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K Kwek

Publications and source records attributed to K Kwek.

10 recordsLinked to original sources

Epidemiology of pre-eclampsia and eclampsia at the KK Women's and Children's Hospital, Singapore.

INTRODUCTION: The incidences and characteristics of pre-eclampsia (PE) and eclampsia in KK Women's and Children's Hospital (KKH), a tertiary obstetrical referral centre in Singapore, were studied. METHODS: The incidences and types of PE between July 1999 and June 2003 were derived from the pregnancy disease databases. The characteristics of women with PE in relation to the general obstetric population were analysed on the age, race, parity, types of delivery, gestation at delivery and mortality. Case records of eclampsia were analysed. RESULTS: A total of 2,213 (3.6 percent) out of 61,595 deliveries were complicated by PE between July 1999 and June 2003. Incidence rates for mild or unspecified PE, severe PE, eclampsia and PE superimposed on hypertension were 2.47 percent (1,518), 0.97 percent (599), 0.02 percent (10) and 0.14 percent (85), respectively. The incidence increased with multiple pregnancies: from 3.5 percent in singletons to 7.5 percent in twins, 19.4 percent in triplets and 25.0 percent in quadruplets. The Caesarean section rate for PE was 46.1 percent compared with 23.7 percent in the hospital population. The proportion of premature birth (<37 weeks) in PE was 31.0 percent and that of severe prematurity (<32 weeks) was 5.7 percent, while hospital population proportions were 9.8 percent and 1.3 percent, respectively. The perinatal mortality rate (PMR) of PE was 11.0/1,000 births (population PMR was 4.4/1,000 births). There were only ten cases of eclampsia out of 61,595 deliveries (1:6160) giving an incidence of eclampsia of 16.2/100,000 deliveries. There was no stillbirth, neonatal and maternal death among the eclamptic patients. CONCLUSION: The incidence and outcome of eclampsia in KKH showed a significant reduction over the years due to improved obstetrical care. While PE is still common, eclampsia is now a very rare disease outcome.

Adult↗

The in vitro effects of clonidine and dexmedetomidine on human myometrium.

BACKGROUND: alpha(2)-adrenergic agonists have been used extensively in the field of anaesthesia. Their direct effect on the human myometrium was investigated in this in vitro study, as this may have clinical repercussions in obstetric anaesthesia. METHOD: Strips of pregnant human myometrium obtained from six individuals at elective caesarean section were mounted on the Mulvany myograph in Krebs solution to which increasing concentrations of clonidine and dexmedetomidine (1x10(-11) to 1x10(-6) g/mL) were added. RESULTS: Dexmedetomidine increased uterine contractility at simulated clinical plasma concentrations (1x10(-9) g/mL). These effects were seen with clonidine only at much higher tissue bath concentrations (1x10(-7) g/mL). CONCLUSION: The effect of dexmedetomidine on human myometrium has profound implications in obstetric anaesthesia and needs further clinical investigation.

Clonidine↗

The Randomized Nitric Oxide Tocolysis Trial (RNOTT) for the treatment of preterm labor.

OBJECTIVE: This study was undertaken to assess the effectiveness of glyceryl trinitrate (GTN) patches in comparison with beta2 sympathomimetics (beta2) for the treatment of preterm labor. STUDY DESIGN: A multicenter, multinational, randomized controlled trial was conducted in tertiary referral teaching hospitals. Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks' gestation were recruited and randomly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours. Obstetric and neonatal outcomes were assessed. RESULTS: Two hundred thirty-eight women were recruited and randomly assigned, 117 to beta2 and 121 to GTN. On a strict intention-to-treat basis, there was no significant difference in the time to delivery using Kaplan-Meier curves (P = .451). At 2 hours, 27% of women receiving beta2 had moderate or stronger contractions compared with 53% in the GTN group (P < .001). This led to 35% of women in the GTN group receiving rescue treatment. If delivery or requirement for beta2 rescue are regarded as treatment failure, then a significant difference was observed between the 2 arms (P = .0032). There were no significant differences in neonatal outcomes. CONCLUSION: GTN is a less efficacious tocolytic compared with ss2 sympathomimetics.

Adrenergic beta-2 Receptor Agonists↗

Evaluation of a bedside test for phosphorylated insulin-like growth factor binding protein-1 in preterm labour.

