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T M Chan

Publications and source records attributed to T M Chan.

At least 91 records · Page 5Linked to original sources
PubMed1999

Comparison of the second-generation digene hybrid capture assay with the branched-DNA assay for measurement of hepatitis B virus DNA in serum.

The optimal hepatitis B virus (HBV) DNA quantitative assay for clinical use remains to be determined. We examined the sensitivity, linearity, and variability of a novel second-generation antibody capture solution hybridization assay, the Digene Hybrid Capture II assay (HCII), and compared it with another widely used solution hybridization assay, the branched-DNA (bDNA) assay (Quantiplex; Chiron Corp.). Our results showed similar and satisfactory assay linearity values, as well as interassay and intra-assay variability values, for both HCII and bDNA assays across different ranges of HBV DNA. Ninety-one percent of 102 serum samples from hepatitis B surface antigen-positive patients showed concordant results with the two assays. The HCII assay was more sensitive than the bDNA assay by 1 dilution, with the lowest reading being 0.9 pg/ml (3.8 pg/ml by bDNA assay). The HBV DNA seropositivity rates for the 102 samples were 58, 67, and 97% by bDNA, HCII, and nested PCR, respectively. While the relationship between results obtained with the bDNA assay and those with the HCII assay was nonlinear, with the bDNA assay yielding values 2.83 +/- 0.92-fold higher than those of the HCII assay, especially at high HBV DNA levels, a linear relationship was observed between the two sets of data after logarithmic conversion. The formula for interassay conversion of results was derived as follows: HBV DNA by HCII (picograms per milliliter) = 3.19 x [HBV DNA by bDNA (megaequivalents per milliliter)](0.866). The HCII assay was technically less complex and required a shorter assay time (4 h) than the bDNA assay (24 h). We conclude that the HCII assay compares favorably with the bDNA assay and offers the additional advantages of increased sensitivity and shorter assay time. The increased sensitivity should be particularly useful in monitoring the efficacy of antiviral therapies and detecting the emergence of drug-resistant HBV mutants.

Biological Assay↗
PubMed1999

Treatment of membranous lupus nephritis with nephrotic syndrome by sequential immunosuppression.

The optimal therapy for pure membranous lupus nephritis (MLN) with nephrotic syndrome remains controversial. While the risk of progressive renal deterioration may be small, persistent heavy proteinuria leads to the complications of oedema, hypoalbuminaemia, hyperlipidaemia, hypercoagulability, and venous thrombosis. We examined prospectively the efficacy and tolerability of a sequential immunosuppressive regimen in a cohort of 20 patients with nephrotic syndrome due to pure MLN (WHO Class Va and Vb). Initial therapy comprised prednisolone (0.8 mg/kg/d p.o.) and cyclophosphamide (2-2. 5 mg/kg/d p.o.). Prednisolone dosage was gradually tapered to 10 mg/d at 6 months, when cyclophosphamide was replaced by azathioprine (2 mg/kg/d p.o.) as maintenance therapy. Within 12 months of therapy 11(55%) patients had complete remission (CR), 7(35%) patients achieved partial remission (PR) (proteinuria reduced from 6.2+/-4.0 to 2.0+/-1.7 g/24 h, P<0.01), and 2 patients failed to respond. Improvements in proteinuria and serum albumin level were observed after 3-6 months of treatment. Non-responders had lower baseline serum albumin compared to complete responders. Renal function remained stable during follow-up for 73.5+/-48.9 months. 8 patients had disease relapse at 47+/-15 months. Early complications (</=12 months) included herpes zoster (40%), minor respiratory or urinary tract infections (25%), mild leukopenia (15%), and transient amenorrhea (14.3%). 4 of the 20 patients developed pulmonary tuberculosis during follow-up, at 35+/-24 months after the diagnosis of MLN. 8 patients had hyperlipidaemia. Haemorrhagic cystitis, permanent amenorrhea, vascular complications, and mortality were not observed. We conclude that this sequential immunosuppressive regimen is effective in 90% of patients with MLN and heavy proteinuria. Prudent consideration of the benefits and potential side-effects is required to determine the optimal management for individual patients.

