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Biomedical subjects

C S Lau

Publications and source records attributed to C S Lau.

At least 37 records · Page 2Linked to original sources
PubMed2003

Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.

OBJECTIVE: To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors. METHODS: Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE. RESULTS: At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients. CONCLUSION: The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.

Adolescent↗
PubMed2003

Interstitial lung disease in systemic sclerosis.

PURPOSE: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. MATERIAL AND METHODS: 45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. RESULTS: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. CONCLUSION: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Exercise Tolerance↗
PubMed2003

Pathogenesis of systemic lupus erythematosus.

The exact patho-aetiology of systemic lupus erythematosus (SLE) remains elusive. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. Multiple genes contribute to disease susceptibility. The interaction of sex, hormonal milieu, and the hypothalamo-pituitary-adrenal axis modifies this susceptibility and the clinical expression of the disease. Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of SLE. The loss of immune tolerance, increased antigenic load, excess T cell help, defective B cell suppression, and the shifting of T helper 1 (Th1) to Th2 immune responses leads to B cell hyperactivity and the production of pathogenic autoantibodies. Finally, certain environmental factors are probably required to trigger the disease.

Antibody Formation↗
PubMed2003

Lupus in Hong Kong Chinese.

Systemic lupus erythematosus (SLE) is a fairly common rheumatic disease among southern Chinese in Hong Kong, with an estimated point prevalence of 0.06% (0.1% among women). Compared with the Caucasians, renal disease and the anti-Ro antibody appear to be more common in our SLE patients. Whether these are related to certain genetic or environment factors remains speculative. Nephritis and its treatment are the major causes of organ damage in our lupus population. With early diagnosis of the disease and its complications, judicious use of immunosuppressive therapy to achieve prompt control of disease activity, and better supportive care for disease- or treatment-related morbidity, the survival of our Chinese SLE patients has improved. In the past decade, considerable effort has been spent on lupus education, medical training and research in Hong Kong, aiming to improve the quality of care of patients with SLE. More grants and funding are being sought for basic and clinical researches in SLE and subsidising patients to receive newer and less toxic treatment options.

Adolescent↗
PubMed2002

A placebo and active comparator-controlled trial of rofecoxib for the treatment of rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy and tolerability of rofecoxib 25 mg and 50 mg once daily versus placebo and naproxen 500 mg twice daily in patients with RA. METHODS: Eligible patients were randomized (double-blind) to placebo (n = 289), rofecoxib 25 mg (n = 306), 50 mg (n = 286) once daily, or naproxen (n = 142) for 12 weeks. Efficacy assessments included the ACR core set, with prespecified primary endpoints: patient and investigator global assessments of disease activity, tender and swollen joint counts. Investigator-reported adverse experiences, routine laboratory and vital sign measurements were monitored. RESULTS: Rofecoxib 25 mg, 50 mg, and naproxen provided similar treatment effects, significantly different from placebo, consistent with improvement, for all primary endpoints. Effects were evident at the earliest assessment (week 2) and sustained for 12 weeks. All treatments were generally well-tolerated. CONCLUSIONS: Rofecoxib 25 mg once daily had similar efficacy to naproxen 500 mg twice daily (a standard dose). No additional benefit was seen with 50 mg rofecoxib.

Adult↗
PubMed2001

Treatment of diffuse proliferative lupus glomerulonephritis: a comparison of two cyclophosphamide-containing regimens.

Cyclophosphamide (CYC) has proven beneficial in preserving renal function in patients with lupus with diffuse proliferative glomerulonephritis (DPGN). However, the optimal route of CYC administration is unknown because direct comparative studies are unavailable. In this open study, we compared the renal outcome of two historical cohorts of patients with diffuse proliferative lupus nephritis (World Health Organization classes IVa and IVb) treated with either intravenous (IV) pulse CYC (group A; n = 22) or sequential oral CYC followed by azathioprine (AZA; group B; n = 21) and followed up prospectively. Both groups of patients had similar clinical, biochemical, and renal parameters at baseline. At 24 months posttreatment, significant improvements in proteinuria, creatinine clearance, serum albumin level, and lupus serological results were evident in both groups. Compared with patients in group A, patients in group B had more complete or partial remission (90% versus 73%) and less risk for treatment failure (5% versus 14%), renal flares (5% versus 14%), and doubling of creatinine levels (5% versus 9%), but the difference was not statistically significant. However, patients treated with oral immunosuppression had an insignificant increase in rates of herpes zoster infection (19% versus 9%) and menstrual disturbance (50% versus 29%). We conclude that sequential oral immunosuppression with CYC and AZA tended to have better efficacy than IV pulse CYC in the treatment of lupus DPGN but was associated with more toxicities. Additional randomized trials involving a larger cohort of patients with a longer period of observation are necessary.

