Biomedical subjects

C E Tan

Publications and source records attributed to C E Tan.

At least 19 recordsLinked to original sources

PubMed2001

Benefits of micronised Fenofibrate in type 2 diabetes mellitus subjects with good glycemic control.

AIMS: To determine the effects of micronised fenofibrate on lipids and low density lipoprotein (LDL) subfraction in well-controlled diabetic subjects with mild elevations in cholesterol levels. METHODS: Thirty-five male type 2 diabetic subjects with LDL(3) greater than 100 mg/dl and good glycemic control (mean HbA1c 6.7%) were treated with micronised fenofibrate in an open labeled study for 6 months. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A-I and B, and LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h, at the beginning and end of the 6 months treatment period. RESULTS: The blood pressure, waist to hip ratio, body mass index and glycemic control remained unchanged throughout the 6 months study period. Mean serum triglyceride fell from 2.49 to 1.72 mmol/l (33%) whilst HDL cholesterol increased from 0.88 to 0.96 mmol/l (10.8%). There were no significant changes in total or LDL cholesterol. Both LDL(1) and LDL(2) rose significantly whilst the dense LDL(3) fell from a mean of 148 to 85 mg/dl (43% reduction). Fenofibrate changed the LDL subfraction distribution from dense LDL(3) particles towards buoyant LDL(1) and LDL(2) particles in 63% of the subjects. No subjects had elevations in transaminases greater than three-fold or creatine kinase greater than ten-fold from pre-treatment levels. CONCLUSION: Diabetic subjects with mild hypercholesterolemia and good glycemic control may benefit from therapy with micronised fenofibrate because of the reduction in serum triglyceride, elevation in HDL cholesterol and a shift in LDL subfraction towards a non-atherogenic form.

Adult↗

PubMed2001

Diabetes mellitus abolishes ethnic differences in cardiovascular risk factors: lessons from a multi-ethnic population.

AIMS: To compare cardiovascular risk factors in diabetic subjects of different ethnic groups, and between new and known diabetic subjects, in the Singapore National Health Survey '92. METHODS: Disproportionate stratified sampling followed by systematic sampling were used in 3568 (total) respondents of whom 2743 were non-diabetics, 179 newly diagnosed diabetics and 150 known diabetics. Amongst the diabetics, there were 185 Chinese, 66 Malays and 78 Asian Indians. Diagnosis of diabetes mellitus (DM) was based on the 2 h glucose alone, after a 75 g oral glucose tolerance test. Blood pressure (BP), lipid profile, glucose, insulin and anthropometric indices were obtained from all subjects. RESULTS: Subjects with diabetes (new and known) exhibited significantly higher triglyceride (TG), lower high density lipoprotein cholesterol (HDL-C) and low density lipoprotein (LDL)/apolipoprotein B (apo B) ratio (LDL size) compared with normoglycaemic subjects. They were more obese (generalised and central) and had higher systolic and diastolic BP. There was no difference in lipid risk factors between the two groups with diabetes although those with new diabetes were more obese whilst those with known diabetes had higher fasting glucose. Amongst subjects with diabetes, there were no significant differences between ethnic groups in TG, HDL-C, LDL/apo B ratio, or waist to hip ratio (WHR). Female Malays with diabetes had higher total cholesterol and were more obese whilst male Asian Indians with diabetes had higher fasting insulin. CONCLUSION: Asian Indians had lower HDL-C and LDL/apo B ratio than Chinese or Malays amongst normoglycaemic subjects. However, these differences between ethnic groups were not seen in subjects with DM.

Adolescent↗

PubMed2001

Cardiovascular risk factors and LDL subfraction profile in Type 2 diabetes mellitus subjects with good glycaemic control.

