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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 19 recordsLinked to original sources
PubMed1992

Audit of compliance with antenatal protocols.

OBJECTIVE: To assess the implementation of action protocols dictated by antenatal risk factors noted at the initial (booking) antenatal visit. DESIGN: Retrospective study of 2000 women delivered between 1 March 1990 and 29 March 1991. SETTING: Maternity department of a district general hospital supporting a multiethnic population in inner London. MAIN OUTCOME MEASURES: Comparison of clinical actions performed against those dictated by the department's protocols. Analysis according to clinical importance, gestation at booking, maternal age, parity, birth order, ethnic origin, and certainty of gestational age. RESULTS: Interobserver agreement between the two auditors was good (kappa statistic for risk factors detected, 0.78; for actions generated, 0.80). Of the 15,658 actions dictated by department protocols, 3673 (23.5%) were actually performed by the clinicians. The 63 combinations of risk factors and actions believed by consultants to be of particular clinical importance had an action rate of 28.3% compared with 18.6% for those considered less important (p < 0.001). Mothers who first visited the hospital antenatal clinic at or before 24 weeks' gestation had 25.2% of relevant protocols fulfilled (p < 0.001). Compliance was significantly improved in women aged 36 or over (32.4%), black women (24.9%), and cases of uncertain gestation (24.5%). Parity and birth order were not associated with an altered action rate. Ethnic origin deemed as "other" (than white, black, Asian, or oriental) or "unknown" was associated with poor compliance (19.3%). CONCLUSIONS: Compliance to a set of agreed protocols was poor even though a computer system was available and a protocol manual had been distributed. Protocols were more likely to be implemented in women who booked early and in some groups of women deemed at high risk including older mothers, black women, and those denoted as having uncertain gestational age.

Clinical Protocols↗
PubMed1992

Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

OBJECTIVES: To assess the implementation of antenatal screening for Down's syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin. DESIGN: Demonstration project of Down's syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis. SETTING: Hospital and community antenatal clinics in four health districts in London. SUBJECTS: 12,603 women of all ages with singleton pregnancies seen between February 1989 and the end of May 1991, with follow up of the outcome of pregnancy completed to the end of 1991. MAIN OUTCOME MEASURES: Uptake of screening, detection rate for Down's syndrome, false positive rate, odds of being affected given a positive result, and uptake of amniocentesis in women with positive screening results, together with the costs of the screening programme. RESULTS: The uptake of screening was 74%. The detection rate was 48% (12/25), and the false positive rate was 4.1%, consistent with results expected from previous work based on observational studies. There was a loss of detection due to the selective use of ultrasound scans among women with positive screening results. One affected pregnancy occurred among 205 reclassified as negative; this illustrated the danger of false negatives occurring in this group and lends weight to the view that if an ultrasound estimate of gestational age is used it should be carried out routinely on all women rather than selectively among those with positive results. The estimated cost of avoiding the birth of a baby with Down's syndrome was about 38,000 pounds, substantially less than the lifetime costs of care. CONCLUSION: Antenatal maternal serum screening for Down's syndrome is effective in practice and can be readily integrated into routine antenatal care. It is cost effective and performs better than selection for amniocentesis on the basis of maternal age alone.

Amniocentesis↗
PubMed1992

Microvillar enzyme activity in amniotic fluid, extraembryonic coelomic fluid and maternal serum in the first trimester of pregnancy.

The activities of two microvillar enzymes, gamma-glutamyl transpeptidase and total alkaline phosphatase, have been measured in samples of amniotic fluid and extraembryonic coelomic fluid obtained by high-resolution transvaginal ultrasound-guided amniocentesis from 40 women between 7 and 12 weeks of gestation. There was a highly significant difference between gamma-glutamyl transpeptidase activity in amniotic fluid (median level 31 U/l; range 2-409 U/l) and extraembryonic coelomic fluid (median level 2 U/l; range less than 2-16 U/l) (P less than 0.001; Mann-Whitney U-test). Alkaline phosphatase activity was not detected in 84% of amniotic fluid samples and 97% of extraembryonic coelomic fluid samples. No difference was found between total alkaline phosphatase activity in these fluids (P = 0.14; Mann-Whitney U-test). Enzyme activities in amniotic fluid increased with gestational age. A significant linear correlation was found between amniotic fluid gamma-glutamyl transpeptidase activity and stage of gestation (r = 0.86; P less than 0.001) and total alkaline phosphatase activity in amniotic fluid and stage of gestation (r = 0.66; P less than 0.001).

Alkaline Phosphatase↗
PubMed1992

Evidence of growth retardation in neonates of apparently normal weight.