Administration, Oral↗
PubMed2001

Use of exogenous estrogens in systemic lupus erythematosus.

OBJECTIVE: To review the current literature on the safety of using exogenous estrogens in patients with systemic lupus erythematosus (SLE). METHOD: A MEDLINE search for articles published between 1970 and 2000 regarding the relationship between estrogens and SLE was performed. Emphasis was put on human studies, treatment trials, and epidemiologic surveys. RESULTS: The use of exogenous estrogens in healthy women increases the risk of SLE development. For patients with established SLE, a hypoestrogenemic state appears to be protective against severe flares, whereas exogenous estrogen administration or hyperestrogenemia induced by hormonal manipulation may exacerbate the disease in certain individuals. Both the use of oral contraceptives and the use of hormonal replacement therapy (HRT) increase the chance of venous thromboembolism. The presence of antiphospholipid antibodies may aggravate the risk of thrombosis in SLE. In retrospective studies, HRT appears to be well tolerated in postmenopausal SLE patients. CONCLUSIONS: There are no prospective data that show a deleterious effect of exogenous estrogens on disease activity in human SLE. Oral contraceptives may be considered for patients with SLE in the absence of active nephritis or antiphospholipid antibodies. The slight increase in venous thromboembolic risk should not be the chief deterrent to the use of HRT in postmenopausal SLE patients, considering its various health benefits.

Estrogens↗
PubMed2001

Strategic planning: a guide to success.

One of the key business concepts applicable to the contemporary dental practice is strategic planning. Just as a dentist diagnoses and treatment plans patients, so too should a business diagnose and treatment plan its future. Strategic planning offers a systematic approach for analyzing a current situation and creating a work plan toward the future goal.

Efficiency↗
PubMed2001

Neuropsychiatric manifestations and their clinical associations in southern Chinese patients with systemic lupus erythematosus.

OBJECTIVE: To study the neuropsychiatric (NP) manifestations in a large cohort of southern Chinese patients with systemic lupus erythematosus (SLE) according to the new 1999 American College of Rheumatology (ACR) case definitions and their clinical associations. METHOD: Patients with SLE who were followed from 1984 to 2000 were retrospectively reviewed. Patients with NP manifestations were ascertained and classified by at least 2 rheumatologists, with the collaboration of neurologists and psychiatrists. The association of NP manifestations with other clinical features and autoantibodies was studied by statistical analysis. RESULTS: Five hundred eighteen patients with SLE were studied. The female to male ratio was 7.8 to 1 and the mean age of disease onset was 29.5 +/- 12.0 years (range 9-80). The mean duration of followup was 7.3 +/- 6.7 years (range 0.3-23.0). Ninety-six patients (19%) had 133 NP events and the mean number of events per patient-year of followup was 0.035. In decreasing order of frequency. these events were: seizure disorder (28%), cerebrovascular disease (19%), acute confusional state (14%), psychosis (11%), myelopathy (8%), mood disorder (6%), headache (4%), movement disorder (2%), cranial neuropathy (3%), demyelinating syndrome (1.5%), anxiety disorder (1.5%), mononeuritis multiplex/mononeuropathy (1.5%), aseptic meningitis (1%), and polyneuropathy (1%). Cognitive dysfunction was not classified because of the lack of standard neuropsychological testing for every patient. Univariate analysis revealed that NP-SLE was associated with a positive lupus anticoagulant (LAC) (p = 0.001), a strongly positive IgG anticardiolipin (aCL) (p = 0.01). leukopenia (p = 0.01), lymphopenia (p = 0.03), thrombocytopenia (p = 0.03), and pulmonary involvement (p = 0.03). Multivariate analysis showed that a strongly positive IgG aCL [RR 3.1 (1.3-7.7), p = 0.01] and a history of cyclophosphamide treatment [RR 4.3 (2.1-9.0), p < 0.001] were independently associated with NP manifestations in our cohort. Among the NP features, cerebrovascular disorder was particularly associated with the presence of LAC [OR 3.3 (1.4-8.0), p = 0.01] and a strongly positive IgG aCL [OR 3.1 (1.1-8.2), p = 0.031]. CONCLUSION: The point prevalence of overt NP manifestations in our cohort of patients with SLE was 19%. This percentage was likely higher if subtle cognitive dysfunction was included. Seizure and cerebrovascular disorders were the most common NP features. The presence of antiphospholipid antibodies was significantly associated with NP manifestations, especially cerebrovascular disorders.