OBJECTIVES: To compare cardiovascular risk factors and LDL particle size in well-controlled Type 2 diabetes mellitus and normal subjects. METHODS: Ninety-three Type 2 diabetic males and 186 age-matched, male controls were studied. Glycaemic control was stable for at least 3 months prior to recruitment. None were on insulin or lipid lowering therapy. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A1 and B, LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h. RESULTS: Diabetic subjects (mean HbA(1c) 6.6%+/-0.10) did not differ from controls in total cholesterol levels (5.04+/-0.08 vs. 5.16+/-0.05 mmol/l, respectively) but had lower serum HDL cholesterol (0.98+/-0.03 vs. 1.12+/-0.02 mmol/l, P<0.001), higher serum triglyceride (2.38+/-0.16 vs. 1.80+/-0.08 mmol/l, P<0.001), lower LDL(1) and LDL(2) and higher LDL(3) concentration. An LDL(3) concentration exceeding 100 mg/dl was found in 59.1% of diabetics and 39.1% of non-diabetics (P<0.001). Diabetic subjects also had higher body mass index, waist to hip ratio and insulin resistance (HOMA). Difference in LDL subfraction between groups disappeared after adjustments were made for either triglyceride or HDL cholesterol. CONCLUSION: Well controlled Type 2 diabetes mellitus subjects exhibit an increased cardiovascular burden through low HDL cholesterol and predominance of small, dense LDL particles.

Adult↗

PubMed2001

Compound heterozygous familial hypercholesterolemia and familial defective apolipoprotein B-100 produce exaggerated hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) represent ligand-receptor disorders that are complementary. Individuals with both FH and FDB are unusual. We report a family with both disorders and the impact of the mutations on the phenotypes of the family members. METHODS: We used single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) for genetic analysis of all 18 exons and the promoter region of the LDL receptor and DGGE for genetic analysis of the apolipoprotein B-100 (apo B-100) gene. The functional significance of the apo B-100 mutation was studied using a U937 cell proliferation assay. Fasting serum lipid profiles were determined for the index case and seven first-degree relatives. RESULTS: One of the patient's sisters had a missense mutation (Asp(407)-->Lys) in exon 9 of the LDL receptor and a serum LDL-cholesterol concentration of 4.07 mmol/L. Four other first-degree relatives had hyperlipidemia but no LDL-receptor mutation. However, these subjects had a mutation of the apo B-100 gene (Arg(3500)-->Trp). The cell proliferation rate of U937 cells fed with LDL from other subjects with the same mutation was fourfold less than that of controls. The index case had both FH- and FDB-related mutations. Her serum LDL-cholesterol (9.47 mmol/L) was higher than all other relatives tested. CONCLUSIONS: Existence of both FH and FDB should be considered in families with LDL-receptor mutations in some but not all individuals with hypercholesterolemia or when some individuals in families with FH exhibit exaggerated hypercholesterolemia.

Adolescent↗

PubMed2000

Making the diagnosis of biliary atresia using the triangular cord sign and gallbladder length.

BACKGROUND: To evaluate the accuracy and utility of the triangular cord sign and gallbladder length in diagnosing biliary atresia by sonography. MATERIALS AND METHODS: Sixty fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically using a 5-10 MHz linear array transducer, focusing on the triangular cord sign (as described by Choi et al. [1]), the gallbladder, and ducts. The triangular cord is defined as a triangular or tubular echogenic density seen immediately cranial to the portal vein bifurcation; it represents the fibrotic remnant of the obliterated cord in biliary atresia. The findings were blinded to blood chemistry, (99 m)Tc-DISIDA hepatobiliary scintigraphy, and liver biopsy. Diagnosis of biliary atresia was confirmed at surgery and histology. Non-biliary atresia infants resolved medically. Comparative charges of the various investigations was made. RESULTS: ++ Twelve infants had biliary atresia, and ten demonstrated a definite triangular cord. The two false-negatives had small or nonvisualized gallbladders. No false-positives were recorded. Gallbladder length ranged from 0-1.45 cm with a mean of 0. 52 cm in biliary atresia compared to a mean of 2.39 cm in nonbiliary atresia infants. (99 m)Tc-DISIDA hepatobiliary scintigraphy showed no excretion (false-positive) in 23 % of nonbiliary atresia cases. Scintigraphy and liver biopsy charges were 2 and 6 times that of sonography, respectively. CONCLUSION: The triangular cord sign and gallbladder length together are noninvasive, inexpensive, and very useful markers for biliary atresia.

