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Biomedical subjects

W B Giles

Publications and source records attributed to W B Giles.

At least 19 recordsLinked to original sources
PubMed2001

Alterations of placental vascular function in asthmatic pregnancies.

Asthma during pregnancy is associated with low-birthweight neonates at term but the mechanisms that cause this outcome are presently unknown. Changes in placental vascular function resulting from asthma or its treatment could contribute to altered fetal growth. We have prospectively followed women with asthma and a control group of women without asthma during their pregnancies, classified them based on asthma severity and glucocorticoid intake, and monitored fetal development and placental blood flow using Doppler ultrasound at 18 and 30 wk gestation. The placentae from these women were collected after delivery and vascular responses to dilator and constrictor agonists assessed using an in vitro placental perfusion method. At 18 wk gestation, umbilical artery flow velocity waveforms were significantly reduced in the moderate and severe asthmatic groups and in those women using high-dose inhaled glucocorticoid for the treatment of their asthma (ANOVA, p < 0.05). However, at 30 wk gestation there were no significant differences in umbilical artery flow velocity between control and asthmatic women (ANOVA, p > 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F(2alpha) were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.

Adult↗
PubMed2000

Fetal placental vascular responses to corticotropin-releasing hormone in vitro. Effects of variation in oxygen tension.

In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F(2alpha)(PGF(2alpha)) (1-100 micrometer). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, >/=450 mmHg and </=50 mmHg, respectively. Secretion of CRH into the maternal and fetal placental circulations was measured during changes in oxygen tension in normal placentae and placentae from abnormal pregnancies complicated by pre-eclampsia. The change from high to low oxygen perfusion resulted in a small increase in the basal perfusion pressure (21+/-3.6 to 28.3+/-2.6 mmHg; (P</= 0.001, Student's paired t -test). During high oxygen perfusion, CRH (0. 3-3000 p m) caused a concentration dependent reduction of the PGF(2alpha)induced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P</= 0.05, regression analysis, ANOVA). The effect of the NO synthase inhibitor l -nitro-omega-arginine methyl ester (l -NAME, 1-100 micrometer), on basal FAP during high and low oxygen conditions was also established. Low oxygen perfusion significantly attenuated l -NAME-induced increases in perfusion pressure (P</= 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the maternal but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from normal controls. In conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be related to reduced NO production. Reduced CRH induced vasodilation is associated with increased secretion of the CRH into the maternal but not fetal circulation.

Adult↗
PubMed2000

First trimester ultrasound with nuchal translucency measurement for Down syndrome risk estimation using software developed by the Fetal Medicine Foundation, United Kingdom--the first 2000 examinations in Newcastle, New South Wales, Australia.

In September 1997 screening for Down syndrome using first trimester ultrasound to measure nuchal translucency, with risk estimation by the software program developed in the United Kingdom by the Fetal Medicine Foundation, was introduced in Newcastle, New South Wales. In the first 2,000 such risk estimations 134 women (6.7 %) were screen positive (with a risk of greater than 1 in 300 at that gestation for Trisomy 21). In the first 1,000 of these 2,000 fetuses delivered thus far there were 8 cases of Trisomy 21, 2 of Trisomy 18 and 1 of 47 XXX. Nine of these 11 were screen positive, the only false negative results being for 2 cases of Trisomy 21. The detection rate for Trisomy 21 was 6 out of 8 (75%) and for every case of Trisomy 21 (Down Syndrome) detected by this process, 11.3 invasive tests would have been needed to make that diagnosis in a screen positive woman.

Down Syndrome↗
PubMed1999

Antenatal hospitalisations in New South Wales, 1995-96.

OBJECTIVES: To provide a population-based estimate of the prevalence of antenatal hospitalisations and to determine the reasons for admission. DESIGN: Descriptive study. Data sources were primarily the New South Wales inpatient Statistics Collection (ISC) and also the linked population-based New South Wales Midwives Data Collection. SETTING AND PATIENTS: All women resident in New South Wales (NSW) admitted to public and private hospitals in NSW for pregnancy complications from 1 July 1995 to 30 June 1996. MAIN OUTCOME MEASURE: Antenatal hospitalisations for pregnancy complications per 100 confinements. RESULTS: There were a total of 25,710 antenatal non-delivery admissions in NSW hospitals among 86,263 confinements, yielding a ratio of 30 antenatal admissions per 100 confinements (21 per 100 excluding day-stay admissions). Women without private health insurance, Aboriginal women and women under the age of 20 had significantly higher rates of antenatal admissions. The principal admitting diagnoses were hypertension (17.6%), threatened preterm labour (14.1%), antepartum haemorrhage (14.0%), threatened labour (after 37 weeks' gestation) (11.1%) and excessive vomiting in pregnancy (9.4%). A majority (58%) of antenatal admissions (including admissions to day-stay facilities) were for one day. CONCLUSIONS: Significant pregnancy-related morbidity, as measured by high ratios of antenatal admissions, is evident in NSW. Sociodemographic factors and health service management protocols appear to account for some of the variability in antenatal admissions.

