Norman F. Gant

A clinical test useful for predicting the development of acute hypertension in pregnancy

Abstract Ninety-three per cent of nulliparous, normotensive young women who subsequently developed pregnancy-induced hypertension demonstrated an increase in diastolic blood pressure of at least 20 mm. Hg when turned from the lateral recumbent to the supine position between the twenty-eighth and thirty-second weeks of gestation. Conversely, 91 per cent of women who did not demonstrate such a rise in diastolic blood pressure when turned to the supine position did not become hypertensive during that pregnancy. Additionally, very close correlations were demonstrated between: (1) a positive supine pressor response and increased sensitivity to intravenously infused angiotensin II, and (2) a negative supine pressor response and increased resistance to angiotensin II.

The metabolic clearance rate of dehydroisoandrosterone sulfate

In the present study, the metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) decreased in normotensive gravidas during short-term studies utilizing angiotensin II-induced elevation of blood pressure. Therapy with hydralazine hydrochloride in chronic hypertensive gravidas resulted in a decrease in blood pressure and an accompanying decrease in the MCRDS. A variable response was observed in the apparent volume of distribution of DS (AVDDS) during therapy with hydralazine hydrochloride. Decreases in MCRDS also occurred in chronic hypertensive gravidas following therapy with 40 mg. of intravenously administered furosemide despite a failure of blood pressure to be altered. The AVDDS increased in four of five patients receiving furosemide, suggesting a possible direct action of furosemide upon vascular smooth muscle.

Infertility and endometriosis: Comparison of pregnancy outcomes with laparotomy versus laparoscopic techniques*

OBJECTIVESnThe null hypothesis of this retrospective literature analysis was that the superiority of laparoscopy over laparotomy to correct infertility resulting from tubal injury has not been proved because of the lack of well-designed comparative studies. The same was true for the correction of infertility caused by minimal and mild endometriosis.nnnSTUDY DESIGNnA retrospective review of the English-language literature since 1975 was made to ascertain whether laparoscopic surgical correction of infertility caused by tubal injury and endometriosis resulted in an increased pregnancy rate compared with laparotomy techniques. Complication rates associated with laparoscopy versus laparotomy were also compared.nnnRESULTSnThere were almost no adequate studies designed and executed to answer these questions based on criteria established by the United States Preventive Services Task Force. Furthermore, there was no evidence in the reported series that laparoscopic surgical procedures were superior to laparotomy in correcting infertility. The complication rates were similar. There was suggestive, but not yet proven, evidence that laparoscopic surgery with laser techniques may be superior to laparotomy in the management of infertility resulting from moderate and severe endometriosis.nnnCONCLUSIONnAlthough results and complications were similar, the cost in savings with respect to decreased hospital expenses and loss of work time favor the use of laparoscopy over laparotomy when results are similar and not associated with increased risk. What has not been established are costs and work-time losses for minilaparotomy compared with laparoscopy.

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.

The metabolic clearance rate of dehydroisoandrosterone sulfate: III. The effect of thiazide diuretics in normal and future pre-eclamptic pregnancies☆

The present study reports that the metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) is decreased by thiazide diuretics during normal and future pre-eclamptic pregnancies. This observation supports the thesis that diuretics represent a potential hazard to the fetus by decreasing placental perfusion.

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

Abstract 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 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.

An analysis of potential biases in the loss of indigent infants to follow-up*

Loss to follow-up is a major problem in indigent inner-city populations. We evaluated a large, well-described, inborn indigent population of high-risk infants (HRI) and control infants (CI) to assess possible selection biases in loss to follow-up at one year adjusted age. Serial clinic visits, phone calls, and letters and payment of

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

20.00 for attending at 1 year was used to minimize patient loss. Yet, the 1 year loss rate was high, and among HRI, greater for ventilator-treated infants greater than 1500 g birthweight (71/114; 62%) than for ventilator-treated very-low-birthweight (VLBW; less than 1500 g) infants (39/108; 36%) or non-ventilated VLBW infants (62/145; 43%) (P less than 0.05). Multivariate analyses indicated that those lost to follow-up were at no greater risk of a poor outcome on the basis of prenatal and perinatal medical and socioeconomic findings than were those in the same risk group (HRI or CI) or subgroup of HRI who were examined at 1 year. In a review of hospital records, similar rates of hospitalization and neurologic problems during infancy were identified for HRI examined and HRI lost to follow-up. The identification of such morbidity during infancy may be less complete for HRI lost to follow-up than for those examined. Thus, the high frequency of deficits observed in follow-up evaluation of indigent HRI is unlikely to result from loss of unaffected infants.

Adenylate cyclase from term human placenta and its regulation

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.

Partial characterization of guanylate cyclase activity of the human placenta

The activation of placental AC by either Mg2+ or Mn2+, in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn2+ enhanced maximally the NaF-stimulated Mg2+-dependent AC activity. The apparent Km of Mg2+-dependent AC for ATP was 0.4 mM, with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg2+-dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 microM. In the presence of GMP-P(NH)P (10 microM) the kinetics of the AC dependence on Mg2+ ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (greater than 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by beta-adrenergic agonists. Placental AC activity was inhibited by p-hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg2+-dependent AC was inhibited by 0.5 mM phenylhydrazine (95 per cent). Mg2+-dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 microM. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17 beta, 2-hydroxyoestreone, 2-hydroxyoestradiol-17 beta, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg2+-dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.