Search PubMed⌕ Search

Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 55 records · Page 3Linked to original sources
PubMed1996

Measurement of interleukin-1 alpha and interleukin-6 in pregnancy-associated tissues.

The concentrations of interleukin-1 alpha (IL-1 alpha) and IL-6 in pregnancy-associated tissues were investigated in term labour and delivery in the absence of labour (elective Caesarean section). Samples of amniotic fluid, placenta, fetal membranes, umbilical venous and, where possible, umbilical arterial blood were collected at delivery (37-41 weeks of gestation). Maternal blood was sampled during labour. Fluid and tissue extracts were assayed for IL-1 alpha and IL-6 by radioimmunoassay. Placenta and membranes were examined histologically for evidence of infection. Concentrations of IL-1 alpha and IL-6 in amniotic fluid and membrane extract, and IL-1 alpha in maternal and fetal blood, were raised after the onset of labour. Concentrations of both cytokines in the placenta remained unchanged. There was a good correlation between concentrations of both cytokines in amniotic fluid and membranes. There was also a significant correlation between concentrations of IL-1 alpha and IL-6 in amniotic fluid, placenta and membranes. It is suggested that the fetal membranes or maternal decidua, but not the placenta, internal fetal or maternal tissues, are the main sources of IL-1 alpha and IL-6 during labour.

Amniotic Fluid↗
PubMed1996

The effects of post-ovulatory administration of onapristone on the developmnent of a secretory endometrium.

The purpose of this study was to assess the ability of the anti-progestin onapristone administered in the immediate post-ovulatory period to disrupt endometrial differentiation as a potential method of fertility control. In all, 10 healthy female volunteers were given 400 mg onapristone 2 days after the mid-cycle luteinizing hormone (LH) surge in urine (LH+2). An endometrial biopsy was taken 4 or 6 days after the LH surge (i.e. LH+4 or LH+6) in a control cycle and on the corresponding day of the treatment cycle. Biopsies were assessed for histological dating and immunolocalization of oestrogen receptors, progesterone receptors and 15-hydroxyprostaglandin dehydrogenase (PGDH). On day LH+12, blood was taken for the measurement of insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14). Hormonal measurements in blood and urine were used to monitor the effects on the menstrual cycle. In addition, the concentration of cortisol in plasma was measured to determine if this dose of onapristone exerted significant anti-glucocorticoid activity. Treatment with onapristone retarded the development of secretory changes within the endometrium without affecting the length of the luteal phase. Intense nuclear immunostaining of oestrogen and progesterone receptors was evident in glands and stroma after treatment, suggesting that the progesterone-dependent down-regulation of steroid receptors was inhibited by the anti-progestin. Onapristone also affected the production of luteal phase endometrial proteins, as judged by the pronounced reduction in immunostaining of PGDH within the glands and the significant reduction in plasma concentrations of PP14. However, plasma concentrations of IGFBP-1 did not differ between cycles. Onapristone did not appear to exert significant anti-glucocorticoid activity because concentrations of cortisol were unaffected. These findings suggest that onapristone could potentially be used as a method of postovulatory fertility control.

Adult↗
PubMed1996

Inhibin in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy.

Inhibins are present in maternal serum during pregnancy. However, the presence of inhibins in the compartments surrounding the fetus in early pregnancy is not well defined. Using novel specific enzyme-linked immunosorbent assays we have demonstrated that the bioactive dimeric inhibin forms, inhibin-A and inhibin-B, and the immunoreactive inhibin forms containing pro- and alpha C sequences are present in different amounts in the extra-embryonic coelomic and amniotic fluids and maternal serum between 8-11 weeks gestation. Of the bioactive dimeric inhibins, both inhibin. A (mean +/- SEM 236.0 +/- 24.8 pg/ml) and inhibin-B (62.0 +/- 8.6 pg/ml) are present in extra-embryonic coelom whereas no dimeric inhibin is present in the amniotic fluid and only inhibin-A (360.2 +/- 32.9 pg/ml) is present in maternal serum. Furthermore, pro-alpha C-related immunoreactivity is present at high concentrations in the extra-embryonic coelom (591.7 +/- 60.5 pg/ml), amniotic fluid (452.4 +/- 76.8 pg/ml) and maternal serum (539.4 +/- 39.5 pg/ml). These findings would indicate that at this stage of gestation inhibin-A, inhibin-B and immunoreactive pro- alpha C-containing inhibin production are likely to arise from different sources including the fetus, placenta and fetal membranes and maternal sources including the ovary. Inhibins may be important regulators of fetal and placental development and involved in the establishment of pregnancy.

Amniotic Fluid↗
PubMed1996

The temporary anatomical structures prominent in the first trimester may be fulfilling exchange functions assigned to the placenta in the second and third trimester.

