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Biomedical subjects

C S Lau

Publications and source records attributed to C S Lau.

At least 55 records · Page 3Linked to original sources

Profile of sex hormones in male patients with systemic lupus erythematosus.

OBJECTIVE: To study the profile of sex hormones in male patients with systemic lupus erythematosus (SLE). METHOD: Serum prolactin (PRL), testosterone (T), estradiol (E2), follicle-stimulating hormone (FSII) and luteinizing hormone (LH) levels were obtained from 35 males with SLE and compared with 33 age-matched normal controls. RESULTS: No significant differences in serum T, E2, PRL levels and E2/T ratio were observed between male SLE patients and controls. However, patients with SLE had significantly higher levels of gonadotrophins (FSH, LH). Five (14%) SLE patients, but none of the controls, had both low testosterone and elevated LH. Hypoandrogenic male SLE patients did not have overt features of hypogonadism but had a higher prevalence of central nervous system disease and scrositis than those with normal androgen levels. Discase flares, on the other hand, were not significantly more frequent in these patients. Although PRL or T levels per se did not correlate with disease activity in our patients, the ratio of PRL to T showed a significant correlation with SLEDAI scores (p = 0.42. P = 0.01). CONCLUSIONS: Hypoandrogenism is present in some male patients with SLE and may be relevant in disease pathogenesis. However, whether these hormonal abnormalities are intrinsic to SLE or the consequence of any non-specific chronic disorders cannot be distinguished from the current data. Further studies involving a larger number of subjects and inclusion of other disease controls are needed.

Adolescent↗

Workshop to identify critical windows of exposure for children's health: cardiovascular and endocrine work group summary.

The work group on cardiovascular and endocrine effects was asked to review the current state of knowledge about children's windows of vulnerability to developmental toxicants and to recommend how that information may be used to improve risk assessment and public health. We considered differences between structural defects, where periods of vulnerability are rather well defined, and functional defects, where periods of vulnerability are quite elusive.

Cardiovascular System↗

Effect of calcitriol on bone mineral density in premenopausal Chinese women taking chronic steroid therapy. A randomized, double blind, placebo controlled study.

OBJECTIVE: To study the effect of chronic steroid therapy on bone mineral density (BMD) in premenopausal women with normal menstrual cycles and its treatment. METHODS: A double blind placebo controlled study to evaluate 81 premenopausal women with systemic lupus erythematosus (SLE), aged 31.1 +/- 6 years, taking chronic steroid therapy, with a mean cumulative prednisone dose of 28 +/- 16.2 g. They were randomly allocated to 3 groups: Group 1: 0.5 microg calcitriol and 1200 mg calcium daily; Group 2: 1,200 mg calcium and placebo calcitriol; and Group 3: both placebo calcitriol and placebo calcium. RESULTS: Baseline T score at the lumbar spine was > -1 in 56.8% and < -2.5 in 3.7% of the patients. At the end of 2 years, patients in the calcitriol group exhibited a significant increase of 2.1 +/- 2.4% in BMD at the lumbar spine compared to baseline value (p < 0.05). This change was not significantly different from the respective change in either calcium or placebo group (0.4 +/- 2.9% and 0.3 +/- 3.5%, respectively). No significant changes were observed in any treatment group in BMD at the hip or radius. Alkaline phosphatase increased both in the placebo (baseline: 57.5 +/- 17.5 IU/I; year 2: 60.9 +/- 15.3 IU/A) and the calcium group (baseline: 53.6 +/- 16.6 IU/I; year 2: 59.0 +/- 22.8 IU/1), but this increase reached statistical significance only in the calcium group, while the same variable remained stable in the calcitriol group (baseline: 53.9 +/- 14.1 IU/I; year 2: 54.6 +/- 12.3 IU/I). CONCLUSION: Premenopausal women with SLE taking prolonged steroid therapy had lower BMD but showed no significant bone loss over the 2 year study period. The beneficial effect of calcitriol treatment in these premenopausal women was small, at least when it was instituted late in the course of steroid therapy.

