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Biomedical subjects

L K Tan

Publications and source records attributed to L K Tan.

At least 19 recordsLinked to original sources
PubMed2006

Tocolytic treatment for the management of preterm labour: a systematic review.

Spontaneous preterm labour and delivery accounts for approximately one-third of preterm births, which is the predominant cause of perinatal mortality and morbidity. This review aims to evaluate the evidence on the benefits and harms of five classes of tocolytic therapy, namely: betamimetics, calcium channel blockers, magnesium, non-steroidal anti-inflammatory agents, and atosiban. We performed a systematic review of the effectiveness of tocolytics to stop uterine contractions (first-line therapy). Reports of randomised controlled trials from searches of MEDLINE, bibliographies of review articles, Cochrane Collaboration and its Pregnancy and Childbirth Review Group between 1966 and 2003 were identified, using the search terms "randomised controlled trial" (RCT), "preterm labor", "tocolysis", "betamimetics", "ritodrine", "prostaglandin synthetase inhibitors", "indomethacin", "calcium channel blockers", "nifedipine", "oxytocin receptor blockers", "atosiban", and "magnesium sulphate". Studies on women with preterm labour comparing the effects of a tocolytic with a placebo or no treatment that met our inclusion criteria, were included. To our knowledge, the trials were conducted mainly before 1999 and there were no placebo-controlled trials after that. Of the 86 articles identified and evaluated, 14 first-line studies met more stringent requirements for meta-analyses. Tocolytics were associated with significant decreases in the odds of delivery within 24 hours (odds-ratio [OR] 0.54, 95 percent confidence interval [CI] 0.32-0.91) and 48 hours (OR 0.47, 95 percent CI 0.30-0.75). These effects were significant for beta-agonists, atosiban and indomethacin, but not magnesium sulphate. Maternal side-effects significantly associated with betamimetics were pulmonary oedema, cardiac arrhthymias and hypokalaemia. Although calcium antagonists have not been evaluated against placebo, comparative trials with beta-agonists have shown more favourable neonatal outcomes and better prolongation of gestation. In conclusion, the management of threatened preterm labour with first-line tocolytic therapy can prolong gestation. However, the time gained in-utero need to be optimised. There is no clear first-line tocolytic agent. The use of tocolytic agents should be individualised and based on maternal condition, potential side-effects and gestational age.

Female↗
PubMed2006

Intrapartum maternal sinus bradycardia with spontaneous resolution following delivery.

Pregnancy is a normal physiological state that is characterised by significant adaptive changes, many of which take place in the cardiovascular system. These adaptations are believed to be the cause for the increased incidence in cardiac arrhythmias in pregnancy and particularly, in labour. We report an unusual case of a healthy 32-year-old primigravida who developed profound intrapartum bradycardia which persisted throughout labour. Spontaneous recovery to pre-labour baseline heart rate occurred following spontaneous vaginal delivery. Maternal and foetal statuses remained satisfactory during labour. This case report underscores the importance of recognising that arrhythmias in various forms are common in labour. In the absence of detectable underlying cardiac disease or maternal and foetal compromise, continuation of the labour with a view to vaginal delivery should be the goal.

Adult↗
PubMed2005

Confinement and other psychosocial factors in perinatal depression: a transcultural study in Singapore.

BACKGROUND: To investigate the prevalence, socio-cultural and psychosocial risk factors for perinatal depression in Singaporean women. METHOD: A prospective cohort of 559 women was interviewed antenatally and at six weeks' postpartum at a tertiary hospital. Women were interviewed for diagnosis of depression using a two-stage design, with a screening questionnaire and diagnostic interview. RESULTS: Postnatally, a negative confinement experience was associated with depression. Other independent factors included poor emotional support, a past history of depression, unplanned pregnancy and perceived potential conflicts with relatives over childcare antenatally and dissatisfaction, poor instrumental support postnatally. The prevalence of depression antenatally and postnatally was 12.2% and 6.8%, respectively. LIMITATIONS: Measures of satisfaction with social support were based on self-report; there were high dropout rates at six weeks' postpartum; and other modulating social factors such as pre-existing interpersonal conflicts were not studied. CONCLUSIONS: Perinatal depression in Singaporean women is common. Contrary to expectations, a negative 'confinement' experience is a significant risk factor for postnatal depression, and is not universally welcomed by women. Depression is modulated by dissimilar sets of psychosocial factors antenatally and postnatally.