Bile Ducts, Extrahepatic↗

PubMed2000

Homeostasis model assessment in a population with mixed ethnicity: the 1992 Singapore National Health Survey.

We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.

Adolescent↗

PubMed2000

Body fat distribution and cardiovascular risk in normal weight women. Associations with insulin resistance, lipids and plasma leptin.

OBJECTIVE: To systematically examine the correlations between insulin resistance, plasma leptin concentration, obesity and the distribution of fat assessed by anthropometry and magnetic resonance imaging in Asian women. DESIGN: A cross sectional study of non-diabetic, normal weight women. SUBJECTS: Twenty-one healthy women aged 38.8 y (s.d. 11.7) and BMI 22.6 kg/m2 (s.d. 2.3). MEASUREMENTS: Intraperitoneal, retroperitoneal and subcutaneous abdominal fat volume was assessed by magnetic resonance imaging. Anthropometric data were collected. Total fat mass was assessed by bioelectric impedance analysis. Fasting serum lipids, insulin and plasma leptin were assayed. RESULTS: Generalized obesity correlated with subcutaneous abdominal fat mass (r=0.83, P<0.001), but not with intra-abdominal fat mass. Both intraperitoneal fat mass and retroperitoneal fat mass increased with age (r=0.58, P=0.005 and r=0. 612, P=0.003, respectively). Abdominal subcutaneous fat mass was the most important determinant of insulin resistance and plasma leptin. Of the serum lipids, only fasting triglyceride correlated significantly with the waist-to-hip ratio. CONCLUSIONS: It is possible that the large size of the subcutaneous depot compared to the intra-abdominal depot overwhelms any metabolic differences between adipose tissue from these two sites, resulting in the stronger correlation between insulin resistance and subcutaneous abdominal fat mass rather than intra-abdominal fat mass. On the other hand, the distribution of fat between subcutaneous fat depots may be important in the metabolic syndrome given the correlation of fasting triglyceride with waist to hip ratio but not with abdominal fat. However, the study population was small, younger and leaner compared to previous studies and we may not be able to generalize these results to all segments of the population. We confirm that subcutaneous fat mass is the major determinant of plasma leptin.

Abdomen↗

PubMed2000

Screening for diabetes mellitus--a two-step approach in individuals with impaired fasting glucose improves detection of those at risk of complications.

AIMS: To compare the new American Diabetes Association (ADA) fasting plasma glucose (FPG) criteria to the 1985 World Health Organization (WHO) 2-h post glucose (2hPG) criteria when used for screening of those with no prior history of diabetes mellitus. METHODS: The study included 3,407 subjects without a history of diabetes in whom both FPG and 2hPG were available from the 1992 Singapore National Health Survey. The agreement (kappa) between FPG and 2hPG for the diagnosis of DM was assessed. The optimal cut-off of FPG for the detection of individuals with 2hPG > or = 11.1 mmol/l was determined by receiver-operating characteristics analysis. RESULTS: The prevalence of diabetes diagnosed by FPG alone was 7.3% compared to 8.4% diagnosed by 2hPG. The prevalence of impaired fasting glucose was 8.0%. FPG and 2hPG showed moderate agreement (kappa = 0.646, 95% confidence interval 0.584-0.708). Age, ethnic group and obesity did not affect the degree of agreement. Of those with 2hPG > or = 11.1 mmol/l, 40.8% had FPG in the non-diabetic range while 24.8% of those with FG > or = 7.0 mmol/l had 2hPG in the non-diabetic range. The optimal FPG for the detection of 2hPG > or =11.1 mmol/l was 6.1 mmol/l. Oral glucose tolerance tests (OGTT) in those with 6.0 mmol/ < FPG < 7.0 mmol/l resulted in the diagnosis of diabetes in 90.7% of individuals at risk of microvascular complications. CONCLUSIONS: FPG provides a simple screening test for diabetes, which shows moderate agreement with the 2hPG. A two-step strategy of OGTT in those with impaired fasting glucose improves the detection of at-risk individuals. However, diabetes should not be diagnosed on a single test. The test should be repeated on another day if an individual tests positive for diabetes.

