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T Chard

Publications and source records attributed to T Chard.

At least 37 records · Page 2Linked to original sources
PubMed1998

The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma.

AIMS: To examine long term survival of women with primary and recurrent cervical carcinoma in relation to (1) excretion of beta-core (a urinary metabolite of beta human chorionic gonadotrophin (beta hCG)) and (2) beta hCG immunostaining of the tumours, to determine the suitability of these markers for assessing prognosis. METHODS: This was a prospective observational study undertaken in a gynaecological oncology centre: 57 women with primary cervical cancer and 42 with recurrent disease were recruited between January 1990 and September 1992. Kaplan-Meier survival analysis with the log rank test was used to assess survival differences with survival rate given per year of follow up. RESULTS: In primary disease, the four year survival for the beta-core negative group was 79%, compared with 14% for the beta-core positive group (p = 0.001). This was still significant for early stage disease or squamous lesions alone. In recurrent disease, beta-core positivity was not prognostically significant. Immunohistochemistry was of no prognostic significance in either group. CONCLUSIONS: beta-core excretion appears to be useful in assessing prognosis of primary cervical cancer but not of recurrent disease. A large prospective study of urinary beta-core in early stage cervical cancer is needed to determine whether it can be used as an index for modifying treatment.

Adenocarcinoma↗
PubMed1998

Dissociation of human chorionic gonadotropin into its free subunits is dependent on naturally occurring molecular structural variation, sample matrix and storage conditions.

Measurement of human chorionic gonadotrophin (hCG) is used in many areas of clinical medicine. Recent interest has focused on the stability of this molecule and its fragments during sample storage. In the body hCG is degraded and removed by specific metabolic processes which begin while the molecule is in the bloodstream. In particular, the receptor binding loop of the beta subunit is cut or 'nicked', initiating a catabolic cascade. Furthermore, the extent and nature of glycosylation is believed to have a significant influence on this process. In these studies we incubated seven glycoforms of hCG, each with different degrees of 'nicking', in phosphate-buffered saline, serum, defibrinated blood and urine from healthy non-pregnant women, under varying conditions. Degradation was expressed as the molar increase in free beta subunit. Under all conditions there was a steady dissociation of hCG over time, the process being more rapid at higher temperatures. 'Nicked' hCG dissociated more rapidly than did non-'nicked' hCG. Glycosylation reduced the rate of dissociation. Dissociation was most rapid in urine and buffer solutions, and slowest in serum and defibrinated blood.

Chorionic Gonadotropin↗
PubMed1998

Measures of urine concentration in maternal urine screening for Down syndrome.

A study was carried out to assess eight methods of normalizing the level of urinary beta-core human chorionic gonadotropin (hCG) for variable urine concentration. We compared the standard approach--creatinine determination by the Jaffe method--with high performance liquid chromatography (HPLC) measurement of creatinine, osmolarity and optical density at five wavelengths. Urine samples were included from a total of 472 women with unaffected singleton pregnancies at 15 weeks' gestation. The median beta-core hCG value was determined for each decile group when the results were ranked in turn according to the different measures of urine concentration. Creatinine using the Jaffe method had a much stronger relationship with median beta-core hCG than the other measures. Linear regression across the decile groups gave an R2 value for Jaffe of 0.85 compared with HPLC of 0.53, osmolarity of 0.52, optical density at 405 nm of 0.72, at 450 nm of 0.57, at 490 nm of 0.33, at 570 nm of 0.34 and at 630 nm of 0.33. We conclude that when screening with urinary beta-core hCG measuring creatinine appears to be an adequate method of allowing for variable urine concentration.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1997

Circulating levels of relaxin are normal in pregnant women with pelvic pain.

OBJECTIVE: The hormone relaxin induces loosening of the pelvic ligaments and joints in several species. Previous studies have suggested a similar role for relaxin during human pregnancy. Furthermore, a correlation has been noted between high circulating levels of this hormone and severe pelvic pain in pregnant women. The present study was designed to evaluate whether serum relaxin concentrations were elevated in pregnant women with clear subjective and objective evidence of pain attributable to relaxation of the pelvic ligaments. STUDY DESIGN: Serum relaxin was measured at week 33 of gestation in 455 pregnant women with clearly defined pain in their pelvic joints and 455 normal pregnant controls matched for age and parity. All participants underwent an examination consisting of a structured questionnaire and fifteen specific tests for pelvic joint pain. The group with pain was further subdivided into four subgroups with different levels of disability and prognosis. Relaxin concentrations were measured using enzyme-linked immunoassay. RESULTS: There was no difference in serum relaxin concentration between the control and study group, nor between the subgroups of women with pelvic pain. CONCLUSION: We failed to confirm an earlier claim that circulating relaxin levels are related to pelvic girdle pain in pregnant women.

