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Biomedical subjects

H K Yap

Publications and source records attributed to H K Yap.

At least 19 recordsLinked to original sources
PubMed2005

Role of urinary screening programmes in children in the prevention of chronic kidney disease.

INTRODUCTION: This article reviews published literature on the usefulness of population-based urinary screening in the Asian paediatric population. METHODS: Articles were found in the Medline database using the key words "paediatrics", "urine screening", "proteinuria", "haematuria" and "population". The Asian countries which had carried out population-based urinary screening of the paediatric population included Taiwan, Japan and Korea. One study was found on urinary screening in a select population in Malaysia. Preliminary results of the urinary screening of school children in Singapore are presented and compared with the results found in the above-mentioned countries. RESULTS: Overall, the proportion of children found to have urinary abnormalities ranged from less than 0.1% of the population screened to almost 50% of a select cohort referred from the screening programmes for the evaluation of urinary abnormalities. In the pilot Singapore school screening programme, the prevalence of clinically significant proteinuria was 1.25 per 1000 children screened. Multivariate analysis showed that low body weight was associated with a 1.8-fold greater risk for proteinuria. The major cause of haematuria and proteinuria in those studies where renal biopsies were performed was glomerulonephritis. The Taiwanese experience also showed a reduction in the incidence of end-stage renal failure diagnosed in children after the onset of urine screening. CONCLUSION: These studies showed that urinary screening programmes in school children allow the early detection of disease. The cost-benefit ratio for specific populations should be determined before the implementation of such programmes.

Asia↗
PubMed2003

Childhood nephrotic syndrome in relapse is associated with down-regulation of monocyte CD14 expression and lipopolysaccharide-induced tumour necrosis factor-alpha production.

Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-alpha (TNF-alpha) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-alpha positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64.4 +/- 13.7%) compared to remission (81.6 +/- 9.0%, P < 0.005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82.9 +/- 10.1% and 1.23 +/- 0.30 micro g/ml, respectively) compared to remission (93.9 +/- 3.2% and 1.77 +/- 0.82 micro g/ml, respectively) (P < 0.003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-alpha in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.

Adolescent↗
PubMed2002

ACE gene polymorphism and disease progression of IgA nephropathy in Asians in Singapore.

The deletion polymorphism of the angiotensin-converting enzyme (ACE) gene has been considered as a risk factor for IgA nephropathy and for its progression to end-stage renal failure. However, results from various studies are conflicting. We had genotyped the ACE gene in 100 patients with IgA nephropathy, 32 of whom were in end-stage renal failure and in 90 normal adult subjects. All DD cases were subjected to confirmation with a second PCR, performed with the insert-specific forward primer. Similar genotype frequencies were obtained for the 90 normal control subjects (II: 47%, ID: 44%, DD: 9%); for the 68 patients not in end-stage renal failure (ESRF) (II: 47%, ID: 46%, DD: 7%) and for the 32 patients with ESRF (II: 53%, ID: 38%, DD: 9%). The genotype frequencies in all 3 series are in Hardy-Weinberg equilibrium. These results suggest that ACE gene polymorphism is not a risk factor for IgA nephropathy and is not a predictor for its progression. Definitive proof of association between ACE gene polymorphism and progression in IgA nephropathy will require a prospective study, controlled for important risk factors, with adequate patient numbers and facility for confirming DD genotypes.

Adult↗
PubMed2001

Eighteen years experience in pediatric acute dialysis: analysis of predictors of outcome.

This study reviewed the 18-year experience of acute dialysis in the pediatric intensive care unit, in order to identify factors that could predict outcome, and to determine whether newer modalities of acute dialysis have influenced this outcome. Sixty-six children (ages 1 day to 19 years) received acute dialysis from May 1980 to April 1998. Factors predicting outcome were analyzed using univariate and Cox regression analysis. Modality of dialysis in the first 15 years was exclusively peritoneal dialysis. with a mortality of 63.9%. However, in the last 3 years, with increasing patient numbers, continuous hemodiafiltration (CHDF) was the modality of choice (56.7%), with a mortality of 73.3%. Univariate analysis showed that age <1 year, coma, acute tubular necrosis, disseminated intravascular coagulopathy, assisted ventilation, and hypotension were associated significantly with poor outcome (P<0.05). Cox regression analysis revealed that mortality was significantly higher in patients on mechanical ventilation (RR 5.96, 95% CI 1.82-19.50), or with age <1 year (RR 2.00, 95% CI 1.08-3.73). In conclusion, despite the increasing use of CHDF over the last 3 years, there was no significant improvement in mortality, probably related to the fact that more critically ill patients were dialyzed.

