, P < 0.001). The number of urinary CD3+, but not CD20+ or CD56+, cell significantly correlated with the overall SLEDAI score (r = 0.46, P = 0.003) as well as the renal score (r = 0.40, p = 0.011). In nine patients with renal biopsy, the histological activity index correlated with the total urinary mononuclear cell (r = 0.75, P = 0.02), CD3+ (r = 0.69, P = 0.04) and CD20+ cell (r = 0.69, P = 0.04). We conclude that urinary mononuclear cell was markedly elevated in patients with active lupus, and the urinary mononuclear cell count correlated significantly with the SLEDAI score and histological activity. CD3+ and CD20+ cells are the major component of urinary mononuclear cell in SLE patients and their number correlates with lupus disease activity.

Adult↗
PubMed2006

Estimation of glomerular filtration rate in patients with systemic lupus erythematosus.

The objective of this study was to compare the limit of agreement of creatinine clearance (CrCl) estimated by different equations with the CrCl measured by 24-hour urine collection in Hong Kong Chinese patients with systemic lupus erythematosus (SLE). Forty-three SLE patients with mild to moderate renal impairment (serum creatinine concentration >80 micromol/L to <300 micromol/L for females; and >106 micromol/L to <300 micromol/L for males) and not requiring renal replacement therapy were assessed. The estimated clearances were calculated by the Cockcroft-Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) study equation and the abbreviated MDRD (aMDRD) study equation. The estimated clearances were compared against the measured CrCl by 24-hour urine collection for their limit of agreement. Forty-three patients with mean (+/-SD) age of 41.6 (+/-8.4) years were assessed. As compared to the measured CrCl in patients with SLE, the clearances by CG equation, MDRD and aMDRD equations predicted a mean difference of -0.8% (95% confidence interval, -43.9-42.3%); -8.6% (95% CI, -24.3-7.2%) and -4.7% (95% CI, -21.4-12%), respectively. There is a tendency for the MDRD and aMDRD study equations to underestimate CrCl. The MDRD and aMDRD study equations have better predictive value than the CG equation.

Adult↗
PubMed2005

Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus.

BACKGROUND: Chemokines are involved in leucocyte chemotaxis. Infiltrating leucocytes play an important role of tissue injury in systemic lupus erythematosus (SLE). OBJECTIVE: To investigate the role of inflammatory chemokines and their association with interleukin 18 (IL18) in SLE pathogenesis and disease activity. METHODS: Plasma concentrations and ex vivo peripheral blood mononuclear cell production of inflammatory chemokines IP-10, RANTES, MIG, MCP-1, TARC, IL8, and GROalpha, and proinflammatory cytokines IL18, IFNgamma, IL2, IL4, and IL10 were assayed in 80 SLE patients with or without renal disease and 40 healthy controls by immunofluorescence flow cytometry and enzyme linked immunosorbent assay. RESULTS: Plasma IP10, RANTES, MIG, MCP-1, GROalpha, and IL18 concentrations in all SLE patients were higher than in controls, and correlated significantly with SLEDAI score (all p<0.05). In SLE patients without renal disease, IP10, RANTES, MIG, MCP-1, IL8, and IL18 correlated positively with SLEDAI score, while in those with renal derangement, IP10, IL8, IL10, and IL18 correlated with disease activity (all p<0.05). Plasma IL18 concentration correlated positively with IP10, MIG, GROalpha, and IL8 in all SLE patients (all p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC, IFNgamma, IL4, and IL10 were higher in all SLE patients regardless of their difference in disease activity (all p<0.05). Patients with renal disease had an augmented ex vivo release of RANTES. CONCLUSIONS: The correlation of raised plasma concentration and ex vivo production of inflammatory chemokines with disease activity, and their association with IL18, supports the view that chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE pathogenesis.

Acute Disease↗
PubMed2005

Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus.

OBJECTIVE: The costimulatory interactions of the B7 family molecules CD80 and CD86 on antigen-presenting cells with their T-cell counter-receptors CD28 and CTLA-4 modulate T lymphocyte-mediated immune responses in a reciprocal manner. We investigated the possible aberrant production of soluble (s) forms of the T-cell costimulatory molecules CD80, CD86, CD28 and CTLA-4 in plasma of patients with systemic lupus erythematosus (SLE), an autoimmune disease arising from T-lymphocyte dysregulation. METHODS: Plasma concentration and ex vivo production of soluble costimulatory molecules of 79 SLE patients with or without active disease and 40 sex- and age-matched healthy subjects were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma sCTLA-4, sCD28, sCD80 and sCD86 concentrations of all SLE patients were significantly higher than concentrations in control subjects (all P<0.01). These increases were observed even in patients with inactive disease [SLE Disease Activity Index (SLEDAI) <3]. Plasma sCTLA-4 concentration in all SLE patients correlated significantly with SLEDAI score (r = 0.228, P = 0.043). Upon mitogen treatment of peripheral blood mononuclear cells, the percentage increases in ex vivo production of sCD28 and sCD80 and the percentage decrease in sCTLA-4 release were all significantly smaller in SLE patients with active disease than in healthy subjects (P<0.01, P<0.05 and P<0.0001, respectively). CONCLUSION: The aberrant production of soluble T-cell costimulatory molecules is important in the immunopathogenesis of SLE, which occurs by the dysregulation of T-lymphocyte costimulation. Plasma sCTLA concentration could potentially serve as a surrogate marker of SLE disease activity.

