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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 91 records · Page 5Linked to original sources

The prognostic significance of urinary beta core fragment in premenopausal women with carcinoma of the cervix.

The mortality of premenopausal women with cervical carcinoma has increased in recent decades despite attempts to provide screening. The urinary concentration of the beta core fragment of hCG has been proposed as a sensitive marker in gynecological malignancies, although most studies have not corrected for urine concentration. We measured the urinary concentration of beta core and creatinine in 61 women who developed cervical cancer premenopausally and expressed the concentration of beta core per millimole of creatinine using the 90th percentile of a control group as a cutoff level. While correcting for urinary concentration results in a reduction in sensitivity of the test (67 to 51%), there is improved correlation with prognosis in that after 18 months 81% of women positive for beta core had died, while 80% of women negative for beta core were still alive. Of those initially presenting and dying there was an increase with increasing stage of disease. For patients with initial presentation disease, 11 (79%) of the 14 patients with elevated levels had died compared with 1 of 21 (5%) who were negative for beta core. Urinary beta core fragment may have a major role as a prognostic indicator in cervical carcinoma rather than as a screening or diagnostic marker and enables identification of patients at higher risk of an aggressive disease.

Biomarkers, Tumor↗

The effects of labor on maternal and fetal levels of insulin-like growth factor binding protein-1.

OBJECTIVE: Our purpose was to determine the effects of labor and fetal hypoxia on the levels of insulin-like growth factor binding protein-1 in the maternal and fetal circulation. STUDY DESIGN: Serum levels of insulin-like growth factor binding protein-1 were determined in maternal and umbilical blood at delivery in two groups. The first group included 43 vaginal deliveries and 23 elective cesarean sections. The second group consisted of 44 women; in 24 the liquor was meconium stained and in 20 it was clear. RESULTS: Levels of insulin-like growth factor binding protein-1 in the neonate were lower in deliveries occurring before onset of labor (p < 0.001), Mann-Whitney U test) and higher in cases with severe meconium staining (p = 0.01). There were no differences in maternal levels of insulin-like growth factor binding protein-1 between subjects in labor and not in labor or those with or without meconium staining. CONCLUSION: The process of labor leads to an increase in fetal levels of insulin-like growth factor binding protein-1. This increase may well be associated with the relative fetal stress that occurs during labor. This suggestion is supported by the finding of the highest levels in labors in which there was thick staining of the liquor.

Adolescent↗

Amniotic fluid erythropoietin levels in normal and Down's syndrome pregnancies.

The aim of this study was to measure the levels of erythropoietin in amniotic fluid from normal and trisomy 21 pregnancies at 10 to 20 weeks gestation. Samples of amniotic fluid were collected from 142 women with singleton pregnancies after genetic amniocentesis; 110 had a normal fetal karyotype and 32 had trisomy 21. Erythropoietin was measured using a double antibody radioimmunoassay. Amniotic fluid erythropoietin levels in normal pregnancies increased from 10 weeks (mean 3.2 mU/ml; range < 2.0-6.3 mU/ml) to 20 weeks gestation (mean 7.9 mU/ml; range 2.0-11.5 mU/ml). There was a significant linear correlation between gestational age and erythropoietin levels (r = 0.543; P < 0.0001). For the 32 patients with trisomy 21 pregnancies the median multiple of the median (MoM) was 1.11 (range 0.42-2.1). There was no difference between erythropoietin levels in amniotic fluid from normal and Down's syndrome pregnancies (U = 2352, P = 0.75, 95% CI = -0.11, 0.18); (Mann-Whitney U-test).

Amniotic Fluid↗

Pregnancy-associated plasma protein A levels in maternal serum, extraembryonic coelomic and amniotic fluids in the first trimester.

First trimester maternal serum levels of pregnancy-associated plasma protein A(PAPP-P) are reduced in women with a Down's syndrome pregnancy. We have examined the concentration of this molecule in the amniotic (AF) and extra-embryonic coelomic (EECF) fluids surrounding the developing fetus. Maternal serum levels of PAPP-A were elevated in all samples and steadily rose from a median of 480 mIU/1 at 8 weeks to a median of 6375 mIU/1 at 14 weeks gestation. Levels of PAPP-A were low in EECF and undetectable in the AF until 14 weeks gestation. This pattern of distribution is in contrast to that of most other trophoblast-associated antigens. This may reflect PAPP-A physiology and its specific production by the syncytiotrophoblast.

