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Biomedical subjects

K C Tan

Publications and source records attributed to K C Tan.

At least 19 recordsLinked to original sources
PubMed1997

LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I.

Acromegaly is associated with changes in lipoprotein metabolism and an excess in cardiovascular mortality. We have examined low density lipoprotein (LDL) subfraction distribution in 24 patients with active acromegaly and in controls matched for age, sex and body mass index. LDL was subfractionated by density gradient ultracentrifugation. The concentration of small dense LDL-III was significantly higher in the acromegalic patients compared to the controls (94.2 +/- 44.9 versus 67.2 +/- 30.4 mg/dl, P < 0.05) and there was a concomitant reduction in the intermediate subfraction LDL-II (124.8 +/- 31.3 versus 149.9 +/- 30.0 mg/dl, P < 0.05). Univariate analysis showed that both growth hormone (GH) and insulin-like growth factor (IGF)-I correlated with LDL-III and inversely with LDL-II. Acromegalic patients were found to have lower hepatic lipase (HL) and lipoprotein lipase (LPL) activities than controls (HL: 13.29 +/- 6.56 versus 21.58 +/- 7.27 micromol FFA released/ml/h, P < 0.001: LPL: 7.22 +/- 3.04 versus 11.53 +/- 7.85 micromol FFA released/ml/h, P < 0.05) whereas plasma cholesteryl ester transfer protein (CETP) activity was significantly increased (8.15 +/- 1.81 versus 5.54 +/- 1.86 pmol/microl/h, P < 0.001). Both GH and IGF-I were significantly associated with HL, LPL and CETP activities. Multivariate analysis on this relatively small sample size showed that in normal subjects, triglyceride and HL activity were the major determinants of LDL-III. In contrast, GH and HDL were the main determinants in acromegaly, accounting for 32 and 24% in the variability of LDL-III respectively. In conclusion, GH excess has a direct effect on LDL subfraction distribution.

Acromegaly↗
PubMed1996

Unusual endocrine presentations of nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is endemic in Southern China and the majority of patients present with local symptoms due to the tumor. METHODS: This report describes two unusual cases of occult nasopharyngeal carcinoma in which the patients initially presented with endocrine manifestations. RESULTS: The first patient presented with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production. Nasolaryngoscopy showed a growth in the left nasal fossa and biopsy revealed a poorly differentiated nasopharyngeal carcinoma that exhibited positive immunostaining for ACTH. The second patient presented with a 10-month history of bone pain over both lower limbs. She was normocalcemic but her serum alkaline phosphatase was markedly elevated. A bone biopsy showed both osteoclastic and osteoblastic activity with widespread fibrosis suggestive of Paget's disease. Three months later, she developed third cranial nerve palsy. Computed tomography investigation revealed a soft tissue mass filling the sphenoid and ethmoid sinuses. Biopsy showed a poorly differentiated nasopharyngeal carcinoma. The bone biopsy was reviewed and immunohistochemistry demonstrated the presence of cells positive for the epithelial marker AE1/3 within the fibrous stroma. Radio-labeled in situ hybridization showed that Epstein-Barr virus early RNA was present in these tumor cells and the bone lesions were in fact metastases. CONCLUSIONS: Nasopharyngeal carcinoma can present with rather atypical symptoms that may lead to a delay in diagnosis. Therefore, in high risk populations, it is important to consider nasopharyngeal carcinoma as a possible primary tumor in patients with occult carcinomas.

ACTH Syndrome, Ectopic↗
PubMed1996

Postprandial lipid metabolism and beta-cell function in non-insulin-dependent (type 2) diabetes mellitus after a mixed meal with a high fat content.

