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Biomedical subjects

S K Tay

Publications and source records attributed to S K Tay.

At least 19 recordsLinked to original sources
PubMed2006

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro.

Ovarian cancer is currently the second leading cause of gynecological malignancy and cisplatin or cisplatin-based regimens have been the standard of care for the treatment of advance epithelial ovarian cancers. However, the efficacy of cisplatin treatment is often limited by the development of drug resistance either through the inhibition of apoptotic genes or activation of antiapoptotic genes. We have previously reported the overexpression of human UO-44 (HuUO-44) in ovarian cancers and the HuUO-44 antisera markedly inhibited NIH-OVCAR3 ovarian cancer cell attachment and proliferation (Oncogene 23: 5707-5718, 2004). In the present study, we observed through the cancer cell line profiling array that the expression of HuUO-44 was suppressed in the ovarian cancer cell line (SKOV-3) after treatment with several chemotherapeutic drugs. Similarly, this suppression in HuUO-44 expression was also correlated to the cisplatin sensitivity in two other ovarian cancer cell lines NIH-OVCAR3 and OV-90 in a dose-dependent manner. To elucidate the function of HuUO-44 in cisplatin chemoresistance in ovarian cancer cell, small interfering RNAs (siRNAs) were employed to mediate HuUO-44 silencing in ovarian cancer cell line, NIH-OVCAR3. HuUO-44 RNA interference (RNAi) resulted in the inhibition of cell growth and proliferation. Importantly, HuUO-44 RNAi significantly increased sensitivity of NIH-OVCAR3 to cytotoxic stress induced by cisplatin (P<0.01). Strikingly, we have also demonstrated that overexpression of HuUO-44 significantly conferred cisplatin resistance in NIH-OVCAR3 cells (P<0.05). Taken together, UO-44 is involved in conferring cisplatin resistance; the described HuUO-44-specific siRNA oligonucleotides that can potently silence HuUO-44 gene expression may prove to be valuable pretreatment targets for antitumor therapy or other pathological conditions that involves aberrant HuUO-44 expression.

Base Sequence↗
PubMed2006

First-line gemcitabine and carboplatin in advanced ovarian carcinoma: a phase II study.

OBJECTIVES: To evaluate tumour response rate and toxicities of gemcitabine and carboplatin in chemonaive subjects with advanced epithelial ovarian cancer. DESIGN: A phase II study. SETTING: Gynaecologic oncologic unit. POPULATION: Twenty chemonaive International Federation of Gynecology and Obstetrics (FIGO) stage IIIc and stage IV subjects with ovarian cancer. MAIN OUTCOME MEASURES: Tumour response, disease free and overall survival and toxicity. METHODS: Intravenous gemcitabine 1000 mg/m2 on day 1 and day 8 and carboplatin at area under centre (AUC) = 5 on day 1 were administered three weekly for six cycles. Subjects who received more than three cycles of chemotherapy were eligible for assessment of tumour response, while all the cycles of chemotherapy were assessed for toxicities. RESULTS: The mean age of the subjects was 57.3 years, and the median follow up was 38.7 months. Of the 18 eligible subjects analysed, 11 (61.1%) showed a complete clinical response, and the overall response rate was 83.3% (15/18). The median overall survival was 29.2 [95% (confidence interval) CI 22.8-35.6] months, and the median progression-free survival was 11.6 (95% CI 4.7-18.5) months. WHO grade 3 anaemia, neutropenia and thrombocytopenia was 7.6, 9.5 and 0%, respectively, on day 8, and 15.5, 12.2 and 15.5%, respectively, on day 15. Two subjects required a total of three hospital admissions for neutropenic sepsis, and two required five hospital admissions for platelet transfusion for severe thrombocytopenia. CONCLUSION: Chemonaive advanced ovarian cancer showed a high response rate to combined gemcitabine and carboplatin chemotherapy. The subjects developed moderate adverse reactions. Phase III study to evaluate the role of combined gemcitabine and carboplatin as first-line chemotherapy in ovarian cancer is warranted.