Adult↗
PubMed2004

Clinico-pathological analysis of myelodysplastic syndromes according to French-American-British classification and international prognostic scoring system.

INTRODUCTION: The aim of this study was to analyse the clinico-pathological features of a cohort of patients with myelodysplastic syndromes (MDS). MATERIALS AND METHODS: The clinical and pathological data of 43 MDS patients over a 3-year period were reviewed. Survival analysis was performed according to the French-American-British (FAB) classification and International Prognostic Scoring System (IPSS) using the Kaplan-Meier method. Selected published studies for comparison were identified from MEDLINE search. RESULTS: The patients were followed up for a median duration of 175 days (range, 2 to 1044 days). The median survival for refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS) has not been reached, but that for refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEB-T) and chronic myelomonocytic leukaemia (CMML) was 250 days, 49 days and 44 days, respectively. The median survival for the low-risk and intermediate-1 IPSS categories has not been reached, while that for the intermediate-2 and high-risk categories was 58 days and 49 days, respectively. The survival analyses, according to the FAB classification and IPSS system, were statistically significant (P <0.05). Comparison of our data with those from neighbouring and Western countries revealed both similarity and disparity. We also noted different cytogenetic information in our cohort of patients. CONCLUSIONS: We found distinctly unique cytogenetic and clinico-pathological characteristics in our MDS patients. However, whether true biological differences exist among MDS patients in different geographies and populations with different genetic and environmental backgrounds require further large multinational study.

Adolescent↗
PubMed2003

Stability of extemporaneously prepared saquinavir formulations.

AIMS: The effects of pH and excipients on the stability of saquinavir in extemporaneously prepared suspensions were assessed. The stability of a developed extemporaneously prepared saquinavir suspension was then determined at 5 and 25 degrees C over 30 days. METHOD: Extemporaneous saquinavir 2 mg/mL formulations were prepared from soft gelatin capsule (Fortovase). Four batches of the formulations were buffered at pHs 2, 4, 5 and 7, whereas the other five batches were prepared in Milli-Q water, 0.5% (w/v) citric acid, 0.1% (w/v) sodium ascorbate, 10% (v/v) syrup and in vehicle containing both 0.5% (w/v) citric acid and 0.1% (w/v) sodium ascorbate. The stability of these formulations was tested at 25 degrees C. A final formulation of saquinavir suspension (60 mg/mL) containing both 10% (v/v) syrup and 0.5% (w/v) citric acid was developed and tested for stability at 5 and 25 degrees C for up to 30 days using a stability-indicating high-performance liquid chromatographic method. RESULTS: Saquinavir was most stable at pH 2-4. Formulations containing sodium ascorbate, citric acid and syrup or both citric acid and sodium ascorbate were significantly more stable than the control formulation (saquinavir 2 mg/mL in Milli-Q water). CONCLUSION: The pH for optimal stability of saquinavir was around 2-4. Besides pH adjustment, saquinavir could also be stabilized by adding anti-oxidants. The saquinavir 60 mg/mL formulation prepared with about a pH of about 4 was stable at both 5 and 25 degrees C for at least 30 days.

Capsules↗
PubMed2003

Obstetric cholestasis: current opinions and management.

