Proceedings of the symposium "progesterone, progestins, and fetal development".
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Biomedical subjects
Publications and source records attributed to R A Chez.
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Amniotic fluid concentrations of zinc and copper were measured in human pregnancy of 12 to 44 weeks' gestation. Although mean values for both metals are relatively flat throughout pregnancy, there appears to be a relative increase in copper levels between 26 and 33 weeks' gestation, and increasing levels of zinc after 34 weeks. Correlations with fetal age or fetal-maternal disease are not apparent in specimens from this heterogenous population.
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This investigation was undertaken to study the effect of reduction of placental surface area on fetal growth. The right horn of the bicornuate uterus was removed in nonpregnant ewes, the ewes were bred and 11 out of 15 became pregnant. Near term, under experimental conditions, maternal and fetal blood gases, pH, uterine and umbilical blood flows were measured or calculated. Fetal, placental membrane, uterine, and cotyledonary weights and number of cotyledons were recorded. The experimental hemi-hysterectomized group was compared to a control group of 14. Results show that: (1) weight per cotyledon was significantly greater (p less than 0.01) in the hemi-hysterectomized series than in the controls, (2) loss of a significant number of placentation sites was compatible with the production of term-sized fetuses, (3) since the difference between the number of cotyledons in the hemihysterectomized and control groups is significantly less than the number of implantation sites removed, the efficiency of implantation is improved, and (4) there were no changes in blood flows, PO2, PCO2, and fetal oxygen consumption.
We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol.
The effects of salbutamol and isoxsuprine upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) were investigated in near-term, nonlaboring chronic sheep preparations. During both intravenous salbutamol and isoxsuprine infusions to the ewe, UtBF and mean maternal arterial pressure decreased significantly. Also, dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred. There were no significant changes in UmBF, mean fetal arterial pressure, or fetal heart rate (FHR) during salbutamol infusions, but UmBF and FHR increased during isoxsuprine infusions. During the 120 minute postinfusion recovery period, UtBF rose significantly after the salbutamol infusions but not after the isoxsupine infusions. The effects and structure-activity relationship of these two drugs are comparable to those of ritodrine and fenoterol, two other beta-adrenergic agonists.
The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120 minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested as the cause of this UtBF increase.
Bethamethasone was administered to pregnant rhesus monkeys of 134 to 150 days' gestation. At operative delivery, umbilical venous plasma cortisol concentrations were significantly lower in the treated group than in the control group, indicating that the agent crossed the placenta. In the treated group, accelerated differentiation was present in several fetal organs including lung, liver, kidney, and adrenal gland. Brain histologic changes suggestive of neuronal injury were found in some instances. There were no differences in the weights of these fetal organs except for liver. It was markedly increased in steroid-treated fetuses and this was accompanied by a fourfold rise in total hepatic glycogen content. These observations suggest that in the subhuman fetal primate, the differentiation of fetal organs in addition to lung is enhanced by short-term corticosteroid treatment while growth is not affected.
Rhesus monkey pancreatic alpha-cell function in streptozotoc-induced glucose-intolerant pregnancy is similar to that in normal primate pregnancy. Specifically, basal maternal and fetal plasma glucagon levels equate, and the fetal alpha cell does not respond to the glucagonogenic stimulus of either intravenous alanine or insulin-induced hypoglycemia. This contrasts with the accelerated maturation of the fetal beta cell in glucose-intolerant pregnancy, and does not support the concept of functional coupling of the pancreatic islet by a common glucose-based process. Fetal plasma glucagon levels do increase after L-dopa injection to the fetus. These data indicate that alpha cell unresponsiveness is a function of the glucagon-releasing mechanism rather than inadequate hormonal synthesis.
The pregnant rhesus monkey's (Macaca mulatta) potential as a model for understanding the dynamics of alpha-fetoprotein (AFP) metabolism in human pregnancy was evaluated. AFP levels in maternal and fetal serum and amniotic fluid were determined by radioimmunoassay. Significant correlations were found between decreasing maternal serum, fetal serum and amniotic fluid AFP concentrations and increasing gestational age. However, these data are not consistent with the AFP changes reported in human pregnancy. It appears that this animal has limited applicability as a model in this aspect of human pregnancy.
