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Biomedical subjects

G S Yeo

Publications and source records attributed to G S Yeo.

At least 19 recordsLinked to original sources

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↗

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↗

Characteristics of six newborn infants with postnatal findings of severe intracranial haemorrhage.

OBJECTIVE: The objective of this study was to study the characteristics of newborn infants with postnatal findings of severe neonatal intracranial haemorrhage. METHODS: All the records of babies who underwent surgery from 1997 to 2002 for intracranial haemorrhage were reviewed. These were correlated with their antenatal records to see if fetal intracranial haemorrhage had been detected at the 20 weeks' screening scan or any other incidental scan e.g. growth scan. The perinatal records were also reviewed to see if there was associated birth trauma such as instrumentation or obstetric manoeuvres at delivery. RESULTS: Six cases of severe intracranial haemorrhage were diagnosed postnatally. Of these, only 1 case was detected antenatally on ultrasound scan. None of the cases were due to birth trauma. Three babies were found to have clotting factor deficiency. One of them subsequently developed cerebral palsy. One baby was diagnosed to have alloimmune thrombocytopenia. One case underwent an emergency Caesarean section for non-reassuring fetal status. Extensive intracranial haemorrhage, attributed to hypoxia, was found. The baby died. CONCLUSIONS: Our study suggests that neonatal intracranial haemorrhages are not exclusively due to birth trauma. The study also shows that fetal intracranial haemorrhage may not be detected antenatally by the routine practice. The causes in our study included clotting deficiency, alloimmune thrombocytopenia and hypoxia.

Humans↗

Advances in imaging in prenatal diagnosis and fetal therapy.

Technological advances in ultrasound have contributed to improvements in prenatal diagnosis. Transvaginal scanning and harmonic imaging have allowed better resolution and improved structural characterisation. Doppler techniques have further been improved, which allow accurate flow studies of vessels in the placenta and fetus. These have contributed much to the management of intrauterine growth restriction, fetal anaemia and twin-twin transfusion syndrome (TTTS). Three-dimensional sonography and magnetic resonance imaging ultrafast sequences are useful adjuncts to conventional 2-dimensional sonography, increasing the confidence and diagnostic accuracy of prenatal diagnosis. Fetal therapy has seen major advances in recent years as well, secondary to improvements in endoscopic instruments and surgical techniques. Selective Nd:YAG laser photocoagulation of communicating vessels and cord occlusion have been used to treat complications of monochorionic twins like TTTS and twin-reversed arterial perfusion sequence.

Female↗

Idiopathic chronic fetomaternal haemorrhage resulting in hydrops--a case report.

INTRODUCTION: We report a case of idiopathic chronic fetomaternal haemorrhage (FMH) that developed in the late trimester. CLINICAL PRESENTATION: The patient presented with decreased fetal movement at 38 weeks gestation. Antenatal follow-up was uneventful with normal serial ultrasound performed at 22 and 35 weeks. Prior to delivery, the cardiotocography (CTG) was abnormal with decreased baseline variability and late deceleration. Emergency lower segment caesarean section was performed. Upon delivery, a hydropic neonate with a haemoglobin level of 3.9 g/dL was noted. The Kleihauer-Betke test was positive, confirming FMH. OUTCOME: The neonate later developed intraventricular haemorrhage (IVH) and spastic cerebral palsy on follow-up. DISCUSSION: It is possible for FMH to occur late at the third trimester leading to detrimental effect. The fact that FMH can occur without antecedent risk factors underscores the importance of further research, and a high index of suspicion.

Adult↗

A case series of pre-viable severe twin-twin transfusion syndrome.

INTRODUCTION: We present a case series of pre-viable severe twin-twin transfusion syndrome (TTTS). CLINICAL PICTURE: In year 2000, there were 16,688 deliveries in KK Women's and Children's Hospital. Four cases that presented before 24 weeks gestation satisfied the sonographic criteria for severe TTTS: same-sex fetuses, absence of twin peak sign, thin intertwine membrane, polyhydramnios associated with large bladder in recipient twin, and oligohydramnios and small or absent bladder in donor twin. TREATMENT: Amnioreduction, septostomy and termination of pregnancy were offered. OUTCOME: In 1 case abortion was chosen. The follow-up was at least 18 months postnatal. There was 1 intrauterine death, 2 with severe neurological handicap and 3 with normal outcome. CONCLUSION: Pre-viable severe TTTS is associated with significant mortality and morbidity rates and should be diagnosed promptly and managed in a tertiary fetal medicine unit with multi-disciplinary input.

Adult↗

A case series of gastrointestinal abnormalities in fetuses with echogenic bowel detected during the antenatal period.

