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Biomedical subjects

S C Lim

Publications and source records attributed to S C Lim.

At least 19 recordsLinked to original sources
PubMed2007

Apolipoprotein E genotype affects the response to lipid-lowering therapy in Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effect of apolipoprotein E (apoE) genotype on baseline lipid levels and the response to hydroxy-methyl glutaryl coenzyme A reductase inhibitors (statins) therapy in Chinese patients with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: We consecutively recruited Chinese patients with type 2 DM requiring lipid-lowering therapy according to current guidelines. Patients were started on either simvastatin 10 mg daily or given an equivalent dose of lovastatin 20 mg. After 12 weeks of statin therapy, patients had fasting lipid profiles repeated. ApoE genotyping was performed by restriction fragment length polymorphism (RFLP). RESULTS: Ninety-six patients were studied. The epsilon3/epsilon3 genotype was in 62.5%, epsilon2/epsilon3 and epsilon3/epsilon4, 16.7 and 20.8%, respectively. After adjusting for confounding variables, baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in those with epsilon3/epsilon4 compared with epsilon2/epsilon3 genotype (6.7 vs. 5.5 mm for TC, 4.5 vs. 3.6 mm for LDL-C; p = 0.015 and p = 0.025, respectively). With statin therapy, epsilon3/epsilon4 patients had significantly greater LDL-C lowering compared with epsilon2/epsilon3 patients (48 vs. 27.7%; p = 0.04). There was no gender difference in baseline lipid parameters or response to statin therapy. CONCLUSIONS: ApoE genotype accounts for interindividual variability of baseline cholesterol levels, and response to statin therapy in Chinese patients with type 2 DM.

Apolipoproteins E↗
PubMed2006

Niacin affects cell adhesion molecules and plasminogen activator inhibitor-1 in HepG2 cells.

BACKGROUND: Beyond lipid-modifying actions, niacin lowers the risk of atherothrombotic events by lowering prothrombotic factors like fibrinogen. Plasminogen activator inhibitor type 1 (PAI-1) is a potential factor for atherogenesis and thrombosis, increased in acute myocardial infarctions and restenosis after angioplasty. Cell adhesion molecules (CAM) mediate adhesion, recruitment and migration of white blood cells through vascular surfaces, an essential process in atherogenesis. ICAM-1 is a significant predictor of future coronary events. Whether niacin affects ICAM-1 expression is unknown. We studied the effects of niacin on PAI-1 and CAM using HepG2 cells. METHODS: HepG2 cells were cultured in DMEM until 90% confluent. After serum starvation, cells were exposed to DME/F12 containing niacin. Transforming growth factor-beta (TGF-beta) was added directly to cell media. Cell lysate and conditioned media were collected for measurement of PAI-1 by ELISA. For measurement of ICAM, cells were treated with tumor necrosis factor-alpha (TNF-alpha) instead. The effect of niacin on mRNA expression of ICAM-1 was studied using RT-PCR. RESULTS: Niacin reduced the TGF-beta-induced rise by 30% to 55% (p=0.002). The differences in degree of PAI-1 reduction, between different niacin concentrations, were not statistically significant. Niacin reduced TNF-alpha-induced rise in ICAM-1 levels by 66% to 89% (p<0.0001), but did not significantly affect TNF-alpha-induced rise in PECAM-1. Semiquantitative RT-PCR analysis showed that reduced TNF-alpha-induced rise in ICAM-1 mRNA expression significantly by 17% (p=0.001). CONCLUSIONS: Treatment with niacin suppressed PAI-1 and ICAM-1 levels in HepG2 cells. Further studies to understand the mechanistic pathways of this suppression, could further explain benefits of niacin in prevention of atherosclerotic disease, and offer therapeutic avenues against the rising burden of atherothrombotic disease.

Cell Adhesion Molecules↗
PubMed2006

Relationship between common functional polymorphisms of the p22phox gene (-930A > G and +242C > T) and nephropathy as a result of Type 2 diabetes in a Chinese population.

