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Biomedical subjects

A A Calder

Publications and source records attributed to A A Calder.

At least 19 recordsLinked to original sources
PubMed1999

The action of prostaglandin E2 on the human cervix: stimulation of interleukin 8 and inhibition of secretory leukocyte protease inhibitor.

OBJECTIVE: The objective of this study was to investigate regulation of inflammatory mediators implicated in cervical ripening and to explore the mechanisms by which the clinically effective agent prostaglandin E2 may mediate cervical ripening. STUDY DESIGN: Cervical biopsy specimens were taken from healthy, nonpregnant women undergoing a hysterectomy for a benign nonmalignant condition and were cultured, with treatments in quadruplicate, for 24 hours in media supplemented with progesterone, dexamethasone, nitric oxide, interleukin 8, and prostaglandin E2. Media were collected and assayed by enzyme-linked immunosorbent assay for interleukin 8, secretory leukocyte protease inhibitor, and prostaglandin E2. Ethical approval was obtained for this study from the local ethics committee. RESULTS: Interleukin 8 release from cervical explants was stimulated by prostaglandin E2 and nitric oxide and inhibited by progesterone and dexamethasone. Secretory leukocyte protease inhibitor release from cervical explants was stimulated by progesterone and inhibited by prostaglandin E2. Prostaglandin E2 release from cervical explants was stimulated by nitric oxide. CONCLUSION: Complex interactions occur between inflammatory cytokines within the cervix; these results further our understanding of the mechanism of cervical ripening.

Adult↗
PubMed1998

Regulation of interleukin 8 production in the term human placenta during labor and by antigestagens.

OBJECTIVE: Our purpose was to assess the effects of labor and antigestagens on production of interleukin 8 by the term human placenta and to localize interleukin 8 in first- and third- trimester placentas. STUDY DESIGN: The study was conducted by the Department of Obstetrics and Gynaecology of the University of Edinburgh. Five placentas were collected after spontaneous and cesarean deliveries. Explants were cultured in the presence of mifepristone, lilopristone, or onapristone. The production of interleukin 8 was determined by specific radioimmunoassay, and the immunolocalization of interleukin 8 was determined in sections of first- and third-trimester placentas. RESULTS: All explants produced interleukin 8. Production was significantly increased (P < .05) after spontaneous delivery. In placentas delivered spontaneously, onapristone significantly increased production of interleukin 8 (P < .05), whereas in those from cesarean deliveries lilopristone caused a significant increase in production (P < .05). In the third-trimester placenta interleukin 8 was localized in the perivascular area of fetal vessels. In first-trimester villi it was peripherally located in syncytiotrophoblast. CONCLUSION: The human placenta at term is capable of producing interleukin 8, which is localized around the perivascular area of the villi. Production is increased after spontaneous labor and to varying degrees by the antigestagens studied. Interleukin 8 may have a role in the onset of parturition by recruiting and activating neutrophils at the placental site.

Culture Techniques↗
PubMed1998

The effects of mifepristone on cervical ripening and labor induction in primigravidae.

OBJECTIVE: To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices. METHODS: This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were randomly assigned to one of three treatment groups. They were assessed at 24-hour intervals for 72 hours, after which labor was induced if it had not occurred spontaneously. RESULTS: Two hundred milligrams of mifepristone resulted in a favorable cervix (with a Bishop score greater than 6 or in spontaneous labor) in significantly more women than placebo (P = .01). An improvement in cervical ripening was seen in the group given 50 mg of mifepristone, but this was not statistically significant. There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo, but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome. CONCLUSION: Mifepristone, a progesterone antagonist, is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity. It is theoretically attractive for use as an adjunct in cervical priming and labor induction. In this study, 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo.

Adolescent↗
PubMed1998

Mechanisms involved in the stimulatory effect of amniotic fluid on prostaglandin production by human fetal membranes.

