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J C Chan

Publications and source records attributed to J C Chan.

At least 127 records · Page 7Linked to original sources
PubMed1998

Antibodies to glutamic acid decarboxylase in young Chinese diabetic patients.

Antibodies to glutamic acid decarboxylase (GAD) are a useful autoimmune marker for type 1 diabetes mellitus in Caucasians. We examined antibodies to GAD and their relationships with clinical features and pancreatic beta cell function in 140 young Chinese diabetic patients. Over an 18-month period beginning in 1995, 140 young Chinese diabetic subjects with age of onset of disease < or = 35 years and age < 40 years were recruited consecutively, irrespective of their modes of presentation. Clinical features, antibodies to GAD and pancreatic beta cell function (using a glucagon stimulation test) were examined. Increased levels of antibodies to GAD (> 18 units) were detected in 12.1% (n = 17) of these subjects. Forty-three (31%) patients had a classical type 1 presentation and 65 (46%) patients were insulin-deficient based on post-glucagon plasma C-peptide levels. Patients who were insulin-deficient and had a type 1 presentation had the highest prevalence of antibodies to GAD (29.0%) compared with patients who had a type 2 presentation and were non-insulin deficient (6.4%, P = 0.003). Patients who had antibodies to GAD had lower body mass index and waist-hip ratio, earlier onset of disease, lower blood pressure, plasma triglyceride and C-peptide, and higher concentrations of plasma high-density lipoprotein cholesterol and glycated haemoglobin, and were more likely to require drug treatment, compared with those without antibodies to GAD. In conclusion, there was a low prevalence of antibodies to GAD in Chinese young diabetic patients although such antibodies remained a relatively specific marker for insulin deficiency and acute presentation. Causes other than autoimmunity should be sought to explain the high prevalence of insulin deficiency in these young Chinese patients.

Antibodies↗
PubMed1998

Effects of fish oil and alpha-tocopherol in immunoglobulin A nephropathy in the rat.

Alpha-tocopherol and fish oil have been reported to modulate the progression of IgA nephropathy in animals and humans. Because fish oil has been reported to exacerbate renal disease in subtotal nephrectomized rats, we investigated the effects of fish oil, with and without alpha-tocopherol, on the course of IgA nephropathy. Experimental IgA nephropathy was induced in male Sprague-Dawley rats, weighing 170-200 g, by oral and i.v. immunization with bovine gamma-globulin for 8 wk. IgA nephropathy was evidenced by hematuria, proteinuria, and IgA deposition in the mesangium. Standard rodent chow, containing 30 IU of alpha-tocopherol/kg of diet, was given to the control and IgA nephropathy rats. Fish oil (20% wt/wt), stripped of alpha-tocopherol preservative, was given to control and a second group of IgA nephropathy rats. Alternatively, corn oil or fish oil was supplemented with alpha-tocopherol at 100 IU/kg of diet and given to the third and fourth groups of IgA nephropathy rats. All animals were killed at 8 wk. Urinary protein excretion, plasma and kidney alpha-tocopherol concentrations, as well as glomerular planar area, and kidney transforming growth factor-beta1 mRNA were analyzed. As determined by reductions in proteinuria, glomerular planar area, and TGF-beta1 mRNA, fish oil with alpha-tocopherol ameliorated the renal injury induced by bovine gamma-globulin, whereas fish oil without alpha-tocopherol did not. Our findings support the importance of alpha-tocopherol, more so than fish oil, in mitigating the injury and promoting repair in experimental IgA nephropathy.

Animals↗
PubMed1998

Glomerulosclerosis in the remnant kidney rat is modulated by dietary alpha-tocopherol.

Glomerulosclerosis and tubulointerstitial injury are characteristic features seen in the subtotal (5/6) nephrectomy remnant kidney model in the rat. Oxidative stress from renal mass reduction contributes to the glomerular and tubular injury. Previous studies have clearly demonstrated the prevention or inhibition of such injury by an antioxidant such as alpha-tocopherol. However, few data are available on the ability of alpha-tocopherol to modulate or arrest progression of the established disease. This study examines whether alpha-tocopherol modulates glomerulosclerosis and tubulointerstitial injury when it is given 2 wk after renal damage has been established. The findings indicate that alpha-tocopherol has the capacity to modulate both tubulointerstitial injury and glomerulosclerosis, lower the elevated expression of transforming growth factor-beta1, and reduce plasma and kidney malondialdehyde concentration, the end product of lipid peroxidation. The results support the potential utility of alpha-tocopherol in reversing established glomerulosclerosis and tubulointerstitial injury in a remnant kidney model.

Animals↗
PubMed1998

Use of the 1997 American Diabetes Association diagnostic criteria for diabetes in a Hong Kong Chinese population.

