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K Y Fong

Publications and source records attributed to K Y Fong.

At least 19 recordsLinked to original sources

Novel brain reactive autoantibodies: prevalence in systemic lupus erythematosus and association with psychoses and seizures.

Autoantibodies can cause neuropsychiatric manifestations in lupus patients by altering the physiological function of neuronal cells. In this study, we identified Brain Reactive Autoantibodies (BRAAs) against murine neuronal membrane proteins (M.W. 27.5 and 29.5 kD) and found them correlating with psychosis and/or seizures in lupus patients. They were specific to neuronal membrane tissues of mammalian origin and are significantly associated with psychosis and/or seizures (p<0.0001). These membrane proteins mass spectrometry profiles did not match to any published protein sequences. These BRAAs may play important roles in the pathophysiology of neuropsychiatric lupus.

Adult↗

Discriminative ability of the short-form 36 health survey: a tale of two versions.

BACKGROUND AND OBJECTIVES: Previous studies suggested that the Chinese version of the Short-Form 36 Health Survey (SF-36) had smaller variability in the physical functioning (PF) and physical component summary (PCS) scores than the English SF-36. This may translate into differences in discriminative ability and sample size requirement. MATERIALS AND METHODS: Data were drawn from a community-based survey and a randomised crossover study of Singaporeans bilingual in the Chinese and English languages. The abilities of the two PF and PCS versions in discriminating subjects who reported chronic illness and acute disease symptoms versus those who did not were compared. RESULTS: In all four comparisons (i.e. two health criteria in two studies) the Chinese version of PF showed a larger effect size than the English version. In three out of four comparisons the Chinese version of PCS showed a larger effect size than the English version. CONCLUSIONS: The Chinese version appeared more efficient in detecting a statistically significant difference between groups. Other factors being the same, the Chinese SF-36 may require a smaller sample size than the English SF-36 for the studies of physical aspects of health-related quality of life.

Activities of Daily Living↗

PCR-RFLP genotyping for exon 1 and promoter region mutations of the human mannose binding lectin (MBL-2) gene.

The Mannose Binding Lectin (MBL) plays an important role in innate immunity and its genetic deficiencies are associated with frequent and prolonged infections. Serum MBL determination may not accurately detect acute phase protein levels and it is also difficult to detect dysfunctional protein. Genotyping of the exon 1 and promoter regions in the MBL gene will provide useful information on the presence of deficiencies in patients. A reproducible PCR-RFLP method is described to accurately detect genotypes of exon 1 and polymorphic haplotypes of the promoter region in the MBL gene.

Base Sequence↗

Modelling variability of quality of life scores: a study of questionnaire version and bilingualism.

BACKGROUND AND OBJECTIVES: Modelling variability of quality of life scores can not only improve our understanding of the characteristics of the measurement tools, but also shed light on sample size requirements. Although the English and Chinese versions of the Short Form 36 Health Survey (SF-36) are commonly considered equivalent, they have not been compared in terms of variability. Furthermore, bilingual and monolingual persons may differ in cognition and responses to questionnaires. METHODS: In a community-based survey of quality of life in Singapore, a society where both English and Chinese are widely used and bilingualism is prevalent, 2590 respondents answered either version of the SF-36. We studied the impact of questionnaire version and bilingualism on the variability of SF-36 scores by regression modelling, with adjustment for covariates. RESULTS: The Chinese version had smaller variances in the physical functioning (PF) and the physical component summary scores than the English version. The variance ratios (VRs) were respectively 0.32 and 0.60 (each p < 0.01), controlling for covariates. Bilingualism was not associated with variability in SF-36 scores except PF (VR = 0.78; p < 0.05). CONCLUSIONS: As a result of a smaller variance, using the Chinese version of SF-36 among bilingual Chinese people may require a smaller sample size than using the English version.

Adult↗

Validity and reliability of the EQ-5D self-report questionnaire in English-speaking Asian patients with rheumatic diseases in Singapore.

Validity and reliability of a Singaporean English EQ-5D self-report questionnaire (EQ-5D) were evaluated among consecutive outpatients with rheumatic diseases attending a tertiary referral hospital in Singapore (a multi-ethnic, urban Asian country). Subjects were interviewed twice within a 2-week period using a standardized questionnaire containing the EQ-5D, Short Form 36 Health Survey (SF-36) and assessing demographic and psychosocial characteristics. To assess validity of the EQ-5D, 13 hypotheses relating responses to EQ-5D dimension/Visual Analogue Scale (EQ-VAS) to SF-36 scores or other variables were examined using the Mann-Whitney test, Kruskal-Wallis test, or Spearman's correlation coefficient. Test-retest reliability was assessed using Cohen's kappa. Sixty-six subjects were studied (osteoarthritis: 9, rheumatoid arthritis: 26, systemic lupus erythematosus: 23, spondyloarthropathy: 8; female: 72.7%; mean age: 44.3 years). Ten of 13 a-priori hypotheses relating EQ-5D responses to external variables were fulfilled, supporting the validity of the EQ-SD. Cohen's kappa for test-retest reliability (n = 52) ranged from 0.29 to 0.61. The Singaporean English EQ-5D appears to be valid in measuring quality of life in Singaporeans with rheumatic diseases; however, its reliability requires further investigation. These data provide a basis for further studies assessing the validity of the EQ-5D in Singapore.