Female↗
PubMed1997

The risk of neonatal death and respiratory distress syndrome in relation to birth weight of preterm infants.

The aim of this study was to determine the risk of respiratory distress syndrome (RDS) and neonatal death (NND) in relation to birth weight in preterm neonates. A group of 255 singleton preterm neonates born at 22-36 weeks were examined. The mean birth weight for each gestational week was estimated from a fitted curve. Each birth weight was recalculated as a multiple of the mean. This approach allowed description of a range of birth weight for the whole population of preterm infants. As expected, the incidence of neonatal death and respiratory distress syndrome was higher among the less mature infants. However, there were no significant differences in outcome (NND, severe RDS) between infants whose birth weight was above or below the mean for gestational age, and no excess of "growth retardation" (birth weight below the 5th centile) in babies with NND or RDS. We conclude that, in our population, the risk of RDS and neonatal death does not appear to be related to the birth weight of preterm neonates but is, of course, related to gestational age.

Birth Weight↗
PubMed1997

Pelvic manikins as learning aids.

The use of pelvic trainers in undergraduate teaching was evaluated, using a questionnaire based on examination findings of a series of four pelvic trainers by 20 medical students and 34 gynaecologists. The main outcome measures were the ability to correctly identify pelvic findings in the trainers, and the numbers of false positive findings. There were two adnexal masses in two of the trainers. One was correctly identified by 33 (14 (70%) medical students and 19 (56%) doctors) in one trainer, whereas the other was missed by 52 of 54 examiners. Prolapse was missed by 41 of 54. The normal pelvis was correctly identified by 30 (16 (80%) medical students and 20 (59%) doctors. There were 15 false positive identifications of adnexal masses (6 by medical students and 9 by doctors) and 22 false positive identification of uterine enlargements (5 by medical students and 17 by doctors). The pelvic trainers were of value in demonstrating the process of pelvic and speculum examination. Some of the clinical conditions emulated were missed by most of the gynaecologists, suggesting that they were not suitable for training students in abnormal findings. Although the figures were not statistically significant, there was a trend for qualified doctors rather than medical students to make false positive findings.

Education, Medical, Undergraduate↗
PubMed1997

Maternal and fetal levels of methionine and homocysteine in early human pregnancy.

OBJECTIVE: To investigate methionine metabolism during normal human embryonic development by measuring levels of methionine and total homocysteine in samples of maternal serum, extra-embryonic coelomic fluid, and amniotic fluid. DESIGN: Cross-sectional observational study. SETTING: Collaboration between St Bartholomew's Hospital, London, and the University Hospital of Nijmegen in The Netherlands. PARTICIPANTS: Twenty-three women with uncomplicated pregnancies between 8 and 12 weeks of gestation before surgical termination of an ultrasonographically normal fetus. METHODS: Maternal serum samples were collected prior to surgery. Samples of extra-embryonic fluid and amniotic fluids were obtained by transvaginal ultrasound-guided coelocentesis and amniocentesis. Methionine was measured using an amino acid analyser and total homocysteine by high performance liquid chromatography. RESULTS: Levels of methionine were four times higher in extra-embryonic coelomic fluid and twice as high in amniotic fluid compared with maternal serum. In contrast, the total homocysteine concentrations were much lower in both extra-embryonic coelomic fluid and amniotic fluid than in maternal serum. All differences were significant (P < or = 0.01). CONCLUSIONS: The comparatively high concentrations of methionine in extra-embryonic coelomic fluid and amniotic fluid, and the concomitant low levels of total homocysteine in these fluids, suggest a role for methionine metabolism during early human pregnancy.

Amniotic Fluid↗
PubMed1997

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer.

OBJECTIVE: To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free beta human chorionic gonadotrophin (hCG) and cancer-associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma. DESIGN: A two year follow up study of survival. SETTING: A tertiary care gynaecological oncology unit. PARTICIPANTS: One hundred and eleven women with histologically confirmed epithelial ovarian cancer. MAIN OUTCOME MEASURES: Survival over a two year period. RESULTS: Stage corrected log-rank chi 2 tests demonstrated a significant effect on survival for all four tumour markers (CA125 P = 0.0142; PLAP P < 0.0001; CASA P = 0.0098; hCG P = 0.0002). This was confirmed when each variable was fitted together with disease stage in Cox proportional hazard models. When fitted as multiple variables in a Cox proportional hazard model, the addition of free beta-hCG and CASA to disease stage, PLAP concentrations and CA125 levels did not demonstrate further prognostic value. CONCLUSIONS: Levels of all four markers correlate with survival in patients with epithelial ovarian cancer. The combination of PLAP and CA125 concentrations together with disease stage may be used to predict survival but the addition of hCG and CASA levels do not give additional prognostic information.