This study aims to investigate potential mechanisms involved in the stimulatory effect of amniotic fluid on prostaglandin production by fetal membranes. A cell culture study of amnion and chorion was obtained following elective caesarean section, incubated with amniotic fluid collected at term (37-42 weeks' gestation) following either spontaneous labour (n = 6) or elective caesarean section (n = 6). The effect of addition of cycloheximide and actinomycin D (inhibitors of translation and transcription respectively), and staurosporine and genistein (inhibitors of protein kinase C and tyrosine kinase respectively) to these cultures was investigated. ANOVA was employed for statistical analysis. Cycloheximide and staurosporine significantly inhibited the stimulatory effect of spontaneous labour and elective section amniotic fluid on PGE2 production by amnion, and PGEM production by chorion. Genistein significantly inhibited the stimulatory effect of spontaneous labour amniotic fluid on PGE2 and PGEM production by amnion and chorion respectively. The stimulatory effect of amniotic fluid on prostaglandin production is dependent on new protein synthesis, presumably cyclooxygenase (COX), and stimulation of cell signal transduction pathways involving protein kinase C and tyrosine kinase.

Amniotic Fluid↗
PubMed1998

Cytokine secretion by human fetal membranes, decidua and placenta at term.

Cytokines such as monocyte chemotactic peptide-1 (MCP-1), interleukin-8 (IL-8), RANTES (Regulated on Activation and Normally T-cells Expressed and presumably Secreted) and interleukin-10 (IL-10) are thought to play pivotal roles in immune recognition, acceptance of the fetal allograft, maintenance of pregnancy and parturition. Their secretion and regulation within the third trimester uterus is, however, less well defined. We therefore investigated the release of these cytokines by third trimester amnion, chorion, placenta and decidua, and studied the influence of prostaglandin E2 (PGE2) infusion on their release in a dynamic placental cotyledon perfusion system. MCP-1 was released predominately by the chorion (78.2 +/- 7.3 pg/mg wet tissue weight; mean +/- SEM), decidua (112.4 +/- 5.2 pg/mg) and placenta (101.8 +/- 5.0 pg/mg) with low amounts from the amnion (1.3 +/- 0.4 pg/mg). High concentrations of IL-8 were released by the amnion (39.9 +/- 5.3 pg/mg), chorion (52.8 +/- 1.9 pg/mg), decidua (42.2 +/- 1.5 pg/mg) and placenta (45 +/- 1.3 pg/mg). Release of RANTES was not detectable from the amnion but was detected in moderate amounts from the chorion (6.0 +/- 1.2 pg/mg), decidua (15.2 +/- 1.4 pg/mg) and placenta (26.9 +/- 1.6 pg/mg). Low concentrations of IL-10 were secreted by the chorion (6.8 +/- 0.8 pg/mg), decidua (9.0 +/- 0.9 pg/mg) and placenta (3.3 +/- 0.3 pg/mg) with none detectable from the amnion. MCP-1, IL-8, RANTES and IL-10 were all released by perfused placental cotyledons. PGE2 stimulated release of MCP-1, IL-8 and IL-10 into the maternal and of MCP-1 and IL-8 into the fetal circulation of the placenta but had no effect on RANTES release. It is suggested that MCP-1 and IL-8 may be involved in the inflammatory process of parturition and IL-10 in the protection of the fetal allograft. In addition, PGE2 may have an important immunomodulatory role within the uterus at term.

Culture Techniques↗
PubMed1998

Differential concentrations of monocyte chemotactic protein-1 and interleukin-8 within the fluid compartments present during the first trimester of pregnancy.

Monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) are important chemokines which effect the chemotaxis of monocytes and neutrophils, respectively. There is increasing evidence that such chemokines play an integral role in the control and maintenance of a normal pregnancy from implantation to parturition. However, little is known about the sites of secretion and function of MCP-1 and IL-8 in particular with respect to establishment of the placenta and membranes during first trimester. The aim of this study was therefore to investigate the concentrations and localization of MCP-1 and IL-8 in amniotic fluid and extra-embryonic coelomic fluid (EECF) collected by ultrasound-guided needle aspiration and maternal serum during the first trimester of pregnancy. Using specific enzyme-linked immunosorbent assays, MCP-1 was present at high concentrations in the EECF, significantly higher than those in amniotic fluid and maternal serum. IL-8 was also present predominantly in the EECF with concentrations being significantly higher than the low values detected in maternal serum and the very low amounts found in amniotic fluid. This strict compartmentalization of these cytokines in the fluid compartments of early pregnancy may be important for establishment and development of a viable pregnancy.

Amniotic Fluid↗
PubMed1997

Differential secretion of chemokines from peripheral blood in pregnant compared with non-pregnant women.

