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N F Gant

Publications and source records attributed to N F Gant.

At least 37 records · Page 2Linked to original sources

Disappointing follow-up findings for indigent high-risk newborns.

Indigent populations have received little attention in neonatal follow-up studies. We conducted "blinded" evaluations one year past term for 204 indigent high-risk infants who were ventilator treated or had a very low birth weight (VLBW) (less than or equal to 1500 g) and 85 healthy term controls from families similar to those of the high-risk infants. Marked developmental delay (Bayley Mental Developmental Index, less than 70) or gross motor abnormality occurred in 2% of controls, 27% of VLBW infants, 33% of ventilator-treated infants, and 39% of ventilator-treated VLBW infants. Despite considerable effort to prevent attrition, 43% of high-risk survivors were unavailable for follow-up at the one-year visit. Even if all of these infants were assumed to be normal, the incidence of developmental delay exceeded that in 11 of 12 recent studies. Indigent high-risk infants deserve considerable follow-up attention because of their high rate of attrition and developmental delay.

Anthropometry↗

Control of vascular reactivity in pregnancy.

Human pregnancy is characterized by a blunted pressor responsiveness to vasopressor substances. This was first reported by Dieckmann and Michel in 1937 in experiments in which they measured vascular reactivity to the pressor effects of a crude preparation of vasopressin. Recently, this has been reported to occur in response to epinephrine, norepinephrine (NE), and angiotensin II (AII). Gant and associates reported that the increasing vascular sensitivity to infused AII not only was characteristic of women who developed pregnancy-induced hypertension, but in fact preceded the development of pregnancy-induced hypertension. Although a variety of factors may mediate this blunted pressor responsiveness, the most likely candidate appears to be the localized production within endothelium and/or vascular smooth muscle of prostaglandins. Indeed, administration of indomethacin or aspirin results in an increased sensitivity to infused AII in normotensive previously AII-refractory women. Administration of the steroid hormone 5 alpha-dihydroprogesterone reverses this apparent prostaglandin-mediated response. In addition, administration of the phosphodiesterase inhibitor, theophylline, results in a restoration of vascular refractoriness to infused AII in women with pregnancy-induced hypertension or in women destined to develop pregnancy-induced hypertension. Although a variety of known and possibly unknown compounds might also effect the control of vascular reactivity during human pregnancy, the prostinoids appear to play a pivotal role in mediation of control of vascular reactivity during human pregnancy.

Angiotensin II↗

The relationship between abortion in the first pregnancy and development of pregnancy-induced hypertension in the subsequent pregnancy.

The relation between pregnancy-induced hypertension and reproductive history was assessed in 29,484 women receiving obstetric care at Parkland Memorial Hospital. The incidence of pregnancy-induced hypertension was 25.4% in primigravid women, somewhat lower (22.3%) in women whose only previous pregnancy terminated in abortion, and much lower (10%) in women who carried two or more successive pregnancies to viability.

Abortion, Induced↗

Prolactin levels in umbilical cord serum and its relation to fetal adrenal activity in newborns of women with pregnancy-induced hypertension.

The effect of hypertension in pregnant women on fetal maturation is an issue of considerable importance. Because of a possible role of prolactin in fetal adrenal steroidogenesis and in fetal lung maturation, we have investigated the relationship between hypertension in pregnant women and levels of prolactin and dehydroepiandrosterone sulfate in serum of newborn infants. It was found that with the mild-to-moderate form of pregnancy-induced hypertension (PIH), there was little effect on prolactin levels in newborn serum. In newborns of women with severe PIH, however, serum prolactin levels were significantly greater (p less than 0.01) than those in newborns of women with uncomplicated pregnancies. Conversely, umbilical serum concentrations of dehydroepiandrosterone sulfate in newborns of women with severe PIH were significantly less (p less than 0.05) than those in newborns of women with uncomplicated pregnancies. These findings are supportive of the view that pituitary function and adrenocortical function of fetuses of women with PIH are different from those of fetuses of normotensive women. These findings are suggestive that PIH alters the function of the fetal pituitary and adrenal cortex.

Adrenal Glands↗

Hemodynamic effects of indomethacin in chronically instrumented pregnant sheep.