Obstetric cholestasis (OC) is a pregnancy-specific liver condition that typically presents with generalised pruritus in the absence of a rash in the late second trimester or third trimester. It is more common in certain ethnic groups, particularly those from South Asian, South American, Nordic and Scandinavian regions, and has a familial and genetic basis. Recent research suggests that the pathophysiology may reside in mutations in genes that code for bile acid transporter proteins. Mutations involving the bile acid transporters may impair maternal excretion and influence transplacental passage of bile acids. It is hypothesised that the surge in pregnancy steroid hormones may result in genetically predisposed women developing cholestasis. The condition is also associated with increased perinatal morbidity and mortality, particularly from preterm labour, fetal distress and intrauterine deaths. Animal studies have shown that bile acids are cardiotoxic, which may help explain the condition's association with fetal distress and stillbirths. Accurate diagnosis relies on a high index of suspicion, and the findings of abnormal liver function tests and raised serum bile acid levels after the exclusion of other organic causes of liver disease. Ursodeoxycholic acid helps relieve symptoms, improve serum bile acid levels and possibly has a cardioprotective effect. Active management, in the form of close antepartum fetal monitoring and delivery before 37 weeks, helps to decrease the risk of intrauterine deaths, though possibly at the expense of increased obstetric intervention. Following delivery, there is usually a dramatic improvement of symptoms and resolution of the condition. Women should be counselled about the high recurrence risk of OC in subsequent pregnancies.

Animals↗
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↗
PubMed2002

A prospective validated model for predicting axillary node metastases based on 2,000 sentinel node procedures: the role of tumour location [corrected].

AIMS: The purpose was to identify the independent predictive factors of axillary lymph-node metastases (ALNM) in infiltrating ductal carcinoma (IFDC) and to create a prospective, validated statistical model to predict the likelihood of ALNM in patients in the present era of sentinel lymph-node (SLN) biopsy and enhanced histopathology. METHODS: Univariate and multivariate analyses of 13 clinicopathological variables (including tumour location) were performed to determine predictors of ALNM in 1659 eligible SLN biopsy procedures. A logistic regression model was developed and then prospectively validated on a second population of 187 subsequent consecutive procedures. RESULTS: Age, pathological tumour size, palpability, lymphovascular invasion (LVI), histological grade, nuclear grade, ductal histological subtype, tumour location (quadrant) and multifocality were associated with ALNM in univariate analyses (P < 0.001). Of these, only palpability and histological grade were not statistically associated with ALNM in the multivariate analysis (P> 0.05). The frequency of ALNM in upper-inner-quadrant (UIQ) tumours was 20.6%, compared with 33.2% for all other quadrants (P<0.0005). There was no statistical difference between UIQ and other-quadrant tumours in any clinicopathological variables analysed. The logistic regression model, developed based on the population of 1659, had the same accuracy, sensitivity, specificity, positive predictive value and negative predictive value when applied prospectively to the second population. CONCLUSION: Tumour size, LVI, age, nuclear grade, histological subtype, multifocality and location in the breast were independent predictive factors for ALNM in IFDC. ALNM is less frequent in UIQ tumours than in other-quadrant tumours. Our prospectively validated predictive model could be valuable in pre-operative patient discussions, although staging of the axilla in the individual patient remains necessary.

Adult↗
PubMed2002

Outcome of pregnancy in Asian women with systemic lupus erythematosus: experience of a single perinatal centre in Singapore.