Postprandial lipid profiles and release of insulin (INS), intact proinsulin (PI), and 32-33 split proinsulin (SPI) in response to a mixed meal with a high fat content were determined over a 12 h period in non-obese control subjects (n = 10) and non-insulin-dependent (Type 2) diabetic (NIDDM) patients with normotriglyceridaemia (NTG; n = 11) and hypertriglyceridaemia (HTG; n = 10), by calculation of the 'areas under the curves' (AUC). The postprandial triglyceride-AUC was significantly greater in HTG-NIDDM patients (p < 0.05) than in NTG-NIDDM or control subjects. Chylomicron clearance was impaired only in HTG-NIDDM patients (p < 0.05). Chylomicron-remnant clearance was impaired in both groups of NIDDM patients (p < 0.05). The postprandial suppression of plasma non-esterified fatty acid (NEFA) content was impaired in HTG-NIDDM patients (p < 0.05). The postprandial INS-, PI- and SPI-AUCS were significantly greater than in the control subjects (p < 0.05). In NIDDM, triglyceride-AUC correlated significantly with PI and SPI release (triglyceride-AUC vs PI, p < 0.05; triglyceride-AUC vs SPI, p < 0.01). Chylomicron AUC was unrelated to the fasting plasma INS, PI or SPI content, unlike chylomicron-remnant-AUC (Chylomicron-remnant-AUC vs INS, p = NS; chylomicron-remnant-AUC vs PI, p < 0.01; chylomicron-remnant-AUC vs SPI, p < 0.01). The NEFA response was associated with fasting plasma SPI content (NEFA-AUC vs SPI, p < 0.05). Postprandial chylomicron AUC was not related to the overall secretion of INS, PI or SPI. However, triglyceride-, chylomicron-remnant- and NEFA-AUCs were all associated positively with the release of PI and SPI (p < 0.05). In multivariate analyses, chylomicron-remnant clearance had the major relationship with the release of insulin precursors, accounting for 23% of the variability (p < 0.01). Inclusion of overall response of free fatty acids improved the model, with both parameters together accounting for 30% of the variability (p < 0.01). The output of the beta-cell over the postprandial period differed between the NIDDM patients and the control subjects in that when glycaemic stimulation was moderate, the proportion of insulin-like molecules as a percentage of the total output was greater than in control subjects but this was not the situation when glycaemia was greatest. We conclude that abnormal postprandial lipaemia in NIDDM is associated with beta-cell output, possibly mediated by the availability of free fatty acids.

Blood Glucose↗
PubMed1996

Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance.

The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. DEB can be inherited in either an autosomal dominant or autosomal recessive pattern, and the spectrum of clinical severity is highly variable. The unifying diagnostic hallmark of DEB is abnormalities in the anchoring fibrils, which consist of type VII collagen, and, recently, mutations in the corresponding gene, COL7A1, have been disclosed in a number of families. In this study, we report six families with glycine substitution mutations in the triple-helical region of type VII collagen. Among the six families, two demonstrated a mild phenotype, and the inheritance of the mutation was consistent with the dominantly inherited form of DEB. In the four other families, the mutation was silent in the heterozygous state but, when present in the homozygous state, or combined with a second mutation, resulted in a recessively inherited DEB phenotype. Type VII collagen is, therefore, unique among the collagen genes, in that different glycine substitutions can be either silent in heterozygous individuals or result in a dominantly inherited DEB. Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent.

Adult↗
PubMed1996

Preradial myxedema: a case report.

We describe a 51-year-old Chinese woman with a 2-year history of swelling of the right forearm and hand, which gradually became hyperpigmented and indurated. This had the typical features of myxedema. The diagnosis was confirmed on histology. She had a past history of thyrotoxicosis and rheumatoid arthritis for which she had undergone treatment. This case is reported as an unusual location of localised myxedema with a literature review and comment on the treatment options. In Singapore only rare similar cases have been reported in the past.

Anti-Inflammatory Agents↗
PubMed1996

Contributions of various major causes of death to life expectancy in Singapore, 1980-1990.