Adult↗
PubMed1999

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↗
PubMed1999

Long-term renal allograft recipients from South-east Asia in the pre-cyclosporin era.

The clinical outcome of long-term renal allograft recipients in the Chinese population has not been reported previously. We analysed patients from the pre-cyclosporin era who had grafts that functioned for > 10 years. Forty-five patients (31 men, 14 women; mean age 30, follow-up duration 13.3 years), representing a 10-year graft survival of 53%, were included. Thirty-six patients (80%) received living-related allografts and 9 (20%) received cadaveric or living-unrelated renal transplantation. The mean serum creatinine at last follow-up was 1.36 mg/dl (range, 0.83-4.08). Major posttransplantation complications included: hypertension in 25 (56%), infection in 16 (36%), acute rejection in 15 (33%), lipid disorder in 13 (29%), liver disease in 7 (16%), osteonecrosis in 5 (11%), malignancy in 4 (9%), coronary artery disease in 3 (7%), and diabetes mellitus in 3 (7%). Five grafts were lost: 3 to chronic rejection, and 2 to patients with stable function who died of non-renal causes. Proteinuria correlated strongly with graft function and survival, and marginally with hypertension. In hepatitis B carriers, serum alpha-feto protein is useful in the early detection of hepatocellular carcinoma. We conclude that while patients in the pre-cyclosporin era can survive with excellent graft function beyond the first decade, the risk of complications leading to significant morbidity still remains even when patients are receiving minimal doses of immunosuppression in the second decade.

Adolescent↗
PubMed1999

Clinical and pathological characteristics of patients with glomerular diseases at a university teaching hospital: 5-year prospective review.

OBJECTIVE: To examine the prevalence of glomerular disease in Hong Kong. DESIGN: Prospective review. SETTING: University teaching hospital, Hong Kong. PATIENTS: All patients who presented with suspected glomerular disease from 1993 through 1997. MAIN OUTCOME MEASURES: Histopathological diagnosis from biopsy examination and clinical features of presentation. RESULTS: A total of 1629 consecutive percutaneous renal biopsies of native kidneys showed glomerular disease in 1413 cases. The most common clinical indication for renal biopsy was persistent proteinuria (n=735; 52.0%), while the most frequently found glomerular lesion was immunoglobulin A nephropathy (n=338; 23.9%). Minimal-change nephrotic syndrome (n=125; 8.8%) and immunoglobulin M nephropathy (n=11; 0.8%), were the most common glomerular diseases that presented with nephrotic syndrome. The male to female ratio for lupus nephritis was 1:14 (n=290), whereas for minimal-change nephrotic syndrome, the ratio was 1.8:1 (n=125). Immunoglobulin A nephropathy and membranous glomerulonephritis (n=117) affected approximately equal numbers of male and female patients. Familial fibrillary glomerulonephritis, a disease hitherto unknown in Hong Kong, was diagnosed in two siblings. CONCLUSION: Immunoglobulin A nephropathy was the most common glomerular disease in this survey and represents an important cause of end-stage renal failure in the Hong Kong population.

Journal Article↗
PubMed1998

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)- one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites.

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzol[b][1,8]naphthyrid in-5(7H)-one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6-, 7-, and 9-carbinols, the glucuronide of the 6-carbinol, and the 6-ketone derived from the parent drug. Although the three carbinols appeared in the liver isolates of all species studied, the relative amounts of these metabolites varied across species. With a high, non-physiological ratio of substrate to liver, the 6-carbinol and its glucuronide were the major metabolites in human and monkey, whereas the 6-ketone was a minor metabolite in dog. Containing a stereogenic axis and center, the 6-carbinol existed as diastereomeric atropisomers. Its structure was established by 13C and 1H NMR spectroscopy, mass spectrometry, and comparison to an authentic sample.

Animals↗
PubMed1998

Treatment of fibrosing cholestatic hepatitis with lamivudine.