OBJECTIVE: The objective of this study was to assess the efficacy of a bedside test kit for phosphorylated insulin-like growth factor binding protein-1 (IGFBP-1) in the diagnosis of preterm labour and the prediction of subsequent preterm delivery. MATERIALS AND METHODS: We performed a bedside test for IGFBP-1 in 47 women who presented to the delivery suite in suspected preterm labour between 23 and 33 weeks. Tocolysis and steroid therapy were administered in all cases. RESULTS: Twenty-nine women (61.7%) tested negative and 18 women tested positive (38.3%). There was no statistical significance between the 2 groups except that the test-positive group had a greater median cervical dilatation (2.0 cm) compared to the testnegative group (1.0 cm) (P <0.05). The women who tested positive had a statistically significant longer median duration of hospitalisation, stay in delivery suite and tocolytic therapy (5.0 days, 56.0 hours and 34.5 hours respectively) compared to women who were test-negative (3.0 days, 19.0 hours and 10.0 hours respectively) (P <0.05). In addition, 91.7% of the patients in the IGFBP-1 negative group had a delay of more than 7 days between the onset of contractions and delivery, while only 44.4% of the women in the pIGFBP-1 positive group experienced such a delay. CONCLUSION: These results suggest that there may be a role for cervical IGFBP-1 test in the management of women presenting with suspected preterm labour. It may allow us to focus our efforts on women who are more likely to have a preterm delivery and perhaps allow us to avoid unnecessary treatment and to contain healthcare costs.

Adolescent↗

Our experience with eclampsia in Singapore.

AIM: To assess the incidence, epidemiological factors, preceding symptoms and signs, management regimens and obstetric outcomes of eclampsia in a tertiary care hospital in Singapore. METHOD: A retrospective study of all obstetric patients who suffered one or more eclamptic seizures in our hospital between January 1994 and December 1999. RESULT: There were 62 cases of eclampsia among 92,305 deliveries (6.7 per 10,000 deliveries). The incidence was highest among Indians. Those aged between 25 and 34 had the lowest incidence, while women younger than 25 or older than 34 had a significantly higher incidence. Forty (64.5%) patients had symptom or sign of impending eclampsia of which headache was the most common. Most of the patients (81.6%) who received antenatal care with us suffered their first eclamptic seizure in hospital, compared to 50% of the unbooked patients. There was one maternal death (mortality rate 1.6%), and 15 (24.2%) women had significant morbidity. There were 61 singleton pregnancies and one twin pregnancy. There were six intrauterine deaths and 57 livebirths. The perinatal mortality rate was 95.2 per 1,000 births. CONCLUSION: Eclampsia is still a major cause of maternal and foetal mortality and morbidity in Singapore. Race and age appear to be risk factors for eclampsia with Indian women and those at the extremes of reproductive age at greater risk. Antenatal care is important in reducing perinatal mortality and possibly maternal complications.

Adolescent↗

Human myometrial genes are differentially expressed in labor: a suppression subtractive hybridization study.

Human parturition is effected by a cascade of factors, of which many are unknown. We aim to identify the genes that are changed by labor in the human myometrium by suppression subtractive hybridization. We also seek to ascertain whether these genes are differentially expressed in the myometrium at the upper or fundal and lower segments of the uterus. Term myometrial tissues were obtained from laboring and nonlaboring women undergoing cesarean section after obtaining informed consent. Total RNA was used in suppression subtractive hybridization (CLONTECH PCR Select) to produce two subtracted cDNA libraries enriched for genes expressed during or before labor, labor and not-in-labor libraries, respectively. Dot blot screening of 400 positive clones, constituting 20% of the two subtracted libraries, revealed 30 differentially expressed clones, 14 of which were up-regulated by labor. Among the 10 known genes that were up-regulated in labor, 6 had apparent immune regulatory and inflammatory roles. Three are well-known inflammatory mediators and modulators that were previously linked with parturition: IL-8, manganese superoxide dismutase (MnSOD), and metalloproteinase-9. Three others, interferon-inducible 1-8d gene, elongation factor 1alpha, and nucleophosmin, have not been previously linked with labor. Constitutively expressed genes, including cyclophilin and alpha-actin, were found to be altered by labor. Quantitative real-time RT-PCR using Taqman probes further confirmed the up-regulation of some of these genes. The amounts of the specific genes assayed were standardized to 18S ribosomal RNA and are expressed as mean +/- SEM. Quantitative real-time RT-PCR showed that IL-8 mRNA rose from 0.003 +/- 0.002 in nonlaboring samples (n = 38) to 0.24 +/- 0.11 (n = 20) in gestational-age-matched spontaneously laboring women (P = 0.035). Similarly, MnSOD rose from 0.11 +/- 0.02 (n = 24) to 1.23 +/- 0.56 (n = 24) in gestational-age-matched women (P = 0.047). Additionally, cyclophilin, often used as a constitutive or housekeeping gene marker, increased from 0.0008 +/- 0.0002 (n = 6) to 0.002 +/- 0.0004 (n = 6; P = 0.008) during labor. Notably, MnSOD mRNA was differentially distributed between the upper (0.63 +/- 0.18) and lower (0.15 +/- 0.05; n = 15; P = 0.022) segments of the uterus, but IL-8 was not (n = 17; P = 0.97). Induced labor further showed significantly higher levels of IL-8 (0.63 +/- 0.21; n = 14) than spontaneous labor (0.22 +/- 0.11; n = 20; P = 0.046), but not MnSOD (P = 0.1). This work identifies novel as well as known genes that were not previously associated with parturition. It extends previous data indicating that there is differential expression of some, but not all genes within the gravid human uterus. Inflammatory genes constitute a major proportion of the known genes found to be up-regulated in labor, lending support to the hypothesis of an inflammatory mechanism for human parturition. This work further indicates that many factors associated with human labor and their complex interactions remain to be elucidated.