Adolescent↗
PubMed2001

Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies.

This paper describes the background and current status of an OMERACT facilitated effort to improve the consistency of adverse event reporting in rheumatology clinical trials. The overall goal is the development of an adverse event assessment tool that would provide a basis for use of common terminology and improve the consistency of reporting severity of side effects within rheumatology clinical trials and during postmarketing surveillance. The resulting Rheumatology Common Toxicity Criteria Index encompassed the following organ systems: allergic/immunologic, cardiac, ENT, gastrointestinal, musculoskeletal, neuropsychiatric, ophthalmologic, pulmonary and skin/integument. Before this tool is widely accepted, its validity, consistency, and feasibility need to be assessed in clinical trials.

Antirheumatic Agents↗
PubMed2000

Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group.

BACKGROUND: The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Whether mycophenolate mofetil can be substituted for cyclophosphamide is not known. METHODS: In 42 patients with diffuse proliferative lupus nephritis we compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months with those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months. Complete remission was defined as a value for urinary protein excretion that was less than 0.3 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration, and values for serum creatinine and creatinine clearance that were no more than 15 percent above the base-line values. Partial remission was defined as a value for urinary protein excretion that was between 0.3 and 2.9 g per 24 hours, with a serum albumin concentration of at least 30 g per liter. RESULTS: Eighty-one percent of the 21 patients treated with mycophenolate mofetil and prednisolone (group 1) had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients treated with cyclophosphamide and prednisolone followed by azathioprine and prednisolone (group 2). The improvements in the degree of proteinuria and the serum albumin and creatinine concentrations were similar in the two groups. One patient in each group discontinued treatment because of side effects. Infections were noted in 19 percent of the patients in group 1 and in 33 percent of those in group 2 (P = 0.29). Other adverse effects occurred only in group 2; they included amenorrhea (in 23 percent of the patients), hair loss (19 percent), leukopenia (10 percent), and death (10 percent). The rates of relapse were 15 percent and 11 percent, respectively. CONCLUSIONS: For the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone but is less toxic.

Adult↗
PubMed2000

Mannose-binding lectin and rheumatoid arthritis in southern Chinese.

OBJECTIVE: Insufficiency of mannose-binding lectin (MBL) is associated with recurrent infections. Rheumatoid arthritis (RA) may represent an aberrant immune response to infections. This study examined the phenotypic expression and variant alleles of the MBL gene and its etiologic role in Chinese with RA. METHODS: We studied 211 RA patients and 196 healthy subjects. Serum MBL concentrations and codon-54 mutation of the MBL gene and its promoter polymorphisms were analyzed. Clinical characteristics and disease activity were also examined. RESULTS: Patients with RA had significantly lower serum MBL levels and higher frequency of codon-54 mutation of the MBL gene compared with controls. Additionally, there was a significant difference in the distribution of promoter polymorphisms, H/L, between RA patients and controls, although the frequencies of Y/X and those of nonstructural polymorphisms, P/Q, did not differ between the 2 groups. Furthermore, patients with RA had a lower incidence of the highest-producing haplotype HY and a higher incidence of the lowest-producing haplotype LX compared with controls. Serum MBL levels did not correlate with drug treatment or with disease activity. However, patients with erosive and serious extraarticular disease had significantly lower serum MBL levels than those without these disease manifestations at the time of study. Also, significantly more patients with erosive disease had a codon-54 mutation of the MBL gene compared with those with nonerosive disease. CONCLUSION: The codon-54 mutation and low-producing promoter polymorphisms of the MBL gene are associated with RA. A low serum level of MBL predisposes to the development of RA and is a risk factor for severe disease in southern Chinese.

Arthritis, Rheumatoid↗
PubMed2000

Corticotropin releasing hormone (CRH) promoter polymorphisms in various ethnic groups of patients with rheumatoid arthritis.

UNLABELLED: The regulatory region of the corticotropin releasing hormone (CRH) is highly conserved and plays a crucial role in the response of the organism to stress. Release of CRH initiates a cascade of events leading to the release of cortisone and the regulation of inflammatory and immune events. OBJECTIVE: Since it has been postulated that the impaired corticotropin releasing hormone (CRH) response to stress in patients with rheumatoid arthritis (RA) has a genetic basis, we investigated the distribution of CRH alleles in a cohort of UK patients as well as in South African RA patients. METHODS: Restriction fragment length polymorphism of PCR amplified DNA products of the CRH promoter. We compared the allele frequencies in the RA patients with the respective healthy control population described previously. RESULTS: As in the control populations we found two biallelic polymorphic sequences (named A1 and A2 and B1 and B2, respectively) in the CRH promoter which could be assigned to compound alleles. The A2B1 compound allele was protective against development of RA in a large group of UK Caucasoid patients (p = 0.03; odds ratio 0.43, 95% confidence interval 0.21-0.88). In contrast, A1B1 was positively associated with RA in a cohort of black South African RA patients (p = 0.05; odds ratio 1.78, 95% confidence interval 1.01-3.15). CONCLUSION: Taken together, these findings support the hypothesis that CRH promoter polymorphism represents a new genetic marker for RA susceptibility and may prove useful for the prediction of RA risk in the future when further genetic and environmental risk factors are determined.

