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Biomedical subjects

M D Kilby

Publications and source records attributed to M D Kilby.

82 records · Page 5Linked to original sources
PubMed1992

The effect of angiotensin II on platelet intracellular free calcium concentration in human pregnancy.

OBJECTIVES: The primary objective of this study was to determine the effect of i.v. angiotensin II infusion on platelet intracellular free calcium concentration in potentially hypertensive primigravid women. DESIGN: Patients at 28-32 weeks gestation were selected on the basis of a diastolic pressure less than or equal to 80 mmHg taken at the antenatal clinic visit. METHODS: An angiotensin II infusion test (4-16 ng/kg per min) was performed in 13 women. Platelet intracellular free calcium concentration, platelet angiotensin II binding site density and plasma angiotensin II concentration were measured before and at the end of the infusion. Pregnancy outcome (normotension or hypertension) was recorded. RESULTS: Platelet intracellular free calcium concentration rose in 12 of 13 women during angiotensin II infusion. This rise was not directly correlated with initial or final platelet angiotensin II binding site density, plasma angiotensin II concentration or the evoked change in systolic or diastolic blood pressure. Five women subsequently developed pregnancy-induced hypertension. Although basal platelet intracellular free calcium concentration did not differ between the two groups, platelet intracellular free calcium concentration rose twice as much in response to angiotensin II in the five hypertensive pregnant women. There was a 12-fold increase in platelet angiotensin II binding in the future hypertensives, although basal angiotensin II was the same in the two groups. CONCLUSION: The enhanced rise in platelet intracellular free calcium concentration in response to angiotensin II administration in women who subsequently became hypertensive, together with their increased angiotensin II binding site density suggest a possible enhanced stimulus-effect coupling. Pregnancy-induced hypertension is a state of marked vasoconstriction, with an enhanced pressor response to angiotensin II. These data supply grounds for a hypothesis concerning the mechanism.

Adult↗
PubMed1992

Calcium and platelets in normotensive and hypertensive human pregnancy.

OBJECTIVES: The primary objective of this study was to determine the baseline platelet intracellular free Ca2+ concentration in normotensive and hypertensive primigravid women and to note any correlation between variables (ie. platelet intracellular free Ca2+ concentration and arterial blood pressure). DESIGN: A cross-sectional study of 24 normotensive and 36 primiparous women whose pregnancies were complicated by gestational hypertension, in the third trimester. METHODS: Platelet intracellular free Ca2+, serum Ca2+, and renal clearance of Ca2+ were recorded. RESULTS: Mean platelet intracellular free Ca2+ concentration was significantly increased in those subjects whose pregnancies were complicated by proteinuric gestational hypertension (pre-eclampsia) compared with the normotensive primiparous control sample. Those subjects with non-proteinuric pregnancy-induced hypertension did not show this significant increase in baseline platelet intracellular free Ca2+ concentration despite having a persistent and statistically significantly elevated systemic arterial blood pressure. On pooling these data for both normotensive and hypertensive primigravidae a significant positive correlation was noted between the variables of platelet intracellular free Ca2+ concentration and arterial blood pressure. The renal clearance of free Ca2+ was progressively reduced with increasing severity of the disease but had returned to normal 6 weeks postpartum. Serum Ca2+ concentrations corrected for albumin were however higher in the hypertensive patients. CONCLUSION: Transmembrane Ca2+ fluxes are altered in hypertensive pregnancy by a specific mechanism, probably of placental origin.

Adult↗
PubMed1992

An assessment of the use of meconium alone as an indication for fetal blood sampling.

OBJECTIVE: To assess the validity of meconium as an indication for fetal blood sampling. METHODS: The study design was a prospective observational study in a teaching hospital. Fetal blood samples were taken from 401 women. One hundred sixty-five patients had meconium-stained amniotic fluid (77 of whom had no cardiotocographic abnormalities). In the remaining 236 patients, the indication for fetal blood sampling was cardiotocographic abnormalities without meconium. The main outcome measures were the values of pH and base excess obtained at fetal blood sampling, 1-minute Apgar scores, and umbilical artery pH values. RESULTS: Patients with meconium alone as an indication for fetal blood sampling had higher scalp sample pH values (P < .001) and 1-minute Apgar scores (P < .01) than laboring patients with both meconium and cardiotocographic abnormalities. The patients with meconium alone had higher scalp pH values than patients with cardiotocographic abnormalities but no meconium (P < .001). In only two patients with meconium alone was a fetal scalp pH less than 7.20 (both infants had good Apgar scores at delivery). However, when cardiotocographic abnormalities were present, the finding of meconium was significant, resulting in lower 1-minute Apgar scores (P < .01) despite a lack of difference in fetal blood sample pH values. CONCLUSION: In the absence of cardiotocographic abnormalities, meconium is not an indication for fetal blood sampling.