OBJECTIVE: The objective was to evaluate the incidence of gastrointestinal abnormalities amongst those fetuses with antenatally diagnosed echogenic bowel (EB). MATERIALS AND METHODS: A retrospective review of all cases delivered from April 2002 to March 2003 with antenatally diagnosed EB was conducted. This was defined as bowel that appeared as echogenic as (if not greater than) the iliac bone on a real-time image. The postnatal outcomes with regard to gastrointestinal abnormalities, till their discharge, were noted. RESULTS: Of the 13,941 patients delivered, there were 70 cases with antenatally diagnosed EB, giving an incidence of 70/13,941 or 0.50%. Of these, 6 defaulted follow-up and 1 had a mid-trimester termination of pregnancy at 21 weeks' gestation for social reasons. Of the remaining 63 cases with EB, 2 were stillbirths at 31 weeks and 35 weeks of gestation, respectively. Three fetuses (3/63 or 4.76%) were diagnosed with gastrointestinal abnormalities. Meconium plug syndrome was diagnosed postnatally in 2 cases, of which, 1 resolved with conservative management while the other required an emergency laparotomy. Intestinal atresia was diagnosed in the postmortem of one of the stillbirths. There was evidence of intrauterine growth retardation (IUGR) in both the stillbirth and the fetus that had required laparotomy. None of the 3 fetuses exhibited clinical features of aneuploidy. CONCLUSION: As the quoted background risk for gastrointestinal pathology is 0.23%, an increased incidence (4.76%) is observed in those fetuses found to have antenatal EB. It is possible that the presence of IUGR is associated with a worse prognosis. Further prospective studies are needed to verify this association.

Abnormalities, Multiple↗

Severe newborn encephalopathy unrelated to intrapartum hypoxic events: 3 case reports.

INTRODUCTION: Newborn encephalopathy is an important clinical problem associated with considerable morbidity and mortality and is pertinent in the assignment of blame in obstetrics litigation. CLINICAL PICTURE: We report 3 babies with severe neonatal encephalopathy. OUTCOME: In all 3 cases, intrapartum hypoxic insult was unlikely to be a significant contributing factor towards the development of neonatal encephalopathy. The aetiology was unclear in the first 2 cases and there was antecedent antenatal cause of feto-maternal haemorrhage in the last case. CONCLUSION: Prevention of neonatal encephalopathy was not possible in these 3 cases. We recommend that umbilical cord blood gases be clearly documented in such cases to reduce unnecessary obstetrics litigation of intrapartum asphyxia as the significant contributing factor to the poor neonatal outcome. Clinicians must have a high index of suspicion of antecedent causes and perform the necessary investigations to elucidate the aetiology of the neonatal encephalopathy.

Adult↗

Fetal congenital complete heart block: prophylaxis with intravenous gammaglobulin and treatment with dexamethasone.

We report a case of complete fetal heart block in a 35-year-old Chinese woman known to be positive for anti-SSA/Ro and anti-SSB/La antibodies. She had fetal hydrops leading to intrauterine death in her first pregnancy Prophylactic intravenous immunoglobulin, given at 14 and 18 weeks' gestation, as well as oral dexamethasone, commenced at 24 weeks' gestation, allowed continuation of the pregnancy until 34 completed weeks of gestation. An external pacemaker was inserted in the baby on the first day of life. Two-and-a-half months later, a permanent pacemaker was inserted.

Adult↗

The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models.

The peptide products of the pro-opiomelanocortin (POMC) gene have established roles in the control of physiological processes as diverse as adrenal steroidogenesis, skin pigmentation, analgesia and inflammation. In the last 5 years, evidence accumulated from murine and human genetic models of disrupted melanocortin signalling has firmly established a central role for a population of hypothalamic neurons expressing POMC in the control of appetite and body weight. Of the five known melanocortin receptors, the MC4R has been most closely linked to body weight regulation. While a-MSH is active at this receptor and suppresses appetite after central injection, important roles for other POMC-derived products have not been excluded. The development of pharmacological agonists acting on, or mimicking, the hypothalamic melanocortinergic pathway may provide exciting opportunities for the therapy of human obesity.

Animals↗

Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.

Over 20 severely obese subjects in 11 independent kindreds have been reported to have pathogenic heterozygous mutations in the gene encoding the melanocortin 4 receptor (MC4R), making this the most common known monogenic cause of human obesity. To date, the detailed clinical phenotype of this dominantly inherited disorder has not been defined, and no homozygous subjects have been described. We determined the nucleotide sequence of the entire coding region of the MC4R gene in 243 subjects with severe, early-onset obesity. A novel two-base pair GT insertion in codon 279 was found in two unrelated subjects, and four novel missense mutations, N62S, R165Q, V253I, C271Y, and one mutation (T112M) reported previously were found in five subjects. N62S was found in homozygous form in five children with severe obesity from a consanguineous pedigree. All four heterozygous carriers were nonobese. Several features of the phenotype, e.g. hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved reproductive function, closely resemble those reported previously in Mc4r knock-out mice. In addition, a marked increase in bone mineral density was seen in all affected subjects. In transient transfection assays, the N62S mutant receptor showed a responsiveness to alphaMSH that was intermediate between the wild-type receptor and mutant receptors carrying nonsense and missense mutations associated with dominantly inherited obesity. Thus MC4R mutations result in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance.

