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Biomedical subjects

Seng-Gee Lim

Publications and source records attributed to Seng-Gee Lim.

11 recordsLinked to original sources
PubMed2006

Impact of new legislation on presumed consent on organ donation on liver transplant in Singapore: a preliminary analysis.

Demand for the liver organ for transplantation vastly exceeded the availability of deceased donor organs. A new law, the revised Human Organ Transplant Act (HOTA), was implemented in Singapore in July 2004, which allowed for recovering four organs, including liver, for transplant unless the deceased give objection prior to their demise. We set to study the impact of the revised legislation by comparing the number of potential suitable donors, liver recovery surgery, and liver transplants two years before and one year after the implementation. There was no change in the number of suitable donors, but there was an increase in the number of liver recovery surgeries and liver transplantation, and a lower refusal rate among suitable donors. Although the revised legislation helped improve the availability of deceased donor organs moderately, other nonlegislative, supplementary measures are needed to further improve the low organ donation rate.

Female↗
PubMed2006

Lack of somatic mutations in EGFR tyrosine kinase domain in hepatocellular and nasopharyngeal carcinoma.

Activating EGFR somatic mutations have been shown to predict treatment response to small molecules targeting the EGFR intracellular tyrosine kinase domain. Recent work on cell-lines and animal models had demonstrated an inhibitory effect of EGFR tyrosine kinase inhibitors in hepatocellular and nasopharyngeal carcinoma, and clinical trials in these tumour types are ongoing. There are few data on the presence or prevalence of EGFR mutations in hepatocellular and nasopharyngeal carcinomas. We studied exons 18-21 of the EGFR gene from 100 hepatocellular and 102 nasopharyngeal carcinomas, and found no exonic mutations of potential significance. Alternative mechanisms may be important for the observed activity of small molecule EGFR tyrosine kinase inhibitors in hepatocellular and nasopharyngeal carcinomas.

Carcinoma, Hepatocellular↗
PubMed2006

Pharmacokinetics of telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis B virus infection: pharmacodynamic implications.

The pharmacokinetics of telbivudine were evaluated in adult patients with chronic hepatitis B virus (HBV) infection following once-daily oral administration at escalating doses of 25, 50, 100, 200, 400, and 800 mg/day for 4 weeks. Telbivudine was rapidly absorbed after oral administration, with the median times T(max) to the maximum plasma concentration (C(max)) ranging from 0.8 to 3.0 h postdosing across cohorts. Single-dose and steady-state maximum C(max)s and the areas under the plasma concentration-time curve from time zero to time t (AUC(0-t)s) increased proportionally with dose. At steady-state, the values of C(max) and AUC(0-t) were higher than those obtained after the administration of a single dose, indicative of a slight accumulation, with the ratios of the steady-state value to the value after the administration of a single dose ranging from 1.14 to 1.49 for C(max) and from 1.40 to 1.70 for AUC(0-t). While the elimination of telbivudine from plasma was apparently monophasic over the 8-h sampling period, the substantial steady-state trough plasma levels observed in the groups receiving doses of 100 to 800 mg were clearly indicative of the presence of a second slower elimination phase, with the mean estimated half-lives ranging from 29.5 to 41.3 h by compartmental modeling analysis. Pharmacokinetic and pharmacodynamic analyses by using maximum-effect modeling established a quantitative relationship between a reduction in serum HBV DNA levels and parameters of drug exposure, in particular, the steady-state C(max) and AUC(0-t). In summary, this study showed that telbivudine exhibits dose-proportional plasma pharmacokinetics with sustained steady-state drug exposure and exposure-related antiviral activity, supporting the need for further clinical studies by use of a once-daily regimen in patients with chronic HBV infection.

Administration, Oral↗
PubMed2005

Validation of four Helicobacter pylori rapid blood tests in a multi-ethnic Asian population.