Adult↗
PubMed1990

A cross-sectional study of basal platelet intracellular free calcium concentration in normotensive and hypertensive primigravid pregnancies.

1. The intracellular free calcium concentration ([Ca2+]i) in washed human platelets was measured using the fluorescent indicator, fura-2, in a cross-sectional study of 36 normotensive, primigravid volunteers, 12 in each trimester of pregnancy and a further 12 at 6 weeks post partum. The results were compared with those obtained from 30 normal female volunteers not using oral contraception. 2. The mean basal [Ca2+]i in the platelets of the pregnant women in the first two trimesters (115.6 +/- 6.7 and 120.1 +/- 5.7 nmol/l, respectively) was not shown to differ significantly from that of normal non-pregnant volunteers (112.3 +/- 2.9 nmol/l). However, during the third trimester a significant increase in [Ca2+]i was noted (134.0 +/- 4.9 nmol/l; P less than 0.05), with a return to normal values in the post-partum period (108.2 +/- 6.1 nmol/l). 3. [Ca2+]i was also measured in the platelets of a group of 12 primigravid pregnant women in the third trimester whose pregnancies were complicated by gestational hypertension (pregnancy-induced hypertension and pre-eclampsia). A significant rise in basal [Ca2+]i was noted in the platelets of primigravidae whose pregnancies were complicated by pre-eclampsia (163.6 +/- 8.8 nmol/l) as compared with normotensive, third-trimester primigravidae (P less than 0.02). However, no correlation could be demonstrated between [Ca2+]i and systemic blood pressure.

Adult↗
PubMedDate not supplied

Left ventricular hemodynamic effects of rapid, in utero intravascular transfusion in anemic fetal lambs.

We investigated the acute hemodynamic effects of in utero fetal intravascular transfusion in anemic fetuses. A conductance catheter technique of measuring left ventricular (LV) volume and pressure-volume analysis was employed in six anemic ovine fetuses of 131 days gestation (range 131-133 days). The mean fetal weight at necropsy was 3,795 +/- 166g. An intravascular transfusion of 120 ml packed maternal red cells was given over 12 minutes (rate of 2.6 +/- 0.1 ml/kg/min) increasing the hematocrit from 22.5 +/- 1.3% to 41.8 +/- 0.8%. The infusion of packed red cells leads to an approximate increase in blood volume of 30%. Heart rate, left ventricular stroke volume, and contractility, as assessed by end-systolic elastance, did not change significantly with transfusion. Left ventricular afterload, as assessed by effective arterial elastance, increased from 11.4 +/- 1.4 to 18.6 +/- 2.8 (P < 0.01) mmHg/ml with transfusion, returning to baseline levels by 60 minutes posttransfusion. During the transfusion, end-diastolic pressure increased from 4.1 +/- 0.4 to 10.6 +/- 0.8 (P < 0.01) mmHg and end-diastolic volume increased from 2.0 +/- 0.3 to 2.9 +/- 0.5 ml/kg. However, by 60 minutes posttransfusion, end-diastolic pressure had returned to baseline levels, whereas end-diastolic volume remained elevated at 3.2 +/- 0.6 ml/kg. We conclude that the persistent increase in end-diastolic volume implies a possible increase in LV diastolic compliance.