OBJECTIVE: Recently, the American Diabetes Association (ADA) has proposed revised diagnostic criteria for diabetes. Lowering of the fasting plasma glucose (FPG) cutoff value is intended to reduce the discrepancy with the 2-h plasma glucose (PG) cutoff value and to encourage the use of FPG. We have applied these new criteria to data collected from a population-based prevalence survey in Hong Kong Chinese subjects of working age. RESEARCH DESIGN AND METHODS: The results of 1,513 oral glucose tolerance tests (OGTTs) from a previously published prevalence survey of glucose intolerance and cardiovascular risk factors in a Hong Kong Chinese working population were reexamined using the new criteria. Of the 1,513 subjects, 27 had a known history of diabetes. Of the remaining 1,486 subjects, 228 were also selected randomly for a second OGTT without prior knowledge of the result of the first test. RESULTS: After exclusion of the 27 subjects with a known history of diabetes, the crude prevalence of diabetes was 2.83% (n = 42) when the World Health Organization's (WHO) criteria were applied. When the criterion of FPG > or = 7.0 mmol/l was used, as recommended by the ADA, the prevalence of diabetes was 1.41% (n = 21). Twenty-nine subjects (1.95%) with FPG < 7.0 mmol/l had a 2-h PG > or = 11.1 mmol/l. Eight subjects (0.53%), previously without a diagnosis of diabetes according to the WHO criteria (FPG < 7.8 mmol/l and 2-h PG < 11.1 mmol/l), had FPG between 7.0 and 7.8 mmol/l and were classified as having diabetes by the ADA criteria. This classification gave a net change of -1.42% in the prevalence of diabetes between the use of FPG > or = 7.0 mmol/l alone and the use of WHO criteria. Among the 1,486 subjects with no known history of diabetes, those classified as having diabetes according to the ADA FPG criterion alone had higher HbA1c and fructosamine levels than diabetic subjects defined by the WHO criteria. Of the 228 subjects for whom two FPG measurements were available, those who had consistent definitions (diabetes, impaired fasting glucose, normal fasting glucose) on both occasions were considered to have reproducible tests, giving an overall reproducibility of 90.8% (207 of 228). CONCLUSIONS: Compared with the WHO criteria, the use of FPG to diagnose diabetes, as recommended by the ADA, was a more reproducible test and identified those subjects who had a greater degree of hyperglycemia. Although lowering of the cutoff value from 7.8 to 7.0 mmol/l increased the number of diagnoses among subjects with low FPG, the omission of the 2-h PG would lead to fewer subjects having their diabetes diagnosed.

Adolescent↗
PubMed1998

Angiotensinogen T235 and ACE insertion/deletion polymorphisms associated with albuminuria in Chinese type 2 diabetic patients.

OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of diabetic proteinuria. Ethnic differences in the frequencies of these genotypes have also been reported. To date, most of these studies have been performed in white and Japanese populations. In this study, we examined the associations between albuminuria and RAS genetic polymorphisms in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a case-control study, the ACE insertion/deletion (I/D) gene, the angiotensinogen (AGT) gene (M235T), and the angiotensin II (AII) type 1 receptor gene (AT1 A1166C) were examined in 110 Chinese type 2 diabetic patients. Increased urinary albumin excretion (UAE) was defined as > or = 30 mg/day on at least two occasions during a 6-week study period. RESULTS: Compared with whites, there were high frequencies of the AGT TT genotype in Chinese control subjects (120/183 = 70%) and type 2 diabetic patients (74/110 = 67%). The frequencies of the MM genotype were 5 and 3%, respectively, and those of the ACE DD genotype were 13 and 10%, respectively. Although 9% of subjects carried the C allele, the AT1 CC genotype was not found in either group. Chinese type 2 diabetic patients with increased albuminuria (n = 56) had higher systolic blood pressure (160 +/- 26 mmHg vs 145 +/- 27 mmHg, P < 0.001) than the normoalbuminuric patients (n = 54). Both the AGT TT genotype (78.6% [44/56] vs. 55.6% [30/54], odds ratio [OR]: 3.0 [1.3-6.8]) and the T allele (88% [99/112] vs. 77% [83/108], OR: 2.5 [1.3-5.4]) were associated with an increased risk of albuminuria. Patients with the AGT TT genotype (n = 74) had higher 24-h UAE than those with the MT or MM genotypes (n = 36) (median: 37.8 mg/day vs. 17.8 mg/day, P < 0.01). This association remained significant in patients with normotension (56 mg/day [n = 19] for patients with the TT genotype vs. 22 mg/day [n = 14] for those with the MT/MM genotype, P = 0.03). The D allele carriers (DD or DI, n = 61) had higher serum ACE activities (75.5 +/- 29 U/l vs. 60.5 +/- 36.3 U/l, P < 0.01) than the noncarriers (II genotype). The median 24-h UAE also tended to be higher in the D allele carriers (38.9 mg/day vs. 21.4 mg/day, P = 0.07). The lowest UAE was observed in patients with the MM/MT/II genotype (16.3 mg/day [n = 18]) and the highest, in patients with the TT/DD/DI genotype (52.3 mg/day [n = 43]). No association was found between the TT genotype or D allele and hypertension. CONCLUSIONS: The high frequencies of the TT genotype and T allele in Chinese populations may contribute to the high prevalence of albuminuria in patients with type 2 diabetes. The possibility of synergism between the AGT TT genotype and the ACE D allele should also be explored.