Adolescent↗

Single-nucleotide polymorphisms of the interleukin-18 gene promoter region in rheumatoid arthritis patients: protective effect of AA genotype.

Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.

Adult↗

Refractory immune thrombocytopenia in systemic lupus erythematosus: response to mycophenolate mofetil.

Immune thrombocytopenia (IT) is a common manifestation of systemic lupus erythematosus (SLE). Although severe IT (<20 x 10(9)/L) occurs in about 5-10% of patients, usually in the context of active disease, the absence of randomized controlled trials has not allowed the development of evidence-based guidelines for managing this condition. Conventionally, high-dose glucocorticoids are considered first-line therapy. Adjunctive medical and surgical treatments for patients with an absent or partial response to glucocorticoids have met with varying degrees of success. We describe an SLE patient with IT refractory to high-dose corticosteroids, pulse methylprednisolone and intravenous immunoglobulin therapy, whose platelet counts normalized during therapy with mycophenolate mofetil (MMF). Pending further controlled studies to confirm this observation, we suggest that MMF may be considered as a therapeutic option in the treatment of glucocorticoid-refractory immune thrombocytopenia in SLE.

Adrenal Cortex Hormones↗

Validity and reliability of the EQ-5D self-report questionnaire in Chinese-speaking patients with rheumatic diseases in Singapore.

OBJECTIVE: We assessed the psychometric properties of a Singaporean Chinese version of the EQ-5D, a health-related quality of life (HRQoL) instrument. MATERIALS AND METHODS: Consecutive outpatients with rheumatic diseases seen for routine follow-up consultations at the National University Hospital, Singapore were interviewed twice within 2 weeks using a standardised questionnaire containing the EQ-5D, the Short-Form 36 Health Survey (SF-36), the Learned Helplessness Subscale, a pain Visual Analogue Scale (VAS) and assessing demographic and psychosocial characteristics. To assess the validity of the EQ-5D, 13 hypotheses relating the EQ-5D self-classifier (5 dimensions) or visual analogue scale (EQ-VAS) to SF-36 scores or other variables were examined using the Mann-Whitney U test, Kruskal-Wallis or Spearman's correlation coefficient. Test-retest reliability was assessed using Cohen's kappa. RESULTS: Forty-eight subjects were studied (osteoarthritis: 16; rheumatoid arthritis: 22; systemic lupus erythematosus: 8; spondyloarthropathy: 2; female: 93.8%; mean age: 56.4 years). Seven of 13 a-priori hypotheses relating EQ-5D to external variables were fulfilled, supporting the validity of the EQ-5D. For example, subjects reporting moderate or extreme problems for EQ-5D dimensions generally had lower median SF-36 scores than those without such problems. Cohen's kappa for test-retest reliability of the self-classifier ranged from 0.41 to 1.00 (n = 42; median interval: 7 days, interquartile range: 7 to 11 days). CONCLUSIONS: The Singaporean Chinese EQ-5D self-classifier appears to be a valid measure of HRQoL in Singaporeans with rheumatic diseases; however, the reliability of the EQ-VAS requires further investigation. These data provide a basis for further studies of the Singaporean Chinese EQ-5D.

Activities of Daily Living↗

Lateral temporal hyperperfusion in postictal psychosis assessed by 99mTc-HMPAO SPECT.

Postictal psychosis is a rare complication of epileptic seizure characterized by reversible psychotic symptoms after flurries of seizure attack. It has been attributed to a phenomenon similar to Todd's paralysis without definitive proof. We studied regional cerebral blood flow (rCBF) of six patients with postictal psychosis by (99m)Tc-HMPAO SPECT scan. Baseline rCBF was compared with the rCBF during postictal psychosis. An asymmetry index (ASI) was calculated as 200 x [(ipsilateral ROI count density - contralateral ROI count density)/(ipsilateral ROI count density + contralateral ROI count density)] %. Significant differences could be found between ASIs during postictal psychosis and interictal state SPECT scan over the lateral temporal neocortex region (P = 0.017). Although hyperperfusion abnormality in SPECT can be found in Todd's paralysis, such findings are more commonly found in cerebral hyperactivity conditions. Taking into account the clinical characteristics of postictal psychosis, namely a preceding lucid interval and crescendo-decrescendo clinical course, these may be an alternative psychopathogenic mechanism for the development of postictal psychosis.

