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Biomedical subjects

E M Wallace

Publications and source records attributed to E M Wallace.

At least 37 records · Page 2Linked to original sources
PubMed2001

Levels of knowledge of Down syndrome and Down syndrome testing in Australian women.

At their first hospital antenatal visit, 209 women were interviewed to explore their level of knowledge of Down syndrome and the available prenatal tests. Overall, the women had limited knowledge. Non-Caucasian women had less knowledge of Down syndrome, available prenatal tests and the association of Down syndrome with advanced maternal age than Caucasian women. Women with a history of a previous pregnancy and women over 35 years of age were not more aware of Down syndrome or the available tests than other women. These findings have significant implications for antenatal education and the implementation of screening programs for Down syndrome.

Adult↗
PubMed2001

The management of extremely premature infants and the perceptions of viability and parental counselling practices of Australian obstetricians.

The attitudes of Australian obstetricians to the resuscitation of extremely premature infants are reported. A structured questionnaire including questions regarding antenatal parent counselling, resuscitation practices, survival rates and personal attitudes about life support was distributed to obstetricians working in Australian hospitals with a Level 3 nursery Eighty-nine (48% response rate) replies were received from 12 units located in seven major cities. Obstetricians are more likely to discuss resuscitation with prospective parents with increasing gestation with a major shift occurring at 23-24 weeks' gestation. They strive for consensus with parents regarding resuscitation options and they act upon the opinion of both the prospective parents and their paediatric colleagues. Threat of litigation rarely influences the decision to limit resuscitation of an extremely preterm infant. Obstetricians may underestimate the prognosis for extremely preterm infants. The data presented offer useful insights into current attitudes and practice of tertiary hospital obstetricians.

Adult↗
PubMed2001

Activin A and activin receptors in gestational tissue from preeclamptic pregnancies.

Maternal serum activin A levels are elevated in women with preeclampsia. To explore whether this could be due, at least in part, to increased production by the gestational tissues, we have measured activin A in the serum of women with (n=23) or without preeclampsia (n=62) at 29-40 weeks of gestation and in placenta and fetal membranes from preterm preeclamptic (PT-PE, n=8), term preeclamptic (T-PE, n=10) and healthy term controls (T-C, n=10). We have also explored if there are associated changes in activin receptor Alk2, ActRII and ActRIIB in these tissues. The relative amounts of receptor proteins were measured by densitometry on Western blots and receptors and activin beta(A) subunit localised by immunohistochemistry in PT-PE, T-PE and T-C gestational tissues (n=8-10/group). Maternal serum activin A levels were significantly elevated in women with preeclampsia (multiples of the normal median (MoM)=3.5, P<0.0001, Mann-Whitney U test) compared with healthy women (median MoM=1.0). Compared with control tissues, the activin A content was significantly higher in preeclamptic placentae (P=0.001 and P=0.0005 for PT-PE and T-PE respectively, Mann-Whitney U test), but significantly lower in the amnion (P=0.005 and P=0.014 for PT-PE and T-PE respectively) and choriodecidua (P=0.009 for T-PE). The maternal serum activin A level in women with preeclampsia was significantly correlated with elevated placental production (P=0.01, Pearson's correlation). Receptor Alk2 protein levels were significantly elevated in T-PE placentae (P=0.0006, Mann-Whitney U test), ActRIIB levels were significantly lower in PT-PE placentae (P=0.01) and ActRII levels were significantly lower in PT-PE choriodecidua (P=0.0002) compared with controls. There were no apparent differences in the distribution of the beta(A) subunit and receptors Alk2, ActRII and ActRIIB between control and preeclamptic tissues. These findings suggest that elevated levels of activin A in the maternal circulation in association with preeclampsia are due, at least in part, to increased placental production, and that the regulation of activin synthesis in placenta and fetal membranes is differentially regulated. Further, the differences in activin receptor protein levels between preeclamptic and control placenta and choriodecidua suggest that activin A-induced regulation may be altered in preeclampsia.