Adult↗
PubMed2005

Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus.

BACKGROUND: Osteopontin (OPN) is an extracellular matrix cell adhesion phosphoprotein with immunological activities including stimulation of macrophage chemotaxis, T-helper type 1 lymphocyte response and B-cell antibody synthesis. Overexpression of OPN has been associated with the development of the autoimmune/lymphoproliferative syndrome. METHODS: We measured the plasma concentration and ex vivo production of OPN, and the plasma proinflammatory IL-18 concentration in 54 SLE patients with or without renal impairment (RSLE group and SLE group, respectively) and 26 sex- and age-matched control (NC) subjects using an enzyme-linked immunoabsorbent assay. RESULTS: Plasma OPN concentrations were significantly higher in RSLE and SLE patients than in the NC group (both P<0.001). Increase in OPN concentration correlated positively and significantly with SLEDAI score in all SLE patients (r = 0.308, P = 0.023). The ex vivo production of OPN upon mitogen activation of peripheral blood mononuclear cells was significantly higher in the RSLE and SLE groups than in the NC group (both P<0.001). In RSLE patients, plasma OPN concentration showed a significant positive correlation with proinflammatory cytokine IL-18 concentration (r = 0.404, P = 0.037). CONCLUSION: The above results suggest that the production of OPN is associated with the inflammatory process and SLE development, and may serve as a potential disease marker of SLE.

Adult↗
PubMed2004

Severe acute respiratory syndrome: correlation between clinical outcome and radiologic features.

PURPOSE: To evaluate whether there is a correlation between the clinical outcomes and radiologic features of severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: The clinical, laboratory, and radiologic features of 138 patients with SARS were analyzed. Three radiologists in consensus retrospectively assessed the frontal chest radiographs obtained at presentation and during treatment (n = 2045) for the distribution (each lung was divided into upper, middle, and lower zones) and extent of lung parenchymal abnormality. Clinical end points included intensive care unit (ICU) admission and death. RESULTS: Thirty-six (26.1%) patients required ICU care, and eight (5.8%) died. The patients who required ICU care and/or died had more extensive consolidation on chest radiographs obtained initially (median percentage of consolidation, 3.30%, with interquartile range [IR] of 1.70%-8.78% vs 1.70% [IR, 0%-3.30%]; P < .001) and on day 7 after fever onset (median percentage of consolidation, 15.00% [IR, 6.48%-28.73%] vs 5.00% [IR, 2.50%-7.50%]; P < .001) than did surviving patients who did not require ICU care. Patients with involvement of more than one lung zone on initial and day 7 chest radiographs were more likely to require ICU care and/or die than were those with involvement of one or fewer zones (P < .001). Patients with bilateral pneumonic changes at presentation were more likely to have an adverse outcome than were those with unilateral pneumonia (P < .001). Involvement of more than one lung zone at baseline chest radiography was an independent predictor of ICU admission and/or death (odds ratio, 3.16; 95% confidence interval: 1.07, 9.32; P = .037) after adjustments for other significant factors (ie, patient age, and baseline neutrophil count and lactate dehydrogenase level). CONCLUSION: More extensive airspace disease at presentation is an independent predictor of adverse outcome in patients with SARS.

Adult↗
PubMed2003

Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis.