Fibrosing cholestatic hepatitis is a histological variant of hepatitis B virus infection with a high rate of mortality. We describe a patient who acquired acute hepatitis B virus infection 8 months after renal transplantation. Clinical features of rapidly progressive liver failure, indicated by prolonged prothrombin time (57 seconds) and increased bilirubin (40.4 mg/dL) and ammonia (129 mumol/L) concentrations, were accompanied by an extremely high serum HBV DNA level (2.153 x 10(6) pg/mL). Liver biopsy specimen showed fibrosing cholestatic hepatitis with widespread balloon degeneration of hepatocytes, focal hepatocyte loss, bile stasis, periportal fibrosis, mild lymphocytic infiltration, and strongly positive immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen. Lamivudine therapy suppressed HBV DNA to < 10 pg/mL within 4 weeks, which was followed by gradual recovery of liver function from a state of hepatic precoma. Twenty-four months after the onset of hepatitis, the patient had normal prothrombin time and bilirubin, transaminase, and albumin levels. She remained HBsAg positive and hepatitis B e antigen negative. Renal allograft function was stable, with a creatinine level of 1.52 mg/dL. HBV DNA remained suppressed after 22 months of lamivudine therapy. Our experience shows that fibrosing cholestatic hepatitis and liver failure caused by HBV infection can be successfully treated with lamivudine.

Adult↗
PubMed1998

Fibrillary glomerulonephritis in siblings.

Fibrillary/immunotactoid glomerulopathy is characterized by organized glomerular deposition of extracellular, nonbranching, immunoglobulin-derived microfibrils, which is not associated with systemic diseases such as amyloidosis, cryoglobulinemia, or monoclonal gammopathy. This is an uncommon condition with an obscure etiology and accounts for approximately 1% of primary glomerular diseases in white populations. We report the first case of familial fibrillary/immunotactoid glomerulopathy affecting a brother and a sister in a Chinese family. Both patients presented with heavy proteinuria, which improved transiently on treatment with prednisolone and cyclophosphamide. Human lymphocyte antigen typing for the siblings showed no haplotype association. Despite the generally poor renal prognosis reported in the literature, with 50% of patients reaching end-stage renal failure within 2 to 4 years, both patients had relative preservation of renal function (creatinine clearance from 79 to 76 mL/min/1.73 m2 after 2 years in one patient and from 111 to 99 mL/min/1.73 m2 after 3 years in the other). Our observations show that fibrillary/immunotactoid glomerulopathy can present as a familial condition. Compared with sporadic cases, patients with familial fibrillary/immunotactoid glomerulopathy may have a more favorable renal prognosis.

Actin Cytoskeleton↗
PubMed1998

Benefits of exercise training in patients on continuous ambulatory peritoneal dialysis.

We examined the effects of a 12-week exercise program on the exercise tolerance, blood biochemistry, blood pressure (BP) control, cardiac function, and quality-of-life (QOL) scores in 13 patients undergoing continuous ambulatory peritoneal dialysis (CAPD; six men, seven women; mean age, 46.5+/-12.8 years; mean duration on dialysis, 4.8+/-3.8 years). The patients underwent exercise training on treadmill, bike, and arm ergometers thrice weekly. Seven CAPD patients matched for age, sex, and duration on dialysis served as controls. The mean peak aerobic capacity (VO2peak) of the exercisers increased by 16.2% after training (pre- and postexercise, 17.2+/-5.2 v 20.0+/-6.4 mL/kg/min; P=0.004). Although there were no significant changes in serum urea, creatinine, albumin, and hematocrit levels; left ventricular diastolic/systolic diameters; and ejection fraction, an increasing trend of high-density lipoproteins (HDLs) was observed in the exercisers (baseline v postexercise, 33+/-11 v 40+/-14 mg/dL; P=0.06). Twenty-four-hour ambulatory BP monitoring showed a significant increase in daytime systolic BP in the exercisers (pre- and postexercise, 142+/-26 v 157+/-22 mm Hg; P=0.003), but no significant changes could be found in the ambulatory daytime diastolic BP, nocturnal BP, and resting clinic BP. The patients' QOL improved after training, with better scores in two Kidney Disease Quality of Life scales (KDQOL): burden of kidney disease and physical functioning. Two mild and uncomplicated hypotensive episodes were reported in two patients immediately after training. No changes occurred in exercise capacity, blood biochemistry, BP profile, and QOL scores in the controls. We conclude that structured aerobic exercise is safe and can improve the exercise tolerance and QOL outcomes in CAPD patients.

