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Biomedical subjects

Warwick Giles

Publications and source records attributed to Warwick Giles.

6 recordsLinked to original sources

Neonatal neurodevelopmental outcomes following tocolysis with glycerol trinitrate patches.

OBJECTIVE: The object of this study was to determine the effects of maternal tocolysis with glycerol trinitrate (GTN) patches on the neurodevelopment of infants. STUDY DESIGN: This was a randomized, multicenter, controlled trial comparing the efficacy of GTN patches with standard beta2 agonist as tocolytic therapy. The previously reported outcomes of this study indicated no difference in neonatal mortality or morbidity to hospital discharge. One hundred fifty-six surviving infants from 2 Australian centers were psychometrically assessed using the Griffiths Mental development Scales (revised) at 18 months of age. RESULTS: There was no difference in psychometric performance between those infants enrolled in either the GTN (81 infants) or beta2 agonist (75 infants) arm of the study. CONCLUSION: This randomized trial supports no significant difference between GTN patches in comparison with standard beta2 agonist for tocolytic therapy. The results underscore the association between premature labor and adverse infant outcomes.

Adrenergic beta-Agonists↗

Renal venous Doppler sonography in preeclampsia.

OBJECTIVE: The elevation in blood pressure associated with preeclampsia appears to be associated with a shift in the renal pressure natriuresis curve. Pressure natriuresis is modulated by renal medullary pressure. In obstructive uropathy, Doppler sonography has been used to indicate changes in renal venous impedance, possibly measuring alterations in medullary pressure and compliance in this condition. The hypothesis tested in this study was that an elevation in renal venous pulsation may occur in preeclampsia compared with normal pregnancy. METHODS: Seven patients with clinical evidence of preeclampsia were referred for fetal well-being confirmation by sonography in the third trimester. Seven pregnant patients without renal disease or hypertension reviewed in the third trimester served as a control group. Doppler studies of the interlobar arteries and veins of both kidneys were performed, with a total of 14 kidneys imaged per group. Arterial and venous impedance indices were obtained. The impedance indices for the patients were compared by the Student t test. RESULTS: No significant difference was noted between the arterial resistive indices. The mean venous impedance index for the hypertensive patients was 0.50 +/- 0.12, and that for the control patients was 0.37 +/- 0.06 (P = .003). CONCLUSIONS: Preeclampsia in the third trimester appears to be associated with altered medullary venous pulsation, possibly indicating reduced medullary pressure.

Adult↗

Tocolysis: current controversies, future directions.

The use of tocolytic agents for the treatment of preterm labor is not supported by the current evidence from placebo-controlled trials. Despite this, tocolytics continue to be widely used in clinical practice. Possible reasons for the lack of observed benefit include the hypothesis that suppression of labor may be harmful in some situations, along with a failure to appreciate the implications of the complex physiology of parturition. Importantly, however, it must be recognized that the quality of evidence addressing the question is poor, with studies significantly underpowered to detect changes in health outcomes. Where tocolysis is used, recent trends have favored agents with lower maternal side effect profiles, including calcium channel blockers and the oxytocin receptor antagonist atosiban. The use of cyclooxygenase-selective inhibitors of prostaglandin synthesis is currently being explored. Future directions in tocolytic research include the use of multiple agent therapies, along with the development of more selective treatments with low side effect profiles. Such agents include oxytocin receptor antagonists with more favorable pharmacological properties and prostaglandin F2alpha receptor antagonists. Future research into tocolytic therapies must focus on evaluating health outcomes from treatments rather than simply the ability to prolong pregnancy, and consequently the design of appropriate clinical studies needs careful consideration with respect to issues such as inclusion criteria, sample size and the selection of appropriate outcome measures.

Animals↗

The Doppler assessment in multiple pregnancy randomised controlled trial of ultrasound biometry versus umbilical artery Doppler ultrasound and biometry in twin pregnancy.

