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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 109 records · Page 6Linked to original sources

Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients.

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.

Adolescent↗

Important role of cardiac spect imaging in patients undergoing percutaneous transluminal coronary angioplasty.

OBJECTIVE: To examine the utilization and contribution of cardiac perfusion scans to patients undergoing percutaneous transluminal coronary angioplasty. METHODS: From July 1996 to January 1998, 34 patients underwent percutaneous transluminal coronary angioplasty and cardiac SPECT imaging was studied. Twenty-five patients had pre-procedure SPECT scans. The agreement between angioplasty strategies and SPECT findings of ischemia and hypokinesia was examined. RESULTS: When radionuclide imaging was performed before revascularization procedures, 84% of the patients had intervention strategies guided by scan findings. Perfusion scan findings including extent and severity of ischemia, degree of hypokinesia directed the selection of target vessel for angioplasty in the patient subgroup with multi-vessel disease. Post-angioplasty radionuclide cardiac scans were performed only on symptomatic patients, demonstrating ischemia and hypokinesia in most of them, conceivably reflected the selection bias. CONCLUSION: We recommend routine pre- and post-angioplasty radionuclide imaging with multigated scans for wall motion assessment for all patients receiving coronary intervention.

Aged↗

Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice.

Matings of mice heterozygous for a protein C (PC) deficient allele, produced by targeted PC gene inactivation, yielded the expected Mendelian distribution of PC genotypes. Pups with a total deficiency of PC (PC-/-), obtained at embryonic day (E) 17.5 and at birth, appeared to develop normally macroscopically, but possessed obvious signs of bleeding and thrombosis and did not survive beyond 24 h after delivery. Microscopic examination of tissues and blood vessels of E17.5 PC-/- mice revealed their normal development, but scattered microvascular thrombosis in the brain combined with focal necrosis in the liver was observed. In addition, bleeding was noted in the brain near sites of fibrin deposition. The severity of these pathologies was exaggerated in PC-/- neonates. Plasma clottable fibrinogen was not detectable in coagulation assays in PC-/- neonatal mice, suggestive of fibrinogen depletion and secondary consumptive coagulopathy. Thus, while total PC deficiency did not affect the anatomic development of the embryo, severe perinatal consumptive coagulopathy occurred in the brain and liver of PC-/- mice, suggesting that a total PC deficiency is inconsistent with short-term survival.

Animals↗

Glycated haemoglobin and cardiovascular risk factors in Chinese subjects with normal glucose tolerance.

Increased plasma glucose concentration is a predictive factor for mortality in both diabetic and non-diabetic subjects. Although glycated haemoglobin (HbA1c) is a useful index of mean blood glucose concentrations over the preceding 1 to 3 months, there are few data regarding its relationship to cardiovascular risk. We have examined the relationship between HbA1c and cardiovascular risk factors in 1280 subjects with normal glucose tolerance. Based on HbA1c tertiles (tertile 1: n = 427, 262 men and 165 women, HbA1c level: 2.9-4.7% in men and 3.2-4.2% in women; tertile 2: n = 426, 261 men and 165 women, HbA1c level: 4.7-5.1% in men and 4.2-4.6% in women; tertile 3: n = 427, 262 men and 165 women, HbA1c level: 5.1-6.7% in men and 4.6-6.9% in women), increasing HbA1c was associated with increasing age, blood pressure, waist-hip ratio, fasting and 2-h plasma glucose, 2-h insulin, cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and urate concentrations. When age and sex were included as covariates, increasing HbA1c remained associated with increasing fasting and 2-h plasma glucose, 2-h insulin, total cholesterol, and low-density lipoprotein cholesterol concentrations. These findings emphasize the importance of hyperglycaemia, as reflected by HbA1c, as a continuum in the evaluation of cardiovascular risk. Furthermore, these findings support the hypothesis that cardiovascular disease risk commences with rising glucose concentrations before 'conventionally-defined' glucose intolerance occurs.

Adult↗

alpha-Tocopherol reduces proteinuria, oxidative stress, and expression of transforming growth factor beta 1 in IgA nephropathy in the rat.