Activin Receptors↗
PubMed2000

Prevention of perinatal group B streptococcal disease: screening practice in public hospitals in Victoria.

OBJECTIVES: To survey clinical protocols for prevention of early-onset group B streptococcal disease (EOGBSD) of the newborn in public maternity hospitals. DESIGN: Postal questionnaire with telephone follow-up when required. SETTING: All hospitals that undertook deliveries in public patients in the State of Victoria, November 1997 to January 1998. RESULTS: The survey was sent to 84 hospitals: 71 responded and 64 met the criteria and provided usable data (76% response rate). These 64 represented 42,784 births (68% of births in Victoria in 1996). Most hospitals (62; 97%) undertook actions that would identify and treat pregnant women at risk of EOGBSD. 48 (75%) performed bacteriological screening for maternal GBS carriage, but only 20 of these had a unified protocol. Screening was mostly by low vaginal swab (15 hospitals) and before 30 weeks' gestation (12 hospitals). Low vaginal swab plus anal swab was used in only one hospital. Bacteriological screening was significantly more common in metropolitan hospitals than in rural hospitals (100% versus 67%; P = 0.007, Fisher's exact test). Targeting of prophylaxis by recognised risk factors was reported by 59 (92%) hospitals, 45 of which also undertook screening. There was considerable variation in the specific risk factors used. CONCLUSIONS: While there was clearly widespread awareness of EOGBSD in Victorian public hospitals, prevention programs varied considerably. The development of consensus practice guidelines might improve EOGBSD prevention, reducing morbidity, mortality and costs.

Antibiotic Prophylaxis↗
PubMed2000

Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action.

Potent and selective non-peptidic inhibitors of human endothelin-converting enzyme-1 (ECE-1) have been designed as potential modulators of endothelin (ET-1) production in vivo. Because of its unique structural characteristics and long duration of action in vivo, the dual ECE-1 and neutral endopeptidase 24.11 (NEP) inhibitor, CGS 26303, was selected as an attractive lead for further optimization of potency and selectivity. Replacement of the P(1)' biphenyl substituent of CGS 26303 by a conformationally restricted 3-dibenzofuranyl group led to more potent and more selective ECE-1 inhibitors, such as the tetrazole 27. The remarkable effect of this P(1)' modification allowed for the first time phosphonomethylcarboxylic acids, such as 29, to display both potent (IC(50) = 22 nM) and selective (104-fold vs NEP) ECE-1 inhibition. Chemoenzymatic syntheses of the new alpha-amino acid (S)-3-dibenzofuran-3-ylalanine intermediate were developed, and improved procedures to generate substituted alpha-aminoalkylphosphonic acids were devised to support the production of various analogues. Although additional gains in intrinsic ECE-1 inhibitory potency could occasionally be achieved by addition of a P(1) side chain, these compounds (e.g. 43a) showed poor functional activity in vivo in the big ET-1 pressor test. Phosphonoalkyl dipeptides featuring 3-dibenzofuranyl groups in both the P(1)' and P(2)' positions were also very potent ECE-1 inhibitors, albeit lacking the desired selectivity against NEP. Functionally, 27and 29 were the two most efficacious compounds from this study, producing sustained inhibition of ECE-1 activity in rats, as measured by their ability to block the hypertensive effects induced by big ET-1. This profile was similar to that of a potent ET(A)/ET(B) dual receptor antagonist, SB 209670. Due to their favorable in vitro and in vivo profiles, 27 (CGS 34043) and 29 (CGS 35066) constitute new pharmacological tools useful in assessing the role of ECE-1 in pathological conditions.

Animals↗
PubMed2000

Sexual origins of placental dysfunction.

Severe placental dysfunction is much more common in pregnancies with a male than with a female fetus. Furthermore, the birthweight/placental weight ratio is increased in these pregnancies, consistent with fetal growth restriction, and is higher with a male fetus than with a female fetus. These observations of placental insufficiency may underlie the increased in-utero loss rate of male fetuses.

Birth Weight↗
PubMed2000

The effect of a residual isthmus of surviving tissue on conduction after linear ablation in atrial myocardium.