OBJECTIVE: To study maternal and fetal outcomes in women with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Retrospective study of 27 pregnancies in 18 women with SLE in a single centre. RESULTS: The mean age was 30 years and most patients were nulliparous. Twenty-six of 27 pregnancies were in disease remission at the time of booking. Renal impairment was present in 7 pregnancies (6 women), of whom 2 were in end-stage renal disease on dialysis. Gestational diabetes developed in 4 pregnancies. There were 6 cases of pre-existing hypertension and 5 with superimposed pre-eclampsia. One woman developed intrapartum eclampsia. Two women had secondary antiphospholipid syndrome (APS) and suffered late fetal losses; in addition, they also developed SLE flares in the form of autoimmune haemolytic anaemia in the postpartum period. There was no maternal mortality. There was one termination of pregnancy for severe renal disease. The median gestational age at delivery was 38 weeks (range, 24 to 40 weeks) and the mean birth weight was 3047 g; the median Apgar scores were 8 and 9 at 1 and 5 minutes of life, respectively. There were 5 cases of intrauterine growth restriction (IUGR), 4 of which occurred in women with renal impairment. There were no cases of congenital heart block or neonatal lupus. There was a late fetal loss at 24 weeks in a woman with secondary APS. There were 2 preterm deliveries (7.4%) due to intervention for IUGR. CONCLUSION: Good pregnancy outcomes can be expected in women with SLE in remission. Pre-pregnancy counselling is crucial to achieve this. All pregnancies should still be considered high risk and be managed jointly between the obstetricians, the perinatologists and the physicians. In particular, those with renal impairment are at increased risk of IUGR, superimposed pre-eclampsia and preterm births. Co-existing APS augurs a poorer prognosis for pregnancy outcome, and may present atypically as autoimmune haemolytic anaemia in the postpartum period.

Abortion, Spontaneous↗
PubMed2002

Management of thromboembolic disease in pregnancy.

Venous thromboembolism (VTE) is the leading cause of maternal mortality and morbidity in developed countries including Singapore. The physiological changes of pregnancy and other factors, such as maternal age, parity, obesity, operative delivery, general anaesthesia and congenital and acquired thrombophilia, further increase the risk of VTE throughout all three trimesters of pregnancy, including the puerperium. VTE has a wide spectrum of clinical presentations and a high index of clinical suspicion is vital. Clinicians should not withhold the use of chest X-rays and ventilation-perfusion (V/Q) lung scans in pregnancy as the radiation emitted is well within the safety limits to the fetus. Most treatment guidelines are based on studies in non-pregnant populations. Heparin is the preferred anticoagulant as it does not cross the placenta and therefore carries no teratogenic risk to the fetus. There is increasing experience and confidence in the use of fixed dose subcutaneous low molecular weight heparin (LMWH) which removes the need for cumbersome monitoring, thereby allowing outpatient treatment. LMWH may also have a lower risk of osteopaenic complications compared to unfractionated heparin. With the exception of acute phase treatment of pulmonary embolism, LMWH is used in all other aspects of the treatment of VTE in pregnancy, including thromboprophylaxis. Risk stratification of women into high and low risk allows judicious use of anticoagulants for thromboprophylaxis. Antenatal thromboprophylaxis with LMWH is reserved for high-risk women, while low-risk women will only require such cover in the postpartum period.

Acute Disease↗
PubMed2002

The course of pregnancy in a patient with nail-patella syndrome.

INTRODUCTION: The nail-patella syndrome is a rare autosomal dominant condition with high penetrance. Pregnancy in such a patient is rare and we believe this to be the first report of a live birth occurring in a patient with nail-patella syndrome. CLINICAL PICTURE: A 25-year-old patient presented in her first pregnancy with nephrotic syndrome associated with characteristic bone abnormalities and nail dysplasia and was later diagnosed to have nail-patella syndrome. In her second pregnancy, the course of her pregnancy was complicated by further deterioration of renal function with superimposed pre-eclampsia resulting in early delivery at 28 weeks. CONCLUSION: Such pregnancies should be regarded as high risk and managed jointly with the renal physician in a tertiary care centre to ensure an optimal outcome to the mother and baby.

Adult↗
PubMed2001

An integrated approach in the discovery and characterization of a novel nuclear protein over-expressed in liver and pancreatic tumors.