Adrenal Cortex Hormones↗

Ovarian failure and flares of systemic lupus erythematosus.

OBJECTIVE: To study the effects of ovarian failure on disease flares in systemic lupus erythematosus (SLE). METHODS: Fifty-four female premenopausal SLE patients who were under the age of 45 years and treated with continuous oral cyclophosphamide (CYC) for no more than 12 months were studied. All patients had been followed up for >5 years following CYC treatment. Demographic characteristics, clinical and serologic profiles, and information concerning disease flares were recorded. Comparison of the number of severe and mild/moderate flares during the first 5 years after CYC treatment was made between patients who developed CYC-induced ovarian failure and those who did not. RESULTS: Fourteen SLE patients had documented ovarian failure with hypoestrogenemia within 2 years after CYC treatment. Compared with the menstruating group of patients, those who developed ovarian failure were significantly older at the time of CYC therapy (mean 37.9 versus 25.5 years; P < 0.001), but otherwise no significant differences in organ manifestations and autoantibody profiles between the 2 groups were observed. Both the ovarian failure group and menstruating group of patients had similar SLE Disease Activity Index scores at the time of CYC treatment (mean 15.6 versus 17.7; P = 0.16), and had comparable treatment durations (mean 8.2 versus 7.8 months; P = 0.68) and cumulative doses of CYC (mean 20.4 versus 17.9 grams; P = 0.34). Flares of SLE were uncommon during the first year following CYC administration. However, during the 5-year followup period, patients who developed CYC-induced ovarian failure had significantly fewer severe flares (mean 0.014 versus 0.075 flares/patient-year; P = 0.01) and smaller total number of flares (mean 0.128 versus 0.250 flares/patient-year; P = 0.03) when compared with those who were still menstruating. CONCLUSION: This study provides an important clinical observation to support the notion that ovarian failure with hypoestrogenemia is protective against lupus flares and emphasizes the importance of estrogen status in the determination of disease activity in SLE.

Adult↗

Mannose binding lectin gene mutations are associated with progression of liver disease in chronic hepatitis B infection.

Mannose-binding lectin (MBL) plays an important role in immune defense. We examined the MBL gene mutations and MBL levels in Chinese hepatitis B and hepatitis C patients with and without symptomatic cirrhosis. We recruited 190 hepatitis B and C patients, and 117 normal Chinese as controls. Serum MBL levels were measured by enzyme-linked immunosorbent assay. MBL gene mutation at codons 52, 54, and 57 was detected by polymerase chain reaction (PCR) assay. In asymptomatic hepatitis B and C patients, there was no increase in codons 52, 54, and 57 mutation, but the MBL levels were significantly lower than those in the controls. Codon 54 mutation rate was increased to 44.4% (P =.007) in symptomatic hepatitis B cirrhosis and 64.3% (P =.0026) in patients with spontaneous bacterial peritonitis (SBP). There was no increase in codon 54 mutation rate in hepatitis B-related hepatocellular carcinoma (HCC). In chronic hepatitis B infection, the odds ratio for an individual with codon 54 mutation to develop cirrhosis was 1.84 (95% CI: 1.21-2. 81) and to develop SBP was 4.58 (95% CI: 1.73-12.16). Chronic hepatitis B and hepatitis C infection lowered the MBL levels, probably by suppressing MBL production. Codon 54 mutation of MBL was associated with progression of disease in chronic hepatitis B infection.

Adolescent↗

Distribution of corticotropin-releasing hormone promoter polymorphism in different ethnic groups: evidence for natural selection in human populations.

