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Biomedical subjects

I A Greer

Publications and source records attributed to I A Greer.

At least 109 records · Page 6Linked to original sources

Nitric oxide concentrations are increased in the fetoplacental circulation in preeclampsia.

OBJECTIVE: The aim of this study was to measure serum concentrations of total nitrites, as an index of nitric oxide synthesis, in the maternal and fetal circulations of normal pregnancies and in pregnancies complicated by preeclampsia. STUDY DESIGN: We studied 32 women with preeclampsia and 36 with uncomplicated pregnancies. Maternal venous blood samples were collected from all of the patients, and umbilical venous blood was collected from 13 of the preeclamptic group and 17 of the control group. Serum nitric oxide concentrations were determined with the Greiss reaction by measuring combined oxidation products of nitric oxide, serum nitrite and nitrate after reduction with nitrate reductase. RESULTS: There were no significant differences in maternal serum nitrite concentrations between the groups (control group 29.8 +/- 1.07 mumol/L, preeclamptic group 29.5 +/- 1.06 mumol/L). Significantly higher serum nitrite concentrations were found in umbilical venous serum in the preeclamptic group compared with the control group (34.59 +/- 1.12 mumol/L vs 23.90 +/- 1.05 mumol/L, p < 0.01). CONCLUSIONS: Total nitrites are increased in the fetoplacental circulation in preeclampsia. These results support the hypothesis that increased nitric oxide production may be a compensatory response to improve blood flow or may play a role in limiting platelet adhesion and aggregation.

Adult↗

Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardation.

Platelets and neutrophils are involved in maternal placental vascular damage in pre-eclampsia. Recruitment of these cells is probably mediated by cell adhesion molecules expressed at the uteroplacental bed. It remains controversial as to whether platelets and neutrophils mediate damage to trophoblast or villous vasculature. The purpose of this study was to determine the expression of cell adhesion molecules in placentae from normal pregnancies and pregnancies complicated by pre-eclampsia and intrauterine growth retardation (IUGR). Immunostaining for platelet endothelial cell adhesion molecule (PECAM) and intercellular adhesion molecule-1 (ICAM-1) was localized mainly to the endothelium of stem villi, intermediate villi, terminal villi and decidual vessels. Scattered staining for ICAM-1 was also evident in the stroma and fetal membranes. The endothelium of stem villi, intermediate villi and terminal villi were all negative for vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin. PECAM, ICAM-1 and ICAM-2 mRNA were all detectable in normal placentae using northern blotting analysis whereas mRNA for E-Selectin and VCAM-1 were both undetectable. There were no differences in cell adhesion molecule immunostaining or mRNA expression in placentae from pregnancies complicated by pre-eclampsia and IUGR inconclusion, expression of cell adhesion molecules in placentae from pre-eclampsia and IUGR are consistent with a normal physiological role in vascular function.

Antigens, CD↗

Endothelin stimulates ACTH secretion in the ovine fetus.

The endothelins are a series of peptides with potent vasoconstrictor effects in vascular tissue; however, they may also have a role as neuroendocrine secretagogues because endothelin and endothelin receptors have been found in hypothalamic and pituitary tissues. Since activation of the fetal hypothalamo-pituitary-adrenal axis is crucial to the process of parturition, the aim of this study was to determine whether endothelin could activate the hypothalamo-pituitary-adrenal axis in the ovine fetus. Catheters were inserted into the carotid artery, jugular vein and lateral cerebral ventricle of six fetal lambs at 118-122 days' gestation. After a 5-day recovery period, endothelin-3 or placebo (saline) was infused intravenously (i.v.) or intracerebroventricularly (i.c.v.) over 30-60 min. The dose of endothelin-3 employed was 0.01 and 0.1 microgram min-1 i.c.v. and 0.1 and 1.0 microgram min-1 i.v. Arterial blood was taken from the fetus before, during and for 1 h after the infusion for measurement of ACTH and cortisol. Blood gas analysis was also performed. Intravenous endothelin-3 produced a dose-dependent increase in ACTH and cortisol concentrations in fetal plasma and was associated with transient fetal hypoxia and acidosis. pH correlated inversely with plasma ACTH (r = -0.701, P < 0.001) and cortisol (r = -0.308, P < 0.001) concentration. An increase in ACTH and cortisol concentrations in fetal plasma was also induced by endothelin-3 administered i.c.v. at 0.1 microgram min-1, and this was not associated with fetal acidosis These data suggest that endothelin administered i.v. will stimulate ACTH and cortisol release indirectly through vasoconstriction and acidosis; however, the response to i.c.v. endothelin administration suggests that it may also act as a central secretagogue for ACTH in the fetus and could therefore play a role in the process of parturition.

