Biomedical subjects

Fionnuala McAuliffe

Publications and source records attributed to Fionnuala McAuliffe.

14 recordsLinked to original sources

PubMed2004

Baf60c is essential for function of BAF chromatin remodelling complexes in heart development.

Tissue-specific transcription factors regulate several important aspects of embryonic development. They must function in the context of DNA assembled into the higher-order structure of chromatin. Enzymatic complexes such as the Swi/Snf-like BAF complexes remodel chromatin to allow the transcriptional machinery access to gene regulatory elements. Here we show that Smarcd3, encoding Baf60c, a subunit of the BAF complexes, is expressed specifically in the heart and somites in the early mouse embryo. Smarcd3 silencing by RNA interference in mouse embryos derived from embryonic stem cells causes defects in heart morphogenesis that reflect impaired expansion of the anterior/secondary heart field, and also results in abnormal cardiac and skeletal muscle differentiation. An intermediate reduction in Smarcd3 expression leads to defects in outflow tract remodelling reminiscent of human congenital heart defects. Baf60c overexpressed in cell culture can mediate interactions between cardiac transcription factors and the BAF complex ATPase Brg1, thereby potentiating the activation of target genes. These results reveal tissue-specific and dose-dependent roles for Baf60c in recruiting BAF chromatin remodelling complexes to heart-specific enhancers, providing a novel mechanism to ensure transcriptional regulation during organogenesis.

Animals↗

PubMed2004

Fetal cardiac troponin I in relation to intrapartum events and umbilical artery pH.

The objective of this study was to measure fetal cardiac troponin I in umbilical artery blood in relation to intrapartum events and umbilical artery pH. Umbilical artery blood samples were obtained after delivery from 110 infants and cardiac troponin I was measured. The onset of labor, mode of delivery, presence of meconium, and umbilical artery pH were examined in relation to cardiac troponin I. The median cardiac troponin I level was 0.03 ng/mL (range, 0.03 to 0.881 ng/mL). Neonates with a cardiac troponin I level above the normal range had a lower umbilical artery pH when compared with those neonates with a normal cardiac troponin I level (p = 0.005). No relationship between the following parameters and cardiac troponin I was observed: gestational age, parity, presence of labor, meconium staining, mode of delivery, birth weight, and Apgar scores. Fetal cardiac troponin I shows little variation at birth. Increased levels of cardiac troponin I are associated with a lower umbilical artery pH.

Adult↗

PubMed2004

Fetal cortisol in relation to labour, intrapartum events and mode of delivery.

We set out to measure fetal cortisol in the human umbilical vein in relation to onset of labour, intrapartum complications and mode of delivery. Umbilical cord venous samples were obtained after delivery from 98 infants and serum total cortisol was measured. The onset of spontaneous labour, induction of labour, elective caesarean section, spontaneous vaginal delivery, emergency caesarean section in labour, instrumental delivery, the presence of meconium staining of the liquor and umbilical artery pH were examined in relation to serum fetal cortisol. Spontaneous onset of labour, mode of delivery, meconium staining of the liquor and gestational age were independent predictors of umbilical venous cortisol levels. Those infants delivered by elective caesarean section had the lowest cortisol levels, while the highest levels were recorded in those infants following instrumental delivery. Fetal cortisol is significantly elevated in association with spontaneous human parturition and is highest Its among babies born by instrumental delivery.

Adult↗

PubMed2004

Pregnancy at high altitude: a hyperviscosity state.

BACKGROUND: Pregnancy at high altitude has been associated with intrauterine growth restriction and preeclampsia. These conditions, at sea level, have been linked to increased hematocrit and blood viscosity. The aim of this study was to investigate the effect of high altitude on maternal hemorheology. METHODS: This was a cross-sectional study. We examined 94 pregnant women at 10-38 weeks of gestation resident at high altitude (4370 m above sea level) and 75 at sea level, and 24 and 17 nonpregnant women at each altitude, respectively. Blood and plasma viscosity, hematocrit, plasma fibrinogen, albumin and total protein concentrations were determined in blood samples obtained after an overnight period of fasting. RESULTS: Pregnancy at high altitude, compared to sea level, is characterized by higher hematocrit, blood viscosity (at high shear rate), plasma viscosity, total protein and fibrinogen concentrations (25%, 38%, 7%, 13.3% and 25%, respectively) and 6% lower albumin concentration. Nonpregnant women at high altitude, compared to sea level, had higher hematocrits, blood viscosity, plasma viscosity, total protein and fibrinogen concentrations (25%, 55%, 18%, 26% and 98%, respectively) and 13% lower albumin concentration. CONCLUSION: Pregnancy at high altitude compared to sea level is characterized by increased blood viscosity as a result of increased hematocrit and plasma viscosity.