AIM: To validate the accuracy of four rapid blood tests in the diagnosis of Helicobacter pylori. METHODS: Consecutive dyspeptic patients scheduled for endoscopy at the National University Hospital, Singapore, were interviewed and had blood drawn for serology. The first 109 patients were tested with BM-test (BM), Pyloriset Screen (PS) and QuickVue (QV), and the next 99 subjects were tested with PS and Unigold (UG). Endoscopies were performed blinded to rapid blood test results and biopsies were taken for culture and rapid urease test. Urea breath tests were performed after endoscopies. The rapid blood test results were compared with four reference tests (rapid urease test, culture, serology, and breath test). RESULTS: The study population composed of 208 patients (mean age 43.1 years; range 18-73 years; 119 males; 174 Chinese). The number of evaluable patients for BM, QV, UG and PS were 102, 102, 95, and 197, respectively. The sensitivity and specificity, respectively were: PS 80.2%, 95.8%; UG 55.9%, 100%; QV 43.3%, 100%; BM 67.2%, 97.1%. CONCLUSION: The rapid blood test kits showed high specificity and positive predictive value (97-100%), while sensitivity and negative predictive value ranged widely (43%-80% and 47%-73%, respectively). Among test kits, PS showed the best sensitivity (80%), best negative predictive value (73%) and best negative likelihood ratio (0.207). PS had a specificity of 96%, positive predictive value of 97% and positive likelihood ratio of 19.1.

Adolescent↗
PubMed2005

Misperceptions among patients with chronic hepatitis B in Singapore.

AIM: To identify the misperceptions among CHB patients, as well as to determine the factors associated with better knowledge. METHODS: A telephone interview was conducted on 192 adult CHB patients, who earlier responded to an advertisement for free screening. The questionnaire included items about socio-demographic factors and a 14-item quiz on knowledge of general aspects, transmission, and management of HBV infection. RESULTS: The mean knowledge score on HBV was 10.4/14. Common misperceptions included availability of treatment for HBV infection and early liver cancer, as well as on transmission. Having completed tertiary education was the only independent factor associated with a high knowledge score, after controlling other demographic factors. CONCLUSION: More educational efforts should be focused on patients' misperceptions and target the less educated HBV carriers.

Adult↗
PubMed2005

Outcome of lamivudine-resistant hepatitis B virus is generally benign except in cirrhotics.

AIM: We set to determine factors that determine clinical severity after the development of resistance. METHODS: Thirty-five Asian patients with genotypic lamivudine resistance were analyzed in three groups: 13/35 (37%) were non-cirrhotics with normal pre-treatment ALT (Group IA), 12/35 (34%) were non-cirrhotics with elevated pre-treatment ALT (Group IB), and 10/35 (29%) were cirrhotics (Group II). Patients were followed for a median of 98 wk (range 26-220) after the emergence of genotypic resistance. RESULTS: Group IA patients tended to retain normal ALT. Group IB patients showed initial improvement of ALT with lamivudine but 9/12 patients (75%) developed abnormal ALT subsequently. On follow-up however, this persisted in only 33%. Group II patients also showed improvement while on treatment, but they deteriorated with the emergence of resistance with 30% death from decompensated liver disease. Pretreatment ALT levels and CPT score (in the cirrhotic group) were predictive of clinical resistance and correlated with peak ALT levels and CPT score. CONCLUSION: The phenotype of lamivudine-resistant HBV correlated with the pretreatment phenotype. The clinical course was generally benign in non-cirrhotics. However, cirrhotics had a high risk of progression and death (30%) with the development of lamivudine resistance.

Adult↗
PubMed2005

Outcome from molecular adsorbent recycling system (MARS) liver dialysis following drug-induced liver failure.

RATIONALE: Fulminant liver failure from drug ingestion is associated with a high mortality, and the introduction of liver transplantation has improved the mortality significantly if done in a timely fashion. Recently, molecular adsorbent recycling system (MARS) liver dialysis has been introduced as a support for liver failure with varying results. We review our experience with drug-induced liver failure and the impact of MARS liver dialysis on the outcome, in a setting where cadaveric liver transplantation is rarely available. RESULTS: A total of 13 patients were treated, and 40 sessions of MARS liver dialysis were conducted in the intensive care unit. The majority of cases were because of herbal medicine toxicity. Total bilirubin, conjugated bilirubin, and delta bilirubin were significantly reduced, with no change in unconjugated bilirubin. All patients satisfied the criteria for urgent liver transplantation with an average Model End Stage Liver Disease (MELD) score of 35. Only one patient received a liver transplantation from a live donor (right lobe). Overall mortality was 85%. Median time-to-death from the start of MARS was 8 days. CONCLUSIONS: MARS liver dialysis in a setting without timely liver transplantation is associated with a poor outcome. It does, however, provide a window of time for consideration of living donors in the setting of limited cadaveric donors.

