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Biomedical subjects

A S Tan

Publications and source records attributed to A S Tan.

At least 19 recordsLinked to original sources
PubMed2004

Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.

INTRODUCTION: Array comparative genomic hybridisation (array CGH) is a powerful method that detects alteration of gene copy number with greater resolution and efficiency than traditional methods. However, its ability to detect disease causing duplications in constitutional genomic DNA has not been shown. We developed an array CGH assay for X linked hypopituitarism, which is associated with duplication of Xq26-q27. METHODS: We generated custom BAC/PAC arrays that spanned the 7.3 Mb critical region at Xq26.1-q27.3, and used them to search for duplications in three previously uncharacterised families with X linked hypopituitarism. RESULTS: Validation experiments clearly identified Xq26-q27 duplications that we had previously mapped by fluorescence in situ hybridisation. Array CGH analysis of novel XH families identified three different Xq26-q27 duplications, which together refine the critical region to a 3.9 Mb interval at Xq27.2-q27.3. Expression analysis of six orthologous mouse genes from this region revealed that the transcription factor Sox3 is expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. DISCUSSION: Array CGH is a robust and sensitive method for identifying X chromosome duplications. The existence of different, overlapping Xq duplications in five kindreds indicates that X linked hypopituitarism is caused by increased gene dosage. Interestingly, all X linked hypopituitarism duplications contain SOX3. As mutation of this gene in human beings and mice results in hypopituitarism, we hypothesise that increased dosage of Sox3 causes perturbation of pituitary and hypothalamic development and may be the causative mechanism for X linked hypopituitarism.

Adolescent↗
PubMed2003

Changing trends in indications for caesarean sections in a tertiary hospital.

OBJECTIVES: To study the caesarean section rate and the trends in indications for caesarean delivery at the Singapore General Hospital (SGH) during two study periods of 6 months each. MATERIALS AND METHODS: The percentages of caesarean sections attributable to specific indications were computed for the first 6 months of 1998 and the last 6 months of 2001. Subgroup analysis of "less common indications" was performed. RESULTS: In the first half of 1998, 170 caesarean sections were performed giving a rate of 16.77%. 54.12% of women were multiparous. The main indication for caesarean section was dystocia (4.24% of deliveries). Two hundred and sixty caesarean sections were performed in the later half of 2001 giving a caesarean section rate of 25.10%. 53.46% of women were multiparous. The main indication for caesarean section was dystocia (5.41% of deliveries). Increase in caesarean section rate in 2001 was attributed to statistically significant increase in caesarean section for previous caesarean section and placenta previa major. Other changes in practice included shorter operating time which may be related to decision not to perform peritoneal closure. CONCLUSION: Studying indications for caesarean section are useful for hospitals, clinicians and researchers in determining strategies to lower primary and repeat caesarean section rate.

Adult↗
PubMed2003

Audit of 'crash' emergency caesarean sections due to cord prolapse in terms of response time and perinatal outcome.

OBJECTIVE: The objective was to audit 'crash' emergency caesarean sections (CS) with respect to response time (the diagnosis to delivery interval [DDI]) and perinatal outcome. MATERIALS AND METHODS: The computerised database at the Singapore General Hospital (SGH) delivery suite was used to identify all cases of 'crash' emergency CS activated for the diagnosis of cord prolapse from 1992 to 2002. Patients' case notes and neonatal charts were reviewed and the following variables were evaluated: parity, gestational age at the time of delivery and the DDI. Neonatal outcome was measured by Apgar scores at 1 and 5 minutes, cord pH and admission to the neonatal intensive care unit (NICU). RESULTS: A total of 34 cases of umbilical cord prolapse were identified from 29,867 deliveries, giving an incidence of 0.11% (1 in 900). The median gestational age was 38.5 weeks (range, 25 to 41 weeks). The median time from diagnosis to delivery was 20 minutes (range, 10 to 40 minutes). Seventy-six percent (19/30) were delivered within 30 minutes. The time of diagnosis was not recorded for 5 cases. Sixty-three percent of neonates had an Apgar score < or = 7 at 1 minute of life, increasing to 97% at 5 minutes. There were 3 NICU admissions for reasons of prematurity. There was no perinatal mortality. Cord pH was not performed for 47% of (14/30) neonates. Among the remaining 16 neonates, an umbilical cord pH of < or = 7.20 was found in 62% (10/16). There was poor correlation between the DDI and umbilical cord pH. CONCLUSION: Three-quarters of our 'crash' emergency CS for cord prolapse were performed within 30 minutes with a good perinatal outcome. However, we have identified areas for improvement to optimise further the operational efficiency of 'crash' emergency CS.

