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Biomedical subjects

T Chard

Publications and source records attributed to T Chard.

At least 109 records · Page 6Linked to original sources
PubMed1994

Insulin-like growth factors and their binding proteins in normal and abnormal human fetal growth.

There is now a well recognized series of findings which suggests that the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may play an important role in both normal and abnormal human fetal growth: (1) IGFs are detectable in many fetal tissues from the first trimester onwards; (2) the levels of the IGFs in the fetal circulation increase during pregnancy, and at term the levels of IGF-I are directly related to birthweight; (3) in mice, disruption of the IGF gene leads to severe growth retardation; (4) in the first trimester the levels of IGFBP-1 are higher in the coelomic fluid than in amniotic fluid or maternal serum; (5) at 9-12 weeks there is a striking increase in IGFBP-1 and IGFBP-2 levels in amniotic fluid; (6) the major binding proteins in the human fetus are IGFBP-1 and IGFBP-2; (7) from as early as 16 weeks there is an inverse correlation between fetal levels of IGFBP-1 and birthweight; (8) in the mother, circulating levels of IGF-I and IGFBP-1 increase during pregnancy; (10) maternal levels of IGFBP-1 are elevated in severe pre-eclampsia and intrauterine growth retardation; (11) fetal levels of IGFBP-1 are elevated in cases of intrauterine growth retardation, especially those associated with specific evidence of reduced uteroplacental bloodflow; and (12) fetal levels of IGFBP-1 are elevated in labour, especially if there is evidence of fetal hypoxia. In conclusion, levels of IGFBP-1 appear to be a sensitive indicator of fetal nutrition, and of the short- or long-term response to reduced fetal nutrition.

Carrier Proteins↗
PubMed1993

Dynamics of prolactin in amniotic fluid and extraembryonic coelomic fluid in early human pregnancy.

Concentrations of prolactin were measured by an immunoradiometric assay in 26 matched samples of amniotic fluid, extraembryonic coelomic fluid and maternal serum from 9 to 12 weeks of pregnancy and in a further 131 amniotic fluid samples from 9 to 20 weeks. Low levels of prolactin (median 40 MU/l) were present in amniotic fluid from 9 to 12 weeks. Levels in the coelomic fluid were higher (median level 371 MU/l; P < 0.0001) than in amniotic fluid. From 13 weeks, there was a rapid rise in amniotic fluid prolactin to reach a peak at 19 weeks (median level 99,850 MU/l). The pattern of increase of prolactin in amniotic fluid is similar to, but occurs 2 weeks later than that for insulin-like growth factor-binding protein-1, another major decidual product.

Amniotic Fluid↗
PubMed1993

Urinary chorionic gonadotropin subunits and beta-core in nonpregnant women. A study of benign and malignant gynecologic disorders.

BACKGROUND: The presence of urinary excretion products of human chorionic gonadotropin (hCG) has been proposed as a tumor marker. To ascertain the clinical value in gynecologic cancers, the authors studied 612 nonpregnant women. METHODS: Three different assays in four clinical groups were compared: no disease, benign disease, malignant disease, and complete remission of previously treated malignant disease. The assays were for the urinary beta-core, "total" beta-hCG, and free alpha-subunit. RESULTS: Measurement of the alpha-subunit was of no obvious clinical value. In some patients with benign disease, hCG metabolites were elevated. In the 141 patients with active gynecologic malignancy the sensitivity of the total beta-hCG assay was 47% and that of the beta-core assay was 36%. The specificities were 80.3% and 90.4%, respectively. Advanced cancers generally had higher levels of total beta-hCG and beta-core. Squamous cell and poorly differentiated cervical tumors had higher levels of total beta-hCG than did adenocarcinomas and well-differentiated cervical tumors. Invasive, serous, endometrioid, and germ cell ovarian tumors had higher total beta-hCG, beta-core, and alpha-subunit levels than did borderline, mucinous, and clear cell ovarian tumors. Six of 16 patients with disease in complete remission had elevated levels. CONCLUSION: The excretion of hCG and its metabolic fragments is a common event in gynecologic cancer, but sensitivity and specificity are low, and there is little consistent relationship between tumor stage and histologic type.

Adenocarcinoma↗
PubMed1993

First-trimester maternal serum Schwangerschafts protein 1 (SP1) in pregnancies associated with chromosomal anomalies.

