Showing papers by "John Radcliffe Hospital published in 1975"

The Mechanism by which Foetal Cortisol Controls the Onset of Parturition in the Sheep

Abstract: The sheep is one of the few species in which there is good evidence that the foetus is involved in determining the length of pregnancy. Parturition in the sheep is prevented by foetal hypophysectomy (Liggins etal., 1967; Comline etal., 1970; Bosc, 1972) or adrenalectomy (Drost & Holm, 1968), and can be induced prematurely by intrafoetal administration of ACTH* or glucocorticoid (Liggins et al., 1967). The foetal adrenal hypertrophies towards the end of pregnancy, doubling in weight during the last 2 weeks (Comline & Silver, 1961), and its ability to respond to ACTH with increased cortisol output also increases during this time (Bassett & Thorburn, 1973). High concentrations of ACTH have been reported in foetal plasma near term (Rees et al., 1973, although it is not clear that the increase precedes the onset of 1abour.Thereisadramaticand sustained increase in the concentration of cortisol in the foetal plasma during the last week of pregnancy (Bassett & Thorburn, 1969; Comline et al., 1970). In addition to these events in the foetus, important endocrine changes occur in the mother before parturition. Placental progesterone production declines, leading to a decrease in the maternal peripheral plasma progesterone concentration (Bassett et a[., 1969; Fylling, 1970), and maternal plasma concentrations of oestrogens, both unconjugated and sulpho-conjugated, rise (Challis, 1971 ; Currie et al., 1973). Uterine prostaglandin production increases, and high concentrations of prostaglandin FIG appear in the uterine venous effluent (Liggins & Grieves, 1971 ; Thorburn et al., 1972). These changes can be monitored in the foetus and mother by the use of indwelling vascular catheters implanted at surgery some weeks before delivery. Investigation of the temporal interrelationships between these endocrine changes has shown that the progesterone concentration in maternal plasma falls at about the same time as that of cortisol in foetal plasma rises, 3-7 days before delivery. Oestrogen concentrations in plasma increase later, generally about 24-48 h before delivery, and are accompanied by rising uterine venous concentrations of prostaglandin F (Thorburn et al., 1972). These changes precede the onset of uterine contractions (Rawlings W Flint et al., 1974). Since oestrogen administration stimulates uterine prostaglandin production in a number of species (including the sheep) both during pregnancy and otherwise, it has been suggested (Liggins et al., 1973) that the elevated oestrogen concentration in maternal plasma is responsible for the increased concentration of prostaglandin F. Prostaglandins cause marked increases in uterine contractility in sheep at term (M. D. Mitchell, A. P. F. Flint & A. C. Turnbull, unpublished work), as in other species, and it is probable that the oestrogens, which themselves cause labour when administered to pregnant sheep (Hindson et al., 1967), act through prostaglandin synthesis. These endocrine events play an important part in controlling the onset of labour in sheep. The foetal cortisol surge is a necessary prelude to parturition at term: foetal hypophysectomy prevents delivery. Involvement of various maternal organs has been ruled out by extirpation : parturition occurs normally after maternal hypophysectomy (Denamur & Martinet, 1961 ; Bosc, 1972), ovariectomy or adrenalectomy (Thompson & Wagner, 1974). The fall in the progesterone concentration in maternal plasma is also a pre-requisite for normal labour. Labour induced with foetal glucocorticoid can be blocked by the simultaneous administration of large doses of progesterone to the ewe (Liggins et al., 1972); and induction of labour with oestrogens (when there is no fall in progesterone concentration) is associated with failure of the cervix to dilate. There

Measurement of heparin in patients receiving subcutaneous heparin therapy.

Abstract: Summary. Heparin assays based on four different tests of clotting function have been compared with a heparin assay utilizing the potentiating effect of heparin on anti-factor Xa in a group of patients receiving subcutaneous heparin therapy during late pregnancy. It is considered that the anti-factor Xa method is a better indication of the antithrombotic effect of heparin. In the presence of high levels of clotting factors, heparin assays based on tests of clotting function can be misleading.

The timing of intraventricular haemorrhage

Abstract: The aetiology of IVH is controversial. Present techniques concerning its timing rely either on clinical observations - namely the occurence of convulsions or collapse, or on sophisticated radiochemical methods. We have continuously measured intra-arterial blood pressure, and central and peripheral temperatures in low birthweight infants at risk of IVH in an attempt to identify factors either causative or indicative of IVH. Since we give regular small transfusions of fresh adult blood to low birthweight infants, frequent estimates of the HbA/HbF ratio /Kleihauer technique/ provide a time-base for comparison with post-mortem samples of ventricular clot. When fresh blood containing HbF is allowed to clot, the HbA/HbF ratio is unaltered. With this technique, we have been able to date ventricular haemorrhage. This seems to have occured before the emergence of overt clinical signs. Differences in patterns of monitored data between these infants and ones who had not developed an IVH will be illustrated.

Etiology of mental retardation.

Abstract: Etiology of Mental Retardation Professor J P M Tizard (John Radcliffe Hospital, Oxford) pointed out the size of the problem, e.g. 6 million mental defectives in the USA, and stressed the multiplicity of factors often involved. Low intelligence could be considered 'physiological' (i.e. analogous with low height), or 'pathological', but in practice it might be impossible to make a hard and fast distinction between the two. In order to illustrate this thesis he recounted a detailed case history. A child born at 36 weeks, with low genetic endowment, developed hypoglycemia. At 3 months he developed infantile spasms. At 2 years an elevated level of blood lead and of antibodies to cytomegalovirus were reported. At 4 years of age the child's mental age was 18 months. Professor Tizard then admitted this case to be of his own invention, but felt that it gave a graphic illustration of the complexity of the situations commonly presenting.

The safety of oestrogen therapy

Abstract: The initial suspicion that oestrogen therapy predisposed to the development of carcinoma has not so far been confirmed. However, the thromboembolic complications of oestrogen therapy are well documented. Not only is the dose of oestrogen important, but there has been recent speculation that the type of oestrogen preparation is also important. Low doses of oestrogen both natural and synthetic alleviate menopausal symptoms, but the dose of oestrogen that has been studied in relation to the prevention of long-term degenerative effects of the menopause, in particular osteoporosis and cardiovascular disease, has usually been high and the oestrogen has been the synthetic preparation mestranol or its metabolite, ethinyl oestradiol.If low doses of oestrogen are to be recommended for long-term use there must be some indication that, as well as alleviating symptoms, they (a) prevent the degenerative process of the post-menopause and (b) are not associated with adverse changes in the coagulation system.The p...