Adult↗
PubMed1997

Gestational age-dependent expression of insulin-like growth factor-binding protein-1 (IGFBP-1) phosphoisoforms in human extraembryonic cavities, maternal serum, and decidua suggests decidua as the primary source of IGFBP-1 in these fluids during early pregnancy.

The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of fetal and maternal tissue development during pregnancy. Posttranslational modification of IGFBP-1 yields up to six IGFBP-1 phosphovariants and a nonphosphorylated form, which in vitro, have some different properties. Nonphospho IGFBP-1 has less affinity for IGFs than the phospho isoforms and also may have IGF-independent actions. Herein, we have investigated the complement of IGFBP-1 phosphoisoforms present in extraembryonic coelomic (EEC) fluid, amniotic fluid (AF), and maternal serum (MS) throughout human gestation. Also, to determine potential tissue source(s) of IGFBP-1 in these fluids, we have quantified IGFBP-1 and examined IGFBP-1 phosphoisoforms in conditioned media (CM) from maternal decidua, fetal liver, and fetal kidney explants throughout gestation. Western immunodetection revealed that IGFBP-1, present in EEC and AF in early pregnancy and in CM from early pregnancy decidua, is primarily in the nonphosphorylated form. MS in this period contains primarily the nonphospho form and, as in nonpregnant adults, the highly phosphorylated form of IGFBP-1. The phosphorylation profile of IGFBP-1 in AF, MS, and decidua CM changes as pregnancy progresses. All the IGFBP-1 phosphoisoforms ultimately are produced by decidua and are present in midgestation MS, and all but the most highly phosphorylated form are present in AF. In late gestation, MS contains primarily the highly phosphorylated form. In contrast, profiles in CM from explants of fetal liver and kidney at different gestational ages remain unchanged. Nonphosphorylated IGFBP-1 is the primary form in fetal kidney CM, whereas fetal liver CM contains all IGFBP-1 phosphoisoforms. Concentrations of IGFBP-1 in fetal liver and kidney CM are significantly lower (482 +/- 146 and 120 +/- 32 ng/mL x 100 mg wet wt tissue, respectively) than in decidua CM (11,417 +/- 2,358 ng/mL x 100 mg wet wt tissue). The data cumulatively suggest that maternal decidua is the primary source of IGFBP-1 in EEC, AF, and MS in early pregnancy and that fetal liver and kidney are not likely significant contributors. The presence of nonphospho IGFBP-1 in AF, EEC, and MS suggests an important role for this isoform during early gestation.

Body Fluids↗
PubMed1997

The relationship of ponderal index and other measurements to birthweight in preterm neonates.

The objective was to determine the relationship between birthweight and anthropometric indices (PI and MAC/ OFC) in preterm infants. A group of 163 singleton preterm neonates born at 24-36 weeks were examined. Measurements were made of crown-heel length, midarm circumference, and occipito-frontal circumference. Birthweights were calculated as multiples of the mean (MoMs) for a given stage of gestation. There was a highly significant correlation between gestational age and MAC/OFC (p < 0.0001) but none with ponderal index. There was a significant correlation between weight expressed as multiples of the mean and both ponderal index (p < 0.008) and MAC/OFC (p < 0.0001). This relationship between birthweight and anthropometric indices suggests that measurement of the ponderal index does not provide a useful index of intrauterine nutrition.

Anthropometry↗
PubMed1997

Urinary beta-core hCG: screening for aneuploidies in early pregnancy (11-14 weeks' gestation).

Initial studies at 17-22 weeks' gestation evaluating urinary beta-core human chorionic gonadotrophin (hCG) as a marker for Down's syndrome had suggested that it may have more potential than its serum counterpart. This study measured maternal urinary beta-core-hCG and creatinine at 11-14 weeks' gestation in a series of 26 aneuploidies (nine trisomy 21, five trisomy 18, four 45,X0, and eight others). The normal range for beta-core-hCG and beta-core-hCG/ creatinine was derived from 198 normal singleton pregnancies. Trisomy 18 cases (n = 5) had low maternal urinary beta-core-hCG creatinine levels (median 0.35 MOM, range 0.08-0.82 MOM). Whereas the other aneuploidies had no particular pattern; in particular, the trisomy 21 cases (n = 9) (median 1.16 MOM, range 0.3-4.74 MOM) did not differ significantly from 1 MOM. The findings imply that maternal urinary beta-core-hCG is not as discriminating for Down's syndrome between 11 and 14 weeks as later on in pregnancy.