Adolescent↗
PubMed2001

Clinical management of PCOS.

The polycystic ovary syndrome (PCOS) is a heterogeneous condition with genetic predisposition. It is characterized by a myriad of symptoms including oligomenorrhea or amenorrhea, anovulation or infertility, hirsutism or acne. Insulin resistance appears to be an important factor in PCOS though the lack of an etiology has led to symptom oriented therapy which includes lifestyle modification, the use of cyclical progestagens and antiandrogens. Ovulation induction by drug therapy and ovarian drilling aims to treat subfertility in women with PCOS. Therapeutic approaches to PCOS remain an ongoing source of debate. Insulin sensitizing agents may bring new hope in therapy. Future research is aimed at shedding light on the pathophysiology so as to optimize treatment of women with PCOS.

Contraceptives, Oral↗
PubMed2001

Relationship between gestational age and frequency of fetal trophoblasts and nucleated erythrocytes in maternal peripheral blood.

The relationship between gestational age and frequency of fetal cells in the maternal blood was studied in order to determine the optimal time for cell recovery. The immunomagnetic colloid system was used to enrich nucleated erythrocytes (NRBCs) and trophoblasts from 20 ml maternal blood samples obtained between 9 and 35 weeks' gestation (n=41). Nested polymerase chain reaction (PCR) for the Y chromosome of enriched NRBCs and trophoblasts showed decreasing negative predictive values with increasing gestational age. The sensitivity and the overall frequency for correct fetal gender diagnosis were the lowest in the third trimester. Fluorescence in situ hybridisation (FISH) using XY DNA-specific probes was used to determine the fetal gender of the trophoblast-enriched fraction. The fetal origin of enriched NRBCs was determined using simultaneous immunophenotyping for fetal hemoglobin and FISH with XY probes. The mean number and mean percentage purity for both fetal trophoblasts and NRBCs showed decreasing values with increasing gestational age. However, statistical analysis showed no relationship between gestational age and frequency of fetal cells even though more fetal cells tend to exist during the first trimester. Nevertheless, the first trimester appears to offer the most optimal time for fetal cell recovery from maternal blood for the purpose of prenatal diagnosis.

Blood Cells↗
PubMed2001

Perioperative management of a patient with congenital myasthenia gravis for elective caesarean section.

Congenital disorders of neuromuscular transmission are commonly referred to as congenital myasthenia gravis because of their clinical similarity to the immune-mediated disease. Differentiation between the immune-mediated and congenital forms of the disease is important, because therapy established for the former may not be appropriate for patients with the latter presentation. The course of this rare neuromuscular disorder during pregnancy and its influence on anaesthesia remain largely unknown. We report on the case of a 32-year-old parturient suffering from congenital myasthenia gravis scheduled for elective caesarean section. The perioperative management of this patient who underwent the operation under spinal anaesthesia was reviewed. The effects of anaesthetic agents and techniques on the course of congenital myasthenic patients may need further review in the light of latest findings in the electrophysiology, genetic and therapeutic studies of this syndrome.

Adult↗
PubMed2001

The glucose challenge test for screening gestational diabetes in pregnant women with no risk factors.