Indomethacin administration has produced decreases in uteroplacental blood flow in several animal studies; therefore, it has been suggested that the maintenance of uterine blood flow is critically dependent on the continued synthesis of vasodilating prostaglandins. However, vasoconstriction following indomethacin administration may be due to mechanisms other than reduced prostaglandin synthesis. We administered indomethacin (2, 5, or 10 mg/kg) intravenously to seven unanesthetized sheep in late pregnancy and determined the time courses of the uteroplacental and systemic hemodynamic responses, comparing these to the concurrent changes in circulating prostaglandins. Indomethacin administration resulted in rapid increases in systemic and uteroplacental vascular resistance (80% to 100%) and mean arterial pressure (approximately 30%) and in decreases in systemic (approximately 30%) and uteroplacental (0% to 30%) blood flows within 5 minutes. Vasoconstriction was transient, however, and after 60 minutes there was no evidence of uterine or systemic vasoconstriction, although systemic and uterine plasma prostaglandin levels remained reduced for 180 minutes. Thus substantial inhibition of prostaglandin synthesis existed without evidence of concurrent systemic or uteroplacental vasoconstriction, suggesting that uterine blood flow is not directly dependent on maintained prostaglandin synthesis in unstressed pregnant sheep. Furthermore, the transient indomethacin-induced vasoconstriction may not be due to inhibition of prostaglandin synthesis.

Animals↗

The effect of hypertension in pregnant women on fetal adrenal function and fetal plasma lipoprotein-cholesterol metabolism.

In the present investigation, we evaluated the effect(s) of long-term hypertension and pregnancy-induced hypertension in women on the activity of the adrenals of their fetuses. We measured dehydroisoandrosterone sulfate, cortisol, and lipoprotein-cholesterol in umbilical cord plasma of newborn infants delivered (30 to 41 weeks' gestation) of 120 women whose pregnancies were uncomplicated and of 98 women with pregnancy-induced or long-term hypertension. Umbilical cord plasma levels of cortisol were similar in both groups of newborn infants at each gestational period. Fetal plasma levels of dehydroisoandrosterone sulfate also were similar in both groups at 30 to 33 weeks of gestation but were significantly reduced in newborn infants of hypertension women who were delivered between 34 and 41 weeks of gestation compared with those of newborn infants of normal women who were delivered at a similar gestational age. At term, umbilical cord plasma levels of total cholesterol and low-density lipoprotein-cholesterol were significantly higher in the newborn infants of hypertensive women compared with those levels in newborn infants of normotensive women; fetal plasma levels of high-density lipoprotein-cholesterol and very low-density lipoprotein-cholesterol were similar in both groups of newborn infants. The lowest plasma levels of dehydroisoandrosterone sulfate and the highest plasma levels of total cholesterol and low-density lipoprotein-cholesterol were found in newborn infants of women with the most severe pregnancy-induced hypertension. Based on these findings, we conclude that maternal hypertension effects a decrease in the rate of steroidogenesis of the fetal zone of the fetal adrenal cortex but does not act in a similar manner to effect steroidogenesis of the neocortical zone and leads to hypercholesterolemia in the fetus as a consequence of reduced adrenal utilization of low-density lipoprotein-cholesterol. In addition, the effects of pregnancy-induced hypertension appear to be manifest in the fetus late in pregnancy at a time when the fetal adrenal normally undergoes an accelerated rate of growth and steroid biosynthesis.

Adrenal Glands↗

The pressor response to angiotensin II: the roles of peripheral and cardiac responses in pregnant and nonpregnant sheep.

A reduced pressor response to infused angiotensin II has been observed in pregnancy. Although this has been considered to reflect reduced sensitivity of the peripheral vasculature to angiotensin II, it has also been suggested that the reduced pressor response is due to a fall in cardiac output during infusion of angiotensin II in pregnancy. In the present study we investigated the hemodynamic responses to infused angiotensin II in chronically instrumented, pregnant and nonpregnant sheep. We measured changes in cardiac output and systemic vascular resistance and related these changes to the increase in mean arterial pressure. The response in systemic vascular resistance to angiotensin II was substantially reduced in pregnant sheep. During angiotensin II infusion cardiac output fell in both groups, but the effect of the fall in cardiac output in reducing the pressor response was greater in nonpregnant animals. Thus, it appears that the reduced pressor response to angiotensin II in pregnant sheep is due to reduced systemic vascular responsiveness and not to differences in cardiac output responses.