The relationship between first-trimester maternal serum Schwangerschafts protein 1 (SP1) and the karyotype of the pregnancy was examined in 692 women who underwent chorionic villus biopsy at 6-12 weeks. There were 30 pregnancies with abnormal karyotypes, consisting of 14 Down's syndrome (DS), eight trisomy 18, and eight other anomalies, two of which were mosaics. The normal ranges and medians for gestation were defined from the 662 cases in which the karyotype was normal. The median SP1 (0.5 MOM) of the abnormal group was significantly lower than that of the normal group (1.0 MOM). This relationship was maintained for the DS pregnancies (0.4 MOM) and for anomalies other than trisomy 18 (0.43 MOM) but not trisomy 18 (1.1 MOM). It is possible that the use of SP1 as a screening test for chromosome anomalies in the first trimester could have a 43 per cent detection rate for a 5 per cent false-positive rate.

Adult↗
PubMed1993

The measurement of urinary beta core fragment in conjunction with serum CA125 does not aid the differentiation of malignant from benign pelvic masses.

The urinary concentration of the renal metabolite of the beta subunit of human chorionic gonadotropin (beta core) has been proposed as a tumor marker in certain nontrophoblastic malignancies including those of the female genital tract. A previous study investigated the use of urinary beta core in conjunction with serum CA125 in distinguishing malignant from benign pelvic masses and showed that the combined test improved the overall sensitivity to 88%; this was greater than that for either test alone. However, the cutoff levels used to distinguish normal from abnormal were approximately six times greater than those generally used for CA125 and four to five times lower than those used for beta core in our laboratory. Furthermore there was no recognition of the possible difference in normal levels of beta core between pre- and postmenopausal women. We have examined a similar group of cases using our cutoff levels for urinary beta core of 0.36 ng/ml in premenopausal women and 0.48 ng/ml in postmenopausal women and 35 u/ml for CA125. We show that measurement of CA125 is substantially more sensitive that that of beta core and that the combination of beta core with CA125 does not improve the overall sensitivity of the test. However, there was a small improvement in positive predictive value if both tests were positive (97.5%) and of specificity when one or the other test was negative (98.5%).

Adult↗
PubMed1993

Placental protein 14 secretion during in vitro fertilization cycles with and without human chorionic gonadotropin for luteal support.

OBJECTIVE: To investigate levels of placental protein 14 (PP14) in in vitro fertilization (IVF) patients with and without exogenous human chorionic gonadotropin (hCG) for luteal support. DESIGN, PATIENTS: Thirty-one women undergoing IVF were studied. For 18 women, hCG was administered in the luteal phase, and 12 became pregnant. Five pregnancies occurred in 13 women not receiving exogenous hCG. SETTING: All the patients attended the University of Southampton/Chalybeate Hospital IVF program. RESULTS: There was no change in PP14 levels 2 days after embryo transfer (ET), but small significant rises were noted by day 8 in all patients. Thereafter, levels rose further in pregnant subjects but showed no change in nonpregnant patients. The highest level of PP14 was seen in the group of women on hCG support, but there was no overall statistical difference between those on support and those not. In the nonpregnant group, there was no significant correlation between progesterone (P) and PP14 8 days from ET, whereas a highly significant correlation was noted in the pregnant group. CONCLUSIONS: Neither hCG nor P are primary factors in the control of endometrial PP14 secretion, but PP14 and P may have common underlying control mechanisms.

Adult↗
PubMed1993

An investigation of awareness of antenatal protocols.

Previous audit at the Homerton Hospital had revealed a poor level of compliance with established antenatal protocols mandated by risk factors detected at the booking visit. Medical staff were questioned as to their awareness of five of the most important protocols and their response was analysed by a new scoring system. The scores were generally low though consultants scored more highly than junior staff. Scores were related to the length of obstetric experience and duration of work in the obstetric unit but were not related to frequency of the use of the protocol manual nor to the last time that reference was made to the manual. To improve compliance within the unit, the following recommendations were made: (1) regular revision of protocols to incorporate the current views of senior clinicians and (2) improved dissemination of information. The scoring system described here should prove to be a simple and effective method for the assessment of protocols within any unit.

Awareness↗
PubMed1993

Circulating placental protein 14: in the first trimester of spontaneous and IVF pregnancies.

Circulating placental protein 14 (PP14) levels were measured during the first trimester in three groups of pregnant women: (i) natural conception (n = 15); (ii) pituitary desensitization with buserelin and ovarian stimulation with human menopausal gonadotrophin (HMG) followed by in-vitro fertilization and embryo transfer (IVF-ET) (n = 15); and (iii) ovarian stimulation with clomiphene citrate and HMG, followed by IVF-ET (n = 16). A 7- to 8-fold increase in serum PP14 levels was observed in normal pregnancies between weeks 4 and 10. This increase was earlier and less marked in group (ii) and absent in group (iii). These findings support the concept that endometrial function is altered in pregnancies achieved following ovarian stimulation. Alternatively, if the ovary is an important source of PP14, then these data suggest that in contrast to ovarian synthesis of steroids and the peptide relaxin, ovarian stimulation results in an impairment of PP14 synthesis, and that this is most marked when clomiphene citrate has been used.