Adult↗
PubMed1998

An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group.

OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period, 126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/- SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit, body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and 24, fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast. RESULTS: Using the intention-to-treat analysis, there were greater reductions in (mean [95% CI]) HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1-h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P = 0.05) in the acarbose group compared with the placebo group. With acarbose treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [-2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group. Using baseline HbA1c and race as covariates, there were no significant interethnic differences in treatment responses (P = 0.232 for treatment-race interaction; P < 0.001 for treatment effect). The dropout rates were similar between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no significant laboratory adverse events in either group. CONCLUSIONS: In this multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure. In some patients with troublesome gastrointestinal symptoms, a lower dosage may be necessary.

Acarbose↗
PubMed1998

Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects.

OBJECTIVE: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.

Adult↗
PubMed1998

Bronchodilator responses to salbutamol using diskhaler versus metered-dose inhaler.

In adults inhaling salbutamol via metered-dose inhalers (MDls) 200 microg doses are recommended, but with diskhalers the manufacturer advocates 400 rather than 200 microg doses. To assess this advice, a partially double-blind, placebo-controlled salbutamol dose response, crossover study (also incorporating MDI doses) was conducted in 12 mild/moderate asthmatics. After active treatment, mean peak expiratory flow rate (PEFR) increments yielded no clinically or statistically significant differences; compared to placebo, respective median differences in PEFR increments (95% Cls) were 10 (-10, 50), 20 (0, 50), and 15 (0, 30) following 400 and 200 microg via diskhalers and 200 microg via MDls. Diskhalers are a suitable alternative for patients with poor MDI technique, but the use of 400 rather than 200 microg salbutamol doses is not supported by evidence.

Adrenergic beta-Agonists↗
PubMed1998

Myelodysplastic syndrome with myelofibrosis and basophilia: detection of trisomy 8 in basophils by fluorescence in-situ hybridization.

We report a case of myelodysplastic syndrome (MDS) with myelofibrosis and pulmonary tuberculosis who had marked basophilia in the peripheral blood. A clonal karyotypic abnormality characterized by trisomy 8 was demonstrated by cytogenetic analysis. By correlation of cell morphology with results of fluorescence in situ hybridization using a chromosome 8 probe, we demonstrated that the basophils were not reactive but belonged to the neoplastic MDS clone.

Adult↗
PubMed1997

Mice lacking factor VII develop normally but suffer fatal perinatal bleeding.

Blood coagulation in vivo is initiated by factor VII (FVII) binding to its cellular receptor tissue factor (TF). FVII is the only known ligand for TF, so it was expected that FVII-deficient embryos would have a similar phenotype to TF-deficient embryos, which have defective vitello-embryonic circulation and die around 9.5 days of gestation. Surprisingly, we find that FVII-deficient (FVII-/-) embryos developed normally. FVII-/- mice succumbed perinatally because of fatal haemorrhaging from normal blood vessels. At embryonic day 9.5, maternal-fetal transfer of FVII was undetectable and survival of embryos did not depend on TF-FVII-initiated fibrin formation. Thus, the TF-/- embryonic lethal and the FVII-/- survival-phenotypes suggest a role for TF during embryogenesis beyond fibrin formation.

Animals↗
PubMed1997

The effect of age on cardiovascular risk factors in Chinese women.

Chinese women traditionally have a low incidence of coronary heart disease. However, information on cardiovascular risk factors in this population are relatively scarce. We examined these risk factors in 601 Hong Kong Chinese women (age+/-SEM, 38.5+/-0.4 years; range, 18-66 years) stratified into four age groups (group 1, < or =30 years; group 2, 31-40 years; group 3, 41-50 years; group 4, > or =51 years). Increasing age in Chinese women was associated with increased body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, fasting plasma total cholesterol, triglyceride, low-density lipoprotein, apolipoprotein B, fasting and 2-h plasma glucose, glycated haemoglobin, fasting plasma insulin and urate concentrations. After adjustment for body mass index, waist-to-hip ratio and smoking, all these age-related associations remained statistically significant except for fasting plasma insulin concentration. There was a progressive increase with age in the prevalence of glucose intolerance, hypertension, dyslipidaemia and obesity. These prevalence rates further increased in subjects aged 51 years (the mean menopausal age in Asian women) or above. These findings suggest that age had an important and independent effect on cardiovascular risk in Chinese women and that, as in Caucasians, the onset of menopause might further increase this risk.