Adrenocorticotropic Hormone↗

Thrombocytopenia, antithrombin deficiency and extensive thromboembolism in pregnancy: treatment with low-molecular-weight heparin.

Pregnancy limits the therapeutic options for managing thrombocytopenia which occurs in 5% of patients on heparin. We describe a case of extensive thromboembolism associated with antithrombin (AT) deficiency complicated by thrombocytopenia which resolved when low-molecular-weight heparin was instituted. A primigravid woman presented at 11 weeks gestation with bilateral femoral occlusive thrombi extending above the renal veins. Investigations revealed AT deficiency, thrombocytopenia and renal infarction. After low-molecular-weight heparin was substituted for unfractionated heparin, the thrombocytopenia resolved and although the pregnancy was lost, the patient made a full recovery.

Adult↗

Elaboration of stem villous vessels in growth restricted pregnancies with abnormal umbilical artery Doppler waveforms.

OBJECTIVE: To assess the elaboration of placental stem villous vessels from pregnancies complicated by intrauterine growth restriction (IUGR) with absent end-diastolic flow velocity detected prior to delivery in the umbilical artery. DESIGN: Comparison between IUGR and control groups of the distribution, in 15 microns increments of 600 randomly chosen stem vessel profiles (post-fixation diameter 10-160 microns) identified by immunohistochemical localisation of alpha-smooth muscle actin in the vessel media. SETTING: Clinical teaching hospital and university anatomy department. SUBJECTS: Paraffin-fixed blocks obtained from placentas of eight pregnancies complicated by IUGR and eight gestational age-matched controls. RESULTS: The distribution of the stem villous vessels in the IUGR placentas, as assessed by the mean vessel diameter in each case, did not differ from the controls (mean vessel diameter 31.8 microns [SD 2.4] vs 29.6 microns [2.3]; P = 0.13). In five IUGR cases alpha-smooth muscle actin positive cells (myofibroblasts) were identified within the stroma of nonmuscularised peripheral (mature intermediate and terminal) villi, but in none of the controls. CONCLUSIONS: Our data do not support the theory that IUGR with absent end-diastolic flow velocity in the umbilical artery is due to a selective loss of small stem villous vessels. The increased impedance in this condition may be conferred more distally within the nonmuscularised capillaries of the peripheral villi.

Actins↗

Technical note: compression stockings and posture: a comparative study of their effects on the proximal deep veins of the leg at rest.

Graduated compression stockings have been shown to reduce the incidence of deep venous thrombosis. While they are thought to act primarily by increasing venous flow velocity, their mode of action remains uncertain. Doppler ultrasound was employed to study the relative effects of three types of support stocking on the deep venous diameter, flow velocity and pulsatility in 10 non-pregnant female subjects. In addition, the effect of altered posture on the same parameters was assessed. Significant effects of the graduated stockings were found at the level of the popliteal vein, where a reduction in both the diameter and the amplitude of respiratory phasicity was recorded (p < 0.05). No significant increase in flow velocities was recorded. Adopting the left lateral position significantly increased flow velocity in the right common femoral vein (p < 0.05). The application of stockings in this position produced no additional increase in flow velocities, but did alter the amplitude of respiratory phasicity. These data do not support the widely held view that graduated compression stockings increase flow velocities at rest. Adopting a lateral recumbent position significantly increases flow velocity in the non-dependent leg.