Acute Disease↗
PubMed2001

Risk factors for steroid dependency in children with idiopathic nephrotic syndrome.

Minimal change disease, the most common cause of idiopathic nephrotic syndrome (INS) in children, has a high relapse rate, with approximately half of patients developing steroid dependency. This study was aimed at determining the predictive risk factors for the development of steroid dependency in children diagnosed with INS. A retrospective study of 123 children with steroid-responsive INS, followed for at least 6 months between December 1974 and December 1999, was conducted. The following parameters were studied as predictors of steroid dependency: age at onset, gender, race, microscopic hematuria at onset, atopy, concomitant upper respiratory tract infections (URTI) during relapses, and days to remission with initial steroid therapy. Of the 91 children who fulfilled the inclusion criteria, 61.5% became steroid dependent. Both univariate and logistic regression analyses revealed that initial remission time of 9 or more days (P=0.02, OR=3.0, 95% CI=1.2-7.9) and concomitant URTI during relapses (P=0.01, OR=3.4, 95% CI=1.3-8.8) were significant predictors of steroid dependency. By identifying those children with predictive factors of steroid dependency, the clinician will be better able to plan the long-term management of these patients and reduce the morbidity seen with the frequent relapses and steroid treatment, in a disease that is otherwise associated with a favorable prognosis.

Child, Preschool↗
PubMed2001

Mitochondrial tubulopathy: the many faces of mitochondrial disorders.

We report a rare presentation of mitochondrial disorder in a child with recurrent carpopedal spasms due to hypocalcemia and hypomagnesemia, secondary to renal proximal tubulopathy and possible hypoparathyroidism. At least two mutant mitochondrial DNA species were identified, and abnormal mitochondria were found in the muscle and renal biopsy specimens. The case illustrates the spectrum and diversity of mitochondrial presentations, arising because of heteroplasmy of mutations and the type of organs affected.

Child, Preschool↗
PubMed2001

IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH.

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.

Adolescent↗
PubMed2000

Hydrophobic extracts of a Chinese herb (CMX-13) exhibit potent immunosuppressive properties and prevent acute rejection in a highly histoincompatible model of rat lung transplantation.

BACKGROUND: The potential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN-->LEW, and on lymphocyte activation and cytokine gene expression in vitro. METHODS: Left lung transplants: the control group (group 1) received only dimethylsulfoxide (DMSO) which is the solvent for CMX-13. Group 2 received intramuscular cyclosporin A (CsA, 25 mg/kg) on day 2 posttransplant. Group 3 and 4 received i.p. CMX-13 (0.5 mg/day, low dose and 5 mg/day, high dose, respectively) on day 1, 2, and 3 posttransplant. All animals were killed on day 6 posttransplant. Several pathological categories of inflammation were examined. In vitro experiments: rat spleen cells were incubated with Con A or irradiated stimulator cells with/without serial dilutions of CMX-13 or CsA. Cell proliferation was measured by 3H-thymidine incorporation. mRNA expression of interleukin-2 and interferon-gamma was examined by reverse transcriptase-polymerase chain reaction. RESULTS: The severity of AR in animals receiving high dose CMX-13 was significantly reduced (stage II, P<0.05) compared with controls (stage IV). Significant differences were also seen when more specific parameters of inflammation were examined (necrosis, 0 vs. 1.7+/-1.0, P<0.05; interalveolar hemorrhage, 0 vs. 3.0+/-0.9, P<0.05). The responses seen in the animals treated with high dose CMX-13 were similar to those in the CsA group. CMX-13 inhibited T cell proliferative responses induced by Con A and alloantigen stimulation in a dose-dependent manner that were similar to CsA. Interleukin-2, and interferon-gamma mRNA expression in Con A-stimulated spleen cells was not inhibited by CMX-13 although CsA showed significant inhibition. CONCLUSIONS: 1) CMX-13 significantly reduces the stage of AR and parameters of inflammation in a highly histoincompatible rat lung transplant model. 2) CMX-13 has equal potency to CsA in the inhibition of Con A and alloantigen stimulated rat spleen cell proliferation. 3) CMX-13 showed no inhibitory effects on IL-2 and gamma-IFN mRNA expression, suggesting that its mechanism of action is different from CsA. 4) CMX-13 or derivatives may have potential utility as an immunosuppressive agent(s) in modulation of AR and management of other inflammatory and immunological disorders.

