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Biomedical subjects

D Chua

Publications and source records attributed to D Chua.

At least 19 recordsLinked to original sources
PubMed2004

Potent antitumoral efficacy of a novel replicative adenovirus CNHK300 targeting telomerase-positive cancer cells.

PURPOSE: Telomerase reverse transcriptase (hTERT) is the key determinant of telomerase activity and plays a crucial role in cellular immortalization and oncogenesis. It will be a promising target for cancer gene therapy. We constructed a novel replicative adenovirus CNHK300 in which hTERT promoter with three extra E-boxes downstream of the promoter was introduced and used to regulate adenoviral E1a gene, and studied its properties of selective replication in cancer cells and antitumoral activity. METHODS: Luciferase assay was used to detect hTERT promoter activity. The selective replication of CNHK300 in cancer cells was investigated by E1a Western blot and green fluorescent protein (GFP) reporter gene assay. The antitumoral activity of CNHK300 and its toxicity were measured on animal models. RESULTS: Luciferase assay showed that introducing extra E-boxes downstream of hTERT promoter is beneficial to decreasing the promoter activity in normal cells without affecting its strong activity in cancer cells. Experiments in vitro and in vivo demonstrated that CNHK300 can selectively target to hTERT-positive cancer cells and replicate in them, resulting in oncolytic or antitumoral effect. CNHK300 is superior to ONYX-015 in terms of selective replication and oncolytic or antitumoral effect. The toxicity assay showed no signs of toxicity to liver cells even at the higher dosage of CNHK300 in vivo. CONCLUSION: The hTERT promoter-controlled, replication-competent adenovirus CNHK300 is a promising system for targeted cancer gene therapy.

Adenoviridae↗
PubMed2003

Open reduction and internal fixation of fractures of the acetabulum--local experience.

INTRODUCTION: It is now widely accepted that open reduction and internal fixation of displaced acetabular fractures should be the standard of care. This paper reports a case series of acetabular fracture fixation performed at the Changi General Hospital by a single trauma surgeon. PATIENTS AND METHODS: A retrospective study was conducted of 15 consecutive cases of displaced acetabular fracture fixation between February 1996 and September 1999. Outcome was assessed radiologically and functionally with the use of a hip scoring system used by Matta. RESULTS: The patients' age had a mean of 34.9 years. All fractures were a result of high energy trauma. The median duration to operation upon admission was eight days. The mean hospital stay was 24.9 days and the mean medical hospitalisation leave was 159 days. Bony union was achieved in all patients. Two patients (13.3%) had a residual displacement of 1 mm. Four patients (26.6%) had a residual displacement of 2 mm. Of these four patients with 2 mm displacement, two eventually developed osteoarthritis. Subsequently, one of the two with OA required revision to a total hip arthroplasty two years post fracture. Other complications include 1 (6%) wound infection and 2 (13%) deep vein thrombosis. There were no complications of heterotopic ossification or sciatic nerve injury. Functional scores with a minimum follow up of one year and a mean of 22.6 months follow-up were excellent in 13.3%, good in 66.7%, fair in 13.3% and poor in 6.7%. CONCLUSION: The number of cases in this paper is insufficient to produce any statisticallly significant outcome predictors but accuracy of reduction is an important factor. A good to excellent result was attained in 80% of the patients which confirms that open reduction and internal fixation is the treatment of choice for displaced and acetabular fractures.

Acetabulum↗
PubMed2001

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma.

Tumor cells from NPC patients are regularly and latently infected with EBV. To examine whether the virus serves as target for immune intervention of the cancer, we determined levels of EBV-specific CTLp in peripheral blood from NPC patients, long-term survivors of the cancer and healthy subjects. CTLp levels of test subjects varied between 3- 3,000/10(6) PBMCs. The plasma EBV burden increased when the CTLp level fell below 150, whereas the EBV burden of PBMCs was not correlated with CTLp level. Compared with healthy carriers, CTLp levels of patients were lower and varied over a wider range, between 3-1,500/10(6) PBMCs. The quantitative immune deficit was probably attributed to the tumor because, first, CTLp in survivors was restored to levels similar to those in healthy carriers after the tumor had been successfully treated. Second, the CTLp level changed as disease progressed, being lower in local disease, increased in locoregional disease and decreased again when the tumor metastasized. Based on these findings, 4 patients with advanced disease were infused with 5 x 10(7)-3 x 10(8) autologous EBV CTLs. The treatment was safe and unaccompanied by inflammatory or other complications, but whether it improved tumor control could not be discerned from the large tumor bulk. Nevertheless, the treatment regularly increased CTLp levels of patients, maintained it at higher levels for protracted periods and, in 3 patients, restored host surveillance of EBV replication, reducing the plasma EBV burden. Taken together, these results provided a rationale to further explore EBV as a target of immune intervention of NPC.

