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Biomedical subjects

C E Tan

Publications and source records attributed to C E Tan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Developing human biliary system in three dimensions.

BACKGROUND: In the development of the human biliary system, although the extrahepatic bile ducts develop from the embryonic hepatic diverticulum, there is increasing evidence to suggest that the intrahepatic bile ducts originate within the liver from the ductal plate. The ductal plate develops as a sheath of primitive biliary epithelium in the mesenchyme along the portal vein branches. Through an orderly process of selection and deletion, the ductal plate is remodelled into the adult system of anastomosing tubular bile ducts. The ductal plate remodelling process occurs at the porta hepatis between 11 and 13 weeks of gestation and progresses towards the periphery of the liver. METHODS: In this project, for the first time, we have used computerised three-dimensional reconstruction techniques to visualise the developing human biliary system. Paraffin-embedded tissue from eight human embryos or fetuses between 5.5 and 16 weeks of gestation were serially sectioned, and their images were aligned, digitised, and used for three-dimensional reconstruction. RESULTS AND CONCLUSIONS: Three-dimensional images of the extrahepatic and the intrahepatic biliary systems were obtained, and the following conclusions were drawn. (1) The intrahepatic biliary system, both at the porta hepatis and within the liver, developed from the ductal plate through a consistent pattern of remodelling. (2) Prior to the remodelling process, the ductal plate was of similar morphology irrespective of site and gestation. (3) The extrahepatic biliary system was in direct luminal continuity with the developing intrahepatic biliary system throughout gestation and did not show the presence of a "solid stage" in any of the embryos or fetuses studied.

Bile Ducts, Extrahepatic↗
PubMed1997

Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease.

Stimulating thyrotrophin receptor antibodies (TRAbs) have been identified as the antibodies responsible for the pathogenesis of Graves' disease (GD) while blocking TRAbs have been implicated as the cause of hypothyroidism in some patients with chronic lymphocytic thyroiditis (CLT). TRAb positivity in patients with other thyroid disorders such as silent thyroiditis, toxic multinodular goitre and subacute thyroiditis has been reported but the role of TRAb in these disorders is unclear. A study was carried out to determine the prevalence of TRAb positivity in Singaporean patients with a spectrum of thyroid diseases. TRAb levels were measured in 181 patients with GD, 54 patients with CLT (37 goitrous and 17 agoitrous), 16 patients with thyroid nodules, 11 patients with subacute thyroiditis, 1 patient with hyperthyroidism due to a human chorionic gonadotrophin (HCG)-secreting tumour, 2 patients with thyroid stimulating hormone-secreting tumours and 2 patients with amiodarone-induced dysthyroidism. Using a cut-off of 10.0 U/L, TRAb levels were found to be positive in 79.0% of GD patients, 9.2% of CLT patients (euthyroid and hypothyroid) and no patients with other thyroid disorders. TRAb was a more sensitive marker of GD than anti-thyroglobulin antibodies (53.2%) but not anti-microsomal (78.3%) antibodies. TRAb levels > 10.0 U/L appear to be highly specific for autoimmune thyroid disease.

Biomarkers↗
PubMed1997

Aldosterone to renin ratios in the evaluation of primary aldosteronism.

Primary aldosteronism, though an uncommon cause of hypertension, causes significant morbidity, making it important to diagnose and treat this condition. Its evaluation requires complex and time consuming investigative procedures in order to confirm the diagnosis and to differentiate between the subtypes of aldosterone producing adenoma and idiopathic hyperaldosteronism. Often, the values of renin and aldosterone are equivocal, and the diagnosis of primary aldosteronism is in doubt. In this study, we examine the use of aldosterone to renin ratios in confirming the diagnosis of primary aldosteronism when the usual criteria of suppressed renin and elevated aldosterone are not met. We have found that an aldosterone to renin ratio of 50 has a 100% specificity and 92% sensitivity for detecting primary aldosteronism. Also, an aldosterone to renin ratio of > 2000 is suggestive of an aldosterone producing adenoma.

Adrenocortical Adenoma↗
PubMed1996

Abnormal thyroid and adrenocortical function test results in intensive care patients.