Adolescent↗
PubMed1997

The mitochondrial tRNA[Leu(UUR)] A to G 3243 mutation is associated with insulin-dependent and non-insulin-dependent diabetes in a Chinese population.

The mitochondrial DNA tRNA[Leu(UUR)] A to G 3243 mutation is associated with maternally inherited diabetes in Caucasians and Japanese. In a Hong Kong Chinese population we have detected the 3243 mutation in 2 of 74 unrelated subjects with well characterized insulin-dependent (Type 1) diabetes mellitus (IDDM) and 2 of 75 unrelated subjects with young onset (<35 years) non-insulin-dependent diabetes (NIDDM). The 3243 mutation has only previously been associated with IDDM in Japanese. Racial differences in association of the mitochondrial 3243 mutation with IDDM suggest the influence of other genes that may increase its diabetogenic pathogenicity in Oriental races. We also found a significant excess of maternal inheritance of diabetes in the young onset NIDDM cohort, with a ratio of diabetic mothers to fathers of 2.4:1, p < 0.005. The 3243 mutation, however, only accounts for a small proportion of the observed excess maternal inheritance, and further study is needed to search for other diabetes associated mitochondrial DNA mutations.

Adolescent↗
PubMed1997

Inhibition of transforming growth factor beta 1 induction by dietary vitamin E in unilateral ureteral obstruction in rats.

Free radical species associated with bilateral ureteral obstruction (BUO) are considered important in the pathogenesis of the glomerular and tubulointerstitial injury in BUO rats. We seek to test the hypothesis that the use of an easily administered antioxidant, vitamin E, at sufficient plasma concentrations, can decrease this release of free oxygen radicals in kidney tissue and ameliorate the increase of the fibrogenic cytokine, transforming growth factor beta-1 (TGF beta-1). We used the unilateral ureteral obstruction (UUO) rat model, because the presence of the uninjured contralateral kidney provides a nonuremic internal milieu, in contrast to the uremic, acidotic, and hypercholesterolemic BUO model. Compared to sham controls, the UUO animals showed a dramatic increase in renal cortical TGF beta-1 mRNA, as quantitated by Northern blot analysis with cyclophilin internal standards. This increase in TGF beta-1 mRNA was reversed in UUO rats treated with vitamin E. The plasma malondialdehyde (MDA) concentration, an index of lipid peroxidation and an indirect index of free radical release, was significantly elevated in UUO animals compared to sham animals. The vitamin E-treated UUO animals showed a significant decrease in both plasma and renal cortical tissue MDA content. Taken together, these findings provide evidence of the important biological role of reactive free radical species in the tubulointerstitial injury of UUO and the novel role of vitamin E in modulating the mRNA of the fibrogenic TGF beta-1 in obstructive uropathy.

Administration, Oral↗
PubMed1997

Computerised infrared imaging system for studying thermal activation on the skull following somatic stimulation in small animals.

A computerised infrared imaging system has been developed to measure infrared radiation as a means of functionally mapping the cerebral cortex. In two species of small mammal, rat and gerbil, the authors localised the thermal changes at the skull overlying the somatic sensory cortex following somatic stimulation of the mystacial vibrissae. Though typically small in magnitude, a thermal response could be detected through the skull. To enhance detection sensitivity, a number of measures were taken to improve various aspects of data acquisition, stimulus delivery and control of experimental conditions. Regarding data analysis, a coordinate system based on skull landmarks was adopted to localise thermally-active regions for comparison across animals of the same species. To extract the region of weak temperature changes, a coarse-to-fine detection strategy was developed, which searched automatically for clusters of temporally- and spatially-correlated pixels above a data-driven threshold. Thus, the dynamic aspect of the thermal changes at any region of interest on the skull could be studied efficiently. The detection algorithm was tested against simulated responses in addition to empirical data obtained from animals. All of the above software was integrated in a user-friendly package.

Animals↗
PubMed1997

Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment.

OBJECTIVE: A single oral dose of paracetamol (20 mg.kg-1) was given to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of renal impairment, with creatinine clearances ranging from 4 to 123 ml.min-1.1.73 m-2. The plasma and urinary concentrations of paracetamol and its major metabolites were measured by high-performance liquid chromatography (HPLC). RESULTS: The absorption and elimination of paracetamol were unaffected by renal impairment. However, the area under the plasma concentration time curve and the elimination half-life of paracetamol metabolites increased significantly with worsening renal insufficiency. Mean renal clearances of paracetamol and its conjugates were significantly reduced in these subjects. There was no evidence of altered metabolic activation with renal impairment. CONCLUSION: The results demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates may occur.

Acetaminophen↗