Anemia↗
PubMed2003

Sperm segregation patterns by fluorescence in situ hybridization studies of a 46,XY,t(2;6) heterozygote giving rise to a rare triploid product of conception with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype.

A blighted ovum diagnosed initially by ultrasound was determined to be a partial hydatidiform mole with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype by cytogenetic analysis. The triploid state arose through dispermy in which both spermatozoa carried rearranged chromosomes, one carrying a balanced translocation through alternate segregation and the other an unbalanced derivative chromosome 6 through adjacent 1 segregation. Segregation analysis of 7,000 spermatozoa from the father was performed with a three-color fluorescence in situ hybridization (FISH) protocol using alpha-satellite 6, telomeric 2p, and telomeric 6q probes. Segregation frequencies of normal and balanced products (alternate segregation), adjacent 1, adjacent 2, and 3:1 were 49.9%, 42.4%, 2.5%, and 4.2%, respectively. The high percentage of alternate segregation is consistent with the knowledge of their preferential outcome. However, the high incidence of adjacent 1 sperm highlights the abnormality risk. Alternate and adjacent 1 segregations (92.3%) accounted for the observed rearranged chromosomes in the triploid. The most viable imbalanced combination would be the one carrying the der(6) chromosome, but since the unbalanced segment comprises 3.6% of the haploid autosomal length (HAL), no risk of a viable imbalanced offspring is indicated. However, an increased likelihood of recurrent miscarriages is likely, and this is confirmed by the couple's two earlier miscarriages. Sperm segregation patterns of translocation carriers determined by FISH can help in ascertaining expected and unexpected karyotypes. The high frequency of adjacent 1 products shows that the presence of the additional derivative chromosome in the partial mole, though rare in occurrence, should be less surprising.

Aneuploidy↗
PubMed2003

Metastatic carcinoma of the cervix presenting as a psoas abscess in an HIV-negative woman.

A case of advanced carcinoma of the cervix presenting as a psoas abscess is described. This unusual presentation has been reported in association with AIDS but is extremely rare in HIV-negative women. This case report emphasises the importance of awareness of unusual causes of the psoas abscess in an era when the classical tuberculous abscess is fast disappearing.

Adult↗
PubMed2002

Identification and characterization of genes involved in the carcinogenesis of human squamous cell cervical carcinoma.

We utilized RT-PCR differential display and cDNA microarrays to identify cellular genes involved in the multi-step carcinogenesis of squamous cell cervical carcinoma. Thirty-eight cervical cancer patients in various stages of the disease and 5 non-cervical cancer patients were studied. Twenty-five cDNA clones were identified and these were subsequently demonstrated to be consistently over-expressed in squamous cell cervical carcinoma biopsies of various FIGO stages. To further evaluate the possible role that these genes may play in the progression of disease, we performed Northern blot analysis and RNA-RNA in situ hybridization studies using cervical cancer biopsies of various FIGO stages. Of particular interest are the 2 clones G32C4B and G30CC that have been identified to be the NADH dehydrogenase 4 gene and the gene that encodes ribosomal protein S12 respectively when compared to sequences available in the GenBank database. Increased expression of these 2 genes were detected in the matched normal tissues collected together with the late FIGO stages of cervical cancer biopsies. In comparison, upregulation of these 2 genes was not detected in cervical squamous epithelium collected from patients admitted for surgery for non-malignant conditions, suggesting that expression of these 2 genes may have altered in the adjacent histopathologically "normal" cervical squamous epithelial tissue from cervical cancer patients. The ribosomal protein S12 and the NADH dehydrogenase 4 genes may therefore be potentially useful as early pre-transformation diagnostic markers for human cervical cancer.

Biomarkers, Tumor↗
PubMed2002

Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix.

To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT--PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA--RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials.

Biomarkers, Tumor↗
PubMed2002

Laparoscopically-assisted vaginal hysterectomy (LAVH)--an alternative to abdominal hysterectomy.