Adoptive Transfer↗
PubMed2001

Anti-tumor effects of human peripheral gammadelta T cells in a mouse tumor model.

Peripheral gammadelta T cells derived from healthy donors were found to exhibit cytotoxicity against a variety of tumor cell lines in vitro, including CNE2, which was established from nasopharyngeal carcinoma (NPC). The anti-tumor effects were further studied in a mouse model. Control nude mice inoculated s.c. with 5 x 10(6) CNE2 cells regularly developed hypodermal tumors, which progressively increased in size, and animals had a mean survival of 35 +/- 3.4 days. Tumor growth was arrested and tumor size was reduced after animals were infused with 5 x 10(7) gammadelta T cells derived from a healthy donor. The anti-tumor effects were temporary, however, and tumor growth was resumed after about 1 week in a group of the animals that had been given a single dose of gammadelta T cells. In another group of animals given 2 doses of gammadelta cells 1 week apart, resumption of tumor growth was delayed for a further week. Mean survival of the 2 groups was increased to 61 +/- 15.7 and 74 +/- 12.9 days, respectively. Immunohistology revealed an accumulation of infused cells in tumors attended by focal tumor necrosis in specimens taken 2 days after infusion. Infiltrative cells virtually disappeared from tumor tissues 6 days after infusion, accompanied by increased mitotic indices of tumor cells. These temporal relationships suggested that the accumulation of infused gammadelta T cells in hypodermal tumors was responsible for the observed anti-tumor effects.

Animals↗
PubMed2001

Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.

Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log(10) reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P <.05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients.

Administration, Oral↗
PubMed1998

Self-expandable metal stents for malignant gastric outlet obstruction: a modified technique.

BACKGROUND AND STUDY AIMS: Endoscopic palliative treatment may be effective in the management of malignant gastric outlet obstruction. However, experience in this area is limited, and the techniques vary widely. In this retrospective study, a uniform technique using nearly identical self-expandable metal stents was employed to assess technical feasibility, safety, and outcome. PATIENTS AND METHODS: Eight patients presenting with clinical findings of gastric outlet obstruction confirmed by upper gastrointestinal radiography underwent endoscopic placement of expandable metal stents. All patients had primary or metastatic malignancy involving the pylorus or duodenum. Endoscopic and Gastrografin-enhanced upper gastrointestinal radiographic evaluations were carried out immediately after stent placement. Complications and clinical outcomes were assessed in each patient. RESULTS: Five patients had extrinsic compression of the descending duodenum due to pancreatic cancer, two had pyloric stenosis from metastatic cancer, and one patient had primary duodenal cancer. Stent placement was successful in all patients, and was followed by clinical improvement. There was one death within 30 days, related to pneumonia. CONCLUSION: Endoscopic self-expandable stent placement appears to be a reasonable therapeutic alternative in patients with malignant gastric outlet obstruction.

Aged↗
PubMed1998

Predictors of early failure of fixation in the treatment of displaced subcapital hip fractures.

OBJECTIVE: To examine predictors of fixation failure in the treatment of displaced subcapital hip fractures. DESIGN: Retrospective study. METHODS: All patients aged sixty-five years and older discharged from a large teaching hospital after treatment for displaced subcapital fracture between April 1, 1989 and February 29, 1995 were identified (n = 344). Of these, 108 patients treated with internal fixation became the study group. Clinical information included demographics, implant, comorbidity, complications, mortality, surgeon' s assessment of reduction, and need for revision. Preoperative x-ray information: Garden grade, Singh Index, Pauwel's angle, medial neck and femoral shaft cortex width, and displacement of fracture fragments. Postoperative: Quality of reduction, a visible gap or step, evidence of union, fracture collapse, and failure. RESULTS: The failure rate was 31 percent. The two most important predictors were varus reduction and perceived difficulty in achieving reduction. If the patient had a varus reduction or the surgeon had difficulty achieving a satisfactory reduction, fixation was 4.3 times more likely to fail (p = 0.007). If the patient had a varus reduction and reduction was difficult, fixation was 13.6 times more likely to fail (p = 0.04). Under this latter scenario, 75 percent of the fixations failed. CONCLUSION: In a fracture of the neck of the femur, if difficulty is encountered in obtaining a closed reduction or there is residual varus angulation, the chance of subsequent fixation failure is high. Hemiarthroplasty may be considered in these cases.