The extra-embryonic coelom (EEC) and secondary yolk sac are prominent structures in the gestational sac during the first trimester of human pregnancy, at a time before the definitive placental circulation becomes established. We propose that the EEC and yolk sac play a critical role in the nutrition of early pregnancy, fulfilling exchange functions which are assumed by the placenta at a later stage.

Amniotic Fluid↗
PubMed1996

Mechanism of action of the intrauterine contraceptive device: evidence for a specific biochemical deficiency in the endometrium.

The precise mechanism of action of the intrauterine contraceptive device (IUCD) is uncertain. In this study we compared the circulating concentrations of a specific endometrial protein, placental protein 14 (PP14), in 62 women with an IUCD and 16 controls. The concentrations of PP14 were substantially lower in IUCD users. There was no difference in the concentrations of another and less specific endometrial protein, insulin-like growth factor binding protein-1 (IGFBP-1). There was no difference in PP14 concentrations between those women with and without intermenstrual bleeding. We conclude that the reduced concentrations of PP14 in IUCD users reflect defective endometrial function in these women, probably related to the contraceptive effect. We propose that the measurement of PP14 might be a means of comparing the efficiency of different devices.

Adult↗
PubMed1996

Raised circulating levels of interleukin-6 in women with an intrauterine contraceptive device.

The aim of this study was to determine whether the presence of an intrauterine contraceptive device (IUCD) causes a systemic elevation of interleukin-6 (IL-6). The control group comprised 29 women with normal cycles and who were not using any form of contraception and the study group comprised 74 women who had had an IUCD in place for 10-24 months. Of these, 45 had intermenstrual bleeding. Systemic IL-6 was undetectable (minimum detection limit of the assay is 5 pg/ml) in the control but was raised in 20% of the women fitted with an IUCD (p < 0.01). There was no difference between IL-6 levels in IUCD users who had intermenstrual bleeding and those who did not. These results suggest that the effects of chronic IUCD usage may not be limited to the endometrium.

Adult↗
PubMed1996

Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birthweight and maternal weight.

Serum levels of IGF-I and IGF-binding protein (IGFBP-1) have been determined in the maternal circulation between 11 and 42 weeks of gestation in women not in labour (n = 335) and in the maternal and fetal circulations at the time of delivery between 37 and 42 weeks (n = 55). Maternal serum (MS) IGF-I levels increased during pregnancy and showed a significant positive correlation with maternal weight (P = 0.0033) but no correlation with birthweight. The MS IGFBP-1 levels did not change during the second and third trimesters and showed a negative correlation with birthweight, maternal weight, placental weight and MS glucose (P = 0.0002, P < 0.0001, P = 0.047, P = 0.024 respectively). MS IGFBP-1 levels were higher in small-for-gestational age babies than in average-for-gestational weight babies (P = 0.026) and lower in the large-for-gestational weight group (P = 0.048). There was a significant rise in mean MS IGFBP-1 levels during labour (P = 0.0005). These findings suggest that IGFBP-1 may be an important factor in pathological growth retardation.

Birth Weight↗
PubMed1995

Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum in early human pregnancy.

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid together with maternal serum were collected from 22 women between 8 and 11 weeks of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P < 0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was no relation between levels in the other fluid compartments.

Amniotic Fluid↗
PubMed1995

Crown-rump length in aneuploid fetuses: implications for first-trimester biochemical screening for aneuploidies.

This study examined the effect of estimation of gestational age from the menstrual history compared with that from crown-rump length (CRL) measurement on the detection rate of screening for aneuploidies in the first trimester. Pregnancy-associated plasma protein A (PAPP-A) was assayed in blood collected prior to chorionic villus sampling in 356 women with unaffected pregnancies and 28 women with an aneuploid pregnancy. There were 14 Down's syndrome (DS) pregnancies. All pregnancies were dated from menstrual history and CRL measurement. The average CRL gestation in the aneuploid population was 2.5 days less than that derived from the LMP (95 per cent confidence interval (CI) for LMP-CRL gestation: using the algorithm based on unaffected pregnancies 0-3.5 days; using the matched case-control approach 1-4.5 days). The average CRL gestation in the DS population was 2 days less but this did not reach statistical significance (95 per cent CI for LMP-CRL gestation: using the algorithm -1 to 4.5 days; using the matched case-control approach 0 to 5.5 days). The detection rate of aneuploidies in the first trimester using maternal serum PAPP-A was reduced by 7 per cent (and by 3 per cent for DS) for a 5 per cent false-positive rate when using CRL rather than LMP to date the pregnancy. This phenomenon is a consequence of an apparent reduction of gestational age when estimated by CRL in the aneuploid population. Further studies are required to evaluate whether CRL is an unbiased estimate of gestation for Down's syndrome pregnancies.