This paper considers the contributions by age of the various major groups of deaths to the increase in life expectancy at birth between 1980 and 1990 for both sexes in Singapore. Sixteen cause groups were used in the study. The data were analysed using LIFETIME, a personal computer package with a wide variety of methods for mortality investigations. Respiratory diseases made the largest contribution to the increase in life expectancy for both sexes. In contrast, ischaemic heart disease made a negative contribution of 1% in the gain in female life expectancy but contributed 12% improvement for males. Life tables for Singaporean males and females in the year 2000 were projected by extrapolating the mortality trends observed in earlier periods. The calculations show that the life expectancy at birth in the year 2000 to be 74.72 years for males and 79.48 years for females.

Adolescent↗
PubMed1996

Molecular detection of human immunodeficiency virus-1 infection among commercial sex workers using the polymerase chain reaction in Singapore.

We studied the sensitivity of polymerase chain reaction (PCR) for detecting early human immunodeficiency virus-1 (HIV-1) in sex workers. Blood samples of sex workers who attended our Sexually Transmitted Diseases clinic were tested for HIV infection by testing for the presence of HIV antibody and HIV-1 proviral DNA using PCR (with the Amplicor HIV-1 amplification kit, Roche) at 00 (when they first register to work as sex workers), 01 and 03 months after starting work. The objective was to detect HIV-1 using PCR in sex workers during the "window" period when their HIV antibody tests were still negative. Sixty-nine blood samples were PCR-tested at 00 month of which 8 were simultaneously positive for HIV antibody and PCR tests. Seventy-seven blood samples were tested at 03 month. We found that PCR test using the Amplicor HIV-1 amplification kit (Roche) to be sensitive in detecting HIV infection in sex workers but the test appeared not sensitive enough to detect HIV-1 infection during the "window" period. We were unable to detect any sex workers with PCR detectable HIV-1 before they seroconverted to become HIV antibody positive. The reason for the failure was attributed to the low infection rate among sex workers and possible lack of sensitivity of the Amplicor PCR/HIV-1 amplification kit to detect early HIV-1 infection. We are currently studying other PCR procedures to improve the sensitivity of the PCR test for HIV-1.

DNA, Viral↗
PubMed1995

Relationship between early liver graft viability and enzyme activities in effluent preservation solution.

Determination of cellular enzyme activities in washout preservation solution used in hypothermic liver graft storage may allow development of an index that could be clinically valuable in prediction of early post-transplant graft function. In the present study, we collected washed out preservation fluid at the time of graft rinsing from 53 liver recipients. Aspartate aminotransferase and, to a lesser extent, lactate dehydrogenase levels correlated with early postoperative graft viability as assessed by 1-month graft survival and standard biochemical indices of liver function. Those patients with the highest aspartate aminotransferase activity in the washout preservation solution experienced the highest levels of this enzyme postoperatively (area-under-the-curve day 1-3; 1340 vs. 788 IU/L), total bilirubin (area-under-the-curve day 1-5; 901 vs. 538 mumol/L), and rejection frequency (67% vs. 31%) (all P < 0.05), with a significantly lower 1-month graft survival rate compared with patients with low effluent levels (62% vs. 92%, P < 0.05). Two markers of endothelial cell damage, purine nucleoside phosphorylase and a creatine kinase isoenzyme, measured in the fluid did not correlate with early graft viability. It is suggested that assay of aspartate aminotransferase activities in preservation fluid washout samples is a clinically useful indicator of graft viability.

Adult↗
PubMed1995

Changes in the contact system during orthotopic liver transplantation with and without aprotinin.