Adult↗
PubMed1993

Serum placental protein 14 concentrations in the first trimester of ovum donation pregnancies.

The concentration of the endometrial glycoprotein placental protein 14 (PP14) has been measured at weekly intervals during the first trimester in serum obtained from women who had become pregnant naturally (n = 15, all singleton) or following ovum donation (n = 16, 15 singleton and one twin) after ovarian failure (n = 13), Turner's syndrome (n = 2) or post-chemotherapy (n = 1). The concentration of PP14 failed to rise in ovum donation pregnancies, and was significantly reduced compared to the concentration in natural conceptions from 5 to 13 weeks gestation (P < 0.05-0.01). These findings demonstrate that the corpus luteum is essential for the normal increase in serum PP14 in the first trimester. Furthermore, they suggest that progesterone is not the major stimulus to PP14 synthesis in early pregnancy.

Female↗
PubMed1993

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype.

OBJECTIVE: To assess the relation between maternal serum pregnancy associated plasma protein A (PAPP-A) in the first trimester and the outcome of pregnancy by karyotype. DESIGN: A retrospective study of PAPP-A levels in blood samples collected prior to chorionic villus sampling. SETTING: Milan, Italy. SUBJECTS: Five hundred twenty-two women aged 20 to 47, at 7 to 11 weeks gestation, prior to undergoing chorionic villus sampling. Four hundred forty-five women had a pregnancy with a normal karyotype; in 30 pregnancies the karyotype was abnormal (including 14 cases of Down's syndrome and 7 of trisomy 18). MAIN OUTCOME MEASURES: Normal or abnormal fetal karyotype. Serum PAPP-A at 6 to 11 weeks gestation measured by radioimmunoassay. RESULTS: The median value of PAPP-A in the abnormal group was 0.27 multiples of the normal median (MoM). This is significantly lower than the median value in the normal group (1.01 MoM) (95% CI for the difference 0.46-0.84 MoM; P < 0.00001 Mann-Whitney test). CONCLUSIONS: There is an association between low levels of PAPP-A in the first trimester with chromosome anomalies. Screening by measurement of PAPP-A might detect 60% of cases of Down's syndrome in the first trimester with a false positive rate of 5%.

Adult↗
PubMed1993

Alphafetoprotein levels in amniotic fluid from 8 to 18 weeks of pregnancy.

OBJECTIVE: The aim of this study was to ascertain the normal range of amniotic fluid alphafetoprotein (AFP) levels from 8 to 18 weeks of pregnancy. DESIGN: Amniotic fluid samples obtained by amniocentesis were analysed by radioimmunoassay for AFP. From 8 to 12 weeks, fluid was obtained by transvaginal amniocentesis prior to termination of pregnancy. Samples from 13 to 18 weeks were obtained from amniotic fluid specimens submitted for cytogenetic analysis. SETTING: A tertiary referral prenatal diagnostic service. SUBJECTS: Two hundred thirty-seven women between 8 and 18 weeks gestation. RESULTS: High levels of AFP were present in amniotic fluid at 8 weeks (median 83.0 kU/ml), falling rapidly to 11 weeks (median 19.9 kU/ml) (P < 0.01). Levels then rose to a peak at 13 weeks (median 30.7 kU/ml), thereafter falling to 18 weeks. CONCLUSIONS: A single coherent view of the levels of AFP from 8 to 18 weeks of pregnancy is presented for the first time. The rapid changes and complex pattern of AFP levels in early pregnancy suggest that interpretation of amniotic fluid AFP levels in the diagnosis of neural tube defects may be more difficult between 8 and 13 weeks of pregnancy than in the second trimester.

Amniocentesis↗
PubMed1993

The coelomic cavity: an important site of materno-fetal nutrient exchange in the first trimester of pregnancy.