Anemia↗
PubMedDate not supplied

Renin gene expression in fetal kidneys of pregnancies complicated by twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates one in five monochorionic pregnancies and is generally associated with high mortality and morbidity. One twin (the recipient) grows appropriately and has polyhydramnios while the other (the donor) may have a reduced growth velocity and severe oligohydramnios. The disparities in amniotic fluid volumes represent differences in fetal urine output. These differences occur secondary to hemodynamic changes, in which the vascular arrangement of placental anastomoses in TTTS leads to unidirectional flow from the donor to the recipient twin. A better understanding of the pathophysiology may contribute to improved management of this morbid condition. We studied three consecutive prospectively diagnosed stillborn twin pairs affected by early-onset TTTS. Renin gene expression was studied in sections of fetal kidneys with immunocytochemistry using a renin antiserum and with in situ hybridization using riboprobes complementary to renin mRNA, and renin-secreting cells (RCC) were counted. The overall maturation of the renal cortex was assessed by the percentage of immature glomeruli. The donor twin kidneys were smaller than those of the recipients, but the maturation of the renal cortex was not significantly different (28.2% immature glomeruli in the donor and 24.4% in the recipient kidney). The donor kidney showed increased renin gene expression with hyperplastic juxtaglomerular apparatuses (JGAs) that contained excess RCCs (median 20.02 [25th-75th centiles, 5.4, 25.1 RCCs per 100 glomeruli]). In contrast, the recipient kidney was virtually devoid of these cells (0.04 [0, 0.36] RCCs per 100 glomeruli; P < 0.05). In the donor kidney, increased renin release may, by a local action, contribute to renal vasoconstriction and oliguria. Increased renin and/or angiotensin II in the blood passing through the placental anastomoses may, by an endocrine action, suppress renin synthesis in the recipient kidney, thereby increasing renal blood flow and causing polyuria and polyhydramnios. These changes in the renal RAS could thus contribute to the pathogenesis of TTTS. The renal renin changes noted here may represent a contributory or compensating mechanism, the success of which may dictate the overall survival of the twin pregnancy and allow better understanding of the pathophysiology and perhaps therapy that may be employed in this condition.

Adult↗
PubMedDate not supplied

The use of laser capture microdissection (LCM) and quantitative polymerase chain reaction to define thyroid hormone receptor expression in human 'term' placenta.

UNLABELLED: Term 'villous' placenta consists of a heterogeneous mix of different cell types comprising the trophoblast layers, villous stroma and fetal blood vessels. The importance of using techniques which allow investigation of pure populations of cells has been increasingly recognised. We demonstrate the use of laser capture microdissection (LCM) in combination with quantitative RT-PCR (QPCR) to assess the relative expression of mRNAs encoding the major thyroid hormone receptor (TR) isoforms (alpha1, alpha2 and beta1) in trophoblasts (syncytiotrophoblast and cytotrophoblast layers) compared with stromal cells in human term placenta. Highly reproducible results for each gene were obtained for each placental sample studied (n = 6). There was significantly less mRNA encoding TRalpha1 (68%; p = 0.05) and TRbeta1 (40%; p = 0.03) in the trophoblast layer compared to the heterogeneous stromal cells. However, there was no significant difference in TRalpha2 mRNA expression between the two groups of cells. CONCLUSION: LCM with QPCR can precisely locate and accurately quantify mRNA expression in specific cell populations from placental tissue.

Adult↗
PubMedDate not supplied

The resolution of fetal hydrops using combined maternal digoxin and dexamethasone therapy in a case of isolated complete heart block at 30 weeks gestation.

The development of hydrops fetalis in cases of isolated complete heart block is associated with a very poor prognosis. Various pharmacological strategies have been proposed, involving both direct fetal access and transplacental therapy, with inconsistent results in small numbers of subjects. The optimal antenatal management will remain uncertain until multicentre controlled trials are organised. We report the complete resolution of fetal hydrops at 30 weeks of gestation using combination of maternal digoxin and dexamethasone therapy, despite persistence of the complete heart block. A Caesarean section was performed at 37 weeks of gestation due to evidence of fetal intrauterine growth restriction. The baby girl is now 8 months of age and remains well, with a heart rate of 45-50 beats per minute on no medication and without pacing.

Adult↗
PubMedDate not supplied

Hepatocyte growth factor concentration in maternal and umbilical cord blood samples and expression in fetal liver.

OBJECTIVE: To determine whether human placenta secretes hepatocyte growth factor (HGF) and could influence fetal liver development. METHODS: Expression of HGF and c-met mRNA in paired samples of first- and second-trimester fetal liver and placenta was compared using a quantitative ribonuclease protection assay. Serum HGF concentration in 30 samples of paired umbilical and maternal blood from term pregnancies was evaluated using an enzyme-linked immunosorbent assay. RESULTS: HGF and c-met mRNA were expressed at similar levels in liver and placenta, with expression increasing from 9 to 16 weeks' gestation. Median serum HGF values were 1.4 ng/mL (maternal venous), 1.2 ng/mL (cord venous), and 1.3 ng/mL (cord arterial). The maternal venous HGF levels were significantly higher than fetal venous levels (P =.02). CONCLUSIONS: This study does not support the hypothesis that the placenta secretes HGF, because maternal serum levels were higher than fetal and there was no significant difference between umbilical arterial and venous samples. Fetal liver expresses abundant HGF mRNA during the first and second trimester and expression increases in line with receptor (c-met) expression, suggesting that hepatic growth and development are independent of placental HGF.

Electrophoresis, Polyacrylamide Gel↗