The main cause of nonsurgical bleeding during orthotopic liver transplantation has been attributed to be hyperfibrinolysis due to high plasma levels of tissue plasminogen activator. The aim of this study was to investigate contact activation and its possible contribution to fibrinolysis during OLT with and without aprotinin. Aprotinin or placebo was given to 20 patients undergoing OLT as part of a randomized double-blind trial. Plasma samples were collected before, during, and after OLT. There were decreased preoperative levels of prekallikrein and factor XIIa (P < 0.05), with a trend for kallikrein and factor XIIa activity to increase during OLT peaking on reperfusion (P < 0.05). Kallikrein inhibition, C1 esterase inhibitor, and alpha-2-macroglobulin levels were normal before surgery, with low normal levels of antithrombin III and alpha-2-antiplasmin; these levels decreased during OLT with no specific change on reperfusion. In the aprotinin-treated group, kallikrein inhibition levels increased (P < 0.05) from preoperative mean (+/- SD) values of 101 +/- 47% to 154 +/- 42% and antiplasmin levels increased (P < 0.05) from 72 +/- 28% to 243 +/- 53% during the anhepatic phase, reflecting the effect of aprotinin. The antifibrinolytic effect of aprotinin was demonstrated by decreased levels of D-dimer on reperfusion (P < 0.05) and at the end of OLT (P < 0.001) in the aprotinin-treated group. We have shown that contact activation during OLT is minimal and that aprotinin does not alter the pattern of contact activation, but provides an antikallikrein effect.

Adult↗
PubMed1995

Importance of concomitant viral infection during late acute liver allograft rejection.

We have determined accompanying events and reviewed the management and outcome of late acute cellular rejection episodes in 384 consecutive liver recipients. A significant proportion of patients experienced concomitant viral infection (group 1, n = 15 [41%]), with CMV infection comprising the largest group and smaller contributions from other viruses (CMV, 30%; HSV, 5%; EBV, 3%; varicella zoster virus, 3%). Thirteen (35%) patients (group 2) developed late rejection associated with low maintenance immunosuppression, and in a further 10 patients (group 3), no accompanying factor could be identified. Refractory rejection was higher in late compared with early rejection episodes in our series (29% vs. 9.2%, P < 0.05). Antiviral chemotherapy administered in rejection episodes with concomitant viral infection, either as sole treatment in cases with accompanying hepatitis or as adjunctive therapy to further supplemental immunosuppression in episodes of steroid-resistant rejection, controlled the rejection process in all treated patients.

Adolescent↗
PubMed1995

Experience of orthotopic liver transplantation and hepatic resection for hepatocellular carcinoma of less than 8 cm in patients with cirrhosis.

Fifteen patients with cirrhosis underwent orthotopic liver transplantation for small hepatocellular carcinoma (HCC) and 12 patients with cirrhosis underwent hepatic resection for similar HCC. All tumours were of the non-fibrolamellar variant. The majority of the patients in the transplant group had Child's grade B or C cirrhosis. Median follow-up was 37 months with a minimum of 18 months. Eleven of 12 patients in the resection group had Child's grade A cirrhosis. Median follow-up was 29 months with a minimum of 16 months. Actuarial survival rates at 1 and 3 years for the transplanted patients were 80 and 63 per cent and all were tumour free. Tumour recurrence rate was 15 per cent. The overall 1- and 3-year tumour-free survival rates for patients in the resection group were 61 and 33 per cent. Tumour recurrence rate was 45 per cent. The results show orthotopic liver transplantation to be an important surgical option in cirrhotic patients with small HCC, particularly in those with moderate to severe hepatic decompensation.

Adult↗
PubMed1995

A technique for hepatic artery anastomosis during orthotopic liver transplantation.

Hepatic artery thrombosis remains the most common technical complication that causes graft failure following orthotopic liver transplantation. The Hepatic artery anastomosis should be performed using meticulous technique and adequate magnification. We report a very low incidence of Hepatic artery thrombosis (1.3%) utilising a modified microvascular 120 degrees triangulating technique in 150 adult liver transplants.

Adult↗
PubMed1995

The incidence and management of biliary complications following liver transplantation in children.

Biliary complications following liver transplantation are a cause of significant morbidity and mortality. During the period 1988-1993 ten cases of biliary complications occurred after 98 transplantations in 78 children. The complications were four bile leaks, three intrahepatic biliary strictures (one with recurrent cholangitis), two anastomotic biliary strictures (one with recurrent cholangitis) and one recurrent cholangitis. All leaks occurred within 6 weeks of transplantation whereas all strictures and cholangitic episodes occurred after 3 months. Two biliary complications (20%) - one intrahepatic and one anastomotic stricture - developed secondary to hepatic artery thrombosis. The incidence of biliary complications was 13.2% with whole liver grafts as compared to 6.7% with partial liver grafts and it was 4.3% with duct-to-duct anastomosis as compared to 12.0% with Roux-en-Y hepatico-jejunostomy. Seven children required intervention for management of biliary complications and three were managed conservatively. There were no deaths related to the biliary complications.