Acute Disease↗
PubMed2000

Membranous nephropathy with anti-tubular basement membrane antibody may be X-linked.

The association of membranous nephropathy with Fanconi syndrome and anti-tubular basement antibodies appears to be a distinct subset of familial membranous nephropathy. We studied two Chinese families with four affected boys to evaluate the mode of inheritance of disease. HLA haplotype analysis of the family members in these two pedigrees did not reveal any significant linkages. However, microsatellite analysis of both pedigrees using markers on the X chromosome suggested linkage to the long arm of the X chromosome between the microsatellite markers DXS1001 and DXS1227. Identification and analysis of additional pedigrees may allow more precise mapping of the disease gene for anti-tubular basement membrane antibody-associated membranous nephropathy.

Autoantibodies↗
PubMed2000

Quantitation of peripheral blood cytomegalovirus DNA for monitoring recurrent cytomegalovirus retinitis in pediatric solid organ transplant recipients.

Cytomegalovirus (CMV) infection is a major concern following solid organ transplantation, especially in the pediatric population who remain at high risk of primary infection. CMV disease leads not only to increased patient and graft morbidity, but also to increased health care costs. This study describes the usefulness of a quantitative CMV polymerase chain reaction (PCR) technique for monitoring peripheral blood CMV DNA in pediatric recipients of kidney and liver allografts who had recurrent CMV retinitis. The incidence of CMV disease in 28 pediatric transplant recipients was 28.6%, one-half of whom developed retinitis. Two of these patients had recurrent retinitis on cessation of anti-viral treatment. A peripheral blood CMV DNA copy number of > or =500/microg of DNA was associated with recrudescence of the retinitis in these patients. We conclude that the measurement of peripheral blood CMV DNA by PCR is a useful tool for the surveillance of disease resolution and recurrence. This is particularly important in patients with CMV retinitis, who may remain asymptomatic for a period of time, despite recurrences.

Adolescent↗
PubMed2000

Traditional Chinese medicines as immunosuppressive agents.

INTRODUCTION: Traditional Chinese Medicines (TCM) have been used for centuries in China to treat various immune-mediated disorders. METHODS: This review focuses on the clinical and experimental studies that have been performed with TCM as immunosuppressive agents for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), atopic eczema and solid organ transplantation. RESULTS: The "thunder god" vine, Tripterygium wilfordii Hook F (TWHf), has been extensively used in China to treat SLE and RA. TWHf not only inhibited mitogen-stimulated lymphoproliferation, but its active derivatives have also been shown to inhibit production of proinflammatory cytokines by monocytes and lymphocytes, as well as prostaglandin E2 production via the cyclooxygenase, COX-2, pathway, a potential mechanism of action in patients with RA. Demethylzelasteral (TZ-93), a triterpenoid isolated from the root cortex of TWHf, the plant alkaloid berbamine, and the hydrophobic extract of a Chinese herbal decoction, CMX-13, were all shown to be active in prolonging allograft survival in experimental animal models of heart, skin and single lung transplants, respectively. There are few well-designed randomised placebo-controlled clinical trials demonstrating the efficacy of TCM in various diseases. Zemaphyte, a decoction of 10 herbs, has been shown to be efficacious in the treatment of atopic dermatitis in both children and adults in two randomised double-blind placebo-controlled trials. CONCLUSION: There is both laboratory and clinical evidence that the derivatives of many of these herbs may have significant beneficial immunosuppressive effects, however, concerns of toxicity must also be addressed, as exact dosing of the active derivatives is difficult to achieve with the current prescriptions of TCM.