To study the immunosuppressive and anti-inflammatory effects of combined leflunomide and methotrexate (MTX) therapy on chemokine expression in patients with rheumatoid arthritis (RA), nine patients were enrolled for the combination therapy for 24 weeks. These patients have been on treatment with MTX 15 mg/week for not less than 3 months before entry to the study. A loading dose of l00 mg/day of leflunomide was given for 3 days, followed by 10 mg/day for the rest of the study period. Plasma concentrations of monocyte chemotactic protein-1 (MCP-1), thymus- and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) were assayed before and after combination treatment by ELISA. Gene expression of inflammatory cytokines and chemokines of peripheral blood mononuclear cells was analysed by cDNA expression array. Plasma MCP-1, TARC and MDC concentrations were significantly lower in patients after combination treatment [median (interquartile range) before versus after treatment: MCP-1 of 118.0 (64.0-515.2) versus 3.2 (0.0-22.8) pg/ml, P < 0.01; TARC of 126.1 (27.2-197.4) versus 0.0 (0.0-52.5) pg/ml, P < 0.05; MDC of 503.3 (446.2-600.9) versus 366.8 (337.4-393.4) pg/ml, P < 0.05]. Positive correlations among reductions in plasma chemokines and clinical outcome measures were also found. Expression of chemokine genes including MDC and TARC was suppressed after combination treatment [% suppression of 38.7 (54.3-13.0) and 53.7 (55.9-28.4), respectively]. Combination therapy with leflunomide and MTX exhibits anti-inflammatory activity in the suppression of chemokine expression and subsequent recruitment of inflammatory cells into the inflammatory sites in RA.

Adult↗
PubMed2003

Intravenous cyclophosphamide improves cardiac dysfunction in lupus myocarditis.

We describe a Chinese woman who developed severe heart failure 3 years from the onset of systemic lupus erythematosus (SLE). Endomyocardial biopsy confirmed lupus myocarditis, with focal infiltrates of small lymphocytes and some polymorphic neutrophils. The conventional treatment for cardiac failure plus oral prednisolone failed to bring clinical and echocardiographical improvement until the addition of intravenous (i.v.) 'pulse' cyclophosphamide. Three weeks after i.v. cyclophosphamide treatment, there was significant improvement of her heart failure symptoms with improvement in the ejection fraction from 19% to 63%.

Adult↗
PubMed2003

Elevated plasma concentrations of nitric oxide, soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the correlations among plasma concentrations of nitric oxide (NO), soluble thrombomodulin (sTM) and vascular cell adhesion molecule (sVCAM-1), and whether these three molecules are associated with renal involvement in patients with systemic lupus erythematosus (SLE). METHODS: Plasma NO concentrations of 73 SLE patients (35 with renal disease, RSLE patients; 38 without renal disease, SLE patients) and 28 age- and sex-matched healthy control subjects were measured by the non-enzymatic Griess assay, and sTM and sVCAM-1 by enzyme-linked immunosorbent assay. RESULTS: In RSLE patients, plasma nitrite concentrations were significantly higher than in control subjects (P=0.009) and correlated positively with plasma sTM, plasma creatinine and urea (all P<0.05). Plasma sTM and sVCAM-1 concentrations were significantly elevated in RSLE and SLE patients (both P<0.0001) compared with controls. Plasma sTM was significantly correlated with plasma sVCAM-1, and both were correlated with plasma creatinine and urea and the SLE Disease Activity Index (all P<0.05). CONCLUSION: Elevated plasma NO, sTM, and sVCAM-1 concentrations have significant intercorrelations and are strongly associated with renal involvement in SLE.

Adult↗
PubMed2003

Mesangial lupus nephritis in Chinese is associated with a high rate of transformation to higher grade nephritis.

Mesangial lupus nephritis was thought to be a mild form of lupus nephritis. However, case reports suggest that this type of nephritis could be associated with a high rate of transformation to more serious classes. We retrospectively reviewed the clinical features, clinical response at one year following treatment, as well as the long-term outcome of patients with mesangial lupus nephritis identified on their first renal biopsy. The possible clinical parameters that may predict poor outcome were examined. Nineteen patients with a median duration of follow-up of 9.6 (2.5-11.4) years were identified. At one year after biopsy, eight patients achieved complete remission, two patients achieved partial remission and nine patients had no response. Of the 10 responders, four relapsed after a median duration of 53 (42-97) months. Nine out of 10 patients (six nonresponders and four responders who relapsed) who underwent a second biopsy showed transformation to a higher grade nephritis. The long-term outcome remained favourable in nine patients. Responders and patients who were given angiotensin-converting enzyme inhibitors were associated with favourable long-term outcome. Our data highlight that renal biopsy should be repeated early in Chinese patients with mesangial nephritis who failed to respond to treatment in order to identify those who may require intense immunosuppressive therapy.

Adolescent↗
PubMed2002

Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus.