The regulatory region of the corticotropin-releasing hormone (CRH) is highly conserved across species 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 cortisol and the regulation of inflammatory and immune events. In this report we describe polymorphisms in the 5' regulatory region of the CRH gene in humans. We studied the distribution of CRH alleles in three different African populations, in white UK Caucasoids, and in a Chinese population. In the African and UK populations we found three new polymorphisms which cosegregated, resulting in two alleles, A1 and A2. Gene frequencies for A1 and A2 were extremely divergent between the African and the UK populations. The African A1 frequency ranged from 0.27-0.3, while the UK Caucasoid frequency was 0.9. Compound alleles could be assigned by taking into account the previously described biallelic polymorphism at position 225 in the CRH promoter. The A2B1 compound allele is the commonest in contemporary African human populations (allele frequency range 0. 44-0.61) and was the only allele observed in a population of chimpanzees from Sierra Leone. Wright's F(ST )for the A2B1 allele over the four sampled populations was 0.612, a value exceeded in human populations only by loci which have apparently been subject to natural selection. Taken together, these findings support A2B1 as the ancestral allele and suggest that the CRH genomic region may have been subject to strong disruptive selection throughout human evolution.

Alleles↗

Lupus nephritis in Southern Chinese patients: clinicopathologic findings and long-term outcome.

Despite the improvement in survival of patients with systemic lupus erythematosus (SLE) and associated nephritis in the past 20 years, few studies of the long-term outcome of large cohorts of patients with well-defined histological classes of lupus nephropathy are available. We examined the long-term outcome of 183 patients with lupus nephritis (LN) followed up by the Division of Rheumatology at Queen Mary Hospital (Hong Kong) between 1976 and 1997. Their renal biopsies were classified according to World Health Organization (WHO) criteria. There were 27 men and 156 women. Initial renal biopsy showed the following WHO classes of LN: 2 patients (1%), class I; 9 patients (5%), class II; 46 patients (25%), class III; 101 patients (55%), class IV; and 25 patients (14%), class V. The mean duration of follow-up from the renal biopsy was 130.7 +/- 5.9 months (range, 13 to 260 months). The overall 5-, 10-, and 15-year survival and renal survival (survival without dialysis) rates were 98.9%, 94.4%, and 94.4% and 92.1%, 81.2%, and 75.2%, respectively. Univariate analysis showed class IV nephritis, hypertension, impaired renal function (glomerular filtration rate < 50 mL/min), nephrotic syndrome at time of renal biopsy, and failure of complete remission in the first year of treatment were unfavorable predictors for renal survival. Multivariate analysis using the Cox regression model also showed persistent hypertension, class IV nephritis, and incomplete renal remission in the first year were independent risk factors for renal failure. Our results showed the renal survival rate of our patients from South China with LN was similar to that of most reported series of white patients. Prospective randomized studies with well-defined treatment protocols are needed to delineate the optimal treatment strategy for LN.

Adult↗

Do flares of systemic lupus erythematosus decline after menopause?

OBJECTIVE: To study whether flares of SLE decline after menopause. METHOD: 34 postmenopausal SLE patients with premenopausal disease onset were studied. The frequency and severity of flares before and after menopause was compared. 17 postmenopausal onset SLE patients were also included for comparison. RESULT: Flares in postmenopausal SLE patients decreased significantly after menopause (total No. of flares/patient-year before and after menopause were 0.50+/-0.10 and 0.14+/-0.05, respectively, p = 0.002). The frequency and proportion of severe flares also dropped significantly. The rate and magnitude of postmenopausal flares in these patients were similar to those of the postmenopausal onset SLE patients, a subset known to run a more benign course. CONCLUSIONS: SLE flares less frequently and seriously after menopause. While this may suggest a protective role of hypoestrogenemia against lupus flares, the contribution of other factors like disease duration and effective treatment to this postmenopausal decline of flares cannot be separated from menopause per se. Further studies are needed.

Adolescent↗

Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy.

