Search PubMed⌕ Search

Biomedical subjects

A A Calder

Publications and source records attributed to A A Calder.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Progesterone control of interleukin-8 production in endometrium and chorio-decidual cells underlines the role of the neutrophil in menstruation and parturition.

Interleukin-8 (IL-8) attracts neutrophils into tissues and causes them to degranulate. Both menstruation and parturition involve neutrophil migration into uterine tissues and therefore IL-8 is a likely mediator of the tissue re-arrangements that accompany these events. We have examined the ability of endometrium explants and chorion cells in culture to synthesize and release IL-8 and the ability of progesterone, a synthetic progestin [medroxyprogesterone acetate (MPA)] and dexamethasone to inhibit this production. In endometrium, the stage of the menstrual cycle did not affect IL-8 production but a 10(-6) M concentration of progesterone or dexamethasone significantly reduced the concentration of IL-8 in medium after 24 h. After a further 24 h with lipopolysaccharide (LPS) stimulation, only MPA and dexamethasone inhibited production significantly. In chorion cells, IL-8 production was significantly decreased by both MPA and dexamethasone in the LPS stimulated cells but the reduction in the first 24 h was not significant. The IL-8 produced in uterine tissues might act synergistically with prostaglandin E (PGE), a likely site for this interaction being blood vessels where PGE production is also repressed by progesterone. Such a cooperative action would maintain low leukocyte entry into uterine tissues in the presence of progesterone and falling steroid levels would induce leukocyte immigration and activation with consequent tissue destruction. Such steroid-dependent interactions are important in our understanding of the mechanisms of menstruation and parturition and could allow new approaches to the treatment of uterine pathology.

Cells, Cultured↗
PubMed1994

Prostaglandins and biological control of cervical function.

The uterine cervix is a vital structure for the success of pregnancy. It must remain firmly closed to contain the developing conceptus within the uterus until the fetus has grown to a stage of maturity appropriate for extra-uterine survival. During the birth process itself, the cervix must undergo the rapid opening known as dilatation to allow the fetus to travel through the birth canal with a minimum of stress and trauma. The process of cervical dilatation must be preceded by the phenomenon of effacement whereby the substance of the cervix shortens and thins out. Both effacement and dilatation would be impossible unless the dense fibrous connective tissue of the cervix had undergone a radical modification. Cervical ripening requires a change of the collagen within the cervical stroma from a highly organised network of tightly bound collagen fibrils to a much looser arrangement whereby the tissue becomes more compliant. This is associated with profound changes in the composition of the ground substance of the cervical stroma with an alteration in the concentration and type of glycosaminoglycans (GAGs) which constitute the proteoglycan complexes. It was formerly assumed that these changes were under the control of those cellular elements within the cervical stroma (fibroblasts and smooth muscle cells) but it seems quite possible that the ripening process is associated with an infiltration of inflammatory cells especially neutrophils. Currently much interest is centering on the possible role of cytokines such as interleukin-8 and there may also be a role in cervical ripening for leukotrienes.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1993

Interleukin-8 production by the human cervix.

OBJECTIVES: Our purpose was (1) to determine whether the human cervix is capable of producing interleukin-8 in vitro and to examine the possibility of stimulating an increase in any such output and (2) to examine the concomitant production of prostaglandins. STUDY DESIGN: Cervical tissue was obtained from 48 women, 29 pregnant women undergoing surgical termination of pregnancy (20 of whom were treated with the prostaglandin analog Cervagem), 14 nonpregnant, premenopausal women, and three postmenopausal women. Explants were cultured and the medium was assayed for interleukin-8 and prostaglandin E2. Analysis of variance and Newman-Keuls statistical tests were used. RESULTS: Significant quantities of interleukin-8 were produced by the tissue, and the data indicate that cervical explants from pregnant and nonpregnant women behave in a similar way when challenged by phorbol myristate acetate but that the postmenopausal cervix loses its capacity for interleukin-8 production. CONCLUSIONS: Human cervix is capable of producing large amounts of interleukin-8 in vitro, and it may be influenced by the steroid hormones. Thus interleukin-8 could be an excellent candidate for a prime role in neutrophil-mediated cervical ripening.

Abortifacient Agents, Nonsteroidal↗
PubMed1993

Labetalol therapy in pregnancy induced hypertension: the effects on fetoplacental circulation and fetal outcome.

We prospectively studied the effects of oral labetalol therapy in patients with moderate to severe pregnancy induced hypertension (PIH). The outcome variables were blood pressure control, effect on umbilical artery flow velocity waveforms (UAFVW) and fetal outcome. Forty-two patients were recruited, all had moderate to severe PIH. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on entry were 154 +/- 7 mmHg and 104 +/- 5 mmHg, respectively. All had significant proteinuria. After 1 week on labetalol therapy, 85% of patients had their blood pressure controlled. The reduction in both SBP and DBP was statistically significant. There were no significant changes in UAFVW, Resistance Index (RI), uric acid or platelets. The mean fetal age on entry was 246 +/- 10 days while gestation at delivery was 258 +/- 17 days. The mean birth weight was 2712 +/- 609 g. No perinatal mortality occurred in this study. Labetalol is an effective drug in controlling blood pressure and does not adversely affect the UAFVW. No neonatal problems were attributed directly to the drug. Fetal outcome was satisfactory despite the 12 fetuses that were growth-retarded. Labetalol allows safe prolongation of pregnancies complicated by PIH.

Adult↗