Computer Systems↗

Current understanding of pre-eclampsia.

INTRODUCTION: Pre-eclampsia is associated with significant morbidity and mortality for mother and baby, with post partum resolution. The disorder is triggered by a placental pathology followed by a wide spectrum of maternal systemic response. However, there remains controversy in practically every aspect of the condition. METHODS: A Medline search and hand search of recent publications pertaining to the scientific basis and clinical management of pre-eclampsia. RESULTS: With current interest in the scientific and molecular basis of the disease process, there has been an improved, albeit incomplete, understanding of the precise aetiology and pathogenesis of pre-eclampsia. Much of this has translated to improved clinical management strategies. The more rational use of various pharmacological agents, timing the delivery to optimise both the maternal and fetal condition, the decreasing rate of eclampsia, as well as trials on various screening and prophylactic strategies are testimony to this improvement. Despite this, many unanswered questions still remain and provide a challenge for both the clinician as well as the researcher. CONCLUSIONS: We reviewed the recent literature in order to provide a contemporary understanding of the basic pathogenesis of the condition as well as to highlight some basic strategies for clinical management. There is a clear need for more research to better understand the basic science behind the genesis of this condition, as well as to improve the level of care we offer to these women through the co-ordination of a multi-disciplinary team of clinicians.

Anticoagulants↗

Effects of nitrovasodilators on the human fetal-placental circulation in vitro.

This study examines the vasorelaxation of isolated human placental chorionic plate arteries and the perfused fetal-placental vasculature, in vitro, to a variety of nitrovasodilator compounds including glyceryl trinitrate (GTN) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-N-glutathione (SNG) and NaNO(2). The effects of these compounds were also examined under conditions of high (>450 mmHg) and low oxygen (<50 mmHg) tension. In a separate series of experiments the effects of GTN and NaNO(2)were further investigated with addition of the antioxidants cysteine (100 microm), glutathione (100 microm) or superoxide dismutase (SOD) (30 I.U./ml). The order of nitrovasodilator potency, when added directly to isolated fetal vessels was GTN=SNP>SNAP=SNG>NaNO(2). The order under low oxygen tension was similar, GTN=SNP>SNG= SNAP>or=NaNO(2). SNG ( approximately fourfold) and NaNO(2)( approximately 50-fold) were significantly more potent under low oxygen conditions. Cysteine, glutathione and SOD were without effect on GTN induced vasodilatation. However, all three agents significantly enhanced (six- to ninefold) the effects of NaNO(2)under similar conditions. When infused directly into the fetal-placental circulation during in vitro perfusion experiments the order of potency was GTN>SNP>or=SNG>or=SNAP>or=NaNO(2). When the nitrovasodilators were infused indirectly via the maternal intervillous space the order of potency was GTN>or=SNP>or=NaNO(2)>or=SNAP=SNG. Our observations suggest that there are important differences in the action of different classes of nitrovasodilator compounds on the fetal-placental circulation. The changes observed with SNG and NaNO(2)may be influenced by levels of tissue oxygenation.

Adolescent↗

Vasoactive effects of 8-epi-prostaglandin F(2alpha)in isolated human placental conduit and resistance blood vessels in vitro.

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Validation of an oscillometric electronic sphygmomanometer in an obstetric population.

Use of an automated electronic sphygmomanometer will allow us to minimize the errors inherent in mercury sphygmomanometry. We conducted this validation according to the 1990 protocol of the British Hypertensive Society. We recruited 87 subjects from the antenatal population of Kandang Kerbau Hospital and took three sequential readings using simultaneously both manual and electronic sphygmomanometry. A total of 261 readings from either method were thus collected and the results analyzed to compare the accuracy of electronically read blood pressure with that assessed manually. We found that 89.9% of the electronically read pressures differed from the manually read pressures by 5 mm Hg or less and 98.9% of the electronic readings differed from manual readings by 10 mm Hg or less; only 0.4% of readings had a difference of more than 15 mm Hg. The accuracy of the device was not affected either by the blood pressure or the arm circumference.

Adult↗