Adolescent↗

The CART gene and human obesity: mutational analysis and population genetics.

The cocaine- and amphetamine-regulated transcript (CART) peptide is a recently characterized neuropeptide implicated in the control of appetite. We hypothesized that genetic variation in CART may contribute to human obesity. The entire coding region of CART was determined by nucleotide sequencing in 91 unrelated subjects with severe early-onset obesity. A novel amino acid change, Ser66Thr, was found in 2 probands and in 0 of 100 control subjects but did not cosegregate with obesity in family studies. Two common polymorphisms were found in the 3'-untranslated region (A1475G and deltaA1457). An effect of these polymorphisms on body composition and intermediate phenotypes related to obesity was examined in a large Caucasian population in the U.K. Neither polymorphism showed any significant relationship with obesity; however, men heterozygous for the A1475G variant had significantly lower waist-to-hip ratio (WHR), fasting plasma insulin, and fasting triglycerides. Regression analysis indicated that the effects on insulin and triglycerides were likely to be secondary to the effects on WHR. Thus, we have conducted the first systematic study of the CART gene in human obesity, and although no clear association with obesity was found, the data suggest that genetic variation in the CART locus might influence fat distribution and variables related to syndrome X.

3' Untranslated Regions↗

Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.

AIM OF STUDY: The aim of our study was to determine the seroprevalence of cytomegalovirus (CMV), toxoplasma and parvovirus infection in our local antenatal population, and to see the effects, if any, of age, race, parity and nationality on its seroprevalence. METHODOLOGY: The sera of 120 consecutive antenatal women seen in KK Women's and Children's Hospital between the period of October 1997 and March 1998 were screened for cytomegalovirus (CMV) IgG, toxoplasma IgG and parvovirus B19 IgG and IgM. An antibody titer greater than 1:32 was regarded as positive. RESULTS: A total of 87.0% of patients were tested seropositive for CMV IgG, 17.2% seropositive for toxoplasma IgG and 30.0% seropositive for parvovirus IgG. There seemed to be a trend of increasing seropositivity with age in all three groups, however only parovirus B19 reached statistical significance. The incidence of all three infections were higher among the Malays, Indians and other races compared to the Chinese. CONCLUSION: CMV is endemic in our population and hence the most common infection. Toxoplasmosis and parvovirus is relatively low in our population but this implies that a large proportion of our antenatal women are still susceptible to these infections. Prevention of congenital CMV, toxoplasmosis and parvovirus infection is mainly by educating the antenatal population.

Adult↗

Confidential enquiry of stillbirths in current obstetric practice.

OBJECTIVE: Confidential panel enquiry into sub-optimal factors relating to stillbirths. METHOD: All 121 stillbirths in KK Women's and Children's Hospital in the years 1995 and 1996 were studied. Three assessors reviewed the case records of each death, and panel consensus was reached regarding sub-optimal antenatal care and factors leading to stillbirths. RESULT: The incidence rate of stillbirth was 4.04 per 1000 deliveries. A total of 76 cases (62.8%) were found to have grade II and III sub-optimal factors in their management. Patients themselves were involved in the sub-optimal management of their own pregnancy in 52.9% of the stillbirths. Primary healthcare givers were involved in 8.3% of all stillbirths, specialist caregivers 12.4% and antenatal care system 4.1%. CONCLUSION: The study has identified sub-optimal antenatal management in over 60% of cases. As patients' factors form the major contribution towards sub-optimal care, management strategy aimed towards improving patients' education and compliance to antenatal care should be a priority.

Adult↗

Generation and analysis of 25 Mb of genomic DNA from the pufferfish Fugu rubripes by sequence scanning.

We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.

Animals↗

Is the vacuum extractor really the instrument of first choice?

This study was a retrospective analysis of the pattern of usage of both the forceps and vacuum extractor as well as the neonatal outcome on all the instrumental deliveries conducted in 1995 at the Kandang Kerbau Hospital, Singapore. There were a total of 927 forceps deliveries and 495 vacuum extractions but neonatal data was available for only 481 forceps and 255 vacuum extractor babies. (There were 2 neonatal units which accepted admissions on alternate days; all of the data were collected from 1 of the units only). Demographic data were comparable in most aspects except that vacuum deliveries were significantly associated with higher parity and shorter labours. There was a trend towards using the vacuum extractor in less difficult cases. Almost all the instrumental deliveries were conducted by specialists. Birth trauma was significantly more likely to occur with the vacuum extractor. Almost all the deliveries were conducted with similar expertise in both groups, yet the use of the vacuum extractor resulted in more birth trauma even in the presence of 'easier' cases. This may suggest an inherent risk in using the vacuum extractor.

Adult↗

Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells.

MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