A prospective, cohort study of 75 consecutive patients requiring management in the medical intensive care unit (MICU) of the Singapore General Hospital was carried out over a five-month period to determine thyroid and adrenocortical profiles and evaluate their use in predicting patient outcome. Up to 88% of patients had at least one abnormal thyroid function and 77% had abnormal adrenocortical function test results. There were significantly lower triiodothyronine, thyroxine and free thyroxine, but not thyrotropin levels, and higher cortisol levels in non-survivors compared to survivors (all P < 0.01). Of the endocrine parameters, triiodothyronine and cortisol concentrations were independent predictors of outcome. The overall predictive accuracy of combining these two variables on admission into the MICU was 74%. The APACHE II (acute physiology and chronic health evaluation II) score alone predicted outcome with 71% accuracy, and in combination with triiodothyronine and cortisol levels improved accuracy to 84%. The use of dopamine alone predicted outcome with 74% accuracy, and in combination with triiodothyronine and cortisol levels, improved accuracy to 84%. Measurements of total triiodothyronine and cortisol concentrations on admission to the MICU, and consideration of the use of dopamine improve on the APACHE II score in outcome prediction.

APACHE↗
PubMed1995

Distortion in TGF beta 1 peptide immunolocalization in biliary atresia: comparison with the normal pattern in the developing human intrahepatic bile duct system.

Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-beta 1 is a cytokine that stimulates mesenchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGF beta 1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGF beta 1 peptide was detected within hepatocytes and ductal plate epithelium from 7 weeks gestation; increased TGF beta 1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGF beta 1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.

Adolescent↗
PubMed1995

Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women.

VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 (P < .001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had and LDL-III in the range associated with high risk of heart disease ( > 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = 39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Measurement and physiological significance of lipoprotein and hepatic lipase activities in preheparin plasma.

A radiochemical method for selective measurement of postheparin lipase activities was adapted to analyze lipoprotein lipase and hepatic lipase in preheparin plasma. The assay sensitivity was increased about four-fold by doubling both the volume of plasma used and the volume of lipolytic products taken for liquid scintillation counting, and was further improved by increasing the incubation period by 50% to 90 min. Rabbit antiserum to human hepatic lipase was unsuitable for the selective measurement of lipoprotein lipase because of apparent endogenous lipolytic activity. Preheparin hepatic lipase, however, was sensitive to inactivation by sodium dodecyl sulfate (SDS), the inhibition being greatest (> 90%) for plasma incubated with an equal volume of 40 mmol/L SDS. Intra- and interassay CVs for the two enzymes were 12.5-14.6% and 17.4-19.7%, respectively. In a cross-sectional study of 84 healthy subjects, pre- and postheparin hepatic lipase activities were higher in men than women, were correlated with indices of obesity, and were significantly correlated with one another, which explained the association of the former with plasma concentrations of high-density lipoprotein (HDL), HDL2, and small, dense low-density lipoproteins. There was no significant relationship between pre- and postheparin lipoprotein lipase activities, but the former were correlated with plasma concentrations of free fatty acids (FFA) and very-low-density lipoprotein. Apparently, preheparin activities of hepatic lipase, but not of lipoprotein lipase, may be a useful measure of the physiological function of "whole body" enzyme activity in cross-sectional and metabolic studies, where heparinization is not possible. Preheparin lipoprotein lipase activities, however, may reflect displacement of the enzyme by FFA and subsequent binding to remnants of triglyceride-rich lipoproteins.

Aging↗
PubMed1995

Management of hyperlipidaemia.

Recent community-based studies have shown that hypercholesterolaemia is common in Singapore. High low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol as well as hypertriglyceridaemia are associated with higher prevalence of cardiovascular disease. The aim of this article is to discuss the clinical management of adult patients with hyperlipidaemia. For practical purposes, the hyperlipidaemias can be divided into four patterns: 1) hypercholesterolaemia with normal triglyceride, 2) moderate hypertriglyceridaemia with normal cholesterol, 3) combined moderate hypercholesterolaemia and hypertriglyceridaemia, and 4) severe hypertriglyceridaemia with moderate hypercholesterolaemia. Each pattern can be attributed primarily to genetic conditions or secondarily to common diseases. It is important to attempt aetiopathogenetic diagnosis for each hyperlipidaemic patient as treatment of an underlying condition may sometimes reverse the hyperlipidaemia eg hypothyroidism and hypercholesterolaemia. In general, a low cholesterol and low fat (particularly saturated fat) diet is useful in patients with all four patterns of hyperlipidaemia. Patients with severe hypertriglyceridaemia and moderate hypercholesterolaemia may benefit from a further drastic reduction in fat intake. Pharmacological therapy is required for patients who do not achieve target lipid levels after diet modification. The choice of drug therapy is, to a large extent, dependent on the pattern of hyperlipidaemia. In some situations, combination drug therapy may be required. Caution is required in combining hypolipidaemic drugs as the side-effects of individual drugs may be potentiated when used in combination.