Adult↗

PubMed2000

Inhibition of ebselen on aflatoxin B(1)-induced hepatocarcinogenesis in Fischer 344 rats.

Aflatoxin B(1) (AFB(1)), a potent hepatocarcinogen, enhances ROS formation and causes oxidative DNA damage, which may play a role in its carcinogenicity. We have demonstrated recently that ebselen, an organic selenium compound, protects against the cytotoxicity of AFB(1) through its antioxidant capability. The present study was designed to investigate the effect of ebselen on AFB(1)-induced hepatocarcinogenesis in an animal model. Fischer 344 rats were first treated with either deionized water or ebselen (5 mg/kg, 5 days/week) via gavage for 4 weeks, then given AFB(1) (0.4 mg/kg, gavage, once a week) or AFB(1) plus ebselen (5 mg/kg, 5 days/week) for another 24 weeks. The results showed that the hepatocarcinogenicity of AFB(1) in rats was significantly reduced by ebselen treatment as indicated by a decrease in: (i) serum gamma-glutamyl transpeptidase activity; (ii) expression of mRNAs of liver alpha-fetoprotein and the placental form of glutathione S-transferase (GST-P); and (iii) the area and mean density of staining of liver GST-P foci. Ebselen treatment significantly reduced the formation of hepatic AFB(1)-DNA adducts and 8-hydroxydeoxyguanosine caused by AFB(1) exposure. These findings suggest that ebselen can inhibit the carcinogenicity of AFB(1). In addition to the reduction of AFB(1)-DNA adduct formation, the protective effect of ebselen against AFB(1)-induced oxidative DNA damage may also, at least in part, contribute to its anticarcinogenic property.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Cardiovascular risk profile in individuals with borderline glycemia: the effect of the 1997 American Diabetes Association diagnostic criteria and the 1998 World Health Organization Provisional Report.

OBJECTIVE: In 1997, the American Diabetes Association (ADA) recommended a new diagnostic category, impaired fasting glucose (IFG), to describe individuals with borderline glucose tolerance. On the other hand, the World Health Organization (WHO) suggested retaining the category of impaired glucose tolerance (IGT). We studied the prevalence of IFG and IGT in a multiethnic society and compared the cardiovascular risk profiles of subjects with IFG, IGT, or both IFG and IGT. RESEARCH DESIGN AND METHODS: A total of 3,568 subjects were examined from the 1992 National Health Survey of Singapore, which involved a combination of disproportionately stratified sampling and systematic sampling. Anthropometric, blood pressure, insulin, lipid profile, and uric acid measurements were taken, and a standard 75-g oral glucose tolerance test was performed after a 10-h overnight fast. RESULTS: The prevalence rates of IFG only, IGT only, and both IFT and IGT were 3.45, 10.2, and 3.4%, respectively. The degree of agreement (kappa) between the two diagnostic criteria (the ADA IFG and the WHO IGT) was only 0.25. A fasting glucose level of 5.5 mmol/l was the optimal cutoff for predicting a 2-h postload glucose level of > or =7.8 mmol/l. The following cardiovascular risk factors were higher in subjects with both IFG and IGT compared with those with either IFG or IGT alone: systolic blood pressure (131 +/- 20 vs. 125 +/- 21 and 125 +/- 19 mmHg, respectively; P < 0.05 and P < 0.001, respectively); diastolic blood pressure (77 +/- 12 vs. 73 +/- 12 and 74 +/- 12 mmHg, respectively; P < 0.05); BMI (26.2 +/- 4.2 vs. 24.4 +/- 4.0 and 24.6 +/- 4.4 kg/m2, respectively; P < 0.01 and P < 0.001, respectively); waist circumference (84.1 +/- 10.3 vs. 79.3 +/- 10.7 and 79.3 +/- 10.6 cm, respectively; P < 0.001); waist-to-hip ratio (0.84 +/- 0.08 vs. 0.82 +/- 0.09 and 0.81 +/- 0.08, respectively; P < 0.05 and P < 0.001, respectively); fasting insulin (12.1 +/- 9.7 vs. 9.2 +/- 5.3 and 9.9 +/- 7.7 mU/l; P < 0.01); insulin resistance (by homeostasis model assessment [HOMA]) (3.41 +/- 2.77 vs. 2.58 +/- 1.50 and 2.43 +/- 1.83, respectively; P < 0.01 and P < 0.001, respectively); total cholesterol (5.81 +/- 1.1 vs. 5.51 +/- 1.1 and 5.53 +/- 1.1 mmol/l, respectively; P < 0.05) and apolipoprotein(B) [apo(B)] (1.5 +/- 0.38 vs. 1.40 +/- 0.34 and 1.39 +/- 0.35 mmol/l, respectively; P < 0.01). The pattern of difference remained significant only for fasting insulin, insulin resistance (HOMA), and apo(B) (borderline) after adjustment for age, sex, and ethnic differences. CONCLUSIONS: Obvious discordance was evident in the classification of glycemic status when applying the criteria proposed by the ADA (IFG) or WHO (IGT) in a multiethnic society like Singapore. However, subjects with either IFG or IGT had similar cardiovascular risk profiles. Therefore, both criteria identified individuals at high risk for cardiovascular disease. Individuals with both IFG and IGT had a greater incidence of the cardiovascular dysmetabolic syndrome.