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The effect of bilateral fetal or maternal nephrectomy on basal and diuretic-stimulated plasma renin activity (Pra) was examined in 9 chronically catheterized Dorset sheep. After fetal nephrectomy, there was an initial rapid decrease in fetal PRA with t1/2 of 42-84 min, followed by a slower decrement with 1/2 350-720 min. There was no change in maternal PRA during this period. Similarly, after maternal nephrectomy, the decrease in maternal PRA had two exponential components and there was no associated change in fetal PRA. These data, and the maternal and fetal PRA responses to intravenous furosemide, have demonstrated that renin does not cross the sheep placenta and that fetal PRA is independent of the maternal PRA level.
The possibility that 24-hour rhythms exist in uterine blood flow (UtBF) and umbilical blood (UmBF) was investigated in 5 days postoperative chronically instrumented near-term pregnant sheep acclimated to a controlled environment. UtBF, UmBF and pressure measurements were made at 15-min intervals over 24 h beginning at 0800 h. Each data series was examined for the presence of significant rhythms of a 24-hour period using a method of Fourier analysis. UtBF 24-hour rhythms were found in all ewes; UmBF 24-hour rhythms were found in 4 of 5 lambs. A consistent reciprocal phase relationship between UtBF and UmBF was evident within animals. There were no associated rhythms in maternal arterial, fetal arterial, or amniotic fluid pressures. These results indicate that the presence of circadian rhythms must be considered as a possible variable when long-term uteroplacental hemodynamic studies are planned.
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Advances in the immunopathology of blistering diseases now provide increased accuracy in the diagnosis of herpes gestationis in pregnancy. Guidelines are presented in this review to determine the presence of the disease. Exogenous corticosteroids will effectively alleviate symptoms and prevent formation of new lesions.
Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits.
The effect of ritodrine upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term chronic sheep preparations. During intravenous ritodrine infusions to the ewe in sequential dose rates from 100 to 800 mug per minute, UtBF fell progressively to 43 per cent below control levels and mean maternal arterial pressure (MMAP) declined 20 per cent. During constant infusions of 100, 400, or 800 mug per minute of ritodrine to the ewe for 120 minutes,, UtBF decreased 10, 37, and 31 per cent, respectively, and MMAP decreased 6, 20 and 25 per cent respectively. Dose-related maternal tachycardia and hyperglycemia occurred. There were no significant changes in UmBF, mean fetal arterial pressure, or fetal heart rate. During all infusions, maternal and fetal arterial pH, PCO2, and PO2 remained within normal physiologic limits. Simultaneous infusion of ritodrine (400 mug per minute) and propranolol (100 mug per minute) blocked the maternal tachycardia, but decreases in UtBF, MMAP, and UmBF were observed. Ritodrine infusions to the fetus (25 mug per minute) resulted in fetal tachycardia and a variable increase in UmBF.
The amniotic fluid lecithin/sphingomyelin (L/S) ratio in normal rhesus monkey pregnancies exhibits a distribution through the latter half of gestation similar to that seen in human pregnancies. Changes in the synthesis and concentration of lecithin in the fetal lung, measured both in vitro and in vivo, are paralleled by changes in the amniotic fluid L/S ratio. Both the amniotic fluid L/S ratio and fetal lung lecithin concentration increase significantly (p less than 0.001) in the final 10 per cent of rhesus monkey gestation, and there is a significant correlation (p less than 0.001) between these two indices of fetal lung lecithin metabolism. Moreover, the onset of these late gestational changes is temporally related to increased activity of the major pathway of de novo lung lecithin synthesis and to the ability of the preterm rhesus newborn infants to remain free of respiratory symptoms after delivery by cesarean section. We conclude that the amniotic fluid L/S ratio is a valid indicator of fetal pulmonary phospholipid metabolism and, therefore, an accurate index of biochemical pulmonary maturity.