AIM OF STUDY: To evaluate the 50 g glucose challenge test as a screening tool for gestational diabetes in pregnant women with no risk factors, to determine the prevalence of gestational diabetes in this population and to determine the perinatal outcomes of pregnancy according to the glucose challenge test. METHODOLOGY: A descriptive prospective study. A total of 146 patients with no risk factors who booked a particular obstetrician and delivered between May 1996 and April 1997 were recruited. Pregnancy outcomes were assessed by the gestation and mode of delivery, neonatal outcomes included birth weights, apgar scores and other neonatal complications. RESULTS: The detected incidence of gestational diabetes was 8.2%. With the threshold plasma glucose level at 7.1 mmol/l, 53 women or 36% needed to undergo the 75 g oral glucose tolerance test and 12 women were found to have gestational diabetes. The diagnostic yield was 22.6%. With 7.8 mmol/l as the threshold value, 28 women or 20% needed the oral glucose tolerance test and eight women with gestational diabetes were detected. The diagnostic yield was 28.6%. Perinatal outcome for these diabetic women who were well-controlled during pregnancy was similar to the rest of the women with normal glucose challenge test. CONCLUSIONS: The 50 g glucose challenge test is a useful screening test for diabetes in Singaporean women with no risk factors. A threshold value at 7.8 mmol/l with a smaller number of women requiring the 75 g oral glucose challenge test may be more acceptable.

Adult↗
PubMed2000

Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents.

Activation of the respiratory burst of granulocytes and macrophages by invading microorganisms is a key first line cellular defence against infection. Failure to generate this response leads to persistent life-threatening infection unless appropriate antibiotic treatment is given. The respiratory burst of neutrophils is usually measured spectrophotometrically by following ferricytochrome c reduction, and histologically by using the tetrazolium salt, nitroblue tetrazolium, which is reduced intracellularly to an insoluble formazan. In both assays, reduction is mediated by superoxide generated via NADPH oxidase. Because ferricytochrome c has a high molecular mass and high background absorbance at 550 nm, the assay lacks sensitivity and is not ideally suited to microplate measurement. We have circumvented these limitations by using the cell-impermeable, sulfonated tetrazolium salt, WST-1, which exhibits very low background absorbance and is efficiently reduced by superoxide to a stable water-soluble formazan with high molar absorptivity. This has permitted adaptation of the WST-1 assay to microplate format while retaining sensitivity. Reduction of WST-1 by activated human peripheral blood neutrophils correlated closely with ferricytochrome c reduction across a range of PMA concentrations and with time of activation by PMA and fMLP. Reduction of WST-1 was inhibited by 98% by superoxide dismutase (20 microg/ml) and by 88% by the NADPH oxidase inhibitor, diphenyleneiodinium (10 microM) but was resistant to catalase, azide and the NADH oxidase inhibitor, resiniferatoxin. WST-1 and ferricytochrome c reduction were also compared using xanthine/xanthine oxidase to generate superoxide. Under optimised assay conditions, both WST-1 and ferricytochrome c reduction were directly proportional to added xanthine. WST-1 generated approximately 2-fold greater increase in absorbance than ferricytochrome c at their respective wavelengths, and this translated into increased assay sensitivity. Addition of the intermediate electron acceptor, 1-methoxy phenazine methosulfate, increased the background of the neutrophil assay but did not affect the overall magnitude of the response. We have used the WST-1 assay to assess human neutrophil dysfunction and to compare anti-inflammatory activity.

Anti-Inflammatory Agents↗
PubMed2000

High-capacity redox control at the plasma membrane of mammalian cells: trans-membrane, cell surface, and serum NADH-oxidases.