An integrated approach in protein discovery through the use of multidisciplinary tools was reported. A novel protein, Hcc-1, was identified by analysis of the hepatocellular carcinoma (HCC)-M cell proteome. The assembled EST sequence of the 210 amino acid novel protein was subsequently confirmed by rapid amplification of cDNA ends (RACE). A total of 687 bp at the 5' untranslated region of Hcc-1 was identified. Promoter activity and several upstream open reading frames (uORFs) were demonstrated at this region. Bioinformatics prediction showed that the first 42 amino acids of the protein is a SAP domain with sequence matches to hnRNP from various vertebrate species. The Hcc-1 protein was localized to the cell nucleus while the gene was localized to chromosome 7q22.1. Hcc-1 cDNA level was increased in pancreatic adenocarcinoma. The level was also increased in well-differentiated hepatocellular carcinoma but decreases as the carcinoma progressed to a poorly differentiated stage.

5' Untranslated Regions↗
PubMed2001

Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice.

BACKGROUND: Germline mutations in the tumor suppressor PTEN predispose human beings to breast cancer, and genetic and epigenetic alterations of PTEN are also detected in sporadic human breast cancer. Germline Pten mutations in mice lead to the development of a variety of tumors, but mammary carcinomas are infrequently found, especially in mice under the age of six months. RESULTS: To better understand the role of PTEN in breast tumor development, we have crossed Pten heterozygous mice to MMTV-Wnt-1 transgenic mice that routinely develop ductal carcinomas in the mammary gland. Female Wnt-1 transgenics heterozygous for Pten developed mammary tumors earlier than Wnt-1 transgenics that were wild type for Pten. In most tumors arising in Pten heterozygotes, the Pten wild-type allele was lost, suggesting that cells lacking Pten function have a growth advantage over cells retaining a wild type allele. Tumors with LOH contained high levels of activated AKT/PKB, a downstream target of the PTEN/PI3K pathway. CONCLUSIONS: An animal model has been developed in which the absence of Pten collaborates with Wnt-1 to induce ductal carcinoma in the mammary gland. This animal model may be useful for testing therapies specific for tumors deregulated in the PTEN/PI3K/AKT pathway.

Journal Article↗
PubMed2001

Lymphovascular invasion enhances the prediction of non-sentinel node metastases in breast cancer patients with positive sentinel nodes.

BACKGROUND: Fifty percent of patients with sentinel lymph node (SLN) metastases have no metastatic disease in non-SLNs on axillary lymph node dissection (ALND). The goal of this study is to determine which patients have metastatic disease limited to the SLN, and, therefore, may not require completion ALND. METHODS: Of the first 1000 patients undergoing SLN biopsy at Memorial Sloan-Kettering Cancer Center, using a combined blue dye and isotope technique, 231 (26%) had positive SLN. Of these, 206 underwent completion ALND. They are the study group for this report. RESULTS: The likelihood of non-SLN metastasis was inversely related to three clinicopathologic variables: tumor size < or = 1.0 cm; absence of lymphovascular invasion (LVI); and SLN micrometastases (< or = 2 mm). None of 24 patients with all three predictive factors had non-SLN metastases, whereas 58% of patients with none of the factors had disease in the non-SLN. CONCLUSION: Patients with small breast cancers, no LVI, and SLN micrometastases have a low risk of non-SLN metastases, and may not require completion ALND.

Adult↗
PubMed2001

A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages.

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.

Antibodies, Viral↗
PubMed2001

Her-2/neu and breast cancer.

Breast cancer is the most common malignancy in women in the United States in the year 2000. The proto-oncogene Her-2/neu (c-erb-B2) has become an increasingly important prognostic and predictive factor in breast cancer. Overexpression/amplification of the Her-2/neu has been associated with a worse outcome in patients with breast cancer. Herceptin, a "humanized" murine monoclonal antibody directed against the extracellular domain of the Her-2/neu protein, is being used to treat breast cancer that overexpresses Her-2/neu. The status of Her-2/neu in the tumor has become a critical factor in the management strategy of a breast cancer patient. The objective of this article is to provide a comprehensive review of all aspects of Her-2/neu in breast cancer, including biology, prognostic and predictive value, targeted Herceptin therapy, and the laboratory testing of Her-2/neu.

Adenocarcinoma↗