Oxidative stress and the fibrogenic cytokine transforming growth factor beta 1 (TGF beta 1) have been implicated in the pathogenesis and progression of IgA nephropathy. In the present study, we used alpha-tocopherol as a dietary supplement to test the hypothesis that the proteinuria, oxidative stress, and TGF beta mRNA can be more effectively lowered with higher doses of alpha-tocopherol. Hematuria, proteinuria, and mesangial IgA deposition are parameters which characterize IgA nephropathy. IgA nephropathy was induced by bovine gamma globulin oral immunization in rats during an 8-week course, and all hallmarks of IgA nephropathy were produced in this 8-week animal model. The elevation in renal malondialdehyde content and TGF beta 1 mRNA, as well as the severity of proteinuria, was blunted by alpha-tocopherol. Our data suggested that conventional dosage of alpha-tocopherol at 100 IU/kg chow lowered kidney TGF beta 1 to control values and increasing the dose by 2 1/2-fold or even 5-fold resulted in no further reduction in TGF beta 1 mRNA. Significant reduction of proteinuria was achieved better with a dose of 250 IU/kg chow of alpha-tocopherol supplementation than with the 100 IU/kg chow. We conclude that alpha-tocopherol at this dose is efficacious in controlling proteinuria, downregulating TGF beta 1, and reducing oxidative stress in experimental IgA nephropathy. Doubling this dose achieved no further benefits.

Animals↗

Increased heat shock protein-70 in unilateral ureteral obstruction in rats.

Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague-Dawley rats (125-150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, during R-UUO, was not different from sham (P, ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.

Animals↗

The association between dyslipidaemia and obesity in Chinese men after adjustment for insulin resistance.

Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.

Adult↗

Evaluation of drug usage and expenditure in a hospital diabetes clinic.

BACKGROUND: Diabetes mellitus is a major public health problem and often coexists with hypertension and dyslipidaemia. A prescription-based survey was conducted to examine the use of antidiabetic, antihypertensive and lipid lowering drugs in a hospital diabetes clinic. The expenditure incurred was also evaluated. METHOD: Prescriptions issued from the diabetes clinic were collected for 4 consecutive weeks. Drugs were categorized into three main classes--antidiabetic, antihypertensive and lipid-lowering drugs. The unit cost of each drug and the total amount prescribed were used to estimate the total drug costs. RESULTS: During the 4-week study period, 534 prescriptions were collected, of which 520 contained antidiabetic drugs. Oral hypoglycaemic agents were prescribed in 379 patients (72.9%). Sulphonylurea was used as a single agent in 119 (22.9%) patients, in combination with metformin in 219 (42%) patients and with insulin in 17 patients (3.3%). Among patients treated with sulphonylureas (n=342), glibenclamide (47.7%) and gliclazide (30.7%) were the main drugs prescribed. Metformin monotherapy was prescribed in only 31 patients (6%). Insulin treatment was prescribed in 141 (27%) patients and in combination with oral drugs in 23 patients (4.5%). Of the 534 prescriptions, 225 (42%) contained antihypertensive drugs. Calcium channel blocking agents and angiotensin converting enzyme inhibitors were the most commonly prescribed drugs in both monotherapy (n=155) and combination therapy (n=70). The antidiabetic and antihypertensive drugs accounted for 45% and 39% of the total drug expenditure, respectively. Lipid-lowering drugs were prescribed in 8% of the diabetic patients. Simvastatin and gemfibrozil were the most common drugs prescribed and accounted for 12% of the total drug expenditure. CONCLUSION: The use of antidiabetic drugs represents a major burden on the health care system. The high proportions of patients requiring antihypertensive drugs and lipid lowering drugs further increase drug expenditure. Most of these treatments have been shown to improve clinical outcomes and quality of life, if used appropriately. The impacts of these long-term medications on health care financing require careful evaluation to assess their cost-effectiveness.

Adult↗

Drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs.