Adult↗

Changes in prostaglandin synthesis and metabolism associated with labour, and the influence of dexamethasone, RU 486 and progesterone.

The objective was to compare the changes in prostaglandin synthesis and metabolism occurring within the fetal membranes that are associated with the onset of parturition and to study the effect of steroid hormones on prostaglandin metabolism. A tissue explant study was made of discs of amnion and chorion obtained from 24 pregnant women at 37-42 weeks' gestation following spontaneous labour and delivery (12 women) and elective caesarean section (12 women). Significantly more prostaglandin E2 (PGE2) and PGF2 alpha were synthesized by amnion obtained following spontaneous labour than elective caesarean section. Arachidonic acid stimulated both PGE2 and PGF2 alpha synthesis by amnion in both groups. Phorbol myristoyl acetate stimulated PGE2 synthesis in both groups. There was no difference between the groups in the capacity of the chorion to metabolize prostaglandins. Mifepristone (RU 486) reduced the metabolism of added PGE2 following spontaneous labour, while dexamethasone and progesterone had no effect on prostaglandin metabolism. In conclusion, the increase in concentration of PGE2 and PGF2 alpha associated with the onset of spontaneous labour is the result of an increase in synthesis rather than a reduction in metabolism. There was no decrease in metabolism to account for the increase in prostaglandin concentrations and, with the exception of mifepristone, metabolism was not altered by the addition of steroid hormones.

Amnion↗

Familial thrombophilia and activated protein C resistance: thrombotic risk in pregnancy?

An abnormal anticoagulant response in vitro to activated protein C (aPC) has been proposed as an aetiological factor in familial thrombophilia. It is postulated that this phenomenon is due to an inherited molecular defect of factor V resulting in poor inactivation by aPC. We conducted a family study when the proband presented in her second pregnancy with superficial phlebitis, a history of deep venous thrombosis and a family history of venous thromboembolic disease. No abnormality of antithrombin activity, protein C activity or deficiency of protein S were demonstrated in the family members tested. The proband had aPC ratios below the laboratory range on three consecutive occasions. In addition, her mother, who had a history of recurrent DVTs and a pulmonary embolus, and also an asymptomatic nulliparous sister, both had aPC resistance ratios below the laboratory range on consecutive samples. Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated.

Adult↗

Corticotrophin-releasing factor immunostaining is present in placenta and fetal membranes from the first trimester onwards and is not affected by labour or administration of mifepristone.

BACKGROUND AND OBJECTIVES: Corticotrophin releasing factor (CRF) is present in the human placenta and fetal membranes. Placental CRF content and plasma CRF concentrations rise throughout gestation and fall rapidly after delivery. The regulation of CRF production from the placenta is poorly understood. The objective of this study was to use the antiprogestin, mifepristone, to determine whether progesterone has a regulatory effect on CRF production in the first trimester of pregnancy. PATIENTS: Women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE1 analogue, gemeprost (16,16-dimethyl-trans-delta 2-PGE1 methyl ester) vaginally 2-4 hours prior to the procedure; or with 600 mg mifepristone 48 hours prior to receiving 1 mg gemeprost vaginally), second trimester therapeutic abortion (600 mg mifepristone, 1 mg gemeprost), in association with preterm delivery (gestation 25-34 weeks) and at term (gestation 35-42 weeks) by spontaneous delivery, induced labour or elective Caesarean section. MEASUREMENTS: Immunohistochemical localization of CRF and quantification of CRF content by radioimmunoassay of tissue extracts, in human placenta and fetal membranes. RESULTS: CRF was immunolocalized to the syncytiotrophoblast cells of the placenta at all stages of gestation from 5 to 42 weeks. In the fetal membranes CRF immunoreactivity was localized in the epithelial and subepithelial cells of the amnion, some cells of the reticular and cellular layers of the chorion, and in decidual stroma. This pattern was seen in all tissues studied. Pretreatment with prostaglandins, mifepristone or both during the first trimester did not alter the distribution or the intensity of the CRF immunostaining. Placental CRF content rose throughout gestation but, consistent with the immunostaining results, was unaffected by the administration of mifepristone or by labour. CONCLUSIONS: CRF is localized in the syncitiotrophoblast cells of the placenta and is clearly present early in the first trimester of pregnancy. The lack of an effect of mifepristone or mode of delivery suggests that syncytiotrophoblast produces CRF constitutively throughout pregnancy.