The high capacity of proliferating mammalian cells to transfer electrons from cytosolic NADH to extracellular electron acceptors like oxygen is poorly understood and not widely recognized. Nevertheless, trans-plasma membrane electron transport (plasma membrane redox control) probably ranks alongside the Na+/H+ antiport system (pH control) and glucose transport in facilitating cellular responses to physiological stimuli. These plasma membrane transport systems are acutely responsive to receptor ligation by growth factors, polypeptide hormones, and other cell activators. A novel tetrazolium-based cell proliferation assay that we have shown to measure an NADH-oxidoreductase component of the trans-plasma membrane electron transport system has allowed direct comparisons with NADH:ferricyanide-oxidoreductase and respiratory burst NADPH-oxidoreductase. In addition, an NAD(P)H-oxidase at the cell surface and an NADH-oxidase activity in body fluids can be measured by modifying the basic cell proliferation assay. As determined by reduction of the cell-impermeable tetrazolium reagent, WST-1, electron transfer across the plasma membrane of dividing cells can exceed that of fully activated human peripheral blood neutrophils. Cellular reduction of WST-1 is dependent on the presence of an intermediate electron acceptor and is inhibited by superoxide dismutase (SOD) and by oxygen, implying indirect involvement of superoxide in WST-1 reduction. Cell-surface NAD(P)H-oxidase and serum NADH-oxidase are shown to be distinct from trans-plasma membrane NADH-oxidoreductase by their differential sensitivity to capsaicin and pCMBS. The glycolytic metabolism of cancer cells may be linked to changes in trans-plasma membrane NADH:WST-1-oxidoreductase activity and to increased serum NADH-oxidase in cancer.

Animals↗
PubMed2000

Cell-surface NAD(P)H-oxidase: relationship to trans-plasma membrane NADH-oxidoreductase and a potential source of circulating NADH-oxidase.

The surface of mammalian cells faces an oxidizing environment that has the potential to damage proteins, lipids, and carbohydrates to which it is exposed. In contrast, the cytoplasm is reducing and its redox state is tightly regulated. Trans-plasma membrane oxidoreductases that shift electrons from cytosolic NADH to external electron acceptors such as oxygen are widely involved in cellular redox control. They reduce oxygen to water and may generate reactive oxygen species such as superoxide and hydrogen peroxide. In addition, external NAD(P)H-oxidases have been demonstrated on intact cells and as eluted proteins, but the relationship between trans-plasma membrane NADH-oxidoreductases and cell-surface NAD(P)H-oxidases is not known. To investigate further the relationship between plasma membrane NAD(P)H-oxidoreductases, and to gain insight into the physiological functions of these redox active membrane proteins, we have adapted a simple colorimetric assay for measuring the trans-plasma membrane NADH-oxidoreductase activity of viable cells to measure NAD(P)H-oxidase at the cell surface in real time. Using the cell-impermeable tetrazolium salt WST-1 in the presence of NADH or NADPH, but in the absence of an intermediate electron acceptor, we show that cell-surface NAD(P)H-oxidase is widely expressed on mammalian cells, being more abundant on rapidly proliferating cells than on resting neutrophils and spleen cells. The ratio of cofactor dependence of NAD(P)H-oxidase (NADH:NADPH) varied widely between different cells (0.7-5.2), suggesting a family of cell surface oxidases or that the activity of these enzymes may be modulated in various ways. Comparison of NAD(P)H-oxidase on the surface of viable cells with trans-membrane NADH-oxidoreductase, measured with WST-1 in the presence of 1-methoxy PMS, showed that cell-surface NAD(P)H-oxidase was differentially inhibited by the cell-impermeable thiol-blocking agent pCMBS, but was unaffected or stimulated by other thiol blocking agents. Capsaicin, which inhibits trans-plasma membrane NADH-oxidoreductase activity, stimulated surface NAD(P)H-oxidase. Metabolic inhibitors had little effect on surface NAD(P)H-oxidase activity but inhibited trans-plasma membrane activity. These results do not support the view the surface NAD(P)H-oxidase is a terminal oxidase for trans-plasma membrane NADH-oxidoreductase.

4-Chloromercuribenzenesulfonate↗
PubMed2000

Overview of legislation and tobacco control in Singapore.

