Tim Chard

Circadian variation of GH-independent IGF-binding protein in diabetes mellitus and its relationship to insulin. A new role for insulin?

Evidence is accumulating that a non‐GH dependent insulin‐like growth factor‐binding protein (IGF‐BP) is not only a carrier protein but also has an active role in the growth process.

Clinical obstetrics and gynaecology

Two prominent guest editors solicit contributions on key clinical topics of interest to practicing physicians. Procedures, current clinical problems, medical and surgical treatments, and effective diagnostic aids are all carefully reviewed in original articles. The result is an instructive resource that dispenses trustworthy clinical guidance that enhances your understanding of key areas of your practice.

Plasma Cortisol and Adrenocorticotropin in Appropriate and Small for Gestational Age Fetuses

Plasma cortisol and adrenocorticotropin (ACTH) were measured in fetal blood samples obtained by cordocentesis from 61 appropriate for gestational age (AGA) and in 41 small for gestational age (SGA) fetuses at 18-38 weeks gestation. Fetal plasma cortisol (mean 74 nmol/l) did not change but plasma ACTH increased between 18 and 36 weeks gestation and the two were not significantly correlated. Plasma cortisol in cord blood samples after vaginal delivery at term (mean 305 nmol/l) was higher than in samples at elective cesarean section (mean 151 nmol/l), and there was a significant correlation between fetal and maternal levels. The findings suggest that in human fetuses a late gestational rise in plasma cortisol may not be necessary for organ maturation and that the high fetal plasma cortisol in spontaneous labor at term is probably the result rather than the cause of labor. In SGA fetuses, plasma cortisol was higher and ACTH lower than in AGA fetuses, and plasma cortisol was inversely correlated to fetal hypoglycemia, suggesting that in the chronically hypoglycemic SGA fetus the fetal pituitary is under negative inhibition.

Vasopressin Analogue DDAVP in Diabetes Insipidus: Clinical and Laboratory Studies

In seven patients with cranial diabetes insipidus an analogue of vasopressin, DDAVP, produced an antidiuresis lasting up to 20 hours after a single intranasal dose. Lysine vasopressin (LVP) in the same dose produced a less potent antidiuresis which lasted for only three to four hours. The plasma half life of DDAVP was 7·8 and 75·5 min for the fast and slow phases, compared with 2·5 and 14·5 min for LVP. Radioiodine-labelled DDAVP was not destroyed by incubation with late pregnancy plasma, which contains an enzyme that inactivates vasopressin. The slow metabolic clearance of DDAVP, its absorption through the nasal mucosa, and its lack of side effects make this the ideal drug for the treatment of vasopressin-sensitive diabetes insipidus. Patients usually require 10 to 20 μg DDAVP given intranasally twice daily for good clinical control of their diabetes insipidus.

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.

Relationship between the pubertal fall in sex hormone binding globulin and insulin-like growth factor binding protein-I. A synchronized approach to pubertal development?

In a cross‐sectional study of 69 normal adolescents we have found sex hormone‐binding globulin (SHBG) levels to fall in both males and females throughout the pubertal period. Multiple regression analysis revealed a close negative correlation with insulin in both sexes. Weaker correlations were also found between SHBG and circulating androgen concentrations, in both males and females. Similar results were also obtained for a second circulating binding protein of primarily hepatic origin. This low molecular weight insulin‐like growth factor (IGF) binding protein I (IBP‐I) is one of two distinct classes of IGF binding proteins which bind IGF‐I and IGF‐II. IGF‐I in turn mediates, at least in part, the actions of growth hormone. IBP‐I also fell throughout puberty, correlating with the increasing insulin levels. In addition IBP‐I correlated with androgen levels in both sexes. These similarities between SHBG and IBP‐I, together with a strong correlation across puberty between the levels of the two binding proteins themselves (r= 0.737, P < 0.001), suggest common mechanisms of control over the circulating levels of these two binding proteins. The association with insulin raises the possibility of a synchronized modulation of the actions of sex steroids and IGFs by nutritional intake. Thus pubertal growth and sexual development may occur over the same time with both modulated according to nutritional intake, linked through pancreatic insulin release, to hepatic production of SHBG and IBP‐I.

A RAPID SEMI‐AUTOMATED METHOD FOR THE MEASUREMENT OF HUMAN CHORTONIC SOMATOMAMMOTROPHIN. THE NORMAL RANGE IN THE THIRD TRIMESTER AND ITS RELATION TO FETAL WEIGHT

A rapid semi‐automated radioimmunoassay for human chorionic somatomam‐motrophin has been developed, based on the use of the Analmatic preparation unit and centrifuge. Several hundred samples can be assayed in a working week and the accuracy with which the individual reactants are added is at least as good as that which can be attained manually. The ease with which large numbers of samples can be assayed has facilitated the introduction of extensive quality controls. Within‐assay precision is excellent, but between‐assay precision is less satisfactory, due to undefined variations between different preparations of labelled hormone. The range of plasma levels of human chorionic somatomammotrophin in the third trimester of pregnancy has been established in 100 normal subjects. A relationship was found between mean circulating levels of the peptide and fetal weight.

Maternal Serum Screening for Down Syndrome in Early Pregnancy

The possibility of improving the effectiveness of antenatal screening for Downs syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Downs syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Downs syndrome in the United Kingdom from about 900 a year to about 350 a year.

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.

A retrospective comparison of water births and conventional vaginal deliveries.

The aim of this study was to document the practice of water births and compare their outcome and safety with normal vaginal deliveries. A retrospective case-control study was conducted over a five year period from 1989 to 1994 at the Maternity Unit, Rochford Hospital, Southend, UK. Three hundred and one women electing for water births were compared with the same number of age and parity matched low risk women having conventional vaginal deliveries. Length of labour; analgesia requirements; apgar scores; maternal complications including perineal trauma, postpartum haemorrhages, infections; fetal and neonatal complications including shoulder dystocias; admissions to the Special Care Baby Unit, and infections were noted. Primigravidae having water births had shorter first and second stages of labour compared with controls (P<0.05 and P<0.005 respectively), reducing the total time spent in labour by 90 min (95% confidence interval 31 to 148). All women having water births had reduced analgesia requirements. No analgesia was required by 38% (95% confidence interval 23.5 to 36.3, P<0.0001) and 1.3% requested opiates compared to 56% of the controls (95% confidence interval 46. 3 to 58.1, P<0.0001). Primigravidae having water births had less perineal trauma (P<0.05). Overall the episiotomy rate was 5 times greater in the control group (95% confidence interval 15 to 26.2, P<0.0001), but more women having water births had perineal tears (95% confidence interval 6.6 to 22.6, P<0.001). There were twice as many third degree tears, post partum haemorrhages and admissions to the Special Care Baby Unit in the controls, although these differences were not significant. Apgar scores were comparable in both groups. There were no neonatal infections or neonatal deaths in the study. This study suffers from many of the methodological problems inherent in investigation of uncommon modes of delivery. However, we conclude that water births in low risk women delivered by experienced professionals are as safe as normal vaginal deliveries. Labouring and delivering in water is associated with a reduction in length of labour and perineal trauma for primigravidae, and a reduction in analgesia requirements for all women.