Adult↗
PubMed1998

Hepatitis C virus genotypes in patients on renal replacement therapy.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is prevalent among patients on renal replacement therapy. Viral genomic differences can contribute to diversities in clinical manifestation. The distribution of HCV genotypes depends on the geographical region and risk factors unique to the patient population. We determined the HCV genotypes in patients on renal replacement therapy in order to define the genotypic profile and examine the relationship between genotype, mode of renal replacement therapy, and the prevalence as well as severity of liver disease. METHODS: HCV genotypes were determined by restriction fragment length polymorphism and sequencing of the 5'-untranslated region in 21 renal allograft recipients, 29 patients on dialysis, and 26 non-renal failure controls. RESULTS: The most prevalent genotype among patients with renal failure was 1b (78%), followed by 1a (10%) and 6a (8%). 2 renal allograft recipients with 6a infection probably acquired HCV from the same donor. The relative prevalence of HCV genotypes was similar to that of controls. While renal allograft recipients demonstrated more severe liver disease than dialysis patients, the prevalence and severity of chronic hepatitis were similar between patients with 1b and non-1b infection. CONCLUSIONS: Resemblance of genotype distribution in Hong Kong to that of southern China and east Asia suggests common epidemiological evolution of HCV infection in these regions. Our results imply that in addition to viral characteristics, host factors such as the immunosuppressed state play an important role in the pathogenesis of liver disease in these patients.

Adult↗
PubMed1998

Rapid cytomegalovirus pp65 antigenemia assay by direct erythrocyte lysis and immunofluorescence staining.

A rapid cytomegalovirus (CMV) pp65 antigenemia assay with direct erythrocyte lysis (DL) with 0.8% NH4Cl, followed by indirect immunofluorescence staining (IF), was evaluated with 82 blood samples from renal transplant recipients, and the results were compared to those of the conventional antigenemia assay with dextran sedimentation and two-cycle alkaline phosphatase, anti-alkaline phosphatase staining (DS-APAAP). The DL-IF modification gave a higher leukocyte yield compared to DS-APAAP (75.4 versus 54.9%; P < 0.05), with similar leukocyte viability rates of >95%. The DL-IF methodology involved fewer technical steps, and the assay time was shortened from 5 h to less than 3 h. Nineteen of the 82 samples concordantly tested positive for pp65 antigenemia by both assays, and the readings showed a good correlation (r = 0.996; P < 0.01). No discordant results were observed. We conclude that the CMV pp65 antigenemia assay by this novel DL-IF modification is technically simpler, cheaper, and less time-consuming but yields results comparable to those of the conventional DS-APAAP assay. The shortened assay time and increased capacity to handle more samples confer distinct advantages in the rapid diagnosis and prompt treatment of CMV disease in immunosuppressed patients.

Antigens, Viral↗
PubMed1998

Castleman's disease and mesangial proliferative glomerulonephritis: the role of interleukin-6.

Renal complications of Castleman's disease (angiofollicular lymph node hyperplasia) are uncommon. The reported cases are very heterogeneous and their renal pathology ranged from minimal change disease, mesangial proliferative glomerulonephritis, to amyloidosis. We have previously reported two cases of Castleman's disease with renal complications. We now present two more such cases. In contrast to other reports, all our cases are of the plasma cell type and their renal pathology showed remarkable similarities, namely mesangial proliferation, interstitial plasma cell infiltration and negative immunofluorescence. The level of serum interleukin-6 (IL-6) in both patients was elevated at presentation and came down with immunosuppressive therapy.

Adolescent↗