Angiotensin II↗

Maternal-infant interactions at one-year adjusted age in infants at low- and high-risk as newborns.

To compare maternal-infant interactions in high- and low-risk groups, we observed infants who had required neonatal intensive care and otherwise similar infants with normal perinatal histories in a follow-up clinic at one year adjusted age. The developmental level as assessed by the Bayley Scales of Infant Development was significantly lower for the high-risk infants than for the control infants at one year of age. Principal component analyses were used to define interaction patterns in each of five situations. Principal component analyses allow a more meaningful analysis of interrelated maternal and infant behaviors than do standard statistical analyses and minimize the likelihood of misleading 'significant' findings resulting from multiple comparisons. Prior to being examined, mothers of control infants were more likely to adopt an 'en face' position, play with, comfort, talk to, and smile at their infants than were mothers of high-risk infants. Control infants were more likely to smile in return. These differences between control and high-risk mother-infant dyads disappeared when the infants' developmental level was statistically controlled. Group differences in maternal-infant interactions independent of the infants' developmental level were observed in only one situation (collection of blood). Specific medical risk factors had little relation to findings at one year. Maternal-infant interaction should be interpreted in relation to the postconceptional and developmental age as well as the postnatal age of the infant.

Child Behavior↗

Extra-adrenal deoxycorticosterone production in hypoestrogenic pregnancies: Serum concentrations of progesterone and deoxycorticosterone in anencephalic fetuses and in women pregnant with an anencephalic fetus.

In a continuing effort to define the origin of and the regulation of the production of deoxycorticosterone, we measured deoxycorticosterone and progesterone in the umbilical cord plasma of 16 anencephalic fetuses and newborn infants (21 to 45 weeks' gestation) and deoxycorticosterone, progesterone, 17 beta-estradiol, and estriol in the plasma of 18 women pregnant (16 to 45 weeks) with an anencephalic fetus. Whereas umbilical cord plasma levels of progesterone in the anencephalic fetuses were similar to those of normal abortuses and newborn infants, those of deoxycorticosterone (1.3 +/- 0.21 ng/ml, mean +/- SE) were significantly lower (P less than 0.001) than those in normal abortuses and newborn infants delivered between 31 and 42 weeks' gestation (3.94 +/- 0.26 ng/ml). We found that plasma levels of deoxycorticosterone were significantly correlated (P less than 0.001) to those of progesterone in women pregnant with an anencephalic fetus, as well as in women pregnant with a normal fetus. Plasma levels of deoxycorticosterone (range = 0.14 to 0.92 ng/ml) in women pregnant with an anencephalic fetus were significantly lower than those in women pregnant with a normal fetus; plasma levels of progesterone were similar in both groups. The plasma levels of 17 beta-estradiol and of estriol were extremely low in women pregnant with an anencephalic fetus compared with those in women with a normal fetus and did not vary as a function of gestational age. In one subject who was pregnant with an anencephalic fetus, we found that estrogen treatment (100 mg of diethylstilbestrol/day) for 6 days caused a progressive increase in the serum levels of deoxycorticosterone and in the ratio of the concentration of concentration of deoxycorticosterone to that of progesterone in serum. Both the serum levels of deoxycorticosterone and the ratio of the concentration of deoxycorticosterone and in the ratio of the concentration of deoxycorticosterone to that of progesterone declined after cessation of estrogen treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗

Effect of hypertonic saline on vascular responses to angiotensin II in pregnancy.