Combined Modality Therapy↗
PubMed1994

Does the morphology of the extrahepatic biliary remnants in biliary atresia influence survival? A review of 205 cases.

Resected extrahepatic remnants taken at the time of portoenterostomy were examined in a single-center review of 205 cases of biliary atresia. The morphological features of the size and number of residual ducts at the porta hepatis and the degree of inflammation at the porta hepatis were analyzed using a semiquantitative scoring system. The morphology of the common hepatic and common bile duct was classified into seven types. These features were then related to age at time of initial surgery and to survival. This showed that few or absent ductal remnants at the porta hepatis and absence of portal inflammation were predictors of poor prognosis. These histological features may represent the "burnt out" end result of the disease process. There was no correlation between age at time of portoenterostomy and either portal duct patency or portal inflammation. The common hepatic and common bile duct were variably involved in the sclerosing process, but the patterns of obliteration were not indicative of prognosis. The severity of intrahepatic biliary cholangiopathy and the extent of liver damage may ultimately be more important to survival in the long term.

Bile Ducts, Extrahepatic↗
PubMed1994

Extrahepatic biliary atresia: a first-trimester event? Clues from light microscopy and immunohistochemistry.

Biliary atresia is an obliterative disorder of the bile ducts, causing obstructive jaundice in neonates. In this study, the developing biliary system of normal human embryos and fetuses was examined and compared with the resected extrahepatic biliary remnants from 205 cases of biliary atresia. At the porta hepatis level, it was found that the primary biliary ductal plate undergoes a specific sequence of remodelling, resulting in the formation of large tubular bile ducts surrounded by thick mesenchyme, between 11 and 13 weeks postfertilisation. These developing ducts are in luminal continuity with the extrahepatic biliary tree throughout gestation. Contrary to long-held belief, no "solid phase" was observed in the development of the extrahepatic bile duct. Examination of the biliary remnants in biliary atresia showed that the porta hepatis is encased in fibrous tissue, and a variable pattern of obliteration of the common hepatic and common bile ducts was observed. Anticytokeratin immunostaining showed similarities between the abnormal ductules within the porta hepatis in biliary atresia, and the developing bile ducts in the first trimester. Biliary atresia may be caused by failure of the remodelling process at the hepatic hilum, with persistence of fetal bile ducts poorly supported by mesenchyme. As bile flow increases perinatally, bile leakage from these abnormal ducts may trigger an intense inflammatory reaction, with subsequent obliteration of the biliary tree.

Bile Ducts, Extrahepatic↗
PubMed1994

The effect of a 5-month supervised program of physical activity on anthropometric indices, fat-free mass, and resting energy expenditure in obese male military recruits.

Studies using mainly dietary restriction have shown that weight loss is associated with a decrease in fat-free mass (FFM) and resting energy expenditure (REE). The aim of this study was to investigate the effects of a weight-loss program relying solely on increased physical activity on FFM and REE. Forty-two overweight male military recruits (12 with initial body mass index [BMI] between 25.0 and 29.9 kg/m2, group 1; 14 with BMI between 30.0 and 34.9 kg/m2, group 2; and 16 with BMI of at least 35 kg/m2, group 3) completed a 5-month program of supervised physical activity that included both aerobic and muscle-strengthening components. All subjects lost significant amounts of weight (group 1, 8.6 kg; group 2, 15.7 kg; group 3, 22.0 kg). This weight loss was accompanied by a significant reduction in the waist to hip ratio (WHR) in all groups. FFM was maintained in all groups. REE tended to decline in all groups (group 1, from 1,595.0 +/- 46.9 to 1,511.7 +/- 53.2 kcal/d; group 2, from 1,751.4 +/- 56.0 to 1,680.0 +/- 63.1 kcal/d; group 3, from 1,901.9 +/- 93.7 to 1,740.0 +/- 67.3 kcal/d), but this decline reached statistical significance only when all 42 subjects were considered. REE normalized for FFM did not decrease except in group 1. Furthermore, differences between the slopes and intercepts of the regression lines relating REE with FFM before and at completion of the 5-month program were not statistically significant, suggesting that the relationship between REE and FFM was maintained after weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗
PubMed1994

The developing human biliary system at the porta hepatis level between 29 days and 8 weeks of gestation: a way to understanding biliary atresia. Part 1.

