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Biomedical subjects

N F Gant

Publications and source records attributed to N F Gant.

At least 73 records · Page 4Linked to original sources

Initiation of human parturition. VI. Identification and quantification of progesterone metabolites produced by the components of human fetal membranes.

The fetal membranes play a central role in the initiation of human parturition, a role that may be subserved in part by quantitative changes in progesterone metabolism. In order to identify and to quantify the metabolites of progesterone produced by the components of the human fetal membranes, amnion and chorion laeve tissues and homogenates were incubated with [3H]progesterone in the presence of added NADPH. The radioactive metabolites, 20alpha-hydroxy-4-pregnen-3-one, 5alpha-pregnane-3,20-dione and 3beta-hydroxy-5alpha-pregnan-20-one, were isolated and identified by derivative formation, a combination of chromatographic techniques, and by crystallization to constant specific activity after addition of authentic standards. A simplified technique of metabolite quantification was developed that involves one thin layer chromatographic procedure and liquid scintillation assay of radioactivity. The accuracy of this method was established by comparison with data obtained using classical techniques. This study demonstrates the presence of human fetal membranes 5alpha-reductase, 20alpha-hydroxysteroid oxidoreductase, and 3beta-hydroxy-steroid oxidoreductase, and a qualitative difference between amnion and chorion laeve.

20-alpha-Dihydroprogesterone↗

The pattern and rates of metabolism of maternal plasma dehydroisoandrosterone sulfate in human pregnancy.

The present study was done to map the metabolic pathways and rates of maternal plasma clearance of dehydroisoandrosterone sulfate (MCRDS) in pregnancy. In the present study, maternal plasma dehydroisoandrosterone sulfate (DS) metabolism was largely accounted for by two major pathways not present or not prominent in the nonpregnant woman. The first major pathway was clearance of maternal plasma DS by placental aromatization of DS to form estradiol (E2). This pathway accounted for approximately 35 per cent of the total clearance. The second major pathway of metabolism of maternal plasma DS was by 16 alpha-hydroxylation within the maternal compartment. This pathway accounted for approximately 32 per cent of maternal plasma DS clearance. Two other minor pathways of DS metabolism, that is, loss to the fetus and excretion as unaltered DS into urine, accounted for less than 1 per cent of total metabolism in each instance. The final pathway of DS metabolism was excretion as neutral steroids such as urinary 17-ketosteroids and other undefined losses. By combining the rate of DS clearance (MCRDS) from maternal plasma via all pathways with that fraction of DS removed uniquely by placental conversion of DS to estradiol (DS leads to E2), the placental clearance of DS leads to E2 (PCDSE2) may be measured. The measurement of PCDSE2 may be expected to reflect uteroplacental perfusion and as such may provide an investigative tool capable of assessing the dynamics of uteroplacental function in a variety of clinical conditions.

17-Ketosteroids↗

The metabolic clearance rate of dehydroisoandrosterone sulfate. IV. Acute effects of induced hypertension, hypotension, and naturesis in normal and hypertensive pregnancies.

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.

Adult↗

Concurrent use of prostaglandin F2alpha and laminaria tents for induction of midtrimester abortion.

One hundred sixteen women between 14 and 20 weeks of gestation were aborted with a combined regimen of intraamniotic prostaglandin F2alpha (PGF2alpha) and intracervical laminaria. Complications among these women were compared to those among 122 patients who aborted after PGF2alpha administration only. Shorter intervals between initiation and completion of abortion were observed in nulliparous women treated with the combined regimen than in nulliparous women treated with PGF2alpha only. In parous patients, the use of laminaria did not shorten the interval from initiation to completion of abortion. A decrease of the hematocrit in excess of 5 points and periabortal infection requiring antibiotic therapy occurred with similar frequency in both treatment groups. However, with the combined regimen no cervical tears were observed in nulliparous patients, and fewer women failed to abort within 48 hours.