Adult↗
PubMed2004

Four years of lamivudine treatment in Chinese patients with chronic hepatitis B.

BACKGROUND AND AIMS: This study assessed the efficacy and safety of up to 4 years of lamivudine treatment and the clinical relevance of the emergence of YMDD-variant hepatitis B virus (HBV). METHODS: Fifty-eight Chinese adult patients with chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5 years and were monitored for YMDD-variant HBV, hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine aminotransferase (ALT) concentrations. Four-year data are reported here. RESULTS: The rate of HBeAg seroconversion increased with extended therapy and also with higher baseline ALT concentrations. YMDD-variant HBV was detected in 67% (39/58) of patients at some point during treatment. After 4 years, a total of 47% (27/58) of patients achieved HBeAg seroconversion. Thirty-three per cent (13/39) of patients with YMDD-variant HBV achieved HBeAg seroconversion; this increased to 57% (8/14) in patients with moderately elevated (>2-5 x upper limit of normal) pre-treatment ALT concentrations. The proportion of patients that achieved normal serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years of treatment. That included 68% (23/34) of patients with YMDD-variant HBV and 73% (8/11) of those without the variant. All patients receiving lamivudine had reduced serum concentrations of HBV-DNA compared with baseline, despite the emergence of YMDD-variant HBV in 39 patients. Lamivudine was generally well tolerated; there was little change in the number or type of drug-related adverse events in the fourth year of the study. CONCLUSIONS: Despite the emergence of YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine.

Adolescent↗
PubMed2003

An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1.

In this study, we used HIV-1 as a model to demonstrate a novel approach for receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120 antibody was engineered with endocytotic and transmembrane motifs from either the cation-independent mannose 6-phosphate receptor or the low-density lipoprotein receptor. Flow cytometry and immunofluorescence studies showed that the chimeric antibodies were expressed on the cell surface and can undergo rapid internalization. Furthermore, one of the chimeric antibodies was able to bind and internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that internalized viruses could undergo replication. Therefore, we have demonstrated a proof-of-principle of a novel method that can be used to internalize virus into cells, without prior knowledge of the cellular receptor for the virus. We propose that this approach would be particularly useful for studying viruses whose cellular receptor(s) is not known.

Amino Acid Sequence↗
PubMed2002

Predicting the decrease of conjugated bilirubin with extracorporeal albumin dialysis MARS using the predialysis molar ratio of conjugated bilirubin to albumin.

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system (MARS) machine is a new supportive intervention for patients with liver failure. It removes bilirubin and other albumin-bound toxins from the patient and has been shown by preliminary studies of liver failure patients to be beneficial. Our study examines the ability of predialysis molar ratio of bilirubin to albumin to predict the decrease of bilirubin by MARS. We had 5 patients and results from 29 treatments. The results showed a significant correlation between the predialysis molar ratio of bilirubin (total and conjugated) to albumin to the reduction in bilirubin (total and conjugated): R(2) = 0.27 and 0.62 respectively, P <.005 for both. There was no significant correlation with the predialysis molar ratio of unconjugated bilirubin to albumin to the reduction in unconjugated bilirubin. The ratio of change in total bilirubin (micromol/L) to the predialysis molar ratio of total bilirubin to albumin and the ratio of change in conjugated bilirubin (micromol/L) to the predialysis molar ratio of conjugated bilirubin to albumin were 6.2 (+/- 4.2) and 10.8 (+/- 4.3), respectively (mean (+/- SD)). The results enable us to predict the likely reduction in bilirubin (especially conjugated) after each MARS treatment and also suggest to us that albumin infusion before MARS treatment may reduce the efficacy of bilirubin removal. Whether this ratio applies to other albumin-bound toxins remains open for investigation.

Bilirubin↗