Adolescent↗

PubMed2000

A man with osteoblastic metastasis and hypocalcaemia.

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.

Aged↗

PubMed1999

A study in the relationships between leptin, insulin, and body fat in Asian subjects.

OBJECTIVE: To study the relationship of leptin concentrations with indices of obesity, fasting insulin, insulin resistance and lipid profiles (total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)- cholesterol and triglyceride) in an Asian cohort. DESIGN: Cross sectional study. SUBJECTS: A total of 133 healthy volunteers were enrolled (64 female: age: 25-61 y, body mass index (BMI): 18.7-45.1 kg/m2 and 69 male: age: 25-61 y, BMI: 19.3-35.0 kg/m2). MEASUREMENTS: Weight, height, waist and hip circumferences, blood pressure, lean body mass (by bioelectric impedence analysis (BIA)), plasma leptin and lipid profiles were taken after a 10 h fast. RESULTS: Percentage of body fat measured by bioelectric impedance was the strongest determinant of plasma leptin (r = 0.844, P < 0.0001). Females had higher leptin concentrations than males for the same fat mass. In a multiple linear regression model, body fat percentage, (percentage body fat* gender), hip circumference and fasting insulin were significant determinants of leptin concentration (r = 0.882, P < 0.0001). CONCLUSION: Leptin concentration correlated closely with percentage body fat in Asian subjects. Hip circumference as a corollary for peripheral obesity, was better associated with leptin than waist circumference or waist-to-hip ratio (WHR). Distribution of fat in females tended to be peripheral and may partly explain the gender difference. Fasting insulin level and central obesity were correlated with HDL-cholesterol, triglyceride and blood pressure, while fasting leptin had little correlation with these metabolic parameters. Therefore, insulin resistance was a better guide to cardiovascular risk assessment than plasma leptin.

Adipose Tissue↗

PubMed1999

Isolated low HDL cholesterol: an insulin-resistant state only in the presence of fasting hypertriglyceridemia.

Individuals with isolated low HDL cholesterol are at increased risk of coronary artery disease. It has been reported previously that this is an insulin-resistant state. We analyzed data from the 1992 Singapore National Health Survey with the objective of defining the clinical and metabolic parameters associated with isolated low HDL cholesterol. A total of 3,568 individuals were selected by stratified random sampling. Subjects with low HDL cholesterol (<0.9 mmol/l) and "ideal" total cholesterol (<5.2 mmol/l) were identified. Data on anthropometry, blood pressure (BP), insulin resistance, glucose tolerance, sex, smoking habit, and ethnic group were examined. We found that this group was heterogeneous. Those with fasting triglyceride (TG) >1.7 mmol/l (low HDL/high TG) displayed features of the insulin resistance syndrome characterized by obesity, higher diastolic BP, greater insulin resistance, and a greater tendency to have diabetes or impaired glucose tolerance (IGT). If fasting TG was <1.7 mmol/l (isolated low HDL cholesterol), individuals were similar to the general population in terms of insulin resistance and obesity. Both groups were more commonly men and Asian Indian. The ethnic difference in prevalence could not be explained by differences in diet, exercise, alcohol ingestion, or smoking. Our data support the view that Asian Indians are genetically predisposed to isolated low HDL cholesterol as well as the insulin resistance syndrome. The higher prevalence of isolated low HDL cholesterol, the young age at which individuals exhibit this phenotype (mean age 32.5 years), along with the greater propensity for Asian Indians to develop insulin resistance and IGT contribute to the threefold increased incidence of myocardial infarction in those <65 years of age in this ethnic group.