Adult↗
PubMed2000

A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population.

OBJECTIVES: To study the survival rate and prognostic indicators of systemic lupus erythematosus (SLE) in a southern Chinese population. METHODS: One hundred and eighty-six patients with SLE diagnosed between 1992 and 1999 were prospectively followed. Clinical features at presentation, subsequent evolving features, autoantibody profile, damage scores and mortality data were obtained. Prognostic factors for survival were studied by statistical analysis. RESULTS: One hundred and sixty-three female and 23 male SLE patients were studied. The female to male ratio was 7.1 to 1 and the mean age at presentation was 33.6 yr (range 12-75). The mean disease duration was 45.2 months. At diagnosis, arthritis, malar rash and alopecia were the commonest features. During follow-up, the prevalence of nephritis, arthritis, photosensitivity and haematological disease increased significantly. Thirty-one per cent of the patients had organ damage at the time of data analysis and renal disease was the commonest cause. Logistic regression revealed that central nervous system disease, discoid lesions and treatment with high-dose steroid were independent predictors for damage. Nine patients died during the study period (three of disease-related complications and six of infections). The 3-, 5-, and 7-yr survival rates of our cohort were 97, 93 and 93%, respectively. Cox regression analysis revealed that thrombocytopenia and high-dose steroid treatment were independent risk factors for mortality. CONCLUSIONS: The survival of SLE in our southern Chinese patients is similar to that of the Caucasian series reported in the 1990s. Although nephritis contributes to organ damage, it is not a major determinant for survival. Infection remains the commonest cause of death. High-dose steroid treatment and thrombocytopenia are independent risk factors for mortality. Judicious use of immunosuppressive agents is necessary to improve the short-term survival of SLE.

Adolescent↗
PubMed2000

Intestinal pseudo-obstruction in systemic lupus erythematosus: an uncommon but important clinical manifestation.

OBJECTIVES: To document intestinal pseudo-obstruction (IpsO) as a recognised clinical manifestation of systemic lupus erythematosus (SLE) and a possible new clinical entity with its apparent association with ureterohydronephrosis. METHODOLOGY: We report six lupus patients who presented with IpsO and review 12 other cases from an English literature search. IpsO is defined as the presence of clinical features suggestive of intestinal obstruction but without organic obstruction, namely absence of bowel sounds, presence of multiple fluid levels on plain abdominal X-rays and exclusion of organic obstruction by imaging or surgical procedure. Other clinical characteristics related to the underlying lupus, serological and histological findings, treatment modalities and outcomes of these patients were reviewed. RESULTS: All 18 patients fulfilled the ACR revised classification criteria for SLE. None showed any clinical features of scleroderma or overlap syndrome. The mean age of onset of IpsO was 29.0 (15-47) y. The female to male ratio was 16:2. Nine patients had IpsO as the initial presentation of their underlying lupus. Coexisting lupus involvement of other organ systems included glomerulonephritis (n=7), thrombocytopenia (n=5) and cerebral lupus (n=3). The serology data and autoantibody profile of some of the previously reported patients were incomplete. In our series, anti-Ro antibody was positive in 5/6 while anti-RNP was found in 1/6 patients only. All our patients had active lupus serology at presentation. 17/18 patients required the use of high dose systemic corticosteroid therapy while one patient responded to topical adrenocorticotrophin hormone treatment. Response was good and was observed early after commencement. Azathioprine was used as maintenance therapy in 6/18 patients with good effects. An apparent association with the presence of bilateral ureterohydronephrosis was found in 12/18 patients. These patients presented with dysuria without positive bacterial culture though features of chronic interstitial cystitis were not invariably found in these patients. CONCLUSION: IpsO is an uncommon but important manifestation of SLE. The underlying pathology is not fully understood but it may be related to immune complex deposition. The finding of coexisting ureterohydronephrosis suggests that there may also be a central smooth muscle motility problem of neuropathic or myogenic pathophysiology which may or may not be secondary to vasculitis. Early recognition and treatment of IpsO in SLE is important.

Adult↗