The aim of this study was to examine the relationship of ponderal index (PI) and the ratio of mid-arm circumference to occipito-frontal circumference (MAC/OFC) to the delivered weight of the child. Measurements were made on 160 singleton neonates with birthweight greater than 2500 g and delivery at 37 weeks or more. Surprisingly, there was a highly significant correlation between PI and birthweight and MAC/OFC and birthweight. We conclude that: (1) values of PI must be evaluated in relation to birthweight, and not against a single absolute standard for the whole normal population; (2) measurement of PI and MAC/OFC may reveal a group of growth-retarded infants amongst infants of apparently 'normal' birthweight; and (3) this group of infants might be a target for the extra care normally accorded to the low birthweight infant.

Anthropometry↗
PubMed1992

Comparative evaluation of fresh, fixed, and cryopreserved solid tumor cells for reliable flow cytometry of DNA and tumor associated antigen.

Five different protocols for the short-term preservation of cells used for multiparameter flow cytometric assay of tumour associated antigens (TAA) and DNA were assessed in cell suspensions prepared by mechanical disaggregation of 15 gynecological tumors. The protocols at 4 degrees C were 1) storage in buffer, 2) storage in 50% methanol, and 3) storage in buffer after formalin fixation. Tissues were also cryopreserved as cell suspensions and tissue blocks. When the TAA expression and DNA histograms of the preserved cells were compared with those in fresh cell suspensions, cryopreservation was found to be the best method: TAA expression was well preserved and there was a good correlation between TAA expression and the quality of the DNA histograms, respectively, in fresh and cryopreserved cells (RS: 0.82-0.91, P less than 0.001 for all TAAs). The cell suspensions preserved at 4 degrees C all showed a significant increase in background fluorescence (P less than 0.05) and a reduction in the TAA specific fluorescence (P less than 0.011). Methanol fixation was better than buffered formalin for the proteins studied, though both gave significantly worse results than cryopreservation. The quality of these cell suspensions and the correlation with TAA measurements in fresh cell suspensions deteriorated progressively with time, particularly if they were stored more than a week.

Antigens, Neoplasm↗
PubMed1992

Alpha-fetoprotein levels and yolk sac size in the first trimester of pregnancy.

Transvaginal ultrasound measurement of the yolk sac and transvaginal amniocentesis were carried out on 94 women prior to first-trimester termination of pregnancy. Maternal serum and fluids from the amniotic cavity and extraembryonic coelom were analysed for alpha-fetoprotein (AFP). No correlation was found between the yolk sac size and the levels of AFP in any of these sites.

Amniocentesis↗
PubMed1992

Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 in early human pregnancy.

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) were measured in amniotic fluid, extraembryonic coelomic fluid and maternal serum from 23 women with apparently normal first trimester pregnancies prior to termination. The levels of IGF-1 and IGFBP-1 were significantly higher in coelomic fluid than amniotic fluid (IGF-1, P = 0.006; IGFBP-1, P = 0.0008 (paired t-test)). The levels of IGFBP-1 were lower in amniotic fluid than in maternal serum (P = 0.017), a finding in sharp contrast to the situation in the second and third trimesters of pregnancy. There was a significant relation between levels of IGF-1 and IGFBP-1 in amniotic fluid (r = 0.43; P = 0.04) and in coelomic fluid (r = 0.81; P less than 0.001) but not in maternal serum. The finding that both the absolute levels of IGFBP-1 and the ratio to IGF-1 were low in amniotic fluid implies that there is a very high level of unbound, biologically active IGF-1 in this compartment in the first trimester. Thus, the regulatory role of IGFBP-1 may change as pregnancy advances.

Amniotic Fluid↗
PubMed1992

Pregnancy tests: a review.

Pregnancy tests are widely used both by the public and by healthcare professionals. All tests depend on the measurement of human chorionic gonadotrophin (HCG) in urine. Other pregnancy-specific materials have been proposed as pregnancy tests but none can better the sensitivity and convenience offered by immunoassay of HCG. Ultrasound detection is also not as sensitive as HCG measurement. The current generation of tests is based on monoclonal antibodies to the beta-subunit of HCG; these virtually eliminate the possibility of cross-reaction with pituitary luteinizing hormone (LH) and it is this feature which permits the high sensitivity. However, it is important to recognize that the 'beta-subunit' antibody reacts with both intact HCG, which is the major component in pregnancy serum, and with fragments of the beta-subunit (beta-core), which are the major form in urine. Both the blood and urine of non-pregnant subjects contain small amounts of HCG. HCG from the implanting blastocyst first appears in maternal blood around 6-8 days following fertilization; the levels rise rapidly to reach a peak at 7-10 weeks. With most current pregnancy test kits (sensitivity 25 units per litre) urine may reveal positive results 3-4 days after implantation; by 7 days (the time of the expected period) 98% will be positive. A negative result 1 week after the missed period virtually guarantees that the woman is not pregnant. With the present generation of test kits, false positive results due to interfering materials are extremely unlikely. Pregnancy tests have now reached a level of sensitivity and specificity which is unlikely to be surpassed either by better tests or alternative technology.

