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Biomedical subjects

M G Elder

Publications and source records attributed to M G Elder.

At least 19 recordsLinked to original sources
PubMed1992

Lack of effect of topical iodostearic acid on cervical intraepithelial neoplasia II-III.

Stearic and iodostearic acid inhibit growth of a cervical carcinoma cell line in vitro. This study was performed to determine if iodostearic acid would induce regression of cervical intraepithelial neoplasia (CIN). Women with histologically-proven CIN II or III were randomised into two groups. Those in the first group were given pessaries composed of iodostearic acid in polyethylene glycol (PEG) base. Women in the second group were given pessaries containing only the PEG base. One pessary was inserted into the vagina nightly for 30 nights, and each woman then had the CIN lesion removed by CO2 laser cone excision. There was no difference in the histology of the cone biopsies between the groups, demonstrating that this regime of iodostearic acid has no useful role in the treatment of CIN II-III.

Adult↗
PubMed1992

Metabolism of prostaglandins E2 and F2 alpha by human fetal membranes.

Prostaglandin E2 (PGE2) is important in the early stages of human labour, leading particularly to cervical ripening and dilatation. The source of PGE2 is thought to be either the amnion or the decidua, but the chorion interposes between the amnion and the target tissues, namely the myometrium and cervix. In order to investigate the role of the chorion in modulating prostanoid production, [3H]PGE2 was added to the amnion side of fetal membranes, and the production of metabolites on both sides of the fetal membrane followed by HPLC. The major metabolite was 13,14-dihydro-15-oxo-PGE2 with smaller amounts of 13,14-dihydro-15-oxo-PGA2 and PGB2. The production of all metabolites of PGE2 was time dependent. [3H]PGF2 alpha, which is normally produced by the decidua, was also added to fetal membranes and found to be metabolised to 13,14-dihydro-15-oxo-PGF2 alpha and PGE2. These results suggest that the metabolic enzymes in the chorion may determine intra-uterine levels of prostaglandins, and may also determine the identity of the eicosanoids released by intact fetal membranes.

Amnion↗
PubMed1992

The mechanisms of preterm labor: common genital tract pathogens do not metabolize arachidonic acid to prostaglandins or to other eicosanoids.

OBJECTIVE: Our aim was to determine the ability of pathogens commonly associated with genital tract infection and preterm labor to incorporate arachidonic acid and to metabolize it to prostaglandins or to other eicosanoids. STUDY DESIGN: Four common genital tract pathogens, Escherichia coli, Streptococcus viridans, Bacteroides fragilis, and a group B beta-hemolytic streptococcus, were incubated with tritium-labeled arachidonic acid for 2 to 48 hours. Uptake of arachidonic acid was calculated from uptake of radioactivity into the organisms. Tritium-labeled arachidonic acid within the medium was separated from any metabolites by high-performance liquid chromatography to assess metabolism of arachidonic acid within the bacteria. RESULTS: Although all organisms were able to take up arachidonic acid, analysis of its metabolism with high-performance liquid chromatography demonstrated that none of these organisms will synthesize cyclooxygenase, lipoxygenase, or epoxygenase products. CONCLUSION: Bacterial infection cannot initiate preterm labor by intrinsic biosynthesis and release of prostaglandins or other eicosanoids by the bacteria themselves.

Arachidonic Acid↗
PubMed1992

A new regime in the management of gastroschisis.

In this review of 24 patients with gastroschisis, we illustrate a regime of management with a low morbidity and no mortality. The essence of the technique relies on antenatal diagnosis, intrauterine transfer, and a planned cesarean section with immediate repair performed at 37 to 38 weeks' gestation. Although the operation may be technically easier at lower gestational ages, we believe the concomitant increase in complications such as respiratory distress syndrome outweigh the advantage of easier surgery. The results of this series compare favorably with other published results.

Abdominal Muscles↗
PubMed1992

The mechanisms of preterm labour; the interaction between amnion cells and leukocytes in the metabolism of arachidonic acid.

Chorioamnionitis is frequently associated with preterm labour. We have used a cell culture model system to examine the effects of leukocytes upon the metabolism of endogenous arachidonic acid from within amnion cells. We have demonstrated that activated leukocytes release substances which increase the overall release and metabolism of endogenous arachidonic acid within amnion cells causing an increase in prostaglandin E2 production as well as a smaller increase in non-cyclo-oxygenase metabolism. When amnion cells and leukocytes are cultured together, in addition to prostaglandin E2 production by amnion cells, arachidonic acid released by the amnion cells appears to be metabolised by leucocytes to prostaglandin F2 alpha, prostacyclin and thromboxane A2. Prostaglandins E2 and F2 alpha are the principal cyclo-oxygenase products of this interaction. We postulate that chorioamnionitis stimulates preterm labour not only by causing an increase in prostaglandin E2 synthesis by amnion cells but by metabolism of amnion derived arachidonic acid to the powerfully oxytocic prostaglandin F2 alpha by leukocytes.