The developing biliary system in normal human embryos from 29 days to 8 weeks post-fertilization was studied. The primitive extrahepatic bile duct that originates from the embryonic hepatic foregut diverticulum is in contact with the hepatic anlage from the start of organogenesis and remains so throughout the gestational ages examined. The primitive extrahepatic bile duct maintains continuity with the ductal plate from which intrahepatic bile ducts are eventually formed. Contrary to long-held concepts of biliary development, no 'solid stage' of entodermal occlusion of the common bile duct lumen was found at any stage of gestation in the material investigated. Therefore, biliary atresia is not caused by incomplete vacuolization of the 'solid stage'.

Adult↗
PubMed1994

The developing human biliary system at the porta hepatis level between 11 and 25 weeks of gestation: a way to understanding biliary atresia. Part 2.

In biliary atresia, inflammation and destruction of extrahepatic and intrahepatic bile ducts with eventual fibrous obliteration occurs, causing neonatal obstructive jaundice. The onset of the disorder may start antenatally and progress after birth, and the porta hepatis is a constant site of involvement. To date, little is known about the intrauterine development of the bile ducts at the porta hepatis. The present work gives an account of the developmental pattern of bile ducts at the level of the porta hepatis in the normal human fetus from the 11th to the 25th weeks of gestation. It has been observed that the proximal portion of the hilar bile ducts derives from the intrahepatic biliary ductal plate. This occurs following a predictable remodeling sequence by which, from many ductal plate-derived ductules, those destined to become definitive bile ducts are enveloped in a concentric cuff of mesenchyma. Those which are not are deleted. The distal portions of the right and left main hepatic ducts develop from the extrahepatic bile duct. There was no gestational period in which the extrahepatic bile duct and the intrahepatic biliary system were separated. Furthermore, the developing intrahepatic bile ducts maintain luminal continuity with the common bile duct from the start of organogenesis. Biliary atresia may result from: (i) failure to establish a definitive type of bile duct; (ii) leakage of bile from primitive bile ducts resulting in an interstitial inflammatory reaction in the adjacent mesenchyma; and (iii) continuous proliferation of primitive bile ducts at the level of the porta hepatis beyond the 25th week of gestation, as a failed compensatory mechanism.

Adult↗
PubMed1994

Metabolic abnormalities in young non-obese males with hypertension.

Essential hypertension has been shown by various studies to be an insulin-resistant state. However, most of these studies have included obese and elderly patients. We were interested to know the extent of insulin resistance in a group of young, non-obese patients with hypertension. A total of 59 male patients with essential hypertension and 31 controls matched for age, sex and body mass index were studied. All the subjects were under 35 years old and had a body mass index of less than 27 kg/m2. Our results showed that such patients with hypertension had significantly higher fasting insulin, total insulin after glucose challenge, insulin/glucose ratio and higher triglycerides than the control subjects.

Adult↗
PubMed1993

Non-communicating multiseptate gall bladder and choledochal cyst: a case report and review of publications.

A 14 year old girl with multiseptate gall bladder and cystic dilatation of the biliary tree is presented. This is the 20th published case report of patients with multiseptate gall bladder and only the second to be associated with a choledochal cyst. The cystic spaces of the gall bladder did not communicate with the neck of the gall bladder or the rest of the biliary tree, and this unusual feature has not been previously described. A multiseptate gall bladder with a normal biliary tree commonly causes symptoms suggestive of cholecystitis, although gall stones are seldom present. Diagnosis is confirmed by an oral cholecystogram or ultrasound scan that may show the fine intraluminal septae, and these features should be looked for in patients with biliary symptoms without biliary calculi. Cholecystectomy is curative for the isolated gall bladder anomaly but hepaticojejunostomy may be necessary for an associated choledochal cyst.

Adolescent↗
PubMed1992

Hyperinsulinaemia in non-obese subjects with hypertriglyceridaemia: a preliminary report.

It has been known for some time that hyperinsulinaemia is associated with hypertriglyceridaemia. However, previous studies looking at the relationship between hyperinsulinaemia and hypertriglyceridaemia have included overweight subjects. The effect of obesity on the insulin status of hypertriglyceridaemic patients is uncertain. We investigated the insulin status of hypertriglyceridaemic subjects in the absence of confounding factors such as obesity, hypertension and diabetes mellitus. Our results demonstrate that basal insulin levels as well as the insulin response after an intravenous glucose challenge are higher in moderately hypertriglyceridaemic patients when compared to age and body mass index matched controls. Hyperinsulinaemia may have pathogenetic significance for hypertriglyceridaemia as well as other features of a constellation of metabolic derangements such as obesity, hypertension and glucose intolerance.

Adult↗