Molecular insights into the structure and function of human chorionic gonadotrophin.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
T Chard
Publications and source records attributed to T Chard.
Insulin-like growth factor-binding protein-1, glucose tolerance and fetal growth in human pregnancy.
Two hundred Chinese primigravidae had 50 g 3-h oral glucose tolerance tests (OGTTs) twice in pregnancy; between 20 and 24 weeks and between 30 and 34 weeks of gestation. In 149 women, a single sample was taken for insulin-like growth factor-binding protein-1 (IGFBP-1) measurement 0, 1, 2 or 3 h after the glucose load at both visits; in 55 women IGFBP-1 levels were estimated in all four OGTT samples. Fetal growth was assessed by ultrasound performed at the first and second visit and, if possible, at term, and by anthropometry of the neonate. Cord serum IGFBP-1 was measured in 144 of the babies. Mothers who developed gestational diabetes were excluded. Maternal levels of IGFBP-1 were inversely related to glucose levels at 0, 1 and 2 h in the third trimester of pregnancy. IGFBP-1 measured at 1 h in an OGTT increased between the second and third trimester. There was an inverse correlation between maternal IGFBP-1 measured in the second trimester and all fetal measurements at that time, and with most neonatal measurements and birthweight. Levels of IGFBP-1 in the third trimester were inversely correlated to neonatal abdominal circumference, skinfold thickness and birthweight. Cord blood IGFBP-1 was inversely related to growth of abdominal circumference. The strongest inverse relationship was between IGFBP-1 and maternal weight. Fasting glucose in the second trimester was positively correlated to fetal subcutaneous fat and growth of abdominal circumference. In the third trimester it was related to fetal abdominal circumference, the growth of abdominal circumference, birthweight and neonatal skinfold thickness.(ABSTRACT TRUNCATED AT 250 WORDS)
Birth Weight↗
Levels of insulin-like growth factor-binding protein-1 increase rapidly in amniotic fluid from 11 to 16 weeks of pregnancy.
Concentrations of IGF-binding protein-1 (IGFBP-1) were measured by radioimmunoassay in 176 amniotic fluid samples from 9 to 20 and 36 to 42 weeks of pregnancy. Low levels of IGFBP-1 were present at 9 and 10 weeks (median values 35.0 and 45.0 micrograms/l respectively). After 10 weeks, the levels increased by four orders of magnitude to reach a peak at 16 weeks (median 145.2 mg/l). After 16 weeks levels fell. Near term, the levels (median 27.1 mg/l) were lower than in the second trimester. The rapid increase in IGFBP-1 shown by radioimmunoassay was confirmed by Western ligand blotting. The findings suggest that the regulatory role of IGFBP-1 in the growth or differentiation of the fetus or of its surrounding membranes may change as pregnancy advances.
Amniotic Fluid↗
Medical audit: the problem of missing case-notes.
This paper reports the results of a case-note audit undertaken to detect the antenatal risk factors found at the initial booking visit, including the subsequent clinical action taken. From a total of 2,139 case-notes of women booked via an obstetric computer system, and delivered between March 1990 and March 1991, 136 (6.4%) were missing. The results showed that these 136 mothers experienced significantly worse delivery outcomes, ie higher incidence of perinatal death; preterm labour; a baby with a low Apgar score and low birth weight. There was also a higher incidence of perinatal death and babies with a low Apgar score for women booked manually compared with those booked via the computer system. These results show that many audit procedures may be the subject of substantial bias due to the problem of missing information. The extended use of a computer-based medical record system should help to resolve this problem, although hybrid information systems can themselves be biased.
Bias↗
Predicting fetal chromosome anomalies in the first trimester using pregnancy associated plasma protein-A: a comparison of statistical methods.
The analysis of the clinical efficiency of a biochemical parameter in the prediction of chromosome anomalies is described, using a database of 475 cases including 30 abnormalities. A comparison was made of two different approaches to the statistical analysis: the use of Gaussian frequency distributions and likelihood ratios, and logistic regression. Both methods computed that for a 5% false-positive rate approximately 60% of anomalies are detected on the basis of maternal age and serum PAPP-A. The logistic regression analysis is appropriate where the outcome variable (chromosome anomaly) is binary and the detection rates refer to the original data only. The likelihood ratio method is used to predict the outcome in the general population. The latter method depends on the data or some transformation of the data fitting a known frequency distribution (Gaussian in this case). The precision of the predicted detection rates is limited by the small sample of abnormals (30 cases). Varying the means and standard deviations (to the limits of their 95% confidence intervals) of the fitted log Gaussian distributions resulted in a detection rate varying between 42% and 79% for a 5% false-positive rate. Thus, although the likelihood ratio method is potentially the better method in determining the usefulness of a test in the general population, larger numbers of abnormal cases are required to stabilise the means and standard deviations of the fitted log Gaussian distributions.