AIM: To study the outcomes of 42 consecutive patients who were scheduled for a laparoscopically-assisted vaginal hysterectomy (LAVH) between I January 1994 to 31 December 1999. METHOD: Retrospective study RESULTS: Two patients required conversion to an abdominal hysterectomy. The range of uteri removed was from six to 16 weeks' size. Menorrhagia was the commonest presenting complaint and uterine fibroids was the commonest diagnosis. The mean duration of surgery (+/- SD) was 131.0 +/- 31.7 minutes. Mean blood loss (+/- SD) was estimated at 417 +/- 169 mls. Six percent of patients required a perioperative blood transfusion. Fifty-five percent of patients did not require any injectable analgesics and 45% were able to ambulate on the day of surgery. The mean duration of hospital stay (+/- SD) was 4.2 +/- 2.3 days;The commonest complication was post-operative fever. CONCLUSIONS: LAVH patients have a quick postoperative recovery with less pain at the expense of a long duration of surgery. LAVH is a feasible option in a selected group of patients who would otherwise require an abdominal hysterectomy.

Adult↗
PubMed2002

Pregnancy after renal transplantation: experience in Singapore General Hospital.

INTRODUCTION: Renal transplantation offers the best hope for those women with end-stage renal disease who wish to have children. However, pregnancy after renal transplantation is associated with increased maternal and fetal morbidity. The aim of this retrospective study was to review the outcome of pregnancy in renal transplant patients in Singapore General Hospital. MATERIALS AND METHODS: Forty-two pregnancies, occurring between December 1986 and December 2000, in 25 out of 141 renal transplant women in their reproductive age group (18 to 45 years old) were identified from our high-risk pregnancy record and retrospectively analysed. RESULTS: Thirteen (31%) pregnancies were unsuccessful; 10 abortions, 2 ectopic pregnancies and 1 stillbirth. The remaining 29(69%) successful pregnancies were complicated by maternal anaemia (65.5%), superimposed hypertension (44.8%), premature rupture of membranes (27.6%), urinary (17.2%) and lower genital tract (13.8%) infections, abnormal glucose tolerance test (13.8%), premature delivery (44.8%), low-birth-weight babies (44.8%), small-for-gestational-age babies (20.7%) and intrauterine growth restriction (20.7%). There were no documented cases of multiple pregnancies, congenital anomalies or deterioration of renal function. The outcome of pregnancy was not statistically influenced by preconception renal function and transplant-conception interval. CONCLUSIONS: Successful pregnancy is possible in women after renal transplantation. Such pregnancy is often associated with increased maternal and fetal complications and should be managed by a multidisciplinary approach in a tertiary centre. The function and survival of renal allograft was not adversely affected by pregnancy.

Abortion, Spontaneous↗
PubMed2001

Monthly variation in human semen quality in male partners of infertile women in the tropics.

The aim of the study was to determine whether there were significant 'seasonal' variations in the rhythm of sperm parameters (i.e. semen volume and sperm density) of men who reside in the tropics. A total of 7656 semen analysis results from the department of obstetrics and gynaecology of a tertiary general hospital was analysed. These samples were obtained as part of an initial screening for male partners of couples with problems trying to conceive who were attending a fertility clinic from 1991 to 1995. The subjects' mean semen volume and sperm density of 2.9 ml and 26.9x10(6)/ml respectively were within the World Health Organization reference values. There were no significant month-to-month variations in the adjusted (for age of subject, year of test and technologist who performed the analysis by analysis of co-variance, ANCOVA) mean semen volume and sperm density over the 5 year period. Variations in semen volume and density observed in the temperate climates are not seen in this study, which was conducted in subjects staying in the tropics. This observation may be related to relative constant temperature and hours of light exposure among men who reside in the tropics. As this study is, so far, published data from only one country, Singapore, it may not truly reflect the actual situation for individuals who are residing in the tropics.