Aneuploidy↗
PubMed1995

Urinary multiple marker screening for Down's syndrome.

We have examined the possibility of using multiple markers in maternal urine rather than serum in order to screen for Down's syndrome. Urine samples were available from 36 cases (24 Down's syndrome, five Edwards' syndrome, three Turner's syndrome, one Klinefelter's syndrome, one triploidy, one triple-X, one twin discordant for Down's syndrome) and 294 controls, including three twins. Three markers were tested: the beta-core fragment of human chorionic gonadotrophin (hCG), total oestrogen (tE) and the free alpha subunit of hCG. Levels were corrected for creatinine excretion and expressed as multiples of the gestation-specific median (MOM) level from the singleton controls. The median value for the singleton Down's syndrome cases was 6.02, 0.74, and 1.08 MOM for beta-core-hCG, tE, and alpha-hCG, respectively. The increases in beta-core-hCG and the reduction in tE levels were highly significant (P < 0.0001 and 0.005, respectively; Wilcoxon rank sum test) but the increase in free alpha-hCG was not (P = 0.40). On the basis of a mathematical model, the expected detection rate for a 5 per cent false-positive rate was 79.6 per cent for beta-core-hCG alone, which increased to 82.3 per cent when combined with tE. Aneuploidies other than Down's syndrome were characterized by low levels of tE and either low or high beta-core-hCG.

Adult↗
PubMed1995

The coelomic cavity--a reservoir for metals.

OBJECTIVE: The concentrations of metals in fluids surrounding the first-trimester fetus were measured. STUDY DESIGN: Atomic absorption spectrometry was used to measure concentrations of metals in matched samples of amniotic and extraembryonic coelomic fluids in 17 women between 9 and 12 weeks of pregnancy. RESULTS: Concentrations of calcium, magnesium, iron, copper, and manganese (but not zinc, cadmium, or lead) were significantly higher in coelomic than in amniotic fluid. There was no significant difference between levels of iron, manganese, and lead in controls and amniotic fluid or between concentrations of manganese, cadmium, and lead in controls and coelomic fluid. There was no relationship between the concentrations of each metal in amniotic and coelomic fluid. CONCLUSION: The extraembryonic coelom is an important site of concentration of metals in early pregnancy. This might represent a store of metals essential for normal embryonic and fetal development or constitute a defense mechanism against environmental conditions adverse to the fetus.

Amniotic Fluid↗
PubMed1995

Insulin-related growth factor binding protein-1 levels in ovum donation pregnancies.

The finding that endometrial maturation may be delayed following hormone replacement therapy has suggested that a generalised endometrial dysfunction may exist in ovum recipients. In order to investigate this suggestion further, circulating levels of IGFBP-1 were measured in samples taken throughout pregnancies conceived either spontaneously or following ovum donation. When analysed at two-weekly intervals, the serum levels of IGFBP-1 in ovum donation pregnancies failed to show the expected peak towards the end of the first trimester and were significantly reduced at week ten (U = 364.5, p = 0.0002) and twelve (U = 138.0, p = 0.0047). For the remainder of pregnancy, circulating IGFBP-1 levels were similar in both groups. The birth weight of children born to the ovum donation group was not significantly different from a normal control group, suggesting that circulating levels of IGFBP-1 in early pregnancy do not reflect local function and that IGFBP-1 does not have an essential function (in relation to birth weight) in early pregnancy.

Birth Weight↗
PubMed1995

Superovulation, IGFBP-1 and birth weight.

In this study, the effect of superovulation on the circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) has been investigated. IGFBP-1 levels were measured in singleton pregnancies achieved either naturally (n = 203) or following superovulation, in-vitro fertilisation and embryo transfer (IVF-ET) with either pituitary desensitisation with buserelin and superovulation with human menopausal gonadotrophin (b/hMG) followed by IVF-ET (n = 15) or with clomiphene citrate and hMG (CC/hMG) followed by IVF-ET (n = 15, 1st trimester only). The circulating levels of IGFBP-1 were similar in all three groups during the first trimester, and in both normal and b/hMG pregnancies in the second, but were significantly higher during the third trimester in b/hMG pregnancies than in normal pregnancies (P = 0.0002). The birth weights were significantly lower in the b/hMG group (P = 0.04), but not in the CC/hMG group compared with natural conceptions. Gestational age at delivery was similar in control and b/hMG pregnancies, but significantly reduced in CC/hMG pregnancies (P = 0.04). These data suggest that pregnancies achieved following superovulation with b/hMG are associated with elevated levels of IGFBP-1 during the third trimester of pregnancy and reduced birth weight.

Adult↗
PubMed1995

The influence on a 'normal' birthweight distribution of a minor population of growth retarded infants: a Monte Carlo simulation.