To investigate the production mechanism and proinflammatory role of the cytokine interleukin (IL-18) in lupus nephritis, we investigated the plasma concentrations of IL-18 and nitric oxide (NO) and the release of IL-18 and NO from mitogen-activated peripheral blood monomuclear cells (PBMC), in 35 SLE patients with renal disease (RSLE), 37 patients without renal disease (SLE) and 28 sex- and age-matched healthy control subjects (NC). IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Gene expressions of IL-18 and IL-18 receptor were analysed by RT-PCR. Plasma IL-18 and NO concentrations were significantly higher in RSLE than NC (both P < 0.01). Elevation of plasma IL-18 in RSLE correlated positively and significantly with SLE -disease activity index and plasma NO concentration (r = 0.623, P < 0.0001 and r = 0.455, P = 0.017, respectively), and the latter also showed a positive and significant correlation with plasma creatinine (r = 0.410, P = 0.034) and urea (r = 0.685, P < 0.0001). There was no significant difference in gene expressions of IL-18 and IL-18 receptor in PBMC among RSLE, SLE and NC. Percentage increase in culture supernatant IL-18 concentration was significantly higher in RSLE than SLE and NC (both P < 0.05). The basal NO release was significantly higher in RSLE than that in SLE and NC (both P < 0.005). IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE.

Adult↗
PubMed2002

Accelerated atherosclerosis in patients with systemic lupus erythematosus: a review of the causes and possible prevention.

Systemic lupus erythematosus is an autoimmune disorder affecting multiple organ systems. Patients with systemic lupus erythematosus exhibit a bimodal pattern of mortality, with those who have had the disease for 5 to 10 years being at increased risk of cardiovascular disease, particularly myocardial infarction. Elevated levels of conventional cardiovascular risk factors promote vascular damage resulting in impairment of normal endothelial function. In addition, autoantibodies directed against oxidised lipoproteins, along with chronic secretion of inflammatory cytokines and suppression of fibrinolytic parameters, are thought to increase atherogenesis. Treatment with corticosteroids may also contribute to the accelerated atherosclerosis observed in these patients. This review discusses the accentuated relationship between conventional cardiovascular risk factors, systemic lupus erythematosus-induced inflammatory changes and the early stages of atherogenesis and how careful monitoring of risk factors and use of appropriate therapies may reduce the progression of atheroma development in patients with systemic lupus erythematosus.

Arteriosclerosis↗
PubMed2001

Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus.

The aim of this study was to determine whether early damage accrued in SLE as measured by the SLICC/ACR Damage Index predicts mortality in an inception cohort of lupus patients that have been followed prospectively in a single centre. SLE patients from the University of Toronto Lupus Clinic presenting within 1 y of their diagnosis prior to 1988 were included. This enabled all patients to be potentially followed for at least 10 y. Yearly SLICC/ACR Damage Index scores were determined for each patient. Early damage was defined as a score > or = 1 and no damage as a score of 0 at the initial assessment. Log rank test was used to compare the survival experience between those with and without damage, with all patients being censored at 10 y. Two-hundred and sixty-three patients were identified in this inception cohort who were followed for 10 y. One-hundred and ninety patients (72%) had a SLICC/ACR Damage Index score of 0 (no damage) while 73 patients (28%) had at least one SLICC/ACR Damage Index item scored (early damage). Twenty-five percent of lupus patients who exhibited damage at their first SLICC/ACR Damage Index assessment died within 10 y of their illness as compared to only 7.3% who had no early damage (log rank P-value = 0.0002). SLE patients who died within 10 y were more likely to have renal damage (P = 0.013), and a trend toward more cardiovascular disease (P = 0.056), compared to patients who were alive. Early damage as reflected by the initial SLICC/ACR Damage Index is associated with a higher rate of mortality.

Adolescent↗
PubMed2000

Hydroxychloroquine has no significant effect on lipids and apolipoproteins in Chinese systemic lupus erythematosus patients with mild or inactive disease.

OBJECTIVE: To investigate the effects of hydroxychloroquine (HCQ) in Chinese patients with systemic lupus erythematosus who were either on a low dose of prednisone or not on prednisone. METHODS: 65 consecutive Chinese lupus patients without features of nephritis underwent assessment of the fasting serum lipid profile, including total cholesterol (TC), triglycerides (TG), HDL-cholesteorl (HDL-C), LDL-cholesterol (LDL-C), apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B) and lipoprotein (a) (Lp(a)). RESULTS: 44/65 (67.7%) patients were on HCQ with a dose of 244 +/- 86 mg daily and 34/65 (52.3%) patients were on 4.3 +/- 2.6 mg daily of prednisone. The percentages of patients taking prednisone and the mean dose in those patients receiving this treatment were not different between the groups with or without HCQ treatment. TG tended to be lower in those patients on HCQ (median and interquartile range) (1.0 (0.7-1.4) mmol/L vs 1.2 (0.8 1.6) mmol/L), but there were no significant differences in TC or other lipid parameters including Lp(a) between the 2 groups of patients with or without HCQ treatment. CONCLUSION: HCQ had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease. This finding probably reflects the low doses of corticosteroid used and a lower background lipid level in this population.

Adult↗