Refractoriness to infused angiotensin II is characteristic or normal human and ovine pregnancy; the mechanisms responsible are unclear. In this study, we sought to ascertain in gravid sheep whether hypertonic saline solution alters the vascular responses to angiotensin II, as in gravid women, and to compare the responses of the systemic and uteroplacental vasculature. Dose-response curves were determined. Mean arterial pressure and systemic vascular resistance increased in a dose-dependent fashion before and after hypertonic saline solution; responses were greater after hypertonic saline solution (p less than 0.01). Responses of cardiac output, heart rate, uterine vascular resistance, and uterine blood flow also were dose-dependent, but were unchanged after hypertonic saline solution. Plasma renin activity fell 45% after hypertonic saline solution. Treatment with hypertonic saline solution results in increased pressor responses to angiotensin II that are not a reflection of altered baroreceptor or chemoreceptor reflexes or of the response in the uteroplacental vascular bed. Rather, the increased systemic vascular responsiveness to angiotensin II after hypertonic saline solution appears to be a reflection of other mechanisms, such as alterations in vessel wall dynamics or receptor affinity.

Angiotensin II↗

Pressor responsiveness to angiotensin II in hospitalized primigravid women with pregnancy-induced hypertension.

Hospitalization of women with pregnancy-induced hypertension is beneficial in improving pregnancy outcome, but how it affects this physiologic process is not clear. In the present investigation, we evaluated pressor responsiveness to angiotensin II in 62 hospitalized women with pregnancy-induced hypertension. Although each of the women became normotensive, at least transiently, all remained sensitive to the pressor effects of angiotensin II. Thus, the beneficial effect of hospitalization on women with pregnancy-induced hypertension cannot be attributed to a decrease in the responsiveness to the action of angiotensin II.

Angiotensin II↗

The endocrinology of pregnancy-induced hypertension.

Discussed in this article are the effects of pregnancy-induced hypertension on the renin-angiotensin-aldosterone system; the possible role of prostanoids, deoxycorticosterone, and deoxycorticosterone sulfate in blood pressure control; and the effect of pregnancy-induced hypertension upon the endocrinology of the maternal-fetal-placental unit.

Adolescent↗

Differences on Bayley's infant behavior record for a sample of high-risk infants and their controls.

3 groups of high-risk newborns and their controls were assessed at 92 weeks post-conceptional age using Bayley's Infant Behavioral Record (IBR). The 3 groups of high-risk infants were those who weighed 1,500 grams or less at birth and required no ventilator therapy, those weighing 1,500 grams or less at birth who required ventilator therapy, and newborns weighing more than 1,500 grams at birth who required ventilator therapy. Controls were healthy term infants matched for 7 socioeconomic and demographic variables. The first principal component of the IBR ratings for the 3 groups of high-risk infants and the controls were similar. All 3 groups of high-risk infants received less desirable IBR ratings on most items than their controls. In addition, there were some differences among high-risk groups; ventilated infants regardless of birth weight received the lowest ratings reflecting overall performance on the IBR, very low birthweight, ventilated newborns were more likely to receive ratings characterizing an overly active infant with a short attention span, and very low birth-weight, never-ventilated infants were most likely to be rated as happy but passive and delayed. The differences between the high-risk infants and controls in large part resulted from infants who were also delayed in terms of their mental and motor development.

Female↗

Placental clearance rate of maternal plasma androstenedione through placental estradiol formation: an indirect method of assessing uteroplacental blood flow.

The metabolism of androstenedione (A) by the placenta in late pregnancy and the early puerperium was studied. The metabolic clearance rate of A (MCR-A) was increased in pregnant women, 2,825 +/- 207 L/24 hr (mean +/- SEM), compared to 2,020 +/- 140 L/24 hr in nonpregnant women of similar body weight. The immediate puerperal MCR-A was 2,538 +/- 50 L/24 hr. Therefore, approximately 10% of maternal plasma A was cleared by the placenta. In the latter half of pregnancy, the extent of conversion of maternal plasma A through estradiol formation, (rho)AE2, was increased, whereas in the immediate puerperium it was normal, 0.018. Moreover, 90% of aromatase activity was attributed to the placenta in late pregnancy. From these data, we computed that the placental clearance rate of A through estradiol (PCAE2) from whole blood was 497 +/- 41 ml/min in women with a single fetus and 691 +/- 102 ml/min in women with twin fetuses. Thus, it appears that the PCAE2 is a sensitive index of maternal-placental perfusion.