The aim of this study was to determine the relationship between the size of discontinuities in lines of ablation and wavefront propagation. Discontinuities in linear radiofrequency lesions used for the treatment of atrial fibrillation may be proarrhythmic and a major clinical problem. A better understanding of the electrophysiological properties of these discontinuities (isthmuses) may assist in their detection and treatment. Linear lesions were made in the right atrial free wall using a Nd:YAG laser in 12 dogs. Conduction properties across the discontinuities were studied by pacing from either side of the lesion. Two of the three isthmuses less than 0.8 mm(2) in cross section (smallest 0.2 mm(2)) conducted at extrastimulus intervals of 300 ms. All three failed to conduct at cycle lengths close to the atrial effective refractory period. Isthmuses above 0.8 mm(2) (n¿=8) conducted at all cycle lengths. Conduction slowing (mean slowest conduction 0.5 +/- 0.3 m/s) occurred in the region of the isthmus but the overall delay was only 6 +/- 6 ms where propagation through the isthmus occurred. The effect on conduction of small discontinuities in linear lesions is dependent on the size of the residual isthmus. All but the very smallest of discontinuities in linear lesions conduct and therefore have the potential to participate in reentrant arrhythmias. Efforts should be directed toward the development of ablation techniques that reliably produce continuous transmural linear lesions for cure of atrial fibrillation and flutter.

Animals↗
PubMed2000

Maternal serum total activin A and follistatin in pregnancy and parturition.

OBJECTIVE: To examine changes in maternal serum levels of activin A and follistatin during pregnancy and labour. DESIGN: In three cross sectional and three longitudinal studies venous blood was collected from women during pregnancy, spontaneous labour, labour induction and prior to elective caesarean section for the measurement of activin A and follistatin. SETTING: Monash Medical Centre, Clayton, Victoria, Australia. POPULATION: One hundred and twenty-three women participated in a cross sectional study in pregnancy, 18 women in two longitudinal pregnancy studies, 36 women in a cross sectional labour study, nine women in a longitudinal study of labour induction. Ten women undergoing elective caesarean section were also studied. METHODS: Activin A and follistatin were measured using two sensitive and specific enzyme-linked immunosorbent assays. RESULTS: In the cross sectional study of pregnancy, mean (SEM) maternal serum activin A and follistatin levels increased towards term (2.4 ng/mL (0.3) and 1.8 ng/mL (0.3) in first trimester to 18.9 ng/mL (3.8) and 5.3 ng/mL (0.9) at term, respectively), but the longitudinal study revealed that levels plateau in the last three weeks of pregnancy (16.0 ng/mL (2.6) and 6.2 ng/mL (1.4) at 37 weeks and 16.6 ng/mL (3.5) and 6.2 ng/mL (0.5) before labour for activin A and follistatin, respectively). There was no difference in levels of activin A and follistatin between women delivered by caesarean section and labouring women at term (14.9 ng/mL (2.8) vs 11.0 ng/mL (0.93) and 5.95 ng/mL (0.67) vs 5.71 ng/mL (0.63), respectively) and levels of both proteins did not alter throughout spontaneous or induced labour. CONCLUSIONS: We believe that these data argue against activin A playing an acute role in the initiation or regulation of human parturition.

Activins↗
PubMed2000

Women's knowledge of and attitudes to first and second trimester screening for Down's syndrome.

One hundred women were interviewed at their first hospital antenatal visit to assess their knowledge of, and attitudes to, first versus second trimester screening for Down's syndrome. Overall, the women had limited knowledge of Down's syndrome, and the prenatal screening and diagnostic tests that are available. However, when informed, the majority of women expressed a clear preference for first trimester screening tests for Down's syndrome, regardless of the rate of miscarriage of Down's syndrome pregnancies between 10 and 15 weeks of gestation. These findings have implications for the planning of prenatal Down's syndrome screening programmes.

Abortion, Spontaneous↗
PubMed2000

Uptake of Down syndrome screening in an Australian Vietnamese population.