Adolescent↗
PubMed1999

Vascular Doppler techniques.

Doppler ultrasound used for the assessment of the fetal umbilical circulation in the human pregnancy has been reported in the scientific literature since the early 1980s and has been rigorously evaluated by randomized, controlled trials. The consensus of the reviewers of these trials is that there do appear to be grounds for including umbilical artery Doppler ultrasound studies in the management of high-risk pregnancies. There is no apparent benefit for low-risk pregnancies or later gestation. Other fetal vascular beds are currently undergoing prospective studies and some limited randomized, controlled trials have been reported; but to date they are not at a point of development to be considered part of clinical management.

Female↗
PubMed1999

U46619-mediated vasoconstriction of the fetal placental vasculature in vitro in normal and hypertensive pregnancies.

OBJECTIVES: To measure in-vitro responses to the thromboxane A2 (TxA2) mimetic U46619 in the fetal placental vasculature of human placentae from normotensive women and those with pre-eclampsia. Furthermore, to compare fetal vascular responses to endothelin-1,5-hydroxytryptamine, potassium chloride (KCl) and prostacyclin (PGI2) in placentae from normal or pre-eclamptic pregnancies. METHODS: Single placental lobules of intact placentae were bilaterally perfused in situ (fetal and maternal) with constant flows of Krebs' solution. Changes in fetal arterial perfusion pressure during intra-arterial infusion of vasoactive agents were recorded. Fetal placental vasoconstrictor concentration response curves were obtained to U46619 (0.01-300 nmol/l), endothelin-1 (0.4-160 nmol/l), KCl (3-300 mmol/l) and 5-hydroxytryptamine (0.03-30 mumol/l). In addition, vasodilator concentration response curves were obtained for PGI2 (1.2-350 nmol/l) in the fetal placental circulation during submaximal increases in perfusion pressure with prostaglandin F2 alpha (PGF2 alpha; 0.7-2.0 mumol/l). RESULTS: The maximum increase in perfusion pressure caused by U46619 in placentae from normotensive women was 194 +/- 25 mmHg. The maximum response to U46619 was significantly reduced in the placentae from women with pre-eclampsia (104 +/- 21 mmHg). In contrast, there were no differences in constrictor responses to endothelin-1,5-hydroxytryptamine and KCl, or in dilator responses to PGI2 in placentae obtained from either normotensive women or those with pre-eclampsia. CONCLUSION: TxA2 receptor-mediated vasoconstriction is reduced in the fetal vasculature of placentae from women with pre-eclampsia, possibly to compensate for the increased levels of TxA2 seen in these conditions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Doppler ultrasound in multiple pregnancies.

This chapter aims to provide a current review of the use of Doppler ultrasound in the management of multiple pregnancies. OVID and Medline searches were undertaken. Randomized controlled trials, where available, were assessed by the Cochrane Review Manager (RevMan-version 3.0). The specific multiple pregnancy problems of fetal growth restriction (FGR), twin reversed arterial perfusion sequence and twin-twin transfusion syndrome (TTTS) were also reviewed. Historically, controlled and randomized controlled trials show a promising reduction in perinatal mortality in twin pregnancies where Doppler ultrasound is used. However, the numbers are small and further trials are recommended. In those twin pregnancies in which there is FGR as a result of placental dysfunction, Doppler ultrasonography will show intertwin discordancy. In those twin pairs where development is complicated by TTTS, there is often discordant fetal size, with concordant fetal Doppler results. Thus Doppler ultrasound appears to be useful in the management of twin pregnancies and in delineating those complicated by FGR and TTTS.

Female↗
PubMed1998

Examination of a low-cost pocket Doppler device for fetal assessment.