It is common practice to define babies below a certain birthweight as 'growth-retarded' or 'small-for-dates'. This presupposes that there is a specific subpopulation of babies who have not achieved their genetic growth potential. The presence of this subpopulation should result in a deviation from a normal distribution in the population as a whole. We have used a mathematical simulation, together with data from an actual sample of 1463 male Caucasian neonates delivered at 40 weeks, in order to define the characteristics of such a subpopulation which would yield deviations from the normal sufficient to be statistically significant. On the basis of this study, there was no evidence for such a subpopulation of low birthweight babies in the 1463 neonates observed.

Birth Weight↗
PubMed1995

Serum is more effective than albumin in promoting human embryo development and implantation.

OBJECTIVE: To compare the effects of serum with those of Albuminar-5 (Armour Pharmaceutical Co., Eastbourne, Sussex, United Kingdom) as medium supplements to Earl's balanced salt solution (EBSS) for IVF and subsequent embryo development. DESIGN: A retrospective study. Gametes and embryos from 318 patients were cultured in the presence of serum (group 1). Gametes and embryos from 130 patients were cultured in the presence of Albuminar-5 (group 2). Embryos obtained from IVF were replaced into the uterus within 48 hours after insemination. Surplus bipronucleate embryos were cultured up to 14 days with either serum or Albuminar-5. SETTING: Two tertiary referral fertility clinics; university teaching hospital. PATIENTS: Four hundred forty-eight patients with a wide spectrum of causes of subfertility, ranging in age from 24 to 43 years. MAIN OUTCOME MEASURES: Fertilization rate, pregnancy rate (PR), implantation rate, and surplus embryo development in vitro. RESULTS: The PR for group 1 patients was higher than that of group 2 (27.0% versus 15.4%, respectively). Although fertilization rates were identical in the two groups, cumulative embryo scores and implantation rates were significantly higher in group 1. There was no difference between the groups in age distribution, types of ovarian stimulation, numbers of patients with day 1 or day 2 transfers, or luteal phase support. Of 31 embryos cultured with serum, 54.8% reached the fully expanded blastocyst stage and 25.8% hatched. Of 19 embryos cultured with Albuminar-5, only 5.3% reached the fully expanded blastocyst stage and none hatched. CONCLUSIONS: The results suggest that, under certain conditions, serum supplementation yields better results than protein supplementation alone. The latter may be suitable only in conjunction with additional components.

Adult↗
PubMed1995

Measurement of urinary beta core fragment of human chorionic gonadotrophin in women with vulvovaginal malignancy and its prognostic significance.

Tumours of the vulva and vagina are rare and there are relatively few studies of circulating markers in these conditions. The urinary measurement of the core fragment of the beta-subunit of hCG has been proposed as a useful tumour marker in non-trophoblastic gynaecological malignancies. This study describe the measurement of urinary beta-core in 50 patients with vulvovaginal malignancy. In contrast to other studies corrections were made for both the effect of urine concentration and the age of the patient. Each patient was followed up for at least 24 months, and at this time their status was correlated with their initial level of urinary beta-core. The sensitivity of beta-core was only 38%, but of those patients with elevated levels 90% had died within 24 months, while only 32% of those with normal levels had died. For both patients at initial presentation and those with recurrent disease, there was a highly significant difference in the survival curve between those with elevated beta-core levels and those with normal levels. This is similar to findings in cervical carcinoma, and suggests that for lower genital tract cancer the measurement of urinary beta-core may be valuable as a prognostic indicator, allowing a more informed approach to treatment and follow-up.

Adult↗
PubMed1995

Maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 in multifetal pregnancies before and after fetal reduction.

The aim of this study was to investigate the changes in maternal plasma insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14) in multifetal pregnancies before and after embryo reduction. Maternal plasma IGFBP-1 and PP14 were measured serially in three groups of pregnant women at 8-21 weeks gestation. Groups 1 and 2 were 12 singleton and 12 twin pregnancies achieved after in-vitro fertilization (IVF). Group 3 comprised 26 women with multifetal pregnancies undergoing embryo reduction to twins. In the IVF pregnancies maternal plasma IGFBP-1 and PP14 increased with gestation to reach a peak at 20 and 10 weeks respectively; the mean concentrations in twin pregnancies were significantly higher than in singletons. In multifetal pregnancies the mean plasma concentration of both proteins was similar to that of IVF twin pregnancies before reduction; after reduction, the values fell to less than those of twins. These findings suggest that the maximum secretory capacity of the endometrium is achieved with twin pregnancies. In multifetal pregnancies undergoing iatrogenic reduction to twins, total residual endometrial function was less than in twin conceptions.

Carrier Proteins↗