Amnion↗
PubMed1992

Interleukin-1 beta stimulates decidual stromal cell cyclo-oxygenase enzyme and prostaglandin production.

The cytokine interleukin-1 (IL-1 beta) increased prostaglandin production by decidual stromal cells in culture in a time and dose dependent manner. Optimum conditions for stimulation were found to be for 24 hours at a concentration of 100 pg IL-1 beta/ml. An apparent increase in cyclo-oxygenase enzyme synthesis accompanied the increase in prostaglandin production, and both changes were inhibited by the protein synthesis inhibitor cycloheximide. This implicates protein synthesis in the stimulatory effects of IL-1 beta, which may be mediated through the increase in cyclo-oxygenase enzyme. A pre-incubation period of 72 hours was found to be necessary to observe the stimulatory effect of IL-1 beta on prostaglandin production, but this did not seem to be due to any change in the sensitivity of the cells to IL-1 beta; the increase in the number of cyclo-oxygenase positive cells was the same if IL-1 beta was added on day 1, day 2 or day 3 of culture, even though prostaglandin production was not stimulated on day 1 or day 2. Cycloheximide increased prostaglandin production on the first two days of culture and had no effect on the third day of culture. This was interpreted as indicating that a factor inhibiting cyclo-oxygenase activity was synthesised during the initial period of culture, which prevented any increase in prostaglandin production following the increase in enzyme synthesis.

Cycloheximide↗
PubMed1992

Effects of platelet-activating factor on prostaglandin E2 production by intact fetal membranes.

OBJECTIVE: The hypothesis tested in this study is that platelet-activating factor increases prostaglandin E2 synthesis from fetal membranes. STUDY DESIGN: Fetal membrane disks obtained before or after labor were incubated with or without platelet-activating factor for time periods of up to 24 hours. The production of prostaglandin E2 and its inactive metabolites was determined by specific radioimmunoassays. RESULTS: Platelet-activating factor (1 to 10 mumol/L) stimulated the production of prostaglandin E2 and its metabolites by intact fetal membranes and chorion-decidua threefold to fourfold after 24 hours of incubation. Platelet-activating factor had far greater effects on the production of prostaglandin E2 by intact fetal membranes obtained after the onset of labor, such that prostaglandin E2 production was increased by tenfold to 100-fold. CONCLUSION: These results suggest that platelet-activating factor mainly stimulates prostaglandin E2 production by the chorion-decidua before labor and that it may act in synergism with other stimulatory factors present in the fetal membranes during labor.

Amnion↗
PubMed1992

Changes in decidual stromal cell function associated with labour.

OBJECTIVE: To determine whether decidual cells produce altered levels of prostaglandins after labour. DESIGN: Decidual stromal cells and macrophages were isolated before and after labour, and the production of prostaglandins E2 and F2 alpha measured. Changes in the numbers of cyclooxygenase enzyme positive cells were assessed by immunocytochemistry. RESULTS: Decidual stromal cells obtained after labour produced 30 times more prostaglandins E2 and F2 alpha in culture than cells obtained before labour. The increased production persisted for up to 72 h of culture, and was associated with an increase in the numbers of cyclooxygenase-positive cells from less than 5% to greater than 95%. No changes in macrophage function were observed. CONCLUSION: Increased levels of prostaglandins E2 and F2 alpha were released from decidual stromal cells after labour, suggesting that these cells may be an important source of prostaglandins in labour.

Decidua↗
PubMed1992

Transfer and metabolism of platelet-activating factor by fetal membranes, amnion and chorio-decidua.

OBJECTIVE: To determine the metabolism of 3H-Platelet-activating factor (3H-PAF) during transfer through human fetal membranes. DESIGN: 3H-PAF was added to the fetal side of cultured intact fetal membranes, amnion and chorio-decidua obtained from three pregnancies ending in elective caesarean section. MAIN OUTCOME MEASURES: Radioactivity was measured on both sides of the tissue, and in the tissue itself. In some experiments, the metabolism of 3H-PAF was assessed by thin-layer chromatography. RESULTS: Very little 3H-PAF crossed the intact fetal membrane (< 2%) during 24 h of culture. Most of the 3H-PAF which accumulated in the membrane was converted to a range of metabolites in the chorio-decidua. CONCLUSIONS: These results suggest that PAF in amniotic fluid may not reach the decidua, and therefore is unlikely to be involved in the control of prostaglandin production from this tissue.

Amniotic Fluid↗
PubMed1991

Changes in platelet function in pregnancies complicated by fetal growth retardation.