Amniotic Fluid↗

Dramatic increase in levels of placental protein 14 in amniotic fluid at 10-15 weeks' pregnancy.

Concentrations of placental protein 14 (PP14) were measured by radioimmunoassay in 103 amniotic fluid samples from 10 to 20 weeks of pregnancy. Low levels of PP14 were present at 10-12 weeks (median values 82-280 micrograms/l). After 12 weeks, the levels increased by two orders of magnitude to reach a peak at 18 weeks (median 11 mg/l). This pattern may reflect the obliteration of the extraembryonic coelom and direct apposition of the decidua with the chorio-amnion.

Amniotic Fluid↗

Low levels of amniotic fluid pregnancy specific beta-1-glycoprotein in Down's syndrome.

Amniotic fluid levels of beta-1-glycoprotein (SP1) were measured in 46 cases of Down's syndrome and compared with levels in 106 pregnancies of normal karyotype from 10 to 23 weeks of gestation. In normal pregnancies, levels rose from 87.5 iu/l at 10 weeks to a peak of 610.0 iu/l at 19 weeks of gestation. In cases of Down's syndrome, levels were reduced prior to 19 weeks of gestation (median multiple of the median, MoM = 0.75, P = 0.02). This effect was most marked prior to 16 weeks of gestation when the median multiple of the median (MoM) was 0.51 (P = 0.006). These data demonstrate that amniotic fluid levels of SP1 are low in Down's syndrome before 19 weeks of gestation.

Amniotic Fluid↗

Production of placental alkaline phosphatase (PLAP) and PLAP-like material by epithelial germ cell and non-germ cell tumours in vitro.

Placental and placental-like alkaline phosphatase (PLAP) levels in the culture media of 87 cell lines of neoplastic and 'normal' origin were measured by a conventional immunosorbent enzymatic assay (IAEA) and by a new immunoradiometric assay (IRMA). The IRMA detected immunoreactive PLAP in 37 of 80 (46%) human epithelial and germ cell cultures, while the IAEA detected PLAP in only 25 (33%). Of the 52 non-germ cell tumour cultures, the IRMA detected expression in 24 (46%) and the IAEA in only 16 (31%). In 17 cases (21%) the IRMA recorded levels double that of the IAEA, while in five cultures (6%) the reverse was true. The IRMA was much more robust than the IAEA and had considerably lower inter- and intra-assay coefficients of variation (3.75-8.5% vs 5.2-46%). Detection of PLAP(-like) expression by IAEA is dependent on neoplastic expression of enzymatically functional molecules and quantification assumes constant enzyme kinetics. PLAP-like material has a higher catalytic rate constant than PLAP and thus will give higher values on a stoichiometric basis in an IAEA. The higher detection rate and levels of PLAP-like material in neoplastic cultures when measured by the IRMA clearly demonstrate ectopic expression of non-enzymatic PLAP and PLAP-like genes. The incidence of PLAP(-like) expression by non-germ cell and possible germ cell tumours has been underestimated and its utility as a tumour marker should be re-examined using assays which measure antigen mass rather than phosphatase activity.

Alkaline Phosphatase↗

Lack of evidence for the production of interferon-alpha-like species by the cultured human pre-embryo.

The aim of this study was to determine if the human pre-embryo produces a substance similar to the trophoblast interferon secreted by ruminant trophoblasts. Human embryos surplus to in-vitro fertilization (IVF) treatment were cultured up to 14 days following IVF. Viable cultures were determined by microscopic examination and by assay of the culture medium for human chorionic gonadotrophin (HCG). Four stages of development were visually identified: pre-blastocyst, unhatched, part-hatched and fully hatched blastocyst. HCG was detected in medium which had contained the more developmentally advanced embryos. A total of 62 samples were assayed for human interferon-alpha (IFN-alpha), including all cultures presumed viable. None contained detectable IFN-alpha immunoreactivity. Out of 14 candidate samples subjected to cytopathic effect reduction assay, none contained antiviral activity. We suggest that a trophoblast-derived interferon, unlike HCG, does not play a significant role in the maternal recognition of pregnancy in humans.