Cesarean Section↗

Lack of association between maternal phosphoglucomutase-1 phenotype and fetal macrosomia in diabetic pregnancy.

OBJECTIVE: To assess the reports that maternal phosphoglucomutase-1 (PGM1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth. DESIGN: A comparative biochemical genetic study. SETTING: A large diabetic pregnancy clinic. SUBJECTS: One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty-six women without pre-existing medical or pregnancy complications who functioned as a control group. MEASURES: PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing. OUTCOME: Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin. RESULTS: No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression. CONCLUSIONS: Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance.

Analysis of Variance↗

The cell adhesion molecule, VCAM-1, is selectively elevated in serum in pre-eclampsia: does this indicate the mechanism of leucocyte activation?

OBJECTIVE: To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre-eclampsia. DESIGN: Serum was prepared from peripheral venous blood and stored at -70 degrees C. The cell adhesion molecules, VCAM-1, E-Selectin and ICAM-1, were measured by ELISA. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. SUBJECTS: Sixteen primigravid women with pre-eclampsia were recruited for the study. The preeclampsia group were compared with 18 healthy primigravid women with uncomplicated pregnancies. RESULTS: The pre-eclamptic group had significantly higher serum levels of the cell adhesion molecule VCAM-1 (t = 3.673; P < 0.001). There were no significant differences in the adhesion molecules ICAM-1 or E-Selectin. CONCLUSIONS: Endothelial damage and dysfunction are common to all the pathological features of pre-eclampsia. This study shows that concentrations of cell adhesion molecules, which indicate leucocyte-endothelial attachment and activation, are elevated in the serum of patients with pre-eclampsia. Such increases in soluble circulating cell adhesion molecules may reflect increased expression of these molecules on the endothelium and thereby explain the mechanism for leucocyte activation in pre-eclampsia.

Adult↗

Causes and clinical consequences of Rhesus (D) haemolytic disease of the newborn: a study of a Scottish population, 1985-1990.

OBJECTIVE: To identify the reasons behind failures to prevent the development of Rhesus (D) haemolytic disease of the newborn. DESIGN: Retrospective analysis of the case records of all pregnancies that resulted in the birth of an infant with a positive direct antiglobulin test on the cord red cells born to Rh(D) negative women between 1 April 1985 and 31 March 1990. SETTING: Obstetric units in the South East Scotland region and the South East Scotland Regional Blood Transfusion Service Antenatal Laboratory. MAIN OUTCOME MEASURES: The causes and clinical consequences of maternal immunisation to the Rhesus (D) antigen. RESULTS: Between 1985 and 1990, 80 pregnancies resulted in the birth of an infant sensitised with anti-D on the cord red cells. There were no deaths due to haemolytic disease, but considerable resources were deployed in obstetric and neonatal care for these pregnancies. Sufficient data were available to categorise the cause of maternal immunisation in 70 pregnancies. Seven cases were due to immunisation by pregnancy before 1970. Sixty-three cases could be attributed to failure of the Rhesus programme: 10 cases (16%) were due to failure to implement the programme adequately, the other 53 cases (84%) were due to failure of the current guidelines to provide adequate protection. Late immunisation in an uncomplicated pregnancy was the single commonest identifiable cause. CONCLUSIONS: It is likely that substantial further reductions in Rhesus (D) immunisation and haemolytic disease of the newborn will require changes in the Rhesus prevention programme. In particular the role of antenatal prophylaxis requires detailed consideration.

Erythroblastosis, Fetal↗