Adolescent↗

A Chinese version of the Rheumatology Attitudes Index is a valid and reliable measure of learned helplessness in patients with SLE.

Despite the prognostic importance of learned helplessness (LH) in rheumatic diseases, there are no validated measures of LH in Chinese or other Asian languages. We therefore assessed the validity of a Chinese translation of the Rheumatology Attitudes Index (CRAI; a widely used measure of LH) and its Helplessness (CHS) and Internality (CIS) subscales in patients with SLE. Chinese-speaking SLE patients (n = 69) completed identical, self-administered questionnaires containing the CRAI and assessing demographic/socio-economic variables twice within 2 weeks. SLE activity, damage and quality of life were assessed using the BILAG, SLICC/ACR Damage Index and SF-36 respectively. Scale psychometric properties were assessed through Cronbach's alpha, intra-class correlations, quantifying test-retest differences, factor analysis and known-groups construct validity. Internal consistency and reliability were acceptable, with Cronbach's alpha for the CHS, CIS and CRAI being 0.70, 0.69 and 0.74, respectively. Mean differences in test-retest scores spanned 1.6-2.4% of possible scale ranges and intra class correlations ranged from 0.72 to 0.88. Factor analysis identified two major factors corresponding to the CHS and CIS subscales of the CRAI. Eight of 10 a priori hypotheses relating the CRAI and CHS to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. The CRAI and its helplessness subscale are valid and reliable measures of learned helplessness in Chinese-speaking SLE patients.

Adolescent↗

Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: disease activity and the use of cytotoxic drugs.

Thrombotic thrombocytopenic purpura (TTP) is a rare and occasionally fatal haematologic disorder that can coexist with systemic lupus erythematosus (SLE) and other autoimmune diseases. We identified all cases of TTP seen in our institution over a 3 year period using a computerized database. We found that SLE activity (measured by the SLE Disease Activity Index) and TTP activity ran a parallel course in three patients with coexistent SLE and TTP. TTP in these three patients, although refractory to plasmapheresis, responded to cytotoxic therapy. These observations further support an autoimmune contribution to the pathogenesis of some cases of TTP. A literature review revealed that mortality in SLE patients with more severe, refractory TTP treated with plasmapheresis and cytotoxics, may not be higher than in patients responding to plasmapheresis alone (who are likely to have milder disease). These data suggest that cytotoxics may have a role in treatment of patients with active SLE and TTP refractory to plasmapheresis.

Adult↗

Measuring health-related quality of life in Singapore: normal values for the English and Chinese SF-36 Health Survey.

OBJECTIVE: To determine norms for assessing Health-related Quality of Life (HRQOL) in Singapore using the Short Form 36 Health Survey (SF-36). MATERIALS AND METHODS: Mean SF-36 scores were calculated for 24 population subgroups (categorised by age, gender, ethnicity and questionnaire language) and for subjects with self-reported co-morbid conditions using data from a community-based survey in Singapore. RESULTS: The English and Chinese SF-36 was completed by 4122 and 1381 subjects, respectively, 58% (n = 3188) of whom had self-reported co-morbid conditions. SF-36 scores varied in subgroups differing in age, gender and ethnicity. In general, subjects with self-reported co-morbid conditions had lower SF-36 scores than those without these conditions, the magnitude of which exceeded 20 points in several instances. A method for calculation of SF-36 scores adjusted for age, gender, ethnicity and questionnaire language is described. CONCLUSION: We present norms for English and Chinese SF-36 versions in Singapore and describe potential uses for these data in assessing HRQOL in Singapore.

Adult↗

Immunotherapy in autoimmune diseases.

Immunotherapy has the potential to modify or re-balance the immune system and hence useful in the management of autoimmune conditions. This article aims to review clinically useful immunotherapies available for treatment of autoimmune conditions, with particular emphasis on Type I diabetes mellitus, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A Medline search for the period 1992 to 2002 (10 years) using the unrestricted keywords "immunotherapy AND autoimmune" was done. Full-length articles were selected for reviews based on the contents of their published abstracts. Additional Medline searches were focussed on the keywords "immunotherapy AND diabetes mellitus", "immunotherapy AND multiple sclerosis", "immunotherapy AND rheumatoid arthritis", and "immunotherapy AND systemic lupus erythematosus". Relevant publications referenced in the reviewed literature were further included for review, if not present in the original Medline search. Immunotherapy in Type I diabetes mellitus has focussed on the induction of tolerance to beta cell antigens, and in multiple sclerosis trials of anti-alpha 4 integrins and altered peptide ligand of myelin basic protein (MBP 83-99) showed initial promising results. The use of anti-cytokine therapy (anti-TNF alpha and IL-1Ra) in rheumatoid arthritis has improved the quality of life of patients with refractory disease. The use of anti-CD20 monoclonal antibody for in vivo B cells depletion and early trials of autologous peripheral stem cell transplants represent additional immunomodulatory treatment modalities for systemic lupus erythematosus patients. Better understanding of autoimmune conditions and advances in the production of humanized monoclonal antibodies, promises better immunotherapy in the near future.