The maintenance of a normal pregnancy is dependent on the delicate interaction between the endocrine and the immune systems. Cytokines are thought to play a key role in pregnancy by way of local modulation of the immune system at the level of peripheral leukocytes. This study examined the potential of peripheral venous blood cultures from pregnant women throughout gestation and from non-pregnant women to produce the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8) and RANTES. Significantly (P = < 0.001), higher levels of MCP-1 were released from peripheral blood cultures from pregnant women at term than during the first trimester or from women who were not pregnant. This could not be accounted for by differences in differential blood counts. Significantly higher levels (P = < 0.05) of MCP-1 were released from PBMC preparations from pregnant compared with non-pregnant women. No 'rebound' increase in MCP-1 was observed on withdrawing progesterone support to the PBMC preparations. MCP-1 was secreted predominately from CD14+ cells with those from pregnant women producing more than those from non-pregnant women. There was no statistical difference in release of IL-8 or RANTES from either peripheral blood or PBMC preparations from pregnant or non-pregnant women. IL-8 and RANTES were secreted from CD14+ and CD14- cells, respectively. The hypothesis proposed is that the monocytes are fundamentally different in pregnancy and that measurement of MCP-1 has the potential to act as a marker of pregnancy status.

Adolescent↗
PubMed1997

Transabdominal cervico-isthmic cerclage in the management of cervical incompetence.

The use of transabdominal cervico-isthmic cerclage is described in 13 patients with a diagnosis of cervical incompetence. The patients were recruited from seven Scottish Maternity Units over a period of 10 years. The 13 patients have had a successful pregnancy in 86.6% of pregnancies with this procedure compared with a success rate of 16% in their previous pregnancies. In carefully selected cases transabdominal cervico-isthmic cerclage is a worthwhile procedure in patients with cervical incompetence when the cervix is so damaged that it would be impossible to insert a vaginal suture or when a vaginal suture has previously failed.

Adult↗
PubMed1997

Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure.

OBJECTIVE: Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11 beta-HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas. DESIGN: Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep-pak Plus) and HPLC. RESULTS: Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11 beta-HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation. CONCLUSION: We conclude that human placental 11 beta-HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Recombinant human relaxin as a cervical ripening agent.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an unfavourable cervix before induction of labour at term. DESIGN: A multi-centre, double-blind, placebo-controlled trial performed in Edinburgh, Glasgow and Oxford. Women were treated with 0, 1, 2 or 4 mg of rhRIx in a gel vehicle administered intravaginally. Analysis of variance tests were performed on all continuous variables, and Cochran Mantel-Haenszel tests employed for all discrete variables. PARTICIPANTS: Ninety-six women at 37 to 42 weeks of gestation with a singleton pregnancy and a modified Bishop score of < or = 4 were recruited. RESULTS: There was no significant difference in the change in modified Bishop score between the four treatment groups. The lengths of the first and second stages of labour were similar in all 4 groups. PGE2 and oxytocin requirements were similar in all groups, as was the mode of delivery. There was no evidence that relaxin was absorbed systemically when given in this way. CONCLUSION: Recombinant human relaxin 1 to 4 mg, administered as an intravaginal gel, has no effect as a cervical ripening agent before induction of labour at term.

Administration, Intravaginal↗
PubMed1996

Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A.

BACKGROUND AND OBJECTIVE: Prenatal maternal serum screening for Down's syndrome has become an important and established part of modern antenatal care. Previously it has been reported that non-specific immunoreactive inhibin may be useful in this context. Using a novel assay we have evaluated dimeric inhibin A as a possible second trimester marker of Down's syndrome. METHODS: From 1992-1993 records, stored sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were identified and retrieved for analysis. These sera had been prospectively collected at 15, 16 and 17 weeks gestation. SUBJECTS: Records revealed 21 women who had had a Down's syndrome pregnancy and who also had serum available for analysis. Sera from 150 chromosomally normal controls, matched for gestation and duration of storage, were also retrieved. MEASUREMENTS: Dimeric inhibin A was measured using a recently developed two-site enzyme-linked immunoassay. This employs a capture anti inhibin beta A-subunit monoclonal antibody, covalently bound to a microtitre plate and a second anti inhibin alpha-subunit antibody conjugated to alkaline phosphatase, allowing detection. RESULTS: The mean (95% CI) maternal serum dimeric inhibin A in the samples from control pregnancies was 237 (201.5-273.4) ng/l, 266.9 (235.4-298.5) ng/l and 207.2 (178.5-235.9) ng/l at 15, 16 and 17 weeks gestation respectively. Expressing the results from the Down's samples as multiples of the normal median (MoM), the median (95% CI) MoM was 2.6 (2.25-3.57), significantly higher than the controls (P < 0.0001, Mann-Whitney U-test). In the sample set tested, for a given false positive rate of 5.3% inhibin A alone afforded a detection rate of 62%, detecting cases previously undetected by routine screening. CONCLUSIONS: Dimeric inhibin A appears to be a promising new marker for the prenatal detection of Down's syndrome. Further prospective evaluation and assessment with other established markers would now be merited.

