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J C Schellenberg

Publications and source records attributed to J C Schellenberg.

28 records · Page 2Linked to original sources

New approaches to hormonal acceleration of fetal lung maturation.

The paper reviews the effects on lung maturation of glucocorticoids in animals and humans and presents relevant recent findings from the author's laboratory. It is now well established that antenatal glucocorticoid treatment reduces the incidence and severity of the respiratory distress syndrome (RDS) in prematurely born infants. The recommended doses of glucocorticoids produce fetal glucocorticoid activity levels similar to those of newborns with RDS or prolonged rupture of the membranes. Extensive follow-up studies have shown that adverse effects on child development are unlikely to occur. It is also evident that a significant number of fetuses do not respond to the treatment, which is of particular consequence in fetuses of less than 28 weeks gestation. These fetuses are less likely to respond to glucocorticoid therapy that fetuses between 28 and 32 weeks gestation and are at a higher risk of developing complications due to their immaturity. In fetal sheep, there is a similar decrease in the efficacy of glucocorticoids on lung maturation with decreasing gestational age. Simultaneous infusion of cortisol, triiodothyronine and prolactin but not of any of these hormones administered singly or in combination of two produced mature lungs in fetal sheep of 125 days gestation. Similar results were obtained with thyrotropin releasing hormone (TRH) and cortisol. It remains to be seen whether the combined administration of glucocorticoids and TRH accelerates lung maturation in human fetuses.

Animals↗

On the origin of dehydroepiandrosterone sulphate in the blood of fetal sheep.

Total sulphoconjugated and unconjugated dehydroepiandrosterone (DHA) and total oestrone were measured in plasma of intact sheep fetuses, fetuses hypophysectomized at 104-112 days and fetuses bilaterally adrenalectomized at 98-101 days. At 120-127 days, the mean concentrations of total DHA and oestrone in intact fetuses (n = 13) were 29.7 +/- 4.2 (S.E.M.) nmol/l and 14.3 +/- 2.8 nmol/l respectively. At term, the values for total DHA and oestrone in hypophysectomized fetuses (n = 13) of 18.0 +/- 1.9 nmol/l and 9.1 +/- 2.0 nmol/l were significantly (P less than 0.05) lower than the intact group whereas in the adrenalectomized fetuses (n = 8) total DHA (80.8 +/- 13.0 nmol/l) was higher (P less than 0.05) and total oestrone values were similar to the intact animals. Intrafetal infusion of cortisol at term (1 mg/h for 84 h) raised levels of total oestrone in intact (n = 6; 12.3 +/- 2.9 vs 31.6 +/- 8.5 nmol/l) and adrenalectomized (n = 4; 14.2 +/- 2.6 vs 190.6 +/- 53.0 nmol/l) fetuses and of total DHA in hypophysectomized fetuses (n = 7; 16.0 +/- 1.9 vs 31.6 +/- 8.5 nmol/l) while infusion of ACTH (1-24) (5 micrograms/h) was without significant effect in any group. It is concluded that the ovine fetal adrenal in late pregnancy makes no significant contribution either to the high circulating concentrations of DHA sulphate or to the substrates for placental oestrogen synthesis.

Adrenal Glands↗

The effects of ACTH1-24 or cortisol on pulmonary maturation in the adrenalectomized ovine fetus.

Pulmonary maturation in 8 ovine fetuses bilaterally adrenalectomized at 98-101 days and infused at term with either ACTH1-24 or cortisol was compared with that in 4 untreated sham-operated controls. Four of the adrenalectomized fetuses were infused intravascularly with ACTH1-24 5 micrograms/h for 84 h before delivery and the other four were infused with cortisol 1 mg/h for 72 h. The high plasma concentrations of immunoreactive ACTH in the adrenalectomized fetuses (2762 +/- 1339 ng/l, mean +/- SD) were not significantly elevated by infusion of ACTH1-24 but were markedly depressed by infusion of cortisol. Distensibility (V40) of the lungs was less than that of controls in both the ACTH1-24-infused and cortisol-infused fetuses (1.86 +/- 0.31 ml/g vs 0.62 +/- 0.13 ml/g and 1.27 +/- 0.34 ml/g respectively) but it was significantly greater in the cortisol-infused fetuses compared to those infused with ACTH1-24. The volume of air retained at 5 cm H2O pressure (V5) during deflation was markedly reduced in adrenalectomized fetuses (controls 1.14 +/- 0.52 ml/g vs 0.25 +/- 0.25 ml/g and 0.12 +/- 0.6 ml/g). The wet weight of the lungs and the concentrations of saturated phosphatylcholine in lung tissue and lavage fluid were lower in the adrenalectomized fetuses than in controls but the differences were not significant. It is concluded that infusion of ACTH1-24 at term in adrenalectomized fetuses is probably without effect whereas cortisol enhances distensibility.

Adrenalectomy↗

The estimation of elastin in fetal tissues by radioimmunoassay of isodesmosine.

A radioimmunoassay was developed for the determination of isodesmosine as the tetraacetyl derivative. Isodesmosine tetraacetate conjugated with bovine albumin was injected into rabbits which developed useful titers of antibodies after five months. The radioligand for the assay was prepared by acetylating isodesmosine with [3H] acetic anhydride. The bound ligand was separated from free ligand by coprecipitation with human gamma-globulin in 46% saturated ammonium sulfate solution. The sensitivity of the assay was 2 ng isodesmosine. The antiserum was specific for isodesmosine tetraacetate and only desmosine tetraacetate gave appreciable cross-reactivity (4%). The assay was found to be suitable for the accurate estimation of elastin in small samples (5 mg dry weight) of rat and ovine fetal lung tissue and for elastin degradation products in amniotic fluid (0.5 ml).

Amino Acids↗

Role of the systemic vasculature in the hemodynamic response to changes in plasma ionized calcium.

Hemodynamic consequences of sustained (one hour) hypocalcemia and hypercalcemia (plasma ionized calcium concentration [Ca++] maintained approximately 60% below or above normal, encompassing the clinical range) were studied and the influence of beta blockade on these hemodynamic alterations examined in 16 anesthetized, closed-chest dogs. Alterations in [Ca++] were associated with directionally similar changes in mean arterial pressure, whereas on the average cardiac output remained unchanged. Thus, the peripheral vasculature played an important role in the hemodynamic response to alterations in [Ca++]. The state of beta adrenergic activity was an important determinant of the hemodynamic response to hypocalcemia. Prior to beta blockade, hypocalcemia was associated with decreased systemic vascular resistance, whereas after beta blockade with propranolol hydrochloride, systemic vascular resistance was not different from control except at the five-minute observation period, and cardiac output and stroke volume fell.

Adrenergic beta-Antagonists↗

Uterine activity during lumbar epidural analgesia with bupivacaine.

Uterine performance (i.e., uterine activity expressed in Montevideo units and in pressure area, number, and amplitude of contractions) was monitored by intra-amniotic tocomanometry in 16 patients with lumbar epidural analgesia. Technically adequate recordings were obtained in 34 top-up doses of which 24 were given in oxytocin-induced or stimulated labor and 10 in spontaneous labor. Thirty-two doses of 10 ml. of 0.25 per cent and two doses of 6 ml. of 0.5 per cent plain bupivacaine were administered. Aortocaval compression was avoided by placing the patients in the lateral (31 doses) or the semirecumbent position (three doses). Statistical analysis by means of Student's test failed to show a difference in uterine performance before and after the top-up dose. It is suggested that aortocaval compression is an essential factor contributing to or responsible for the temporary depression of uterine activity that has been observed by other authors after epidural injections of local anesthetic agents.

Adult↗