Adolescent↗

PubMed1999

Prevalence of diabetes and ethnic differences in cardiovascular risk factors. The 1992 Singapore National Health Survey.

OBJECTIVE: The purpose of the 1992 Singapore National Health Survey was to determine the current distribution of major noncommunicable diseases and their risk factors, including the prevalence of diabetes and dyslipidemia, in Singapore. RESEARCH DESIGN AND METHODS: A combination of disproportionate stratified sampling and systematic sampling were used to select the sample for the survey. The final number of respondents was 3,568, giving a response rate of 72.6%. All subjects fasted for 10 h and were given a 75-g glucose load, except those known to have diabetes. Blood was taken before and 2 h after the glucose load. Diagnosis of diabetes was based on 2-h glucose alone. RESULTS: The age-standardized prevalence of diabetes in Singapore residents aged 18-69 years was 8.4%, with more than half (58.5%) previously undiagnosed. Prevalence of diabetes was high across all three ethnic groups. The prevalence of impaired glucose tolerance was 16.1%, that of hypertension was 6.5%, and 19.0% were regular smokers. The total cholesterol (mean +/- SD) of nondiabetic Singaporeans was 5.18 +/- 1.02 mmol/l; 47.9% had cholesterol > 5.2 mmol/l, while 15.4% had levels > 6.3 mmol/l. Mean LDL cholesterol was 3.31 +/- 0.89 mmol/l; HDL cholesterol was 1.30 +/- 0.32 mmol/l, and triglyceride was 1.23 +/- 0.82 mmol/l. CONCLUSIONS: Prevalence of diabetes was high across all three ethnic groups. Ethnic differences in prevalence of diabetes, insulin resistance, central obesity, hypertension, smoking, and lipid profile could explain the differential coronary heart disease rates in the three major ethnic groups in Singapore.

Adolescent↗

PubMed1999

Development of the human intrahepatic biliary system.

In the development of the human biliary system, the extrahepatic bile ducts (EHBD) develop from the embryonic hepatic diverticulum, while the intrahepatic bile ducts (IHBD) originate within the liver from the ductal plate. The ductal plate is a flat muralium of primitive biliary epithelium that develops in the mesenchyme along the branches of the portal vein, by a process which requires a delicate balance between cell proliferation and death. The ductal plate is thus remodelled into the adult system of tubular anastomosing bile ducts and this process is called ductal plate remodelling. Computerised three-dimensional reconstruction of the developing ductal plate has shown that the ductal plate remodelling process starts at the porta hepatis around 11 weeks of gestation and progresses towards the periphery of the liver. The extrahepatic biliary system is in direct luminal continuity with the developing intrahepatic biliary system throughout gestation and does not have a "solid stage" as suggested previously. The ductal plate remodelling is controlled by many biochemical and molecular factors, some of which have been identified and studied. It has been suggested that abnormalities in the development of the IHBD could lead to a spectrum of diseases called ductal plate malformation. Biliary atresia is one of the conditions in this spectrum. Currently, we are studying the IHBD in biliary atresia in comparison to the normal developing IHBD, the results of which are presented in this review. Both morphologically and biochemically the IHBD in biliary atresia resembles the primitive foetal ductal plate suggesting a disruption in ductal plate remodelling.

Bile Ducts↗

PubMed1999

Experimental models of hepatic fibrosis in the rat.