Arthritis, Rheumatoid↗
PubMed2000

Minimal change nephrotic syndrome--a complex genetic disorder.

INTRODUCTION: Minimal change nephrotic syndrome (MCNS) is the most common primary nephrotic syndrome in childhood. While the pathogenesis of this disease is still unknown, there is considerable evidence that it is an immune disease. This role of genetic susceptibility in this disease is the subject of this review. METHODS: Reported studies addressing potential genetic factors in MCNS were reviewed. These factors included human leukocyte antigen (HLA) associations, genes involved in the renin-angiotensin system and cytokines. RESULTS: Several authors have reported the presence of familial clustering, human leukocyte antigen (HLA) associations, and association with asthma and atopy, suggesting a genetic susceptibility to the disease. Moreover, recent studies on the role of the renin angiotensin system, cytokines and their respective receptors on the severity and clinical course of the disease, have lent further support to the immunogenetic basis of this disease. CONCLUSION: Knowledge of the genetic basis of MCNS may have important therapeutic implications in this disease, in particular, the role of cytokines and their respective receptors, including the influence of environmental factors on their expression.

Cytokines↗
PubMed1999

Improvement in lupus nephritis following treatment with a Chinese herbal preparation.

OBJECTIVE: To study the effect of a Chinese herbal decoction (CM), which contained 21 different herbs, on clinical remission in a patient with lupus nephritis and chronic nephrotic syndrome. DESIGN: Case report describing the clinical and laboratory markers of lupus activity in the patient before and after treatment with CM. We also studied the in vitro effect of CM and its hydrophobic extract on spontaneous IgG production by peripheral blood mononuclear cells (PBMCs) from 12 patients with systemic lupus erythematosus (SLE) compared with 9 healthy control subjects. RESULTS: Spontaneous PBMC IgG production was significantly higher in patients with SLE (mean +/- SD, 20.4+/-10.6 x 10(-5) g/L) compared with controls (4.7+/-1.9 x 10(-5) g/L) (P<.001). Addition of CM and its hydrophobic extract to PBMCs from patients with SLE resulted in significant suppression of spontaneous IgG production. CONCLUSIONS: The CM may contain some active pharmacological compound with immunosuppressive properties useful in the treatment of SLE. Further controlled studies are important to evaluate the efficacy of this medicine, potential toxic effects, and the possible immunosuppressive mechanisms of the active component(s).

Adolescent↗
PubMed1999

Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse.

Idiopathic nephrotic syndrome of childhood is thought to be associated with T lymphocyte dysfunction often triggered by viral infections, with the production of circulating factor(s) resulting in proteinuria. In view of the conflicting evidence of T cell activation and Th1 or Th2 pattern of cytokine synthesis in this disease, this study examined the mRNA expression of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL-13 from CD4+ and CD8+ T cells in steroid-responsive nephrotic patients in relapse and remission. Fifty-five children with steroid-responsive nephrotic syndrome were included in this study, together with 34 normal controls and 24 patient controls with viral infections. RNA was isolated from purified CD4+ or CD8+ cells from peripheral blood and subjected to reverse transcription-PCR. Cytokine mRNA expression was measured semiquantitatively, and a cytokine index was derived from densitometric readings, with cyclophilin as the housekeeping gene. Both cross-sectional and paired data showed an increased CD4+ and CD8+ IL-13 mRNA expression in patients with nephrotic relapse as compared to remission, normal, and patient controls (P < 0.008). This was also associated with increased cytoplasmic IL-13 expression in phorbol myristate acetate/ionomycin-activated CD3+ cells (6.66+/-3.39%) from patients with nephrotic relapse compared to remission (2.59+/-1.35%) (P < 0.0001). However, there was no significant difference in CD4+ or CD8+ IL-2, interferon-gamma and IL-4 mRNA expression. IL-13 is an important T cell cytokine with anti-inflammatory and immunomodulatory functions on B cells and monocytes. It is conceivable that IL-13 may act on monocytes to produce vascular permeability factor(s) involved in the pathogenesis of proteinuria in patients with relapse nephrotic syndrome.

Adolescent↗