Chorionic Gonadotropin↗
PubMed1992

Erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy.

OBJECTIVE: The aim was to measure erythropoietin levels in amniotic fluid and extraembryonic coelomic fluid from 7-12 weeks' gestation. SUBJECTS: Twenty healthy women with ultrasonographically normal first trimester pregnancies prior to surgical termination. METHODS: Paired samples of amniotic fluid and extraembryonic coelomic fluid were collected by transvaginal ultrasound guided needling. Erythropoietin was measured in both pregnancy fluids using a radioimmunoassay. RESULTS: There was a highly significant difference between erythropoietin levels in extraembryonic coelomic fluid (median level 15.45 mU/ml; range 6.8-32.1 mU/ml) and those in amniotic fluid (median 5.0 mU/ml; range < 5.0-5.8 mU/ml) (P < 0.0001; Mann-Whitney U-test). The levels of erythropoietin in maternal serum (median 15.4 mU/ml; range 5.6-29.4 mU/ml) were similar to those in the extra-embryonic coelom (P = 0.81; Mann-Whitney U-test). No relation was demonstrated between erythropoietin levels in amniotic fluid or coelomic fluid and stage of gestation. CONCLUSION: High levels of erythropoietin in coelomic fluid suggests that the hormone is involved in the process of human extraembryonic erythropoiesis. The exact regulatory role remains unknown.

Amniotic Fluid↗
PubMed1992

Biochemical composition of amniotic fluid and extraembryonic coelomic fluid in the first trimester of pregnancy.

OBJECTIVE: To determine the biochemical composition of amniotic fluid and extraembryonic coelomic fluid between 8 and 12 weeks gestation. DESIGN: Prospective observational study. SUBJECTS: 40 women with a normal pregnancy between 7 and 12 weeks gestation having termination of pregnancy. INTERVENTIONS: Before termination the women had a transvaginal ultrasound guided amniocentesis. Pure samples of amniotic fluid and extraembryonic coelomic fluid were obtained from each woman and standard biochemical variables were measured in each fluid sample immediately after collection. RESULTS: Levels of sodium, potassium and bicarbonate were significantly higher in amniotic fluid whilst chloride, urea, bilirubin, protein, albumin, glucose, creatinine, calcium and phosphate were present in higher concentrations in extraembryonic coelomic fluid. All differences in concentration were significant (P less than 0.05; unpaired t-test). No relation was demonstrated between electrolyte concentrations in amniotic fluid or coelomic fluid and stage of gestation. CONCLUSIONS: Amniotic fluid and extraembryonic coelomic fluid have a widely differing biochemical composition. The biological significance of these differences remains unexplained.

Amnion↗
PubMed1992

Role of the ovary in the synthesis of placental protein-14.

Women with absent ovarian function provide an opportunity to investigate the ovarian contribution to secretion of placental proteins (PP), such as PP14, in early pregnancy. We present data on serum PP14 levels in 12 women (median age, 30.5 yr; range, 26-37 yr) with premature ovarian failure (POF) who conceived after ovum donation and embryo transfer with exogenous sex steroid support using transdermal (n = 5) or oral (n = 7) estradiol and vaginal (n = 8) or im (n = 4) progesterone. The women were closely monitored throughout early pregnancy, with measurement of serum levels of estradiol (E2), progesterone (P4), and PP14. Levels of E2 and P4 were entirely normal. Levels of PP14 were significantly subnormal (P = 0.008) in all 12 agonadal women compared with levels of PP14 in a control group of women with normal ovarian function between 6-12 weeks gestation. Basal and peak levels for subjects with absent ovarian function were 40 and 124 micrograms/L, respectively. For each week between 6-12 weeks of pregnancy, the mean serum levels of PP14 for women with normal ovarian function were between 706-940 micrograms/L. These observations support the concept that PP14 arises from the ovary in early pregnancy or that factors under the control of the maternal ovary are involved in its production by the endometrium.

Adult↗
PubMed1992

Chromatographic characterization of insulin-like growth factor-binding proteins in human pregnancy serum.