The rat is a frequently used experimental model in studies involving human disease. We review several methods of inducing hepatic fibrosis and cirrhosis in rats. These include induction by hepatotoxins and hepatocarcinogens such as carbon tetrachloride, dimethylnitrosamine, thioacetamide and furan; the hepatoxin-cum-nutrient, alcohol; a high fat-low choline-low protein diet; immunologic agents such as heterologous serum or bacterial cell wall products; and obstructive jaundice and biliary cirrhosis by common bile duct ligation.

Animals↗

PubMed1999

A study to assess the effect of dietary supplementation with soluble fibre (Minolest) on lipid levels in normal subjects with hypercholesterolaemia.

Hypercholesterolaemia is one of the major risk factors in the development of coronary artery disease. In recent years, many nonprescription treatments have become available for cholesterol lowering. Minolest is a product that contains guar gum and psyllium as the principal active ingredients. We conducted a randomised, placebo-controlled, double-blind, parallel-group study to assess the efficacy of Minolest as a lipid-lowering agent. Secondary aims included assessment of the effect on blood pressure and obesity. We also looked at the acceptability of the product and side effects associated with its ingestion. After a 4-week run-in period, 83 subjects were randomised to receive placebo or Minolest (16.5 g/day) for 3 months. Seven subjects defaulted follow up, 5 in the placebo group and 2 in the active treatment group. In addition, 9 subjects (5 on active treatment and 4 on placebo) had total cholesterol fall into the optimal range (< 5.2 mmol/l) during the run-in phase and were removed from the study. At baseline in the active treatment group, total cholesterol was 6.1 (5.43 to 8.06) mmol/l, triglyceride 1.54 (0.56 to 4.19) mmol/l, HDL cholesterol 1.32 +/- 0.43 mmol/l and LDL cholesterol 4.1 (3.10 to 6.27) mmol/l. In the placebo group, total cholesterol was 5.84 (5.32 to 8.38) mmol/l, triglyceride 1.47 (0.69 to 11.0) mmol/l, HDL cholesterol 1.15 +/- 0.33 mmol/l and LDL cholesterol 3.87 (2.46 to 5.14) mmol/l. The differences in the baseline characteristics were not statistically significant except the LDL-cholesterol. Minolest produced a 3.24% (SD = 7.85%, P = 0.020) decrease in total cholesterol and 5.45% decrease in LDL cholesterol (SD = 10.25%, P = 0.0034) but no significant difference in serum triglyceride, weight, body mass index or blood pressure. This was not seen in the placebo group. The percentage fall in LDL cholesterol increased to 7.16% and 7.37% in subjects who consumed at least 50% and 70% of the treatment respectively. There were few side effects. The authors conclude that this product has a small impact on the lipid profile and may be useful only in subjects with mild hypercholesterolaemia and a low risk of coronary artery disease.

Adult↗

PubMed1999

Measurement of obesity by anthropometry and bioelectric impedance analysis: correlation with fasting lipids and insulin resistance in an Asian population.

Obesity is associated with increased coronary artery disease risk. This is at least partially mediated by increased prevalence of other risk factors such as dyslipidaemia and insulin resistance. Various anthropometric indices have been used to quantify generalised and central obesity. Correlations between these measurements and risk factors are specific to the population and findings cannot be extrapolated to other ethnic groups. Bioelectric impedance analysis (BIA) is a simple means of estimating percentage body fat. We compared body mass index (BMI), waist circumference, waist-hip ratio (WHR) and percentage body fat measure by BIA as predictors of fasting lipid profiles and insulin resistance in 109 Singaporean Chinese. BMI was significantly correlated with insulin resistance and there appeared to be a threshold at 26 kg/m2 above which the regression line became more steep. WHR best predicted fasting triglyceride in both men and women. In women, it was inversely correlated with high density lipoprotein cholesterol. A similar association was seen in men but this did not reach statistical significance. We conclude that measurement of BMI and WHR should be part of the assessment of cardiovascular risk in our population as they connote different aspects of risk. BIA was not found to be a useful tool for the prediction of coronary artery disease risk factors in our population.

Adult↗