OBJECTIVE: Genetic determinants are important in diabetic nephropathy (DN). Oxidative stress has also emerged as an important pathogenic factor in DN and vascular NADH oxidase is a major source of reactive oxygen species (ROS). Previous small studies reported a strong but contradictory association between functional genetic variation of p22(phox), an important subcomponent of NADH oxidase, and DN. We investigated the association between two common functional single nucleotide polymorphisms (SNPs) (-930 A > G and +242 C > T) and DN in a much larger group of Chinese patients with Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Case-control study of Chinese subjects with long-standing T2DM (> 10 years). Cases (n = 306) were subjects with a spot urinary albumin : creatinine ratio (ACR) of > 113 mg/mmol or elevated serum creatinine. Control subjects (n = 306) had ACR < 3.3 mg/mmol and normal serum creatinine. Genotyping was carried out by standard PCR and restriction fragment length polymorphism analysis. RESULTS: Gender distribution, age, duration of diabetes and HbA(1c) were similar in cases and control subjects. Distribution of genotypes in the control subjects for both SNPs was consistent with the Hardy-Weinberg equilibrium. Distribution of genotypes did not differ significantly between cases and control subjects for both polymorphisms-+2424C > T: cases CC 84.6%, CT 15.0%, TT 0.4% and control subjects CC 87.6%, CT 11.8%, TT 0.6% (P = 0.45); -930 A > G: cases AA 40.5%, AG 41.8%, GG 17.7% and control subjects AA 38.2%, AG 49.0%, GG 12.8% (P = 0.12). Distribution of alleles was also similar-+2424 C > T: cases C 92.2%, T 7.8% and control subjects C 93.5%, T 6.5% (P = 0.66); -930 A > G cases A 61.4%, G 38.6% and control subjects A 62.7%, G 37.3% (P = 0.38). We estimated that our study has approximately 80% power to detect a relative risk of 1.65 (for +242 C > T) and 1.35 (for -930 A > G) conferred by the minor allele, respectively. CONCLUSIONS: In contrast with previous small studies, our data suggest that these SNPs do not confer significantly increased susceptibility to DN secondary to T2DM in Chinese subjects.

Aged↗
PubMed2006

Oxidative burden in prediabetic and diabetic individuals: evidence from plasma coenzyme Q(10).

AIM: Individuals with diabetes and prediabetes are at risk of vascular injury. However, the exact mechanisms are unclear. The mitochondria mobile electron carrier coenzyme Q(10) (CoQ(10)) is a potent lipophilic antioxidant. We hypothesize that oxidative stress, detectable as changes in plasma CoQ(10) concentrations and composition, plays an important role in vascular disease in diabetes. METHODS: We measured plasma CoQ(10) concentrations (including reduced ubiquinol and oxidized ubiquinone subfractions) in 60 subjects with normal glucose tolerance [NGT; fasting plasma glucose (FPG) < 5.5 mmol/l], 63 with impaired fasting glucose (IFG; FPG 5.6-6.9 mmol/l) and 69 with Type 2 diabetes (DM; FPG > 6.9 mmol/l). RESULTS: In men and women, the total CoQ(10)/total cholesterol ratio was reduced in DM (mean +/-sd) [male (M) 0.09 +/- 0.04; female (F) 0.07 +/- 0.04] compared with NGT (0.29 +/- 0.08; 0.21 +/- 0.07) and IFG (0.27 +/- 0.07; 0.23 +/- 0.07) (DM vs. NGT and IFG P = 0.001). A stepwise reduction in the plasma ubiquinol fraction (ubiquinol/total CoQ10) was observed from NGT (M 0.93 +/- 0.06; F 0.95 +/- 0.06) compared with IFG (0.43 +/- 0.25; 0.41 +/- 0.15) and DM (0.24 +/- 0.11; F 0.29 +/- 0.16) (DM vs. IFG vs. NGT P = 0.001). In contrast, the plasma ubiquinone/ubiquinol ratio increased from NGT (M 0.08 +/- 0.07, F 0.06 +/- 0.08) to IFG (2.14 +/- 1.84, 1.75 +/- 1.04) to DM (4.77 +/- 4.88, 3.81 +/- 3.71) (DM vs. IFG vs. NGT P = 0.001). These differences remained after adjusting for age, body mass index and FPG. CONCLUSIONS: The change in CoQ(10) with increasing FPG concentration suggests an increase in oxidative burden, already evident in the prediabetic IFG individuals. This increase in oxidative stress might contribute to the increased risk of vascular disease.

Adult↗
PubMed2006

Factors causing delay in discharge of elderly patients in an acute care hospital.