Adult↗
PubMed2001

Occupational risk for male infertility: a case-control study of 218 infertile and 227 fertile men.

The aim of the study was to determine if certain occupations pose an increased risk for infertility (of no known cause) among a group of infertile men compared with a group of fertile men. A total of 640 consecutive men whose spouses were unable to conceive were recruited from an infertility clinic. Of these, 218 men (cases) were found to have no known cause for their infertility. A total of 227 men whose spouses were pregnant at the time of the study were recruited as controls. The Singapore Standard Occupational Classification was used to code the subjects' occupations. Semen parameters (density, total sperm counts, motility, viability, and normal morphology) in all of the cases were significantly poorer than those in the controls. The risk for infertility is associated with smoking adjusted odds ratio (OR) 2.85 and 95% confidence interval (CI) 1.91 to 4.24. Work, independently, is not a risk factor for infertility. Engineering technicians (adjusted OR, 2.75; 95% CI, 1.36 to 5.54), finance analysts (adjusted OR, 4.66; 95% CI, 1.90 to 11.40), corporate and computing managers (adjusted OR, 2.49; 95% CI, 1.04 to 5.98), and teachers (adjusted OR, 7.72; 95% CI, 1.86 to 32.10) were at a greater risk of infertility compared with "services and clerical workers." Using services and clerical workers as a reference group, certain occupations are at a higher risk for infertility. Higher work demands and possible electromagnetic field exposure could be contributory factors for infertility.

Adult↗
PubMed2001

The use of vigabatrin in infantile spasms in Asian children.

BACKGROUND: The use of adrenocorticotrophic hormone (ACTH) and prednisolone in the management of infantile spasms has been well established, but is associated with significant morbidity and cannot be used as long-term medication. Since the introduction of vigabatrin, results have been promising with suggestions currently that it should be used as first-line management of infantile spasms. AIM: The aim of this study was to establish the efficacy, tolerability and problems associated with the use of vigabatrin, in Asian children with infantile spasms. MATERIALS AND METHODS: Eighteen local Asian patients with infantile spasms were given vigabatrin, in 8 as first-line monotherapy and in 10 patients as add-on therapy to pre-existing anti-convulsants. RESULTS: Thirty-nine per cent (7/18) showed 100% suppression of seizures at 2 weeks and 50% (9/18) showing complete suppression of seizures at 4 weeks after starting therapy. There was however, a high relapse rate (56%) in complete responders within the first 6 months of therapy. This was probably due to a lower maintenance dose in the patients, as those who relapsed were on an average dose of 59 mg/kg/day at the time of relapse and responded to a stepped up dose of 83 mg/kg/day. Vigabatrin was well tolerated and only 2 patients developed somnolence and irritability. CONCLUSION: A dose of at least 70 mg/kg/day may be necessary to achieve adequate control and yet avoid the common adverse affects of vigabatrin.

Anticonvulsants↗
PubMed2001

Diagnosing and prognosticating acute meningitis in young infants within 24 hours of admission.

INTRODUCTION: The early diagnosis and prognosis of acute meningitis in young infants (infants 90 days old or younger) have not been well studied. We therefore investigated the diagnostic and prognostic factors for acute meningitis obtainable within 24 hours of admission. METHODS: Data were obtained through a retrospective case review of 55 young infants from 1991 to 1999 inclusive. RESULTS: The 3 commonest symptoms of acute meningitis were fever, abnormal activity and decreased feeding. The 3 commonest signs were temperature > 38.0 degrees C, irritability/crying and abnormal tone/reflexes. The best predictor of acute bacterial meningitis (ABM) was the cerebrospinal fluid (CSF)-to-blood glucose ratio. A glucose ratio of < or = 0.8 can be used to diagnose ABM with 100% sensitivity and 100% negative predictive value. Furthermore, a ratio < or = 0.3 can be used to diagnose ABM with 100% specificity and 100% positive predictive value. The best predictor of unfavourable neurological outcome (UFNO) was also the CSF-to-blood glucose ratio. A glucose ratio of < or = 0.3 again can be used to prognosticate for UFNO with 100% sensitivity and 100% negative predictive value. CONCLUSIONS: Diagnosis of acute meningitis by history and physical examination alone is difficult. However, with the aid of laboratory tests, in particular the CSF-to-blood glucose ratio, one can diagnose ABM and prognosticate for unfavourable neurological outcome with high sensitivity and high negative predictive value within 24 hours of admission.