OBJECTIVE: To evaluate the efficacy of calcitriol and hormonal replacement therapy (HRT) in the treatment of steroid-induced osteoporosis in hypogonadal women. METHODS: We studied 28 young patients (aged 37 +/- 6 yr) with systemic lupus erythematosus (SLE) on chronic steroid therapy for 130 +/- 22 months and requiring more than 10 mg/day prednisone. They were amenorrhoeic for more than 2 yr with proven ovarian failure. All had osteopenia with a T score at L2-4 of less than -1. They were randomized to receive HRT (conjugated oestrogen 0.625 mg daily from day 1 to day 21 plus medroxyprogesterone acetate 5 mg daily days 10-21) or calcitriol 0.5 microg daily. All received calcium carbonate 1 g/day. RESULTS: There were no differences in the baseline demographic, bone mineral density (BMD) and biochemical data between the two groups. Lumbar spine BMD increased by 2.0 +/- 0.4% after 2 yr with HRT (P<0.05), but reduced by 1.74 +/- 0.4% (P<0.05) with calcitriol treatment. No change was seen at the distal one-third radius with HRT treatment but significant bone loss (2.3 +/- 1.4%, P<0.02) was observed with calcitriol therapy. BMD at the hip did not change in both groups. Comparing both treatment groups, significant differences in the BMD at the spine (P<0.03) and radius (P<0.05) were seen at the end of 2 yr. The changes in urinary n-telopeptide excretion but not serum osteocalcin at 6 months and 12 months were inversely correlated with the changes in lumbar spine BMD at 24 months. HRT did not cause an adverse effect on SLE disease activity. CONCLUSION: HRT but not calcitriol could prevent bone loss in young hypogonadal women on chronic steroid therapy.

Adult↗

Peripheral neuropathy in systemic lupus erythematosus.

The prevalence of clinically apparent peripheral neuropathy in systemic lupus erythematosus is reported to be between 2% to 18%. The purpose of this prospective case-control study was to determine the prevalence of peripheral neuropathy (PN) using electrodiagnostic criteria. Subgroup analysis was performed to determine whether PN correlated with disease activity, renal involvement, or serum immune markers. Fifty-four systemic lupus erythematosus patients and 30 controls were recruited in the study. The right median, ulnar, peroneal, tibial, and sural sensory and motor nerve conduction studies were obtained. PN in our study was defined as any abnormal values in motor and sensory distal latency, sensory action potential, motor action potential, or conduction velocity affecting 2 or more nerves. Of the 54 patients studied, PN was present in 15 patients (27.8%) of which 4 were symptomatic. There was a significant correlation between PN and anti-SM antibody, and there was a trend showing decreased motor and sensory action potential amplitudes in our systemic lupus erythematosus group compared to the controls. This observation was also seen in an active disease group when compared to those with inactive disease. The amplitude of the action potential was more often affected than the distal latency, and sensory nerves were more susceptible than motor nerves. The sural sensory action potential amplitude appears to be the most sensitive indicator of PN which may be used as an index to monitor disease activity.

Adolescent↗

Clinical characteristics and outcome of southern Chinese males with systemic lupus erythematosus.

The aims were to study the gender differences in clinical manifestations, disease course and organ damage in systemic lupus erythematosus (SLE). Clinical manifestations, autoantibody profile, relapses and damage scores were obtained from 51 Chinese males with SLE and compared with 201 consecutive female SLE controls. Fifty-one males were identified among 630 SLE patients who attended our clinics, giving a male prevalence of 8% and a female to male ratio of 11.4-1. Both the male SLE patients and the female controls had similar age and SLEDAI score at disease onset. Male SLE patients had less alopecia (P = 0.03), Raynaud's phenomenon (P = 0.01) and anti-Ro (P = 0.049) during the course of the disease but none of the differences were statistically significant after correction for multiple observations. The prevalence of major organ involvement in either sex was not different. Both groups of patients had a comparable mean duration of follow-up (104 vs. 102 months, P = 0.87). Males had a significantly lower rate of relapses (total No. of flares/patient-year: 0.23 in men vs. 0.33 in women, P = 0.04), but the frequency of severe flares (No. of severe flares/patient-year in men 0.08 vs. 0.12 in women, P = 0.16) was not significantly different from the females. Male patients with positive anti-Ro had significantly less overall flares than their female counterparts who were anti-Ro positive (0.16 vs. 0.34, P = 0.006). However, the use of immunosuppressive agents for disease control in patients of both sexes was similar. 22 (43%) of the males and 78 (39%) of the females had organ damage. A higher percentage of male patients had impairment of renal function (P = 0.006) but the proportion of patients who required dialysis was not different (4% in men vs. 2% in females. P = 0.92). There was also a trend of more cardiovascular damage in the males but the difference was not statistically significant (P = 0.09). The mean SLICC/ACR scores were not significantly higher in the males than the females (0.71 vs. 0.60, P = 0.47). Males tend to differ from females in clinical manifestations, immunological profile and disease course in SLE. However, there was no gender difference in the involvement of major organs/systems. Males had less overall disease flares than the females but the rate of severe flares was not significantly lower. For patients who were anti-Ro positive, males had significantly less total number of flares/patient-year than their female counterparts. More renal impairment and cardiovascular damage was present in our male lupus patients but the overall damage scores were not significantly higher.