INTRODUCTION: Prolonged hospitalisation not only increases cost, it is also associated with other complications. Length of stay (LOS) is one of the indicators that reflect total cost of care during hospitalisation. So, it is of paramount importance to find out why elderly patients overstay in acute care hospitals and address these issues proactively. Since no local data is available, a study was planned to ascertain reasons why the discharging of elderly patients from hospital is delayed and whether these reasons are avoidable. MATERIALS AND METHODS: Long-stay patients were defined as those whose LOS had notably exceeded the average LOS for the Diagnosis Related Group (DRG), based on principal admitting diagnosis. A separate analysis showed that the specialty-specific long-stay marker for geriatric medicine was 28 days, so casenote review was done for all patients with LOS of more than 28 days who were discharged from geriatric medicine service of an acute care hospital during a 1-year study period. Information was collected on demographic profile, functional and cognitive status, past medical and social history, admitting medical diagnoses, discharge limiting and delaying factors. RESULTS: During the study period, 150 patients stayed over 28 days and 137 casenotes were available for review. The mean age of the patients was 84 years, 55.5% were female, 77.4% were Chinese, mean abbreviated mental test (AMT) score was 3 and mean modified Barthel's score was 11. The commonest primary diagnosis was sepsis followed by neurological problems, falls-related complication and cardiovascular diseases. The 2 most common discharge limiting factors (the final event which resulted in delay in discharge) were social issues (54, 39.4%) and sepsis (47, 34.3%). Of 47 patients with sepsis, 37 (78.7%) were nosocomial infection. Urinary tract infection and pneumonia were the 2 most common nosocomial infections. The 4 most common factors contributing to delayed discharge (various problems that surfaced throughout the hospital stay) were sepsis (94, 68.6%), deconditioning (65, 47.4%), social issues (52, 38.0%) and cardiovascular disorders (37, 27.0%). CONCLUSION: Elderly patients are more prone to hospitalisation-related complications like nosocomial infection and deconditioning leading to prolonged hospital stay. Early interventions can reduce these complications. Early identification of social issues and prompt discharge planning should be done to avoid delay in discharge.

Acute Disease↗
PubMed2006

Microalbuminuria prevalence study in hypertensive patients with type 2 diabetes mellitus in Singapore.

INTRODUCTION: Microalbuminuria is a marker of increased cardiovascular morbidity and mortality. It represents the earliest clinical evidence of diabetic nephropathy. Its early detection allows for implementation of individually-tailored cardiovascular risk reduction management programmes. Despite this, information on the prevalence of microalbuminuria in hypertensive patients with type 2 diabetes mellitus in Singapore is limited. METHODS: The Microalbuminuria Prevalence Study (MAPS) assessed the prevalence of macroalbuminuria and microalbuminuria in consecutively-screened hypertensive adult patients with type 2 diabetes mellitus in ten Asian countries. This paper presents the results of a sub-analysis of data from patients in Singapore. RESULTS: Singapore contributed seven percent of the overall enrolment into MAPS; a total of 499 patients were enrolled and 388 constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). Overall, the prevalence of diabetic kidney disease was high. In our study population, 23.5 percent of patients had macroalbuminuria (95 percent confidence interval [CI] 21.3-25.6), and 48.5 percent of patients had microalbuminuria (95 percent CI 45.9-51.0). Only 28.1 percent (95 percent CI 25.8-30.4) of patients were normoalbuminuric. Associated factors were poor glycaemic control and poor blood pressure control. CONCLUSION: The high prevalence (72 percent) of microalbuminuria and macroalbuminuria found in hypertensive patients with type 2 diabetes mellitus in Singapore is a cause for concern. These findings highlight the need to screen for microalbuminuria and better manage hypertensive patients with type 2 diabetes mellitus, if we are to avoid a major increase in end-stage renal disease.

Albuminuria↗
PubMed2005

CD24 and human carcinoma: tumor biological aspects.