Adult↗
PubMed1995

Fetal osteocalcin levels are related to placental 11 beta-hydroxysteroid dehydrogenase activity in humans.

OBJECTIVE: Overexposure to glucocorticoids in utero reduces birth weight and, in animals, leads to persistent hypertension in the offspring. The fetus is normally protected from maternal glucocorticoids by placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) which catalyses the conversion of cortisol to inert cortisone. In adult humans, osteocalcin is a sensitive marker of glucocorticoid exposure. The aim of this study was to determine whether cord blood osteocalcin levels were related to the ability of placental 11 beta-HSD to inactivate maternal cortisol. DESIGN: Cross-sectional study examining the relation between cord blood levels of osteocalcin and placental glucocorticoid metabolism at term. PATIENTS: Twenty-one women attending for delivery at the Simpson Memorial Maternity Pavilion in Edinburgh had cord venous and arterial blood samples collected at delivery. MEASUREMENTS: Cord plasma levels of osteocalcin, cortisol and cortisone were measured by radioimmunoassay and indices of placental 11 beta-HSD activity were calculated. RESULTS: All indices of placental 11 beta-hydroxysteroid dehydrogenase activity correlated directly and significantly with cord blood osteocalcin levels. For cord blood osteocalcin and the placental 11 beta-HSD Activity Index, Pearson's r was +0.58, r2 = 0.33 and P < 0.02. CONCLUSION: We conclude that term cord blood osteocalcin level reflects the effectiveness of placental glucocorticoid inactivation, and may be a marker for the development of adult hypertension.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Effects of gemeprost and mifepristone on the mechanical properties of the cervix prior to first trimester termination of pregnancy.

OBJECTIVE: To study the effects of oral mifepristone and vaginal gemeprost on the mechanical properties of the cervix prior to first trimester termination of pregnancy by vacuum aspiration. DESIGN: A comparative study. Each patient served as her own control. SETTING: The Royal Infirmary of Edinburgh, Scotland, UK. SUBJECTS: Forty nulliparous women at six to twelve weeks of pregnancy. INTERVENTIONS: The women received either gemeprost (1 mg) 3 h prior to termination of pregnancy or mifepristone (200 mg) 48 h before operation. MAIN OUTCOME MEASURES: Two different objective methods of assessment of the mechanical properties of the cervix, one measuring the distensibility of the cervix before drug administration and immediately before the operation, and the other measuring the force necessary to dilate the cervix; incidence of new symptoms following drug intake; immediate complications and estimated blood loss. RESULTS: Both treatments significantly increased cervical distensibility. Baseline dilatation was greater in the mifepristone group. The force required to dilate the cervix was significantly reduced in mifepristone-treated patients. There was a good correlation between the two different methods of assessment of the mechanical properties of the cervix only in the gemeprost group. CONCLUSION: Cervagem and mifepristone can be used to increase cervical distensibility. Cervical dilatation is easier with a 48 h regimen of mifepristone than with gemeprost.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Successful excision of a giant acoustic neuroma in the third trimester of pregnancy.

Intracranial neoplasms presenting during pregnancy are uncommon. We report the case of a woman with a giant acoustic neuroma, presenting with hyperemesis gravidarum, and detail the surgical excision of the tumour during the third trimester. The case illustrates the unusual presentation and that such surgery can be performed safely without detriment to mother or fetus.

Adult↗
PubMed1995

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↗
PubMed1994

Antenatal screening for cystic fibrosis: a trial of the couple model.

OBJECTIVE: To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. DESIGN: Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. SETTING: Two large maternity hospitals in Edinburgh. SUBJECTS: Screening was offered to all couples who booked at one of the two hospitals. MAIN OUTCOME MEASURES: (a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. RESULTS: Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive--that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. CONCLUSIONS: Antenatal couple screening is a satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.

Anxiety↗