The objective of this study was to evaluate a pocket Doppler device (Multi Dopplex II) for the waveform analysis of umbilical artery systolic/diastolic (S/D) ratios and resistance index (RI). A prospective, paired study was undertaken in a perinatal ultrasound unit in a tertiary referral hospital. Forty-three high-risk pregnant women beyond 16 weeks' gestation had fetal umbilical artery flow velocity waveforms recorded with both Multi Dopplex II and duplex Doppler devices and the waveform analyses were calculated. The Multi Dopplex II falsely indicated absent diastolic flow in two cases and failed to produce a flow velocity waveform in the presence of maternal obesity, polyhydramnios and some cases of anterior placenta (n = 8). As well as this, the limits of agreement overall for both S/D ratio and RI were wide (for S/D ratio, -1.6 to 2.2 and for RI, -0.20 to 0.20). Even though the levels of agreement were better for the third trimester (for S/D ratio, -0.8 to 1.1 and for RI, -0.10 to 0.20), we concluded that the limits of agreement were too wide for clinical use.

Blood Flow Velocity↗
PubMed1996

Abnormal umbilical artery Doppler waveforms and cord blood corticotropin-releasing hormone.

OBJECTIVE: To determine whether placental secretion of corticotropin-releasing hormone into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. METHODS: Twenty women with abnormal Doppler umbilical artery flow velocity waveforms and six women with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms had cord blood concentrations of corticotropin-releasing hormone, ACTH, cortisol, and beta-hCG estimated. RESULTS: The mean cord blood corticotropin-releasing hormone concentration was significantly higher in pregnancies with abnormal umbilical artery flow velocity waveforms than in normal pregnancies (108 +/- 27 versus 24 +/- 8 pg/mL, P = .019). Elevated cord blood corticotropin-releasing hormone levels were seen in the abnormal group regardless of the presence or absence of preeclampsia or fetal growth restriction. There were no significant differences in cord blood cortisol, ACTH, or beta-hCG concentrations. CONCLUSION: The concentration of corticotropin-releasing hormone in the fetal circulation is significantly increased in pregnancies complicated by abnormal umbilical artery flow velocity waveforms. This may represent a stress-responsive compensatory mechanism in the human placenta.

Adult↗
PubMed1995

Vascular responses to sodium nitroprusside in the human fetal-placental circulation.

This study examined the activity of sodium nitroprusside (SNP) in the human fetal-placental circulation in vitro in pathological and experimental conditions in which vascular function may be impaired. SNP (13-3400 nM) caused a concentration-dependent reduction in fetal arterial perfusion pressure (FAP) in Krebs' perfused placental cotyledons, at basal tone and following pre-constriction with prostaglandin F2 alpha (PGF2 alpha). SNP-induced reduction in FAP in the PGF2 alpha pre-constricted fetal-placental circulation was enhanced approximately six-fold (5.85) in those placentae pre-treated with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (100 microM). Reductions in FAP in the preconstricted fetal-placental vasculature caused by SNP were not altered by prior infusion of ouabain (100 nM) into the fetal circulation or during low oxygen perfusion (O2 tension < 50 mmHg). No differences were observed in the responses obtained to SNP in placentae obtained from women with normotensive pregnancies or those associated with (i) pregnancy-induced hypertension, (ii) intra-uterine growth retardation, or (iii) an elevated umbilical-artery Doppler-ultrasound systolic/diastolic ratio, in either preconstricted placentae or those at basal tone. These findings are consistent with an up-regulation of guanylate cyclase/cGMP-mediated vasodilatation in the fetal-placental vasculature following complete blockade of endogenous NO production.

Adolescent↗
PubMed1995

Corticotropin-releasing hormone-induced vasodilatation in the human fetal-placental circulation: involvement of the nitric oxide-cyclic guanosine 3',5'-monophosphate-mediated pathway.

This study has used an in vitro perfusion method to investigate the mechanism by which CRH causes vasodilatation in the human fetal-placental circulation. In normal term placentas, vasodilatory responses to human CRH (24-7000 pmol/L) were examined during submaximal vasoconstriction (100-120 mm Hg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (0.7-2 mumol/L), KCl (50-100 mmol/L), or the thromboxane A2 mimetic, U46619 (0.05-0.5 mumol/L). Infusion of CRH caused a concentration-dependent vasodilatation that was similar in the presence of each constrictor agent (P > 0.05). The CRH antagonist, alpha-helical CRH-(9-41) (200 pmol/L), and a polyclonal CRH antiserum significantly inhibited CRH-induced vasodilatation during constriction with prostaglandin F2 alpha (P < 0.05). Vasodilatory responses to CRH were attenuated by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 mumol/L; P < 0.05), and the guanylate cyclase inhibitor, LY 83583 (1 mumol/L; P < 0.05), but not by the cyclooxygenase inhibitor, indomethacin (3 mumol/L; P > 0.05). In placentas of women with increased fetal vascular resistance, as demonstrated by Doppler ultrasound waveforms in vivo, CRH-induced vasodilatation was significantly reduced (P < 0.05). These results indicate that in the human fetal-placental circulation, CRH causes a vasodilatory response via a nitric oxide-/cGMP-dependent pathway. CRH may play a role in the control of vascular resistance to blood flow in the normal human placenta, and there may be a deficiency in the CRH signaling pathway of placentas with increased fetal vascular resistance.