OBJECTIVE: To assess the addition value of umbilical artery Doppler ultrasound added to standard ultrasound biometry measurements in the management of twin pregnancies. DESIGN: A prospective randomised controlled multicentre trial of women with twin pregnancies. SETTING: Tertiary level referral hospitals in Australia, New Zealand and Southeast Asia. POPULATION: Pregnant women with twin pregnancies. METHODS: Women were randomised at 25 weeks of gestation to receive either standard ultrasound biometric assessment or standard assessment plus Doppler ultrasound umbilical artery flow velocity waveform analysis. The studies were repeated at 30 and 35 weeks unless otherwise indicated. Physicians were advised to institute close fetal surveillance in the presence of an abnormal umbilical artery Doppler study or with biometry indicators of fetal compromise. MAIN OUTCOME MEASURES: Standard obstetric (mode of delivery, perinatal mortality, hypertension, antenatal admissions and gestation at delivery) and neonatal (5 minute Apgar scores <5, admissions to neonatal nursery and requirements for ventilation) outcomes and statistical analysis was on intention-to-treat. There were no significant differences between the two groups with respect to demography, antenatal, peripartum and neonatal outcomes. There was no difference in the perinatal mortality rate in the no Doppler group (n = 264), which was 11/1000 live births, and the Doppler group (n = 262), which was 9/1000 live births. There were three unexplained intrauterine deaths in the no Doppler group and none in the Doppler group (OR 0.14, 95% CI 0.01-1.31). Two intrauterine deaths in the Doppler group were due to cord prolapse in labour and a fetomaternal haemorrhage, both very unlikely to be influenced by Doppler surveillance. CONCLUSIONS: In this study, close surveillance in twin pregnancy resulted in a lower than expected fetal mortality from 25 weeks of gestation in both the no Doppler and Doppler groups. The lower rate of unexplained fetal death in the no Doppler group was not significantly different from the Doppler group.

Adult↗

Maternal plasma corticotropin-releasing hormone trajectories vary depending on the cause of preterm delivery.

OBJECTIVE: Although second trimester maternal plasma corticotropin-releasing hormone concentrations are elevated in women who are destined to deliver preterm, the sensitivity and positive predictive value of an individual test of corticotropin-releasing hormone concentration is low. This poor screening performance may be due in part to the observation that the causes of preterm delivery are heterogenous, with potentially different effects on corticotropin-releasing hormone production. We have reanalyzed data from a previous cohort of women with multiple samplings to determine whether the trajectory of increase of placental corticotropin-releasing hormone provided more information than did a single sample. STUDY DESIGN: In this cohort, where 2 to 4 samples that had been assayed for corticotropin-releasing hormone were available on 305 women, the general form of the exponential equation y = ae(bt) was fitted to the corticotropin-releasing hormone data of each individual by the Gauss-Newton nonlinear least squares method, which generated the parameters, y-intercept and rate of rise, in corticotropin-releasing hormone concentration for each woman. Nonparametric statistical techniques, including bootstrapping, were applied to compare the results for the group of women who delivered at term with the group of women who delivered spontaneously preterm and the group of women who were delivered preterm by induction or cesarean delivery because of obstetric indication. RESULTS: The 3 clinically defined groups have significantly different parameters, y-intercept and rate of rise, which describe the corticotropin-releasing hormone trajectory. The group that delivered preterm because of obstetric indications had a similar mean y-intercept but significantly greater mean rate of rise in corticotropin-releasing hormone concentration than the term group (0.3491 vs 0.1788; 95% CI, 0.2331-0.4615 vs 0.1394-0.2330). The group that delivered spontaneously preterm had a significantly greater mean y-intercept than the group that delivered preterm because of obstetric indication (17.08 vs 1.83; 95% CI, 5.89-28.43 vs 0.03-5.19) but a similar mean rate of rise to the group that delivered at term. CONCLUSION: These data suggest that spontaneous preterm delivery is associated with an abnormal setting of the production of corticotropin-releasing hormone that is present from very early in pregnancy, although women who experience an induced preterm delivery are characterized by rapidly rising placental corticotropin-releasing hormone concentrations. These data further suggest that clinical abnormalities that are associated with preterm delivery by induction or cesarean delivery are associated with abnormalities that lead to a rapidly increasing corticotropin-releasing hormone concentrations. Trajectories for corticotropin-releasing hormone provide information beyond that obtained from a single sample.

Cesarean Section↗