Acute Disease↗
PubMed2001

[Loop electrosurgical excision procedure: a valuable method for the treatment of cervical intraepithelial neoplasia].

OBJECTIVE: To determine the effectiveness and safety of loop electrosurgical excision procedure (LEEP) for the management of cervical intraepithelial neoplasia (CIN) and the significance of positive margins in cervical cone biopsy specimens with the relationship of prognosis. METHODS: LEEP under local anesthesia and colposcopic guidance was performed in an outpatient of colposcopic clinic. Records of 135 patients treated between Feb 1992 and Jul 1999 were reviewed prospectively. RESULTS: The median age of patients in this study was 42 years (range 18-67 years), parity 2.2 times (range 0-8 times). High-grade squamous intraepithelial lesion (HGSIL) accounted for majority of diagnosis according to pap smear (65.9%) and colposcopy (75.6%) respectively. The results of LEEP demonstrated negative histology in 7 patients (5.2%), human papilloma virus (HPV) infection in 2 patients (1.5%), CINI in 15 patients (11.1%), HGSIL in 108 patients (80.0%) which including 20 patients (14.8%) of CINII, 88 patients (65.2%) of CINIII, microinvasion in 3 patients (2.2%). Clear resection margin of lesion in cervix was noted in 78 (57.8%) patients. Unclear margins were appeared in 57 (42.2%) patients including 21 cases (15.6%) of resection margin positive and 36 cases(26.7%) of resection margin undetermined. HGSIL accounted for the majority (54 cases, 94.7%) in this kind of patients. The residual CIN occurred in 1 patient (4.8%) with the resection margin positive and 3 patients(8.3%) with the resection margin undetermined respectively. In 2 patients (2.6%) with the resection margin clear. Recurrence CIN occurred in 1 patient (4.8%) with the resection margin positive and 2 patients (5.6%) with the resection margin undetermined respectively, none of the patients (0.0%) with the resection margin clear. The overall cure rate in this study was 93.3% after first LEEP done. The residual CIN was identified in 6 (4.4%) patients. The recurrence CIN occurred in 3 (2.2%) patients. Complications of LEEP occurred in 14.1% (19/135) patients in this study. CONCLUSIONS: LEEP is a kind of effective and safe method for the treatment of cervical intraepithelial neoplasia. The status of resection margin should be concerned. Margin involvement of specimen is the risk factor for residual and recurrence of CIN.

Adolescent↗
PubMed2000

Factors associated with male infertility: a case-control study of 218 infertile and 240 fertile men.

OBJECTIVE: To determine the likely risk factors, such as smoking and drinking habits, and occupational groups, for infertility in a group of infertile men with no known cause, compared with a group of fertile men; and to examine the effects of the semen parameters, such as volume, density, motility, viability and normal morphology, on fertility. DESIGN: A case-control study. SETTING: The department of obstetric and gynaecology of a tertiary general hospital. PARTICIPANTS: Six hundred and forty consecutive male partners of couples trying to conceive were recruited from an infertility clinic. Of these, the cases comprised 218 men who had no known cause for their infertility. Two hundred and forty men whose wives were pregnant at the time of the study were recruited as controls. RESULTS: The semen parameters (e.g. density, total sperm counts, motility, viability and normal morphology) of all cases were significantly poorer than that of the controls. The risk of infertility is associated with smoking (crude OR 2 x 82, 95% CI 1 x 93-4 x 13; adjusted OR 2 x 96; 95% CI 1 x 98-4 x 42). Technicians (adjusted OR 2 x 81; 95% CI 1 x 51-4 x 24) and professional, senior officials and managers were also at a greater risk of infertility (adjusted OR 2 x 36; 95% CI 1 x 26-4 x 40), compared with service and clerical workers. The significant factors predicting infertility were smoking, density of sperm, and viability of sperm. Smoking increased the odds of being infertile. Higher sperm counts and larger percentage of viable sperm decrease the odds of infertility. Based on the multiple logistic regression model, the odds ratio for infertility = (94 x 70) x (2 x 88(smoking)) X (0 x 29(logdensity)) X (0 x 95(viability)). CONCLUSION: Smoking, density of sperm and the viability of sperm are significant predictors for infertility among men.