Adult↗

PubMed2004

Respiratory function in pregnancy at sea level and at high altitude.

OBJECTIVE: To determine the effect of pregnancy on respiratory function in a non-Caucasian group and determine whether there was an interaction between pregnancy and altitude of residence. DESIGN: Prospective cross sectional study. SETTING: Antenatal clinics in Peru, at sea level in Lima and at high altitude in Cerro de Pasco. SAMPLE: Peruvian women with singleton pregnancies; 122 living at sea level and 192 living at 4300 m altitude in the Peruvian Andes. At each location, 19 non-pregnant women were also studied. METHODS: Respiratory function was measured in pregnant and non-pregnant women living at sea level and at 4300 m. MAIN OUTCOME MEASURES: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), total lung capacity (TLC), inspiratory capacity (IC), residual volume (RV), expiratory residual volume (ERV) and functional residual capacity (FRC). RESULTS: At sea level, RV and TLC were higher in the third compared with the first trimester (P < 0.05). At high altitude, FEV1 (P < 0.01), ERV (P < 0.01) and FRC (P < 0.01) were lower in the third compared with the first trimester. Pregnant and non-pregnant women at high altitude were 4 cm shorter (P < 0.0001) and had larger lung volumes (P < 0.01); their total lung capacities were approximately 1 L greater than women living at sea level (P < 0.0001). CONCLUSION: These results suggest that the effect of pregnancy on the respiratory function of healthy women is influenced by altitude of residence.

Altitude↗

PubMed2004

Maternal cardiac function during pregnancy at high altitude.

OBJECTIVE: To investigate the maternal cardiovascular adaptation in pregnancy at high altitude, compared with that at sea level. DESIGN: Cross sectional study. SETTING: Two maternity units providing routine antenatal care: one at 4370 m above sea level (Cerro de Pasco, Peru) and one at sea level (Lima, Peru). POPULATION: We examined 175 pregnant women at 5-41 weeks of gestation and 16 non-pregnant controls resident at high altitude and 132 pregnant women and 18 non-pregnant controls at sea level. METHODS: Two-dimensional and M-mode echocardiography of the left ventricle. MAIN OUTCOME MEASURES: Maternal cardiac output and left ventricular longitudinal and transverse systolic function indices. RESULTS: Pregnancy at high altitude, compared with sea level, is associated with 11% lower birthweight and 31% lower maternal cardiac output, due to 15% lower stroke volume and 11% lower heart rate. The lower stroke volume was due to a lower preload and impaired longitudinal and transverse left ventricular systolic function. Mean arterial pressure was about 8% lower during pregnancy at high altitude versus sea level. Pregnant women at high altitude failed to expand their intravascular space to the same extent as the sea level group: cardiac output increased by 17%, left atrial diameter by 12% and end-diastolic diameter by 1% at high altitude versus 41%, 25% and 5%, respectively, at sea level. CONCLUSIONS: Pregnancy at high altitude, compared with sea level, is characterised by lower cardiac output due to lower heart rate and lower stroke volume and reduced expansion of the maternal intravascular space compared with the non-pregnant state.

Adaptation, Physiological↗

PubMed2003

Pulmonary diffusing capacity in pregnancy at sea level and at high altitude.

The impact of pregnancy on respiratory function and whether this is influenced by living conditions, such as altitude of residence, must be determined if the management of pregnant women, particularly those with pulmonary disease is to be optimized. Pulmonary diffusing capacity, corrected for haemoglobin concentration (DL(COc)), therefore, was measured in 112 healthy Peruvian women with singleton pregnancies living at sea level and 192 living at 4300 m. At each location, 19 non-pregnant women were studied. The mean DL(COc)s of the pregnant and non-pregnant women studied at sea level were similar but lower than those of their high altitude counterparts (P<0.001, P<0.001). At high altitude, the mean DL(COc)s of women studied in the first and second trimester were similar to that of non-pregnant women, but the mean DL(COc) of pregnant women studied in the third trimester was lower than that of the non-pregnant women (P<0.01). Our results demonstrate that the effect of pregnancy on pulmonary diffusing capacity is influenced by altitude of residence.

Altitude↗

PubMed2003

Maternal electrolyte and liver function changes during pregnancy at high altitude.