CD24 is a mucin-like adhesion molecule that has recently raised attention and lent substantial improvements for our understanding of tumor biology. Functionally, CD24 enhances the metastatic potential of malignant-cells, because it has been identified as a ligand of P-selectin, an adhesion receptor on activated endothelial cells and platelets. Moreover, it has been described as a diagnostic molecular marker of malignant tumor and for patient prognosis. This article reviews the experimental and clinical data on CD24 expression and carcinomas from the point of view of tumor biology. Based on the research, CD24 expression will be analyzed as a potentially significant parameter for a wide variety of human cancer diagnoses. Understanding the functions and implications CD24 might aid the clinician in the selection of an appropriate therapy for individual patients: for example, the intravenous administration of C1324-specific antibodies to treat cancers.

Animals↗
PubMed2005

Expression of c-erbB receptors, MMPs and VEGF in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are characterized by a marked propensity for local invasion and cervical lymph node metastasis. The aim of this article was to review the expression of epidermal growth factor receptor (EGFR), c-erbB-2, vascular endothelial growth factor (VEGF) and matrix metal loproteinases (MMPs) in HNSCC patients and to study their possible correlation to various clinicopathologic parameters. Based on this review, the expression of EGFR, c-erbB-2, VEGF, or MMPs play important roles for tumor growth, invasion and metastasis in HNSCC. c-erbB receptors, MMPs and VEGF might aid the clinician in the selection of an appropriate therapy for individual patients and help to predict the prognosis of patients.

Carcinoma, Squamous Cell↗
PubMed2005

Refeeding oedema in anorexia nervosa.

Refeeding oedema in patients with anorexia nervosa is a known but yet under-reported and poorly-understood condition. We illustrate this condition in a 19-year-old girl with anorexia nervosa who developed bipedal oedema after she was started on nutritional therapy. It is important to be aware of the differential diagnoses of oedema in such cases, which includes heart failure and previous diuretic abuse. Refeeding oedema generally resolves spontaneously but some individuals may require treatment.

Adult↗
PubMed2005

Patients with low levels of high-density lipoprotein cholesterol: to treat or not to treat?

Clinical evidence indicates that a low level of high-density lipoprotein cholesterol (HDL-C) is a major risk of atherosclerosis. Raising HDL-C reduces this risk significantly, making HDL-C levels an important target of treatment for dyslipidaemia, especially in pre-existent atherosclerosis. HDL-C is protective against atherosclerosis, largely due to its function of reverse cholesterol transport. Additionally, some important roles include fibrinolysis, antioxidant functions, and reduction of platelet aggregability. A number of agents potentially modify HDL favourably. Niacin is the most potent HDL-C raising agent currently available in clinical practice, followed by fibrates. CETP inhibitors show greater HDL-C rising, but are still used in trial settings only. HDL mimetic agents are another group of agents that offer much promise. Clinical outcome data are awaited for these newer therapeutic agents.

Apoproteins↗
PubMed2002

Self-similar Gaussian processes for modeling anomalous diffusion.

We study some Gaussian models for anomalous diffusion, which include the time-rescaled Brownian motion, two types of fractional Brownian motion, and models associated with fractional Brownian motion based on the generalized Langevin equation. Gaussian processes associated with these models satisfy the anomalous diffusion relation which requires the mean-square displacement to vary with t(alpha), 0<alpha<2. However, these processes have different properties, thus indicating that the anomalous diffusion relation with a single parameter is insufficient to characterize the underlying mechanism. Although the two versions of fractional Brownian motion and time-rescaled Brownian motion all have the same probability distribution function, the Slepian theorem can be used to compare their first passage time distributions, which are different. Finally, in order to model anomalous diffusion with a variable exponent alpha(t) it is necessary to consider the multifractional extensions of these Gaussian processes.

Journal Article↗
PubMed2002

Gestational diabetes mellitus: a call for systematic tracing.

INTRODUCTION: Women with history of gestational diabetes mellitus (GDM) have up to 50% lifetime risk of developing frank diabetes mellitus (DM). They are an ideal group of patients to implement early interventional measures to halt the progression to diabetes. The success of any early intervention programme would depend largely on postpartum follow-up. We set out to study the response rate to postpartum oral glucose tolerance test (OGTT) and to profile the non-responders on 105 women who attended our Gestational Diabetes Joint Clinic (GDJC). MATERIALS AND METHODS: We divided these women into 3 groups according to their response to postpartum OGTT and compared their weights, glycaemic parameters and other clinical characteristics during gestation. Group A comprised non-responders or those who did not turn up for postpartum OGTT; group B comprised responders with a normal postpartum OGTT; and group C comprised responders with an abnormal postpartum OGTT defined as 2-hour plasma glucose equal or more than 7.8 mmol/L. RESULTS: The non-respondent rate to postpartum diabetes screening was 37.1%. The non-responders were found to be significantly heavier, with more severe hyperglycaemia during their pregnancy (in terms of glycosylated haemoglobin and results of antepartum OGTT) and had bigger babies compared to the responders with normal postpartum OGTT. Their features instead resembled those who had failed their postpartum OGTT. CONCLUSION: The group of non-responders was probably at similar risk of developing glucose intolerance postpartum as those who were tested abnormal. A more effective call and recall system and education programme is, therefore, needed to ensure postpartum attendance of all patients with GDM.