OBJECTIVES: To examine the prescribing patterns, particularly antihypertensive and antidiabetic drugs, in a hospital outpatient clinic and to evaluate the expenditure incurred. METHODS: Prescriptions from a general medical outpatient clinic in a teaching hospital were collected for 4 weeks. Drug expenditures were calculated. RESULTS: A total of 622 prescriptions containing 1903 items were collected. Antihypertensive and antidiabetic drugs accounted for 25.9 and 9.1% usage, respectively. Calcium channel blocking agents, angiotensin converting enzyme inhibitors and beta-blocking agents were the most popular antihypertensive drugs used. Sulphonylureas were the most frequently prescribed antidiabetic agents. Amlodipine, doxazosin and sotalol accounted for 4.5% of all prescription items but 27.8% of the total drug expenditure. CONCLUSION: The use of antihypertensive and antidiabetic drugs accounted for most of the drug usage in this study. Use of newer and more expensive agents has further increased drug expenditure. Monitoring drug usage and their correlations with clinical outcomes are warranted.

Aged↗

Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.

OBJECTIVES: To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. METHOD: Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. RESULTS: A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. CONCLUSION: Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.

Aged↗

Retroperitoneal ancient schwannoma: review of clinico-radiological features.

A case is reported here of an ancient schwannoma in the retroperitoneum. The findings of abdominal ultrasound and CT in a patient with a retroperitoneal ancient schwannoma are presented, and the clinical and radiological features of this unusual tumour are reviewed. The presence of a large, well-delineated complex cystic mass in the deep soft tissues should raise the possibility of an ancient schwannoma. It is important to recognize these tumours as benign with excellent prognosis so as to avoid unnecessary radical surgery.

Aged↗

Lessons from 20 years of leading a pediatric nephrology program.

The patterns of patient referrals, the guidelines for diagnostic procedures and treatment, and the academic leadership have continued to change in the last two decades. The revolution brought about by molecular biology has dramatically changed the pace and direction of medical research during this period. In addition, the introduction of managed care competition in the past decade has dramatically challenged the practice of medicine. The effects of all these changes on nephrology and some lessons learned from developing and leading a regional pediatric nephrology program will be discussed. The role of the National Institutes of Health in changing research focus will be examined. These observations may be useful to those preparing to meet the challenges of clinical care and research in this competitive era.

Child↗

Chronic renal failure: an overview from a pediatric perspective.

We present data on the costs and impact of chronic renal failure, the primary renal diseases leading to end-stage renal disease in children, and review the adaptive responses and the pathophysiology and complications of uremia in experimental animals and in man. A treatment strategy is summarized.

Adaptation, Physiological↗

The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors.

We examined the reproducibility of oral glucose tolerance tests (OGTT) using the World Health Organization criterion in 212 Chinese subjects (male 149, female 63) who underwent two 75 g OGTTs within a 6-week period. The overall reproducibility was 65.6% (139/212) of which 74 subjects had normal glucose tolerance, 24 had diabetes and 41 had impaired glucose tolerance (IGT) on two occasions. The subjects were divided into three groups [group 1: normal OGTTs on both occasions (n = 74); group 2: one abnormal OGTT (either diabetes or IGT (n = 51); group 3: 2 abnormal OGTTs (n = 87)]. Subjects in group 1 were younger, had lower blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), fasting and 2 h plasma insulin levels, triglyceride, very-low density lipoprotein and apolipoprotein-B concentrations than both groups 2 and 3. Group 2 had similar characteristics as group 3 except for a lower glycated haemoglobin (HbA1c), fasting and 2 h plasma glucose during the two OGTTs. With receiver operating characteristic curve (ROC) analysis, a HbA1c of 5.3% gave an optimal sensitivity of 70.7% and specificity of 74.3% to predict diabetes as defined by a 2 h plasma glucose value > or = 11.1 mmol/L in the first OGTT. Of the 212 subjects, 73 had HbA1c > or = 5.3%. The reproducibility of OGTT was 56.2% for these 73 subjects. With ROC analysis, a BMI of 25 kg/m2 gave an optimal sensitivity of 53.7% and specificity of 56.7% to predict diabetes. For the 36 subjects with BMI > or = 25 kg/m2, the reproducibility of OGTT was 58.3%. Similarly, for the 140 subjects with WHR > or = 0.9, the reproducibility of OGTT was 57.9%. These findings confirmed the poor reproducibility of OGTT which was not improved even amongst subjects with high HbA1c, BMI or WHR. Furthermore, subjects with one abnormal OGTT, whether reproducible or not, had a higher cardiovascular risk profile compared to subjects who had two normal OGTTs.

Adult↗