Adolescent↗
PubMed1995

Orthotopic liver transplantation for hepatic-based metabolic disorders.

Between January 1989 and June 1993, a total of 470 liver transplantations were performed at King's College Hospital. Thirty-seven transplantations were performed in 34 patients with liver-based metabolic disease. There were 16 females and 18 males with a median age of 19 years (range 1 month to 62 years). There were 14 patients under 16 years of age. The indications for liver transplantation were Wilson's disease (n = 16), alpha 1-antitrypsin deficiency (n = 10), tyrosinaemia (n = 2), primary hyperoxaluria type 1 (PH1; n = 2), congenital haemochromatosis (n = 1), familial amyloidotic polyneuropathy (FAP; n = 1, familial hypercholesterolaemia) (n = 1) and Crigler-Najjar syndrome type I (CNS1; n = 1). These included two patients who received combined heart-liver grafts for familial hypercholesterolaemia and FAP, respectively. Two patients received combined liver-kidney transplants for PH1. There were four deaths: from sepsis (n = 2), acute hepatic vein obstruction in a left lateral segment graft (n = 1) and portal vein thrombosis with liver necrosis (n = 1). Three patients were retransplanted, one for chronic rejection and two for hepatic artery thrombosis, giving an overall graft survival of 81% and patient survival of 88% (30/34), at a mean follow-up of 34 months (range 10-64 months).

Acute Disease↗
PubMed1995

Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia: the involvement of insulin, insulin precursor species and insulin resistance.

We have studied low density lipoprotein (LDL) subclass distribution in a group of male patients with non-insulin-dependent diabetes mellitus (NIDDM) and investigated its relationships to fasting and postprandial triglyceride (TG)-rich lipoproteins, insulin resistance, lipoprotein lipase (EC 3.1.1.3; LPL), hepatic lipase (EC 3.1.1.34; HL), lecithin:cholesterol acyl transferase (EC 2.3.1.43; LCAT) and cholesteryl ester transfer protein (CETP) activities. LDL was subfractionated by density gradient ultracentrifugation. Postprandial lipoproteins were measured after an oral fat load using retinyl palmitate as a marker for intestinal TG-rich lipoproteins. Hypertriglyceridaemic NIDDMs (HTG) had a preponderance of small dense LDL particles present in the plasma and reduced amounts of large buoyant species when compared to normotriglyceridaemic patients (NTG) and controls. Both groups of diabetics were more insulin resistant than the controls (P < 0.05) and had raised concentrations of proinsulin (P < 0.05), although insulin content did not differ significantly. 32-33 split proinsulin (SPI) was the major insulin-like molecule present in HTG and was present in significantly higher amounts in these patients (P < 0.05) than either NTG or control subjects and correlated significantly with the presence of small dense LDL particles. After a test meal, the postprandial chylomicron response was greater in HTG than either NTG diabetics or controls (P < 0.05). Chylomicron remnants were present to a greater extent in HTG than in NTG and controls (P < 0.05), although in this case NTG also contained more chylomicron remnants than control subjects (P < 0.05). There was no difference in the LPL activity, CETP and LCAT between diabetics and controls, whereas an increase in hepatic lipase activity was seen in the HTG diabetics (P < 0.05). Both CETP and LCAT activities increased postprandially. Multivariate analysis showed that TG, HDL content and HL activity were the most important determinants of small dense LDL concentration in the fasting state (R2 = 67%). Postprandially, chylomicron remnant clearance, HL and insulin resistance were the major determinants (R2 = 61%) of LDL-III.

Case-Control Studies↗