Platelet function was investigated in three patients with severely decreased fetal growth rates detected by ultrasound scanning. Only one patient had hypertension, which was mild and developed after decreased fetal growth and altered platelet responses had been detected. Much higher concentrations of platelet-activating factor (PAF) (20-500 nM) were required to stimulate maximal platelet aggregation in all three patients compared with the concentrations of PAF (5-10 nM) required in control pregnancies of similar gestational age. In a fourth patient, platelet desensitisation was observed 5 weeks before the detection of decreased fetal growth. These results are similar to those observed in women with hypertensive disorders of pregnancy, and indicate that there may be a similar change in platelet function in gestational hypertension and in fetal growth retardation, although the clinical manifestations are different.

Blood Platelets↗
PubMed1991

Detection of platelet desensitization in pregnancy-induced hypertension is dependent on the agonist used.

The aggregation of platelets from women with pregnancy-induced hypertension (P.I.H.), or with normal pregnancies, in response to arachidonic acid, ADP, collagen or platelet activating factor (PAF) was examined. No differences in platelet aggregation between the normotensive and hypertensive women were detected when arachidonic acid or collagen were used to stimulate in vitro platelet aggregation. Higher concentrations of ADP and PAF were required to aggregate platelets from women with P.I.H. compared with platelets from normotensive controls. Platelets from women with normotensive pregnancies (n = 80) aggregated maximally in response to 20 nM PAF without exception. Reversible aggregation by platelets from women with P.I.H. (n = 25) was observed at the same concentration of PAF; again, this was found in all subjects tested. These results indicate that PAF at a concentration of 20 nM can clearly demonstrate differences in aggregation of platelets from women with normotensive pregnancy and women with P.I.H.

Adenosine Diphosphate↗
PubMed1991

A comparison of two populations of decidual cells by immunocytochemistry and prostaglandin production.

The decidua has been implicated in the control of human labour, particularly through changes in prostaglandin production, but this tissue contains a number of different cell types. A density gradient system was used to obtain two populations of cells from term human decidua, and these populations were characterised. The more dense cells (population B) was a mixed population, predominantly macrophages (80%), but small numbers of T- and B-lymphocytes were also present, as identified by immunocytochemistry. Most of these cell types also contained detectable levels of cyclooxygenase enzyme. The less-dense cell population (population A) did not contain significant numbers of the above cell types and released prolactin, suggesting that they were decidual stromal cells. This preparation of decidual stromal cells may be of use in defining the functions of these cells in labour.

Antibodies, Monoclonal↗
PubMed1991

The efficacy and acceptability of a low-dose levonorgestrel intravaginal ring for contraception in a UK cohort.

The efficacy and acceptability of a levonorgestrel-releasing intravaginal ring (IVR) for contraception was assessed in a British cohort studied as part of a multicentre, multinational clinical trial performed under the auspices of the World Health Organisation. One-hundred-and-fifty women took part in the study in two UK centres and completed 1417.5 months of method use. Fifty-nine women discontinued use of the IVR before the end of one year giving an overall discontinuation rate of 39.9 per 100 woman-years. The discontinuation for pregnancy with the ring in situ, was 3.0 per 100 woman-years (life table analysis). Menstrual disturbance, vaginal problems and involuntary expulsion resulted in discontinuation rates of 8.9, 8.4 and 1.6 per 100 woman-years, respectively. This method is an acceptable and effective method of contraception for women.

Adolescent↗
PubMed1991

Prostaglandin production in human endometrium following continuous exposure to low-dose levonorgestrel released from a vaginal ring.

Arachidonic acid metabolites produced by primary cultures of human endometrial cells derived from biopsies obtained before and after exposure to 20 micrograms/day levonorgestrel for 84 +/- 1 days were analysed by reverse phase HPLC. This revealed a significant increase in PGF1 alpha and an epoxide metabolite upon levonorgestrel stimulation. The proportion of epoxide metabolite, PGF1 alpha and PGE2 were positively correlated with serum levonorgestrel levels while HETES, PGE2 and epoxide were similarly correlated with serum oestradiol. The extent of intermenstrual bleeding during exposure to levonorgestrel was correlated with the proportion of epoxide and HETES products in vitro which is discussed in relation to their physiological function.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Production of urinary 11-keto-thromboxane B2 in normal and hypertensive pregnancies.

Urinary levels of 11-keto-thromboxane B2 (11-keto-TXB2), were elevated at all gestational ages (12-41 weeks) compared with non-pregnant levels. 11-keto-TXB2 levels exceeded those of TXB2 throughout pregnancy, which suggested that 11-keto-TXB2 may be the major urinary metabolite of TXA2 in normotensive pregnancy, as in the non-pregnant state. This was reversed in women with mild pregnancy-induced hypertension (P.I.H.), such that urinary levels of TXB2 were higher (p less than 0.01) than those of 11-keto-TXB2. Since the 11-thromboxane dehydrogenase enzyme is found in the placenta, the low levels of 11-keto-TXB2 may be the result of placental damage decreasing the activity of the enzyme. The relationship between these findings and the aetiology of P.I.H. is not clear, but changes in urinary 11-keto-TXB2 may be of use in identifying those women at risk of developing P.I.H.

Adult↗