It has been previously shown that the uptake of prenatal diagnosis by Victorian women of a non-English speaking background is significantly lower than that of comparable English speaking women. To explore this further we have examined the uptake of Down syndrome screening and diagnosis by Vietnamese women attending a community-based antenatal clinic in metropolitan Melbourne over a two year period. Of the 207 women studied, 161 (78%) were offered screening or diagnosis and of these women 139 (86%, 95%CI 81-92%) accepted the offer, representing 67% (95%CI 61-74%) of the entire population. Of the 127 women who had screening, rather than diagnosis, 12 (9%) had an 'increased risk' result. Eleven of these women accepted diagnosis. We also explored the reasons why 45 (22%) of women were not offered screening. Almost half (44%) of these women first attended the clinic at a too advanced stage of gestation but in 25 women there were no obvious reasons. These results are discussed in the context of current prenatal screening and diagnostic practice in Victoria and simple recommendations made.

Adult↗
PubMed2000

The utilisation of nuchal translucency as a prenatal marker of Down syndrome, 1993-1999.

A sample of 6,038 obstetric ultrasound referrals and reports between January 1993 and June 1999 in a single Melbourne private ultrasound practice was reviewed to determine whether the referral and reporting pattern for nuchal translucency (NT) measurement has changed. The proportion of both 10-14 week ultrasound scans and mid trimester fetal anatomy scan referrals increased significantly over the study period (p < 0.001 and p < 0.001, respectively). There was also a significant increase in NT reporting and the number of specific referrals for an NT measurement over the study period (p = 0.01 and p < 0.001, respectively). If current trends continue it is likely that the 10-14 week scan for NT measurement will become a routine component of antenatal care. Therefore, as a matter of urgency, it is imperative that the best and most cost-effective screening strategy for Down syndrome in an Australian population is defined.

Biomarkers↗
PubMed2000

Effect of atrial radiofrequency ablation designed to cure atrial fibrillation on atrial mechanical function.

INTRODUCTION: The effects of linear radiofrequency lesions in the atria for cure of atrial fibrillation on atrial contraction have not previously been quantified. METHODS AND RESULTS: Atrial function was measured before and 30 +/- 24 days after a biatrial ablation procedure designed to cure atrial fibrillation in eight dogs and after a sham procedure in three dogs. Atrial mechanical function was assessed using Doppler diastolic blood flow velocities, atrial systolic pressure wave amplitude, and assessment of atrial contribution to cardiac output estimated by comparison of AV sequential pacing to ventricular pacing at the same heart rate. The mitral Doppler A/E velocity ratio was 1.03 +/- 0.45 before and 0.72 +/- 0.43 after ablation (P = 0.048). The tricuspid A/E ratio was 0.88 +/- 0.17 before and 0.71 +/- 0.12 after ablation (P = 0.04). The estimated atrial contribution to cardiac output was 18% +/- 9% before and 5% +/- 4% after ablation (P < 0.01). The left atrial systolic pressure wave amplitude was 2.8 +/- 1.5 mmHg before and 1.7 +/- 1.0 mmHg after ablation (P = 0.1). These changes were not observed in control dogs. Lesions covered 25% +/- 6% of the atrial endocardial surface. CONCLUSION: Multiple linear radiofrequency lesions in the atria designed to cure atrial fibrillation may impair atrial contractility. Reduced atrial function is partly due to loss of atrial myocardial mass, but regional delays in atrial activation and splinting of the atria by scarring also may contribute.

Animals↗
PubMed2000

The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women.

Macrophage inhibitory cytokine-1 (MIC-1) is a recently described divergent member of the transforming growth factor-ss superfamily. MIC-1 transcription up-regulation is associated with macrophage activation, and this observation led to its cloning. Northern blots indicate that MIC-1 is also present in human placenta. A sensitive sandwich enzyme-linked immunosorbent assay for the quantification of MIC-1 was developed and used to examine the role of this cytokine in pregnancy. High levels of MIC-1 are present in the sera of pregnant women. The level rises substantially with progress of gestation. MIC-1 can also be detected, in large amounts, in amniotic fluid and placental extracts. In addition, the BeWo placental trophoblastic cell line was found to constitutively express the MIC-1 transcript and secrete large amounts of MIC-1. These findings suggest that the placental trophoblast is a major source of the MIC-1 present in maternal serum and amniotic fluid. We suggest that MIC-1 may promote fetal survival by suppressing the production of maternally derived proinflammatory cytokines within the uterus.