Adult↗
PubMed2000

Sandhoff disease--a case report of 3 siblings and a review of potential therapies.

INTRODUCTION: Sandhoff disease is a GM2 gangliosidosis that may present within the first 6 months of life with developmental regression. This is the first report of a pedigree from Southeast Asia. CLINICAL PICTURE: All the affected siblings presented in the first year of life with developmental regression, spasticity, seizures and loss of vision. The diagnosis was confirmed by an enzymatic deficiency in both beta-hexosaminidase A and B. CONCLUSION: As the disorder is autosomal recessive, and no curative therapy is currently available, genetic counselling is necessary to prevent the burden of this devastating disease. We review the potential strategies of treatment for Sandhoff disease.

Child, Preschool↗
PubMed2000

Transaminitis in Duchenne's muscular dystrophy.

BACKGROUND: Persistently raised transaminase levels often prompt the clinician to investigate for liver pathology. Previously, some of our patients with Duchenne's muscular dystrophy have had investigations to look for liver disorders when the alanine transaminases (ALTs) were found incidentally to be high. AIM: The objective of the study was to ascertain the levels of the transaminases in patients with Duchenne's muscular dystrophy and to see if the levels of transaminases correlated with muscle enzymes such as creatine kinase (CK). MATERIALS AND METHODS: This is a case series of 19 patients with Duchenne's muscular dystrophy. Alanine and aspartate transaminase (AST) levels and CK levels were measured in the serum of the patients. RESULTS: In this series, ALT and AST levels were all found to be raised significantly in patients with biopsy-proven Duchenne's muscular dystrophy and Becker's muscular dystrophy. Alanine transaminase, in particular, was raised to a mean of 356 mmol/L, 9 times above the mean for normal. There was also good correlation between ALT and CK levels with a correlation coefficient of r = 0.80 and P value 0.01. Similar to CK, the transaminase levels were inversely proportional to mobility and to age. CONCLUSION: The presence of hypertransaminasemia in patients with muscular dystrophy should be attributed to muscle breakdown rather than to liver pathology and such patients should not be over-investigated for liver disease. In the absence of liver pathology, raised transaminases may be an early sign of occult muscular dystrophy and such patients should have CK levels checked to look for evidence of muscular dystrophy.

Alanine Transaminase↗
PubMed2000

Technical aspect of ThinPrep.

AIM OF STUDY: To analyze the common technical problems encountered in ThinPrep preparations. METHOD: A prospective and retrospective study of eight hundred and fifty (n = 850) conventional cervical smears with its corresponding paired ThinPrep specimens from July 1998 to December 1998. RESULTS: 139 ThinPreps were found to be technically suboptimal. Of these, 81 showed "patchy cells lost"; 18 showed "thick preparations"; 24 demonstrated "halo effect'" where the cellular material collected at the periphery of the cell circle, and 16 had "obscuring blood and amorphous debris", rendering the preparations "satisfactory for evaluation but limited" by the presence of the above artifacts. CONCLUSION: Despite its many advantages in providing standardization of specimen preparation, superb cellular presentation, reduction in the number of unsatisfactory reports and increased lesion detection rate, ThinPrep has its own limitations in terms of technical problems, ease of operation and cost effectiveness.

Culture Techniques↗