Adult↗

Pulmonary hypertension secondary to systemic lupus erythematosus: prolonged survival following treatment with intermittent low dose iloprost.

Pulmonary hypertension (PHT) associated with systemic lupus erythematosus (SLE) has a dismal prognosis. Vasodilators and immunosuppressive therapy have been tried over the years with discouraging results. Prostacyclin (PGI2) which has potent vasodilatatory and anti-platelet effects has been demonstrated to significantly decrease pulmonary arterial pressure and pulmonary vascular resistance during acute infusion. Satisfactory response has been reported in SLE patients with PHT treated with short-term intravenous continuous PGI2 infusion. We report here a 48-month experience of the use of monthly low dose infusion of a PGI2 analogue, iloprost, in a SLE patient with pulmonary hypertension in New York Heart Association functional Class III. There was an initial haemodynamic response to an acute infusion of iloprost. Repeated infusions were followed by marked improvement in her functional status and her mean pulmonary arterial pressure dropped from 80 mmHg in the first few months and remained static at around 55 mmHg for the subsequent years.

Adult↗

Comparison of counter immunoelectrophoresis with immunoblotting for detection of anti-extractable nuclear antigen antibodies in systemic lupus erythematosus.

Anti-extractable nuclear antigen (ENA) antibodies were assayed by counter immunoelectrophoresis (CIE) and immunoblotting in patients with systemic lupus erythematosus (SLE). We found the two methods showed good concordance rates, the lowest being 67% for anti-SS-A. Immunoblotting was more sensitive in detecting anti-Sm, anti-SS-B and anti-PCNA (proliferating cell nuclear antigen); CIE was more sensitive for anti-nRNP and anti-SS-A. Overall, the prevalence of these anti-ENA antibodies in SLE was increased by 9-20% if immunoblotting was used in addition to CIE. Sera specific for the 52 kDa peptide of the SS-A antigen (anti-52kDa SS-A) were better detected by immunoblotting. Anti-PCNA antibody was found in 6.3% of SLE patients and was associated with active disease and hemolytic anemia. The positive rate of anti-Sm was 9% by CIE and 23.7% by immunoblotting and this antibody was a specific marker for SLE using either method. It was concluded that using immunoblotting in addition to CIE, the overall sensitivity of detection of anti-ENA antibodies in SLE was increased and clinically useful antibodies such as anti-52kDa SS-A and anti-PCNA could be detected.

Anemia, Hemolytic↗

Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy.

OBJECTIVE: To determine the incidence of ovarian failure after cyclophosphamide (CYC) treatment for systemic lupus erythematosus (SLE) and to identify the risk factors for this complication. METHODS: The records of 70 premenopausal female SLE patients treated with CYC were reviewed retrospectively. Information on demographic features, autoantibody profiles, and CYC treatment was obtained, and comparisons were made between those who developed ovarian failure and those who did not. Data on the CYC-treated patients were also compared with data on 2 control groups of non-CYC-treated SLE patients. RESULTS: Eighteen patients developed ovarian failure after CYC treatment, for an overall incidence of 26%. The incidence of ovarian failure showed a linear trend of increase with increasing age at the start of CYC (P = 0.007). The cumulative CYC dose was significantly higher in the patients with ovarian failure than in those without (28.3 gm versus 15.4 gm; P = 0.004). The risk of ovarian failure also showed a linear trend of increase with increasing cumulative CYC dose (P < 0.001). Using multiple logistic regression, the age at the time of CYC treatment initiation (beta = 0.37, SE = 0.11, P = 0.001) and the cumulative dose of CYC received (beta = 0.69, SE = 0.29, P = 0.02) were found to be independent risk factors for CYC-induced ovarian failure. CONCLUSION: In our population of female SLE patients, CYC-induced ovarian toxicity is a significant problem, particularly in patients above the age of 40. The age at the start of CYC therapy and the cumulative dose are the major determinants for the development of this complication. For older patients with SLE in whom the use of CYC is warranted, a shorter course and lower dosage should be considered.