Blastocyst↗

Circulating levels of placental protein 14 in ectopic pregnancy.

OBJECTIVE: To determine circulating levels of placental protein 14 (PP14) in complications of early pregnancy. DESIGN: Biochemical monitoring of women presenting with vaginal bleeding and/or abdominal pain. SETTING: An emergency gynaecological ultrasound clinic in a London teaching hospital. SUBJECTS: Venous blood samples were obtained from 67 women with normal pregnancy (n = 9), ectopic pregnancy (n = 26) and failed intrauterine pregnancy (n = 32). This group included anembryonic pregnancy (n = 18), missed miscarriage (n = 2), spontaneous miscarriage of a previously demonstrated live fetus (n = 6), incomplete miscarriage (n = 4), complete miscarriage (n = 1) and molar pregnancy (n = 1). MAIN OUTCOME MEASURES: Serum PP14 levels in the group of women with a failed intrauterine pregnancy in relation to the normal range for PP14. RESULTS: Eighty-one percent of women who miscarried spontaneously had normal serum PP14 levels; 81% of women with ectopic pregnancy had depressed (< 5th centile) serum PP14 levels. CONCLUSION: Measurements of PP14 may be useful in distinguishing spontaneous miscarriage from ectopic pregnancy, but not in the management of threatened miscarriage.

Abdominal Pain↗

Evaluation of an antenatal HIV testing programme in an inner London health district.

OBJECTIVE: To study an antenatal human immunodeficiency virus (HIV) testing programme in an inner London health district. DESIGN: A standardised research interview was given to women in the first half of pregnancy and the findings were compared with those of the routine clinical interview. The observations were analysed in relation to the results of HIV antibody testing, either attributable by consent or anonymously, in these women. SETTING: The Homerton Hospital, London. SUBJECTS: Three thousand seven hundred and twenty-nine women, of whom 1696 (45.5%) consented to testing. RESULTS: Four women who had consented to testing had a positive result. Amongst the 2,033 women (54.5%) who declined the test, four (or five) had a positive result. The number of risk factors ascertained by the research study interview was substantially greater than that elicited by the preceding routine interview. In addition, more information was obtained by a routine computer interview than by its unstructured equivalent. There was no obvious association between the presence of a risk factor and whether or not the women had consented to the test. CONCLUSIONS: Our formal voluntary testing programme detected nearly 44% of HIV seropositive individuals. Thus, there were four known positives during the study period against a total of nine detected by anonymous testing. Since all the known positive results in the study were associated with recognised risk factors, there is some doubt as to the value of a universal testing programme. However, if testing is to be based upon the existence of a risk factor elicited at the booking history, then the deficiencies in this history revealed by the present study need to be corrected.

Female↗

Concentrations of vitamins A and E in amniotic fluid, extraembryonic coelomic fluid, and maternal serum in the first trimester of pregnancy.

Paired samples of amniotic fluid and coelomic fluid were obtained by transvaginal ultrasound guided amniocentesis from 15 women with an ultrasonographically normal pregnancy between 8 and 12 weeks' gestation. Vitamins A and E were measured in the two pregnancy fluids and in maternal serum by high performance liquid chromatography with detection by ultraviolet absorption and fluorimetry respectively. Concentrations of vitamins A and E were higher in maternal serum than in coelomic fluid and were generally undetectable in amniotic fluid. All differences in concentration were significant. The vitamin E/cholesterol ratio was similar in maternal serum and coelomic fluid. No correlation was shown between the vitamin concentrations in the three fluids. These findings suggest that the coelomic cavity plays a part in the maternofetal exchange of these vitamins.

Amniotic Fluid↗

Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract.

AIM: To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS: PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS: Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS: Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission.