Adult↗
PubMed1993

HIV infection in obstetric and gynaecological practice.

The initial impact of HIV infection on the practising obstetrician and gynaecologist was specifically related to the treatment of HIV positive women who were pregnant. The current North American experience suggests that HIV will be an important consideration in gynaecology from now on.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Review of obstetric operative intervention rates.

The trends in obstetric operative intervention at a major teaching hospital in Sydney, Australia, were reviewed during the decade 1979-1989. While the caesarean section rate has increased by 36.4%, forceps deliveries have decreased. The normal delivery rate has remained constant at 67%.

Cesarean Section↗
PubMed1991

Biophysical assessment of placental and membrane dysfunction.

During the 1960s and 1970s, the fetoplacental unit was assessed by means of biochemical studies in the form of oestriol and human placental lactogen assays. With the advent of both real-time ultrasound and fetal heart rate monitoring, the accent on fetal assessment has changed. More recently (the late 1980s) the use of Doppler ultrasound has expanded the non-invasive assessment of the fetoplacental unit. This review discusses these modalities along with reports of randomized controlled trial assessments of these modalities.

Amnion↗
PubMed1991

Fetal umbilical artery velocity waveforms and subsequent neonatal outcome.

Flow velocity waveforms (FVWs) from the fetal umbilical artery were recorded from 2178 pregnant women over a 6-year period. All of them had an obstetric factor indicating increased risk of fetal compromise. A total of 6749 studies was recorded. The systolic diastolic (AB) ratio was measured and classified as normal (less than 95th centile), elevated (95-99th centile), high (greater than 99th centile) or extreme (absent diastolic flow). The results of these studies have been related to subsequent fetal and neonatal outcome. An abnormal umbilical artery FVW was associated with shorter gestation and infants with lower birthweight, shorter length and lower ponderal index. There was a highly significant association between an abnormal FVW and the birth of an infant small for gestational age. The significance of the association increased with the increased abnormality of the umbilical artery FVW and this was independent of gestational age. Preterm infants associated with high or extreme AB ratios spent twice as long in the neonatal nursery than those with normal AB ratios. Analysis of 794 pregnancies studies serially indicated that an abnormal FVW in which the AB ratio was increasing, in contrast to a decreasing AB ratio, predicted a poor outcome for both size at birth and duration of neonatal intensive care. We conclude that in high risk pregnancy Doppler umbilical artery FVW studies predict the most compromised fetuses in terms of growth retardation and requirements for neonatal intensive care.

Adult↗
PubMed1991

The short-term outcome of singleton infants delivered before 28 weeks' gestation.

The short-term outcome of 271 singleton infants born at Westmead Hospital between 20 and 28 weeks' gestation, during a 5-year period are reported. The earliest gestation at which there was a survivor was 23 weeks. Survival rates from 23-23+6 weeks to 27-27+6 weeks, excluding congenital abnormalities, were 8.3% to 77.5% respectively. Overall 21.9% of deaths occurred in the delivery suite, 63.4% in the neonatal period, 3.7% in the postneonatal period in hospital and a further 11% after discharge from hospital. Of survivors at 12 months, 18.8% were judged to have a major impairment.

Birth Weight↗
PubMed1991

The short-term outcome of infants of multiple pregnancies delivered before 28 weeks' gestation.

The short-term outcomes of 29 multiple pregnancies delivered at Westmead Hospital between 20 and 28 weeks' gestation, during a 5-year period are reported. The earliest gestation at which there was a survivor was 24 weeks. The overall survival rate was 25%. Of deaths, 11.1% occurred in the delivery suite, 85.2% in the neonatal period with a further 3.7% in the postneonatal period in hospital. The outcomes for second twins were generally poor. Of survivors at 12 months, 44% were judged to have a major impairment. Extremely preterm multiple pregnancies have a high mortality and morbidity rate.

Birth Weight↗