Aged↗
PubMed1998

The economics of breastfeeding in Singapore.

A study of 340 mothers was conducted in Kandang Kerbau Hospital on September 1992 to determine if it were more economical for households to breastfeed or bottle-feed an infant for the first three months. Two economic models, a low cost model and a high cost model, were adopted incorporating a mathematical expression from Almroth's work in 1979. The savings in a mother's gross income for the period ranged from 3% to 9% for the low cost model and from 8% to 21% for the high cost model. From the household perspective, two components contributed to the economic savings of breastfeeding over artificial feeding: the cost of goods consumed and the time taken to feed the baby. It was noted that the time taken to artificially feed is longer than the time taken to breastfeed an infant. The results of this study provided more concrete basis for policy makers and advocates of breastfeeding to promote breastfeeding in Singapore. The amount of savings from breastfeeding could be considered for the health care system from the public perspective.

Breast Feeding↗
PubMed1997

Temporal trends and geographic variations in surgical treatment of femoral neck fractures.

BACKGROUND: The objectives of this study were to examine temporal trends in treatment of femoral neck fractures, factors associated with treatment, and variations in practice patterns among counties and hospitals in Ontario, Canada. METHODS: Hospital discharge data were analyzed. Cases were defined as age > 50 years with a surgically treated femoral neck fracture between 1981 and 1992 (n = 29,391). RESULTS: The age-adjusted and sex-adjusted proportion of patients treated with hemiarthroplasty (HA) increased from 45% in 1981 to 61% in 1992 (p < 0.0001). HA is more likely to be performed among women, older patients, and nursing home patients. Among counties there was a 38-fold variation for total hip arthroplasty (0.5-38%) and a 9-fold variation in use of HA (9-83%). The degree of variation in treatment was mainly the result of individual hospitals. CONCLUSION: The wide regional variations in treatment of femoral neck fractures reflect a lack of consensus in Ontario.

Age Factors↗
PubMed1997

An orthopedic surgeon survey on the treatment of displaced femoral neck fracture: opposing views.

OBJECTIVE: To examine the reasons for practice variation in the treatment of displaced femoral neck fractures. DESIGN: A survey, asking surgeons to choose either hemiarthroplasty or internal fixation for 2 different female patients with a displaced femoral neck fracture. SETTING: The Canadian Orthopaedic Association Meeting, Halifax, May 1995. PATIENTS: The scenario in the first patient was of an independent 70-year-old woman with no pre-existing medical conditions. The scenario in the second patient was of a housebound 84-year-old woman with co-morbidity. MAIN OUTCOME MEASURES: Proportion of surgeons choosing either hemiarthroplasty or internal fixation for each case scenario. Distribution of reasons to explain the treatment decision. RESULTS: Ninety-nine surgeons responded. For the case of the 70-year-old woman, 47% chose hemiarthroplasty and 53% chose internal fixation (p = 0.60), and for the 84-year-old woman, 96% chose hemiarthroplasty. These findings were consistent within the subgroups of teaching surgeons and community practice surgeons. Surgeons with 10 years or less of practice tended to favour hemiarthroplasty whereas those with more than 15 years' practice favoured internal fixation. Important reasons for treatment choice were avoidance of reoperation in the hemiarthroplasty group (85%) and better hip function in the fixation group (83%), durability (83%) and ease of revision (77%). CONCLUSION: The surgeon's interpretation of the importance of reoperation and function underlies the differences in treatment decision regarding the management of femoral neck fractures in elderly patients.

Aged↗
PubMed1996

The detection of clinically occult nasopharyngeal carcinoma in patients following radiotherapy--an analysis of 69 patients.