Androstenedione↗

Effect of volume expansion on pressor response to angiotensin II in pregnant ewes.

Vascular refractoriness to infused angiotensin II (AII) characterizes normal human and ovine pregnancy. To ascertain whether the refractoriness in the gravid ewe is mediated by either endogenous plasma concentrations of renin and AII or vasomotor reflexes, effects of acute volume expansion (VE) on the pressor response to AII were studied in chronically instrumented nonpregnant and near-term pregnant sheep. Dose-response curves describing the pressor response (delta BP) were determined before and after infusions of 1.0 1 of isotonic saline (NS) or 0.5 1 of 10% dextran (D). In nonpregnant sheep, hematocrit (Hct) and plasma renin activity (PRA) fell in all animals after NS (n = 7) and D (n = 6) (P less than 0.005). After VE with NS and D, delta BP increased at each dose of AII (P less than 0.05). The pressor response to AII in pregnant sheep was not altered by NS although decreases in Hct and PRA were comparable to those in nonpregnant sheep. Baroreceptor responses were not altered. Vascular refractoriness to infused AII in pregnant sheep is not due primarily to changes in plasma concentrations of renin-AII but more likely to another factor, vessel wall refractoriness. In this respect, the ewe is similar to the human.

Angiotensin II↗

The chronically instrumental ewe: a model for studying vascular reactivity to angiotensin II in pregnancy.

Vascular refractoriness to the systemic pressor effects of angiotension II (AII) develops normally during human pregnancy. To ascertain if the ewe might provide a suitable animal model to study the mechanisms responsible for this response (unique to pregnancy) we studied this phenomenon in unanesthetized, chronically instrumented nonpregnant and pregnant sheep, 68-143 d gestation. In these studies dose-response curves were established for changes in both mean arterial pressure and uterine blood flow. The pressor response to continuous infusions of AII increases as a function of the dose of AII in both nonpregnant and pregnant animals (P less than 0.001), R = 0.943 and 0.879, respectively. However, the pregnant animals were refractory to the pressor effects of AII, requiring 0.016 microgram of AII/min per kg to elicit a 20 mm HG rise in mean arterial pressure, in contrast to 0.009 for nonpregnant animals. The slope and intercept for the regression lines are different at P less than 0.001. In pregnant animals the dose-response curve for uterine blood flow was also determined. Increases in uterine blood flow were observed at doses of AII less than 0.016 microgram/min per kg, while larger doses resulted in a progressively greater reduction in blood flow. It appears likely that the ewe may serve as an animal model suitable for the further study of the unique pregnancy-modified systemic and uteroplacental vascular responses elicited by AII.

Angiotensin II↗

Hormone production during pregnancy in the primigravid patient. II. Plasma levels of deoxycorticosterone throughout pregnancy of normal women and women who developed pregnancy-induced hypertension.

The plasma concentration of deoxycorticosterone (DOC) was determined serially in a large group of primigravid women from 10 weeks' gestation to term. The plasma level of DOC in women whose pregnancies were uncomplicated (n = 44) was 234 +/- 33 pg/ml (mean +/- SE), at 10 to 14 weeks' gestation, a level two times that of nonpregnant subjects. The plasma level of DOC in these women rose to 778 +/- 65 pg/ml at 23 to 26 weeks' gestation, and at term (39 to 42 weeks) was 1,309 +/- 155 pg/ml. The plasma levels of DOC in women (n = 31) who eventually developed pregnancy-induced hypertension (PIH) were similar to those in the women who remained normal at all stages of pregnancy. We also found that, in women with normal pregnancies as well as in all stages of pregnancy. We also found that, in women with normal pregnancies as well as in women destined to develop PIH, the plasma concentration of DOC fluctuated in a manner parallel to that of progesterone throughout gestation; however, changes in the plasma level of DOC did not mirror those of cortisol. These data suggest that excessive plasma levels of DOC are not necessarily associated with the development of PIH. These data also support the view that, in pregnant women, a fraction of circulating DOC may arise via extra-adrenal 21-hydroxylation of progesterone rather than through adrenal secretion.

Adolescent↗