BACKGROUND: High-altitude (HA) hypoxia leads to profound cardiovascular, respiratory and electrolyte changes, and pregnancy at HA has been associated with increased incidence of preeclampsia and intrauterine growth restriction. OBJECTIVE: To examine the effect of high altitude on maternal serum electrolytes and liver enzymes. DESIGN: Cross-sectional study of 77 pregnant women at 6-40 weeks of gestation resident at HA (4370 m above sea level) and 80 at sea level (SL) and 13 and 15 nonpregnant women at each altitude, respectively. Serum electrolytes (sodium, potassium, calcium and phosphate), creatinine, bilirubin and liver enzymes (alkaline phosphatase (ALP), aspartate transaminase (AST) and gamma-glutamyl transferase (gamma-GT)) were measured. RESULTS: Pregnancy at HA, compared to SL, was associated with higher serum osmolality (0.4%), sodium (0.7%), creatinine (14%) and phosphate (5%) concentrations and lower potassium (10%) concentration. Calcium and albumin-corrected calcium concentrations were higher at HA compared to SL in nonpregnant women (8%), with no difference in pregnant women. AST, gamma-GT and ALP concentrations were not significantly different between HA and SL, neither in pregnant nor in nonpregnant women. AST and gamma-GT were lower in pregnant compared to nonpregnant women (30%) at HA, whereas the difference was not significant at SL. Total bilirubin concentrations were higher at HA compared to SL by about 25% both in pregnant and in nonpregnant women, the difference reaching statistical significance only in the pregnant group. CONCLUSIONS: Pregnancy at HA is associated with increased osmolality, sodium, creatinine, calcium, phosphate and total bilirubin concentrations. Liver enzyme activities are similar to SL.

Adult↗

PubMed2003

Maternal cardiac function in twin pregnancy.

OBJECTIVE: To investigate maternal cardiac function in twin pregnancy. METHODS: We conducted a cross-sectional study of 119 pregnant women with twin pregnancies at 10-40 weeks' gestation. Two-dimensional and M-mode echocardiography of the left ventricle was performed in the left lateral decubitus position to assess left ventricular longitudinal and transverse systolic function. The measurements were compared with those obtained from 128 women with singleton pregnancies previously reported. RESULTS: In twin pregnancies, compared with singletons, maternal cardiac output was greater by 20% (P <.001), because of a greater stroke volume (15%, P <.001) and heart rate (3.5%; P =.04). Furthermore, in women with twins there were greater left ventricular end-diastolic and left ventricular end-systolic dimensions, left ventricular mass (13.5%; P <.001), fractional shortening (3%; P =.04), and ejection fraction (2.5%; P =.04). Mean arterial pressure and global time to shortening in women with twins, compared with singletons, were less in the first trimester by approximately 2%, but after midpregnancy they increased progressively, so that at term the measurements were greater by 3% and 5.7%, respectively (P =.03). Conversely, long axis shortening in women with twins, compared with singletons, was greater in the first trimester by approximately 6.5%, but at term it was 3% less (P =.01). Twin pregnancies that subsequently developed preeclampsia had a hemodynamic profile similar to the rest of the twin population. CONCLUSION: Twin pregnancy is characterized by an even more hyperdynamic circulation than singleton pregnancy. Left ventricle longitudinal systolic function and mean arterial pressure are more abruptly affected after 20 weeks compared with singleton pregnancies.

Adult↗

PubMed2002

Maternal serum insulin-like growth factor binding protein-1 in pregnancy at high altitude.

OBJECTIVE: To investigate the effect of environmental hypoxia at 4300-m altitude on the maternal serum concentration of insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: We conducted a cross-sectional study of 108 pregnant women in Peru, 62 from high altitude (4300 m, 14100 ft) and 46 from sea level at 14-42 weeks' gestation. For comparison, 20 healthy nonpregnant women (ten from high altitude and ten from sea level) were also examined. Total and nonphosphorylated IGFBP-1 were measured in maternal serum. RESULTS: Both total and nonphosphorylated IGFBP-1 were higher at high altitude than at sea level in the pregnant groups (ratio = 1.28, P =.008, and ratio = 1.45, P =.003, respectively), and there was significant interaction between high altitude and sea level (P =.037 and P =.043, respectively). The threshold model showed that the difference became significant from 25 weeks' gestation onwards. CONCLUSION: Before 25 weeks of pregnancy, there was no significant difference in IGFBP-1 between women living at high or low altitude, suggesting that the increased IGFBP-1 at high altitude is unlikely to be related to inadequate trophoblast invasion resulting in placental hypoxia. In the second half of pregnancy, the maternal and fetal demands increase dramatically, and low atmospheric oxygen with resulting maternal systemic hypoxemic hypoxia may cause placental hypoxia. This stimulates increased production of IGFBP-1, which in turn restricts the insulin-like growth factor-mediated fetal growth as an adaptive mechanism to prevent worsening of the fetoplacental hypoxia.