Adult↗
PubMed1996

IGFBP-1 in the placenta, membranes and fetal circulation: levels at term and preterm delivery.

Samples of maternal blood, amniotic fluid, placenta, fetal membranes and umbilical venous blood were collected from 59 women at vaginal delivery (32-41 weeks gestation) and 15 women at delivery by Caesarean section (37-41 weeks gestation). Umbilical vein levels of IGFBP-1 were significantly lower in deliveries prior to the onset of labour (elective Caesarean section) than those during normal vaginal delivery. These levels were, in turn, significantly lower than those delivered by emergency Caesarean section. This difference was not seen in any of the other tissues examined. Concentrations of IGFBP-1 were lower in placenta and membrane extracts from preterm deliveries than in term deliveries. This difference was not observed in maternal or fetal serum or in amniotic fluid. This study confirms that the fetal membranes are a major source of IGFBP-1 and that fetal circulating levels are raised where there is evidence of fetal hypoxia. The absence of a comparable rise in levels in placenta, membranes or amniotic fluid suggests that the origin of this increase is from fetal tissue.

Amniotic Fluid↗
PubMed1996

The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines.

The effects of human chorionic gonadotrophin (hCG) and its subunits on in vitro bladder cancer cell growth have been assessed using the a tetrazolium salt reduction assay (MTT). Intact hCG, alpha-hCG and beta-core hCG all had no effect on cell growth, while beta-hCG increased MTT reduction in all four bladder cancer lines tested. The magnitude of beta-hCG stimulation was maximal in the T24 line, which does not itself produce beta-hCG and appeared to be correspondingly lower in beta-hCG-secreting lines. The addition of antibodies to beta-hCG inhibited MTT reduction among high secretors but failed to inhibit MTT reduction in non-beta-hCG producers. These results are consistent with the poor prognosis associated with beta-hCG expression by bladder tumours in vivo and suggest an autocrine/paracrine stimulation of tumour growth by endogenously produced beta-hCG.

Cell Division↗
PubMed1996

Urinary concentration of human chorionic gonadotrophin and its fragments as a prognostic marker in bladder cancer.

OBJECTIVE: To examine the prognostic significance of elevated urinary beta human chorionic gonadotrophin (beta-hCG) in patients with bladder cancer. PATIENTS AND METHODS: Total beta-hCG was measured in the urine of 142 patients referred for cystoscopic examination. Patients were followed for a minimum of 17 months and grouped according to stage of disease. Because the water output by individual patients varied, urinary creatinine levels were measured as an indicator of the concentration of the urine sample. Patient outcomes were correlated with urinary total beta-hCG levels both corrected and uncorrected for creatinine concentration. After correcting for urinary creatinine levels, 40 patients were excluded because the sample was too dilute (undetectable beta-hCG and a creatinine level of < 4 mmol/L). A further four patients were excluded as they had concurrent malignancies not in the bladder and one patient was lost to follow up. RESULTS: None of the 52 patients with benign conditions, nine of the 27 with Ta-T1, and nine of the 25 with T2-T4 bladder disease had urinary total beta-hCG levels > 3.74 IU/mmol/L creatinine. There was no significant association between urinary total beta-hCG concentrations and the rates of recurrence or progression for Ta-T1 disease at 17 months of follow-up. For patients with T2-T4 disease there was a significant association with widespread metastasis (P < 0.01) and mortality (P < 0.01) at 17 months of follow-up. These associations persisted when urinary total beta-hCG levels were not corrected for urinary creatinine concentration (metastasis, P < 0.01; mortality, P = 0.07; Kaplan-Meier survival time analysis, uncorrected for creatinine P = 0.027, corrected for creatinine P < 0.001). This association could not be accounted for by differences in age, histopathology or treatment. CONCLUSION: Although sample concentration was a serious confounding factor, after correcting for dilution using the creatinine content, the elevated urinary levels of total beta-hCG indicated those T2-T4 lesions which were likely to metastasize and those patients likely to die early. If this test is to be used clinically, concentrated samples, i.e. early-morning urine, and a more sensitive beta-hCG assay are required. Nevertheless, for T2-T4 bladder tumours, an elevated pre-treatment level of urinary beta-hCG is a marker of poor prognosis and may prove useful in deciding appropriate therapy.

Aged↗
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↗