Adult↗
Binding characteristics of insulin-like growth factor-binding proteins in maternal and cord sera.
Insulin-like growth factor-binding proteins (IGFBPs) in sera from non-pregnant and pregnant women, and from the umbilical cord at the time of delivery, were separated by gel filtration chromatography. The binding characteristics of the 150 and 40 kDa binding proteins were examined by Scatchard analysis. In serum from pregnant women, the affinity of the 150 kDa binding proteins (IGFBP-3) decreased as pregnancy progressed, with an apparent increase in the maximum binding capacity. In contrast, the affinity of the 40 kDa binding proteins showed a slight increase. In umbilical cord serum, the binding affinity of both the 150 and 40 kDa binding proteins was similar, whereas the binding capacity was two-fold higher in the 40 kDa than in the 150 kDa group. Both maternal and umbilical cord serum (artery and vein) contained unoccupied IGFBPs. Following acid treatment, there was an increase in binding of 125I-IGF-I to umbilical cord serum but a decrease in that to maternal serum. These changes in the characteristics of the binding proteins in the pregnancy sera are probably due to partial degradation of the 150 kDa binding proteins by proteases. The present data confirm that IGFBP-3 is the main binding protein for IGFs during pregnancy, although its affinity is decreased. In fetal circulation, the 40 kDa binding proteins appear to be the major IGFBP with a high affinity and high capacity.
Adolescent↗
Substantial urinary concentrations of material resembling beta-core fragment of chorionic gonadotropin beta-subunit in mid-menstrual cycle.
We measured the day-to-day variations in concentrations of beta-core, luteinizing hormone (LH), and alpha-subunit in urine during the menstrual cycle. The alpha-subunit concentrations showed a pattern similar to that of the LH concentrations. beta-Core-like material was increased during and up to 3 to 4 days after the surge in urine LH. The urine LH concentration was associated with the presence of beta-core immunoreactivity during the urine LH peak. Chromatography showed that, at the peak LH concentration and at 2 days after the LH peak, beta-core immunoreactivity could be accounted for by the presence of a peptide of low molecular mass similar to the beta-core molecule of hCG, but probably originating from the degradation of LH. The prolonged excretion of gonadotropin metabolites in the midcycle must be considered when beta-core is being assessed as a tumor marker.
Adult↗
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↗
Early prediction of uteroplacental complications of pregnancy using Doppler ultrasound, placental function tests and combination testing.
In a prospective, blind study of 183 unselected women attending for routine booking scan with a singleton pregnancy at 16-24 weeks' gestation, uteroplacental resistance index, and peripheral levels of alpha-fetoprotein, human chorionic gonadotropin, human placental lactogen, Schwangerswaft protein, pregnancy-associated placental protein A and insulin-like growth factor (IGF) binding protein 1 were measured. High levels of alpha-fetoprotein and IGF 1 binding protein 1 (> 90th centile) were associated with small-for-gestational age babies (< 10th centile) (sensitivity 24% and 22%; specificity 90% and 91%). High levels of alpha-fetoprotein, human chorionic gonadotropin and pregnancy-associated placental protein A (> 90th centile) were associated with one or more of three severe complications of pregnancy: very small-for-gestational age (< 3rd centile), severe proteinuric hypertension or intrauterine death (sensitivity 20%, 20% and 57%; specificity 90%, 95% and 91%, respectively). A uteroplacental resistance index > 90th centile was also associated with small-for-gestational age and severe complications (sensitivity 24% and 50%, specificity 90% and 90%). A combination of resistance index and a placental function test improved the prediction for a group of patients that included any complications (sensitivity 31% and specificity 89%). Doppler ultrasound was a more efficient predictor than individual placental function tests but screening predictions can be improved by combining Doppler parameters and placental protein estimations. Combinations of placental function tests might provide equivalent, or complementary, information. This preliminary work demonstrates the potential value of combining biophysical and biochemical tests to predict complications of pregnancy.
Journal Article↗
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↗
Pregnancy associated plasma protein A in Down's syndrome.
Explore the source record for details and available documents.
Down Syndrome↗
Pregnancy associated plasma protein A in Down's syndrome.
Explore the source record for details and available documents.
Down Syndrome↗
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↗
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↗
Customised antenatal growth charts.
Explore the source record for details and available documents.
Biometry↗
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↗
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↗