Adult↗

Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus.

OBJECTIVE: To study the genetic association of interleukin-10 (IL-10) promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus (SLE), and to investigate possible associations with clinical manifestations of the disease. METHODS: DNA was extracted from 88 Chinese patients with SLE and 83 ethnically matched controls. The IL-10 promoter region between positions -533 and -1120 was amplified by polymerase chain reaction, and polymorphisms were detected by restriction-enzyme cleavage. RESULTS: No significant difference in the allele or haplotype frequencies between SLE patients and controls could be demonstrated. The *A and *C alleles at the -597 position were linked to the *T and *C alleles at the -824 position, respectively. However, when clinical features were examined, the *A allele at the -597 position and the *T allele at the -824 position were significantly associated with lupus nephritis, by chi-square analysis (P < 0.001, odds ratio 4.19, 95% confidence interval 2.02-8.71). Similarly, the haplotype -1087*A/-824*T/-597*A was also associated with renal involvement (P < 0.001, odds ratio 3.62, 95% confidence interval 1.80-7.31). CONCLUSION: IL-10 promoter polymorphisms are not strong determinants of susceptibility to the development of SLE, per se, in Southern Chinese individuals. However, IL-10 genotypes are strongly associated with certain clinical manifestations of SLE and may have a role in predicting disease prognosis.

Adult↗

Features of spondyloarthritis around the world.

This article elucidates the prevalence and pathogenic roles of the MHC and microbial infections and clinical features and treatment of SpA across different populations from the arctic and subarctic regions to Central America, Asia, and Africa. Preliminary evidence suggests significant genetic and environmental influences on the onset and presentation of SpA, particularly AS, in these populations, which are different than those reported in white Caucasians; however, community surveys and longitudinal and case control studies are difficult to undertake in many of the developing countries. Thus, most of the currently available data have been devised from short-term and retrospective studies and should be treated with caution. Differences in referral and follow-up practices and the availability of rheumatology expertise and relevant resources may explain some of the differences observed in the populations discussed in this article. Furthermore, widely accepted criteria for the classification of SpA may not be applicable to non-Caucasians and need to be evaluated in these subjects. With gradual improvement in the economic status in many of the developing countries in Asia and Africa, it is hoped that with improvement in medical services, more physicians and specialty clinics in rheumatology, and changing referral patterns, better documentation of the various aspects of different SpA can be achieved. Future research should focus on the evaluation of specific risk or protective factors in population groups to better delineate the relative importance of genetic and environmental effects in the pathogenesis of SpA.

Arthritis, Psoriatic↗

Measurement of anti-dsDNA: a comparative study of two ELISA and the Crithidia assay.

We compared the measurement of anti-dsDNA by a commercial ELISA test (DIASTAT), an in-house ELISA and the Crithidia luciliae assay in cross-sectional sera samples of 209 systemic lupus erythematosus (SLE) patients and 64 patients with a variety of rheumatological, autoimmune and non-autoimmune diseases in Hong Kong. The Crithidia assay was found to be the least sensitive (17%) but most specific (95%) method for detection of a positive result in SLE patients. The DIASTAT assay has a higher sensitivity (68%) but lower specificity (80%) than the in-house ELISA test (32% sensitivity and 89% specificity). The positive predictive value of the three assays are comparable at 90-92% while DIASTAT had the highest negative predictive value (44%). There was good linear correlation (r = 0.7) between the two ELISAs. ELISA can serve as a useful screening test for anti-dsDNA in SLE patients and doubtful cases can then be confirmed by another method such as radio-immunoassay.

Animals↗