Arthritis, Rheumatoid↗

Clinical outcomes of patients with biopsy-proven lupus nephritis in NUH.

OBJECTIVE: To review the clinical outcomes of Systemic Lupus Erythematosus (SLE) patients with biopsy-proven lupus nephritis with regards to the histological features and treatment. METHOD: Patients (1) with SLE, (2) had renal biopsy in NUH for lupus nephritis, and (3) on follow-up from the period of January 1998 to April 2001, were reviewed. RESULT: Fifty patients were reviewed with female to male ratio of 4:1. Mean age was 35.4 years. Sixty-eight percent had renal involvement at diagnosis of SLE. At least 50% had other major organ systems involvement. Forty-two patients had WHO Class IV lupus nephritis. Biopsy showed crescents in 17 patients, microangiopathy in 19, and vasculitis in two patients. All patients received prednisolone. Forty-one had IV cyclophosphamide, two had oral cyclophosphamide and seven had cyclosporin A. Azathioprine was used in 41 patients, pulse methylprednisolone in eight, IVIG in four, plasma exchange in three and mycophenolate in two patients. OUTCOME: Forty-four percent were in complete remission, 26% in partial remission, 34% had relapsed nephritis, 4% had chronic renal failure and 12% progressed to ESRD. There were five deaths. CONCLUSION: Renal involvement in SLE occurs early in the disease and is associated with other organ systems involvement. Only 44% were in complete remission. Thirty-four percent had relapsed. Renal survival was 88% in this cohort.

Adolescent↗

A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992.

OBJECTIVE: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors. RESULTS: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Adolescent↗

A community-based study of scaling assumptions and construct validity of the English (UK) and Chinese (HK) SF-36 in Singapore.

Scaling assumptions and validity of the English (UK) and Chinese (HK) short form 36 health survey (SF-36) were assessed in a community-based survey of 5,503 Chinese, Malays and Indians in Singapore using the international quality of life assessment project approach of item and scale level validation. Missing data for SF-36 items and scales occurred in less than 1.0% of subjects. Item level validation of both versions generally supported assumptions underlying Likert scoring and hypothesised item-order clustering. Item level factor analysis supported the eight-scale structure of the SF-36. In scale level validation, SF-36 scale scores showed wide variability and acceptable internal-consistency reliability (Cronbach's alpha > 0.70 for six English and seven Chinese scales), conformed to hypothesised patterns and generally varied according to hypotheses in subjects known to differ in quality of life. Scale level factor analysis of both versions yielded very similar patterns of factor correlation, comparable to that found in Japan, but differing from that seen in Western populations. Taken together, these results support the validity of the English (UK) and Chinese (HK) SF-36 versions in the multi-ethnic Asian socio-cultural context of Singapore.

Adult↗

Peptide mimicking antigenic and immunogenic epitope of double-stranded DNA in systemic lupus erythematosus.

Autoantibodies to double-stranded (ds) DNA are an important diagnostic marker and pathogenic factor for systemic lupus erythematosus (SLE). Identifying dsDNA mimotopes is a way to discover diagnostic and therapeutic candidates for SLE. 'Mono-specific' SLE anti-dsDNA antibodies were obtained by affinity purification using dsDNA-coupled Sepharose column. Using the anti-dsDNA antibodies to screen a phage peptide library, we were able to identify a mimotope that has a motif peptide sequence of RLTSSLRYNP. This chemically synthesized peptide could be recognized by 88% (37 out of 42) of anti-dsDNA antibody-positive SLE sera with a cut-off point at mean + 3 SD of the negative control sera at OD(492). The reaction of the peptide with SLE sera in ELISA was highly correlated with that of dsDNA (r = 0.809, P < 0.0001). Of particular interest, not only dsDNA but also single-stranded (ss) DNA and native RNA could inhibit the binding of the peptide with SLE sera, suggesting that the mimotope is shared by ds and ssDNAs as well as native RNA, whereas denatured RNA was not observed to inhibit the binding. The peptide was also able to elicit an immune response in rabbits and the anti-peptide rabbit serum was observed to cross-react with the peptide, ss and dsDNAs, and ss and dsDNAs could inhibit the binding of the anti-peptide serum and the peptide. However, the inhibition was not obtained with RNA. Our findings demonstrate the potential of the peptide mimic in diagnostic tests of SLE, and in the investigation of anti-DNA antibody origin and of DNA-anti-DNA antibody interaction.

Adolescent↗