A prospective analysis of 69 patients who had been treated for nasopharyngeal carcinoma (NPC) by external radiotherapy was carried out. Biopsies from the posterior nasopharynx were performed and analyzed by in situ hybridization using an antisense Epstein-Barr Early RNA (EBER) radio-labelled riboprobe. None of the patients had evidence of disease in the nasopharynx. One patient was found to have nasopharyngeal carcinoma detected only by in situ hybridization. In the subsequent 18-month follow-up of these clinically- and biopsy-negative patients, only one patient developed relapse in the nasopharynx. In situ hybridization is a valuable tool for the detection of NPC and should be routinely available in histopathology laboratories where NPC is regularly diagnosed.

Antisense Elements (Genetics)↗
PubMed1993

The effect of methylprednisolone on porcine bone morphogenetic protein in fracture healing. An experimental allograft model in rabbits.

Four different experiments were performed to study the effect of methylprednisolone on porcine bone morphogenetic protein (pBMP) in an allograft in adult rabbits. In each animal, a 2-cm segment of radius was excised and replaced with frozen allograft. Fifteen milligrams pBMP was applied over the graft-host junction in Groups I and III, and 30 mg pBMP was applied in Groups II and IV. In Groups III and IV, methylprednisolone was given intramuscularly for three weeks. Incorporation was assessed by roentgenography, analysis of the area of callus formation and histologic and biomechanical analysis at four and eight weeks. Methylprednisolone inhibited pBMP-induced bone formation and incorporation of frozen cortical bone allograft.

Animals↗
PubMed1987

Changing incidence of adenocarcinoma of the lung: a brief review.

The autopsy of lung cancer at Hines Veterans Administration Hospital was reviewed for a 27-year period, between 1957 and 1983. There has been a changing histologic pattern with a recent increase in adenocarcinoma and a relative decrease of the other cell types. This observation, based on a virtually all-male patient population, is partly attributed to better and improved diagnostic procedures.

Adenocarcinoma↗
PubMed1986

Estradiol binding capacity of breast cancer cell line in correlation with cell cycle.

The specific estrogen binding capacity of the MCF-7 cells has been studied throughout the cell cycle. Two days after plating 1-4 X 10(5) cells per well, we observed that cell number, protein concentration and DNA level began to rise but the estrogen binding capacity was lowered. At logarithmic phase the binding increased gradually then sharply to just before confluency. When the cells reached the quiescent phase the estrogen binding capacity fell rapidly. Since estrogen binding capacity of the intact MCF-7 cells varies with different phases in the cell cycle as well as the incubation temperature and time and the plating density, all these factors should be taken into consideration when this cell line is used for hormone studies.

Breast↗
PubMed1986

Quality control of estrogen and progesterone receptor assays.

The intra-laboratory QC materials for estrogen and progesterone receptor assays were prepared using different methods. The most convenient and economical method was found to be the use of lyophilized rat uterine cytosol. The level of receptors remained stable for 12 months when stored at -70 degrees C with the inclusion of 10 mM phenylmethyl sulfonyl-fluoride in the cytosol extraction buffer. For inter-laboratory comparison, we received QC materials from Dr E D Ryan (McMaster University, Canada) monthly and our results fell within +/- 1SD of the mean value of 15 centres from North America and Europe participating in this program.

Animals↗
PubMed1980

The evaluation of tumour marker proteins in the diagnosis of primary hepatocellular carcinoma.

The sera of 122 patients with biopsy confirmed primary hepatocellular carcinoma (PHC) were examined for the presence of alphafoetoprotein (AFP), alpha 1antitrypsin 1 (AAT), alpha 1acidglycoprotein (AGP) 1, gammaglutamyl transpeptidase (GGT), carcinoemryonic antigen (Roche) (CEA) and the "Hepatoma-Liver antigen" H-L Ag). 83% of patients had elevation of AFP of more than 18 ng/ml 7.4% and 15.5% had levels between 19--100 ng/ml and 100-500 ng/ml respectively. Raised AAT, AGP, GGT, CEA and HL Ag were found in many patients with PHC. Grossly elevated AFP were usually diagnostic of PHC. The combination of AAT, AGP, CEA and HL Ag were useful in the diagnosis of AFP negative cases.

Antigens, Neoplasm↗