Legislative measures against smoking in Singapore began in the early 1970s, and can be said to have been the start of a comprehensive smoking control programme. With the launch of the National Smoking Control Programme (NSCP) in 1986, a National Smoking Control Coordinating Committee was set up to look into legislation and fiscal measures. To further increase the dimension and impact of the programme, a Civic Committee on Smoking Control was formed in 1996. This committee also looks into and recommends legislative measures. The NSCP is an ongoing programme that aims to reduce smoking rates through a combination of strategies, including education, establishment of no-smoking areas and increasing taxation and legislative measures. Existing legislation is regularly and systematically reviewed and revised, and new laws are recommended to strengthen our smoking control efforts. Concurrently, penalties and ways to improve enforcement of the legislation are also updated. The legislative measures that have been implemented in Singapore over the years include prohibition of tobacco advertising and promotion, restrictions on the sale of tobacco products, licensing of sales outlets, use of health warnings on cigarette packets, controlling and labelling of tar and nicotine contents, restriction of smoking in public places and prohibition of smoking in public by the under-eighteens. Several factors have helped make legislative measures work in Singapore. These include political will and support, starting legislation early, comprehensive legislative measures, enforcement measures and continuous review. To sustain these efforts, Singapore needs to continue to stay abreast of world-wide measures on smoking control.

Advertising↗
PubMed2000

Retroperitoneal Castleman's disease in the perinephric space--imaging appearance: a case report and a review of the literature.

INTRODUCTION: Castleman's disease (CD) is a rare lymphoid tumour usually found in the mediastinum. Extrathoracic sites are uncommon. Its radiological findings may be similar to other retroperitoneal tumours, making diagnosis difficult. CLINICAL PICTURE: A 54-year-old female was found to have an incidental hypoechoic mass in the left posterior perinephric space on routine ultrasound. Abdominal computed tomography (CT) scan demonstrated an isodense mass which enhanced brightly with intravenous contrast. Angiogram confirmed a hypervascular mass. TREATMENT: The retroperitoneal mass was excised. OUTCOME: Histology revealed CD of hyaline-vascular type. CONCLUSION: CD should be considered in the differential diagnosis of a retroperitoneal mass, which demonstrates homogeneous and intense enhancement.

Biopsy, Needle↗
PubMed1998

Acute regulation of glucose transport after activation of human peripheral blood neutrophils by phorbol myristate acetate, fMLP, and granulocyte-macrophage colony-stimulating factor.

Activation of human peripheral blood neutrophils by pathogens or by phorbol myristate acetate (PMA), fMLP, or myeloid growth factors generates a respiratory burst in which superoxide production plays an important role in killing invading microorganisms. Although the increased energy demands of activated neutrophils would be expected to be associated with increased glucose uptake and utilization, previous studies have shown that PMA inhibits 2-deoxyglucose (2-DOG) uptake. In this study, we show that PMA activation of neutrophils, isolated by methods not involving hypotonic lysis, increases the rate of 2-DOG uptake and results in a 1.6-fold to 2.1-fold increase in transporter affinity for glucose without changing Vmax. Increased transporter affinity in response to PMA was also observed with 3-O-methyglucose, which is not phosphorylated, and inclusion of glucose in the activation medium further increased respiratory burst activity. Increased 2-DOG uptake and increased transporter affinity for glucose were also observed with the peptide activator, fMLP, and with granulocyte-macrophage colony-stimulating factor (GM-CSF). The protein kinase C (PKC) inhibitor, calphostin C, and the tyrosine kinase inhibitor, genistein, inhibited both PMA- and fMLP-stimulated 2-DOG uptake. In contrast, genistein inhibited fMLP-induced superoxide production, but had little effect on the PMA-induced response, while staurosporine differentially inhibited PMA-induced superoxide production. These results show that neutrophil activation involves increased glucose transport and intrinsic activation of glucose transporter molecules. Both tyrosine kinases and PKC are implicated in the activation process.

Biological Transport↗
PubMed1997

The hemopoietic growth factor, interleukin-3, promotes glucose transport by increasing the specific activity and maintaining the affinity for glucose of plasma membrane glucose transporters.