Insulin-like growth factor-binding proteins (IGFBPs) in maternal and umbilical cord sera have been analysed by combinations of gel filtration chromatography, affinity cross-linking and electrophoresis. On gel filtration chromatography, the majority of circulating IGF-I in non-pregnant and pregnant women was present in the large molecular mass (150 kDa) binding proteins (IGFBP-3). In umbilical cord serum, by contrast, most IGF-I was present in the 40 kDa binding proteins (consisting of IGFBP-1 and IGFBP-2). Western blots demonstrated an apparent progressive attenuation of IGFBP-3 and IGFBP-2 in serum from pregnant women with an increase in IGFBP-1. After prior cross-linking with disuccinimidyl suberate, the 150 kDa fractions (IGFBP-3) from non-pregnant and pregnant serum showed a similar pattern on SDS-PAGE (several bands at different molecular masses). However, IGFBP-2 (one of the components of the 40 kDa fractions) was undetectable, even after cross-linking, in serum from pregnant women later than 8 weeks of gestational age and in a mixture of maternal serum at term delivery and serum from non-pregnant women. This suggests that serum IGFBP-2 was degraded by specific proteases present in pregnancy serum. Following acid treatment, the 150 kDa fractions from pregnancy serum were split into smaller subunits or fragments while the 40 kDa fractions remained unchanged, suggesting that the 40 kDa binding proteins, are acid-stable. The present data demonstrate that IGFBP-3 is the principal IGFBP in pregnancy serum even though there is an apparent reduction in serum IGFBP-3 activity as revealed on Western blots. The absence of IGFBP-2 in serum from pregnant women may be due to degradation by proteases. In the fetal circulation IGFBP-1 and IGFBP-2 appear to be the major binding proteins for IGF-1.

Blotting, Western↗
PubMed1992

Immunoreactive beta-core-like material in normal postmenopausal urine: human chorionic gonadotrophin or LH origin? Evidence for the existence of LH core.

Material with the immunochemical properties of the beta-core of human chorionic gonadotrophin (hCG) can be found in the urine of normal postmenopausal women. However, we have been unable to detect intact hCG (using an assay which is specific for the alpha-beta heterodimer of intact hCG) in serum of such subjects. The levels of serum LH and urinary beta-core were compared in matched samples from 28 women (serum LH: median 27 U/l, range 4-70 U/l, urinary beta-core: median 0.27 microgram/l, range less than 0.05-0.645 microgram/l). Urine (4 litres) from three postmenopausal women was concentrated, dialysed and subjected to gel exclusion chromatography on Sephadex G-100. Fractions were analysed by specific assays for LH, intact hCG, total beta-hCG (free beta-subunit and intact hCG), free alpha-subunit and beta-core. Material eluting at the expected position of the beta-core fragment of hCG was detected in all three samples by the beta-core, beta-hCG and LH assays, despite the fact that the LH antibody does not recognize the authentic beta-core of pregnancy. Electrophoresis and Western blotting of the concentrated urines revealed that material of the same molecular size as beta-core was recognized by the antibody to LH but not by a monoclonal antibody raised to free beta-hCG which also recognizes the beta-core molecule of hCG. We conclude that the predominant core-like material identified in postmenopausal urine is probably derived from the beta-subunit of LH.

Aged↗
PubMed1992

Human chorionic gonadotrophin and subunit composition of maternal serum and coelomic and amniotic fluids in the first trimester of pregnancy.

Sixteen matched samples of first trimester amniotic fluid (AF), extraembryonic coelomic fluid (EECF) and maternal serum (MS) were assayed for intact human chorionic gonadotrophin (hCG) and free subunits. Total beta-hCG (free beta-subunit and intact hCG) levels in the EECF (median 410 kIU/l) were 61 times greater than levels in AF (median 6.73 kIU/l) and 2.8 times greater than in MS (median 141.5 kIU/l). Levels of intact hCG in the EECF (median 245 kIU/l) were 142 times greater than in AF (median 1.73 kIU/l) and 1.6 times greater than in MS (median 157 kIU/l). Free alpha-subunit levels in EECF (median 17.3 mg/l) were 66 times greater than in AF (median 0.262 mg/l) and 12 times greater than in MS (median 1.3 mg/l). Virtually all of the total beta-hCG immunoreactivity in MS can be attributed to intact hCG, but only 60% of total beta-hCG in the EECF and 20% of that in AF can be accounted for by the intact hormone. In both EECF and AF the free alpha-subunit was a major constituent; on a molar basis the ratio of free alpha:free beta:intact hCG was 1:1.2:0.3 in AF, 1:0.6:0.5 in EECF and 1:0:5 in MS. Chromatography of MS, EECF and AF on Sephadex G-100 confirmed the hCG and subunit composition of the fluids. On the basis of these findings it seems likely that previous studies showing very high levels of hCG in AF during the first trimester may have incorrectly sampled the EECF. In reality, the levels of total hCG (and free subunits) are low in the AF, and only 20% is intact hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