OBJECTIVE: To measure levels of folate and vitamin B12 in matched samples of amniotic fluid and extra-embryonic coelomic fluid from 9 to 12 weeks' gestation. DESIGN: Prospective observational study. SETTING: Homerton Hospital, London. SUBJECTS: Twenty-two women with ultrasonographically normal pregnancies before surgical termination. METHODS: Transvaginal ultrasound-guided needle aspiration of amniotic fluid and extra-embryonic coelomic fluid was performed. Pure samples of amniotic fluid and extra-embryonic coelomic fluid were obtained from each pregnancy, and folate and vitamin B12 were measured using microbiological assays. RESULTS: Levels of folate and vitamin B12 were higher in extra-embryonic coelomic fluid than in amniotic fluid and maternal serum. Amniotic fluid folate levels were lower than in maternal serum whereas vitamin B12 levels in amniotic fluid were higher than in maternal serum. All differences in concentration were significant (P < 0.0005; paired t-test). Positive correlations were found between the concentrations of folate and vitamin B12 in each fluid. There was a linear correlation between gestational age and amniotic fluid folate levels (r = 0.648; P = 0.001). CONCLUSIONS: High concentrations of folate and vitamin B12 in coelomic fluid suggest that the coelomic cavity plays an important role in the materno-fetal exchange of these nutrients.

Amniotic Fluid↗
PubMed1993

Low levels of amniotic fluid placental alkaline phosphatase in Down's syndrome.

OBJECTIVE: To investigate amniotic fluid placental alkaline phosphatase (PLAP) levels in normal and trisomy 21 pregnancies. DESIGN: Cross sectional study. SETTING: A tertiary referral prenatal diagnostic service. SUBJECTS: Three hundred and eleven women with singleton pregnancies of normal karyotype between 10 and 23 weeks gestation and 31 women with pregnancies associated with trisomy 21 Down's syndrome. OUTCOME MEASURES: PLAP levels were measured by immunoradiometric assay in amniotic fluid obtained by amniocentesis. RESULTS: Amniotic fluid PLAP was detectable from 12 weeks gestation and the median value rose to a peak of 4.57 iu/l at 18 weeks. Pregnancies associated with Down's syndrome had significantly lower levels with a median multiple of median (MoM) of 0.638, (U = 3374, P = 0.0016, 95% CI = 0.50, 0.89). For the 20 women with trisomy 21 pregnancies detected at 16 to 18 weeks, the median MoM was 0.482, (U = 3694, P = 0.0011, 95% CI = 0.37, 0.85). CONCLUSION: These data demonstrates that PLAP levels are reduced in the amniotic fluid of women carrying a fetus with trisomy 21.

Alkaline Phosphatase↗
PubMed1993

A national survey to assess current use of computerised information systems in obstetrics.

OBJECTIVE: To ascertain the number and type of obstetric computer systems (OCS) in Great Britain, and to ascertain user satisfaction with these systems. DESIGN: A postal questionnaire was circulated to every consultant obstetrician in Great Britain at the beginning of 1992. MAIN OUTCOME MEASURES: Information was sought on the hardware, software and uses of obstetric computer systems. Satisfaction with, benefits and problems of the system were also assessed. RESULTS: There was an 87.5% response rate. Of the 264 units questioned, 100 units reported that they had a computer system. Sixty-five units used terminals connected to a mainframe or minicomputer and 17 used stand-alone personal computers (PCs). Local area networks (LANs) were used in 19 units and wide area network (WANs) in 22 units. Software varied from commercial turnkey systems to in-house systems. The quoted annual running cost ranged from 50 pounds to 48,000 pounds. Most units were satisfied with their system. Problems included slow operating times, unreliability, user unfriendliness, deficiencies in training and inadequate customer support services. CONCLUSIONS: Obstetric computer systems are now coming into widespread use. Despite problems, the use of such systems is likely to increase. This survey establishes a database for those units who are considering acquiring or changing their computer system for the purpose of audit or research.

Attitude to Computers↗
PubMed1993

Levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in pregnancy with preterm delivery.

OBJECTIVE: To investigate the relationship between preterm delivery and maternal serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-1 (IGFBP-1) levels. DESIGN: A study over a 12 month period in which all samples were collected according to a pre-set protocol. SETTING: St. Bartholomew's Hospital, London. SUBJECTS: Thirty-eight nonpregnant adult females, 456 pregnant women at various gestational ages, 84 women with average-for-gestational-age babies at term delivery, and 49 pregnant women with preterm delivery (44 with singleton pregnancy and five with twin pregnancy). MAIN OUTCOME MEASURES: Serum IGF-I and IGFBP-1 levels were determined by radioimmunoassay. RESULTS: Serum IGF-I concentrations increased as pregnancy progressed. In the third trimester, serum IGF-I levels in singleton preterm deliveries were lower than those in normal pregnancies, and IGFBP-1 concentrations were higher than those in normal pregnancies. This phenomenon was not obvious in the second trimester. Maternal circulating IGFBP-1 levels were correlated inversely with birthweight in women with singleton preterm delivery. CONCLUSIONS: Neither IGF-I nor IGFBP-1 appears to play a significant role in preterm delivery since maternal serum IGF-I and IGFBP-1 levels are similar in preterm and term deliveries.

Birth Weight↗