Most mammalian cells rely on an external supply of glucose for survival, proliferation, and function. Glucose enters cells through specific transporter molecules at the plasma membrane by a facilitative process that does not expend energy. Regulation of glucose transport into cells is thought to occur largely through transporter expression at the cell surface, but the extent to which the intrinsic properties of glucose transporters are regulated is at present controversial. Using a bone marrow-derived cell line that responds to the hemopoietic growth factor, interleukin-3 (IL-3), we investigated IL-3 regulation of glucose transport. IL-3 significantly increased 2-deoxyglucose (2-DOG) uptake within 1 h (26 +/- 8.0%, n = 11) with a maximum 73% increase after 6 h. Withdrawal of IL-3 resulted in decreased uptake within 1 h and this continued to decline to 43% of initial uptake by 16 h. To determine whether these changes in 2-DOG uptake were associated with corresponding changes in glucose transporter expression, subtype-specific antisera against Glut-1 and Glut-3 were used. Little change in membrane expression of these transporters was observed prior to 16 h. Fractionation of cell membranes on Nycodenz gradients showed that the majority of each transporter subtype was associated with the plasma membrane (63-93%) and that transporter distribution did not change markedly in response to addition or withdrawal of IL-3. These results demonstrate that IL-3 regulates glucose uptake by modulating the intrinsic transporting ability of glucose transporters. Decreased transporter affinity for 2-DOG and 3-O-methylglucose was observed following IL-3 withdrawal. Similar affinity changes were observed with 2-DOG following exposure of IL-3-stimulated cells to the protein kinase inhibitors, genistein and staurosporine. In contrast, the tyrosine phosphatase inhibitor, vanadate, acted like IL-3 to increase transporter affinity for glucose. Together these results demonstrate that IL-3 acts to maintain the intrinsic transport properties of glucose transporters without markedly affecting their expression or translocation.

3-O-Methylglucose↗
PubMed1997

Does a prenatal diagnosis of congenital heart disease alter short-term outcome?

Congenital heart disease (CHD) is the most common fatal congenital anomaly in the first year after birth. Fetal echocardiography has become accepted as a method of diagnosing CHD in utero, but the benefits of prenatal diagnosis have not been evaluated. We performed a cohort analysis of neonates with CHD in the absence of other life-threatening conditions. One group (I) consisted of neonates who had been diagnosed as fetuses to have CHD and who were delivered at Yale-New Haven Hospital. The other group (II) consisted of neonates who were not diagnosed to have CHD until after birth, and were either delivered at, or transferred to, the same hospital. Costs of initial hospitalization, length of hospitalization, and survival to discharge home with the parents were primary outcome measures. Our primary hypothesis was that all outcome measures would be improved by prenatal diagnosis. We also examined secondary hypotheses that these same measures would be improved among selected subgroups, including those requiring univentricular management, those amenable to biventricular repair, those with ductal dependent lesions, and those requiring any surgery during the primary admission. From January 1, 1991 to June 30, 1996 we identified 45 antenatal cases and 54 postnatal cases of CHD that met the study entry criteria. The median length (+/- SE) of initial hospitalization was 16 +/- 3.8 days in group I, and 11 +/- 3.8 days in group II (p < 0.08). The median cost of initial hospitalization was $57,678 +/- 12,340 vs. $53,604 +/- 7249 (not significant). Eighty percent of group I survived to hospital discharge compared with 67% of group II (p = 0.14). There was no difference in survival among those requiring univentricular management (64 vs. 44%), but costs and length of hospitalization were greater in group I, regardless of whether or not surgery was performed postnatally. Surgery was undertaken more often among the prenatal diagnosis group with univentricular hearts (86 vs. 56%, p < 0.05). Among those fetuses amenable to biventricular repair, survival was better (96 vs. 76%, p < 0.05) and the cost of hospitalization was lower ($30,277 +/- 16,869 vs. $64,616 +/- 9441, p = 0.06) in the prenatal diagnosis group. Prenatal diagnosis of CHD does not result in the expected savings in cost, length of hospitalization or survival in the overall group of patients. The prenatal diagnosis group showed a skew towards single ventricle physiology. Within that group a high rate of pregnancy termination results in a group of parents who are likely to choose postnatal surgery despite high short- and long-term mortality risks.

Adult↗