Adult↗
PubMed2000

Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders.

Activin A levels are elevated in maternal serum of pregnant women with hypertensive disturbances. Because follistatin is a circulating binding protein for activin A, the present study was designed to evaluate whether serum follistatin and activin A levels also change in patients with hypertensive disorders in the last gestational trimester. The study design was a controlled survey performed in the setting of an academic prenatal care unit. Healthy pregnant women (controls, n=38) were compared with patients suffering from pregnancy-induced hypertension (PIH, n=18) or pre-eclampsia (n=16). In addition, the study included a subset of patients with pre-eclampsia associated with intrauterine growth restriction (IUGR, n=5). Maternal blood samples were withdrawn at the time of diagnosis (patients) or in a random prenatal visit (controls), and serum was assayed for follistatin and activin A levels using specific enzyme immunoassays. Hormone concentrations were corrected for gestational age by conversion to multiples of median (MoM) of the healthy controls of the same gestational age. Follistatin levels were not different between controls and patients, while activin A levels were significantly increased in patients with PIH (1.8 MoM), pre-eclampsia (4.6 MoM), and pre-eclampsia+IUGR (3.2 MoM, P<0.01, ANOVA). The ratio between activin A and follistatin was significantly increased in patients with PIH (1.5 MoM) and was further increased in patients with pre-eclampsia (4.5 MoM) and in the group with pre-eclampsia+IUGR (2.6 MoM). Follistatin levels were positively correlated with gestational age in control subjects (r=0. 36, P<0.05) and in patients with PIH (r=0.46, P<0.05) or pre-eclampsia (r=0.61, P<0.01), while activin A correlated with gestational age only in the healthy control group (r=0.69, P<0.0001). The finding of apparently normal follistatin and high activin A levels in patients with PIH and pre-eclampsia suggests that unbound, biologically active, activin A is increased in women with these gestational diseases.

Activins↗
PubMed1999

Effect of antenatal betamethasone administration on placental vascular resistance.

BACKGROUND: High placental vascular resistance is an important cause of fetal growth restriction and subsequent perinatal mortality. Identification of affected pregnancies allows appropriate fetal surveillance and delivery, but there are no known therapeutic strategies to decrease resistance and improve blood flow. However, placental corticotropin-releasing hormone (CRH) is thought to be a potent fetoplacental vasodilator, and exogenous corticosteroids can increase placental CRH secretion. Therefore, we examined whether corticosteroids could improve fetoplacental blood flow in pregnancies with increased vascular resistance. METHODS: A retrospective review of umbilical-artery flow-velocity waveforms (FVWs) before and after betamethasone administration was undertaken in pregnancies with increased placental vascular resistance, as shown by umbilical-artery absent end-diastolic flow (AEDF). FVWs were obtained by pulsed-wave doppler ultrasonography. We studied all 28 pregnancies monitored at the maternal-fetal medicine unit of a university teaching hospital since 1995. FINDINGS: The median duration of gestation at presentation with AEDF was 27 weeks (range 23-33). In 19 (68% [95% CI 49-86]) pregnancies, umbilical-artery diastolic flow returned within 24 h after betamethasone administration, consistent with decreased resistance. The median duration of this effect was 3 days (range 2-7). There were no differences in duration of gestation at diagnosis or delivery, or in birthweight between fetuses showing a return of flow after betamethasone and those not showing a return of flow. INTERPRETATION: In pregnancies with umbilical-artery AEDF, betamethasone treatment is associated with decreased placental vascular resistance, possibly induced via increased placental CRH secretion. This study does not provide insights into whether this effect would be beneficial or harmful to the fetus.

Anti-Inflammatory Agents↗