Adenocarcinoma↗

Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and proteolyzed IGFBP-3 in embryonic cavities in early human pregnancy: their potential relevance to maternal-embryonic and fetal interactions.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are believed to be important in fetal growth and development. In the current study, the developmental changes in the IGF and IGFBP axis were examined in 23 paired samples of human amniotic fluid (AF), extraembryonic coelomic (EEC) fluid, and maternal serum (MS) between 9 and 12 weeks gestation. Levels of IGF-I were very low in AF (7 +/- 3 ng/mL) and EEC (10 +/- 3 ng/mL) compared to those in MS (237 +/- 42 ng/mL). In contrast, IGF-II concentrations were 210 +/- 36 and 174 +/- 22 ng/mL in AF and EEC, respectively, and were approximately 25% of MS serum levels (884 +/- 122 ng/mL). There was no dependence on gestational age for either peptide in AF or EEC during the period of gestation examined. IGFBP-1 levels in AF increased about 20-fold (1.6 +/- 0.3 to 33.0 +/- 0.1 ng/mL) between 9 and 12 weeks of pregnancy, and IGFBP-1 levels were nearly 2 orders of magnitude higher in EEC, increasing about 100-fold (365 +/- 119 to 3014 +/- 100.0 ng/mL) by the end of the first trimester. In contrast, IGFBP-1 levels were low in MS (24.9 +/- 3.5 ng/mL) and showed no gestational age dependence. Using RIA, high levels of IGFBP-3 were found in EEC (2062 +/- 177 ng/mL) and MS (6590 +/- 357 ng/mL) compared to those in AF (152 +/- 24 ng/mL). Levels of IGFBP-3 in MS and EEC did not change significantly with gestational age, whereas an increase in IGFBP-1 was observed in AF after the tenth week of pregnancy. In contrast to high levels of IGFBP-3 in MS and EEC, determined by RIA, the 37- to 43-kilodalton IGFBP-3 doublet was barely detectable by Western ligand blot analysis. This discrepancy suggested the presence of an IGFBP-3 protease in EEC, as has been found in MS, that decreases the affinity of this BP for IGF peptides and, therefore, renders it less readily detectable by Western ligand blot analysis. Using [125I]IGFBP-3 as substrate, lower levels of IGFBP-3 protease activity were detected in EEC compared to MS, and nearly undetectable levels were found in AF. By Western immunoblotting, a smaller (28-kilodalton) immunoreactive form of IGFBP-3 was detected only in MS and EEC, suggesting proteolyzed IGFBP-3 in MS and EEC, but not in AF, during this gestational period.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗

Is ovarian relaxin a stimulus to placental protein 14 secretion in pregnancy?

The objective of this study was to investigate whether relaxin might be involved in placental protein 14 (PP14) secretion by measuring serum levels of PP14 during labour and post partum in normal women with a term pregnancy given vaginal human recombinant relaxin (rhRlx) gel for induction of labour. A randomized double-blind controlled trial was conducted on 11 women with a singleton pregnancy at term admitted for induction of labour. Comparison of serum PP14 and relaxin concentrations in the control and treated groups of subjects revealed that there was an increase in serum relaxin concentrations in women receiving 3 mg or 6 mg relaxin. There was no difference in serum PP14 levels between the control and treatment groups. These findings do not support the hypothesis that relaxin is involved in the control of PP14 secretion. However, the failure of any response might be a consequence of the very small increase in systemic levels of relaxin produced by topical vaginal administration of rhRlx. Furthermore, these measurements were made in late pregnancy and hence may not relate to the events in early pregnancy, when serum levels of PP14 are maximal.

Adult↗

Levels of insulin-like growth factor-binding protein-2 and insulin-like growth factor-II in maternal serum, amniotic fluid and extraembryonic coelomic fluid at 9-20 weeks of pregnancy.

Insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 (IGFBP-2) were measured in amniotic fluid, extraembryonic fluid and maternal serum from 20 women with apparently normal first trimester pregnancies prior to termination. A further 111 specimens of amniotic fluid were collected from women at 10-20 weeks of pregnancy. Levels of IGFBP-2 were similar in coelomic fluid and maternal serum. Levels in amniotic fluid were lower than those in serum and coelomic fluid (Mann-Whitney test; P = 0.0002 and P < 0.0001 respectively). The levels of IGF-II were much higher in maternal serum than in coelomic fluid, and higher in the latter than in amniotic fluid (Mann-Whitney test; P < 0.0001 for both situations). The levels of IGFBP-2 were relatively low at 10-11 weeks (medians 19.8 and 61.1 micrograms/l) but thereafter increased to 20 weeks (median 1400 micrograms/l). The levels of IGF-II showed a similar pattern. The findings suggest that the role of IGF-II and IGFBP-2 in the regulation of growth or differentiation of the fetus or of its surrounding membranes may change with advancing pregnancy.

Adult↗