Adult↗
PubMed2001

Apoptosis and bcl-2 expression as predictors of survival in radiation-treated non-small-cell lung cancer.

OBJECTIVES: We assessed the role of apoptosis and the expression of bcl-2, p53, and c-myc oncoproteins in pretreatment histologic specimens as a predictor of response to radiation therapy and survival in non-small-cell lung cancer (NSCLC) patients. METHODS: Pretreatment biopsy specimens of 68 patients with NSCLC (62 squamous cell carcinoma, 6 adenocarcinoma) were stained with hematoxylin and eosin. From 5 high-powered fields, the apoptotic index (AI) was calculated as the ratio of apoptotic tumor cells to the total number of tumor cells. Bcl-2, p53, and c-myc oncoprotein expression was detected by immunohistochemical staining. RESULTS: Twenty-nine cases showed partial or complete remission, whereas 39 showed no response. AI ranged from 0.2 to 12.0% (mean +/- SD; 4.3 +/- 2.6%, median 4.0%). There was no difference in AI between responders (4.0 +/- 2.3) and nonresponders (4.5 +/- 2.8, p > 0.05). However, in the responders, AI was correlated with the degree of change in tumor volume (r = 0.41, p < 0.05). In an analysis of 53 subjects who survived more than 1 month after the completion of radiation therapy, the patients with a higher AI (n = 27, MST = 22.8 m) survived longer than those with a lower AI (n = 26, MST = 9.2, log-rank, p = 0.03). Patients expressing bcl-2 had poorer survival (n = 22, MST = 6.0 m) than patients without bcl-2 (n = 31, 22.8 m, p < 0.003). According to multivariate analysis, three variables, bcl-2 expression, AI, and response to radiation, were independent prognostic factors for survival. CONCLUSION: A low level of spontaneous apoptosis and expression of apoptosis blocking bcl-2 protein in pretreatment histology predict a poor prognosis for radiation-treated NSCLC patients.

Adenocarcinoma↗
PubMed2001

Modeling of locally self-similar processes using multifractional Brownian motion of Riemann-Liouville type.

Fractional Brownian motion (FBM) is widely used in the modeling of phenomena with power spectral density of power-law type. However, FBM has its limitation since it can only describe phenomena with monofractal structure or a uniform degree of irregularity characterized by the constant Holder exponent. For more realistic modeling, it is necessary to take into consideration the local variation of irregularity, with the Holder exponent allowed to vary with time (or space). One way to achieve such a generalization is to extend the standard FBM to multifractional Brownian motion (MBM) indexed by a Holder exponent that is a function of time. This paper proposes an alternative generalization to MBM based on the FBM defined by the Riemann-Liouville type of fractional integral. The local properties of the Riemann-Liouville MBM (RLMBM) are studied and they are found to be similar to that of the standard MBM. A numerical scheme to simulate the locally self-similar sample paths of the RLMBM for various types of time-varying Holder exponents is given. The local scaling exponents are estimated based on the local growth of the variance and the wavelet scalogram methods. Finally, an example of the possible applications of RLMBM in the modeling of multifractal time series is illustrated.

Journal Article↗
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

The relationship between microvessel count and the expression of vascular endothelial growth factor, p53, and K-ras in non-small cell lung cancer.

Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, and vascular endothelial growth factor (VEGF) in 61 surgically resected non-small cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significantly higher than that of tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200 field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras-positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ according to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF expression, leading to angiogenesis and ultimately lymph node metastasis. Correlations between variables in close approximation and the lack of prognostic significance of individual molecular alterations suggest that tumorigenesis and metastasis are multifactorial processes.

Adult↗