Adult↗

PubMed2002

Flow-mediated dilatation of the brachial artery in pregnancy at high altitude.

OBJECTIVE: Pregnancy at high altitude has been associated with increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on endothelial function during pregnancy as assessed by a non-invasive method. DESIGN: Cross-sectional study. SETTING: Two maternity units providing routine antenatal care: one at high altitude (District General Hospital--IPSS in Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru). POPULATION: Sixty pregnant women at 6-42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively. METHODS: Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution ultrasound. MAIN OUTCOME MEASURES: Differences in flow mediated dilatation of the brachial artery in two groups of pregnant women, one at high altitude and one at sea level. RESULTS: Both at high altitude and sea level flow-mediated dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls. However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59% lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance. CONCLUSION: These data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the brachial artery, is not impaired.

Adult↗

PubMed2002

Respiratory function in singleton and twin pregnancy.

OBJECTIVE: Singleton pregnancy causes important changes in respiratory function. The incidence of twin pregnancies is increasing, but it is not known whether affected women suffer greater respiratory compromise. The aim of this study was to determine if changes in respiratory function during pregnancy in healthy women were greater in those with a twin pregnancy compared with those with a singleton pregnancy. DESIGN: Cross sectional study. SETTING: London teaching hospital. POPULATION: Healthy pregnant women attending the antenatal clinic and ultrasound department. METHODS: A cross sectional study of respiratory function was performed in 68 women with twin pregnancies (17 examined in the first trimester, 35 second trimester, 16 third trimester) and 140 women with singleton pregnancies (28, 80, 40, respectively) and 22 non-pregnant women. Women were examined once between 7 and 40 weeks of gestation. Forced vital capacity, relaxed vital capacity, forced expiratory volume in 1 second (FEV1), peak flow, inspiratory capacity, functional residual capacity (FRC), expiratory reserve volume, pulmonary diffusing capacity and minute ventilation were measured. RESULTS: Both in twin and singleton pregnancies, the mean FRC and expiratory reserve ventilation of women studied in the third trimester and minute ventilation of women studied in each trimester differed significantly from that of the non-pregnant women. There were, however, no significant differences demonstrated in respiratory function between healthy women with twin as compared with singleton pregnancies. CONCLUSION: In healthy women, the extra demands of atwin compared with a singleton pregnancy do not compromise further the respiratory system.

Adult↗

PubMedDate not supplied

Detection of fetal structural abnormalities with US during early pregnancy.

Ultrasonography (US) is performed during early pregnancy for dating, determination of the number of fetuses, assessment of early complications, and increasingly for evaluation of the fetus, including measurement of the thickness of the nuchal translucency (NT). Measurement of NT thickness between 11 and 14 weeks gestation, combined with maternal age and maternal serum biochemistry, can be an effective method of screening for trisomy 21 and other chromosomal abnormalities. Furthermore, an increased NT thickness in the presence of a normal karyotype is associated with an increased frequency of structural defects and genetic syndromes. Therefore, this finding is an indication for a more detailed anatomic survey of the fetus. Besides nuchal abnormalities, a wide range of other congenital anomalies can be diagnosed with US at 11-14 weeks gestation, including defects of the central nervous system, heart, anterior abdominal wall, urinary tract, and skeleton. The anatomic survey can be performed with a standardized protocol by using transabdominal US and, when necessary, transvaginal US. A thorough knowledge of the US features of normal fetal development is necessary to avoid potential diagnostic pitfalls.

Abdominal Wall↗

PubMedDate not supplied

Tetrasomy 9p mosaicism associated with a normal phenotype.

Isochromosome (tetrasomy) 9p is a rare chromosomal aberration characterized by phenotypic abnormalities ranging from mild developmental delay to multiple anomalies including intrauterine growth retardation, cerebral ventriculomegaly, dysmorphic facial features, cleft lip or palate, abnormal genitalia and renal anomalies. We present a patient with isochromosome (tetrasomy) 9p mosaicism who is a healthy normal adult male with oligospermia who has fathered two normal children. This chromosomal abnormality may be tissue specific, with a higher detection rate in cultured lymphocytes compared with fibroblasts. Therefore, there is an increased chance of missing the abnormality prenatally by amniocentesis or chorionic villus sampling. We are aware of only one other patient in the literature with a normal phenotype associated with mosaicism for this chromosomal abnormality.

Adult↗