Abortion, Induced↗

Metabolic clearance rate of dehydroisoandrosterone sulfate. V. Studies of essential hypertension complicating pregnancy.

The metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) was determined prospectively in gravidas with and without chronic essential hypertension. In normotensive patients, the MCRDS increased in linear fashion throughout pregnancy. In patients with chronic essential hypertension the MCRDS also increased progressively, but at higher values than in normotensive subjects. In normotensive gravidas who ultimately developed pregnancy-induced hypertension, the MCRDS increased progressively at a higher level than in gravidas who remained normotensive until approximately 4 weeks prior to the onset of clinical symptoms, at which time the MCRDS slowly decreased. Similarly, in gravidas with chronic hypertension who developed superimposed pregnancy-induced hypertension, the MCRDS increased progressively at higher levels than all groups studied until approximately 4 weeks prior to onset of hypertension, when a progressive decline in the MCRDS began.

Chronic Disease↗

Metabolic clearance rate of dehydroisoandrosterone sulfate. VI. Studies of eclampsia.

The metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) was measured in 11 women during an eclamptic episode, and the subjects were then followed for at least 5 years. The MCRDS was usually decreased in primigravid women with eclampsia. However, in eclamptic primigravid women who later developed essential hypertension and/or recurrent hypertension in subsequent pregnancies the MCRDS was elevated. Also, in multiparous women with chronic essential hypertension plus superimposed eclampsia, the MCRDS was increased to above normal values.

Adult↗

Metabolic clearance rate of dehydroisoandrosterone sulfate. VII. Effect of lateral versus supine recumbency.

The physiologic events which may occur with the gravid women in the supine position suggest that uteroplacental blood flow may be impaired as a consequence of decreased venous return to the heart and the resulting decrease in cardiac output. Since the metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) previously has been shown to reflect alterations in uteroplacental perfusion, the MCRDS was measured in a variety of different obstetric conditions during lateral and supine recumbency. No significant difference in the MCRDS was induced by this specific positional change, suggesting that uteroplacental perfusion was not altered. Experimental data are discussed which support this observation, and a possible mechanism for maintenance of uteroplacental blood flow under these circumstances is presented.

Dehydroepiandrosterone↗

The clearance rate of maternal plasma prehormones of placental estrogen formation.

A method has been established for the determination of the placental clearance of maternal plasma prehormones by placental estrogen formation during human pregnancy. Utilizing this concept, the placental clearance is calculated as the product of the metabolic clearance rate from maternal plasma of the prehormone and its fractional conversion to estrogen by the placenta. This value equals the volume of maternal plasma cleared of that prehormone by the irreversible formation of its estrogenic product hormone per unit of time. The placental clearance rate technique can be performed by intravenous infusion of isotope-labeled prehormone and product, and the metabolic clearance rate as well as the transfer constant can be measured by techniques employing plasma values or by a combination of plasma and urinary methods. Utilizing this type of study, the placental clearance of plasma prehormones has been observed to be increased initially in women destined to develop pregnancy-induced hypertension but declines prior to the onset of hypertension and continues to decline until delivery is effected. Moreover, the administration of diuretics and/or the institution oental clearance of plasma prehormones from the maternal compartment in normal gravidas, in those destined to develop pregnancy-induced hypertension, and in gravidas who are hypertensive from any cause.

Androstenedione↗

Complications following prostaglandin F2alpha-induced midtrimester abortion.

Prostaglandin F2alpha (PGF2alpha) was injected intraamniotically in 122 patients between 14 and 20 weeks' gestation in the dosage schedule recommended by the drug manufacturer to induce abortion. Significantly more multiparous (47.5%) than primagravida patients (21.5%) aborted within 16 hours, but the mean duration between PGF2alpha injection and abortion was not significantly different. Complications occurred in 52 (42.6%) patients and included: fall in hematocrit of more than 5 percentage points, failure to abort within 48 hours after injection, infection requiring antibiotic therapy, cervical laceration or fistula, and uterine rupture. The atypical dilatation and effacement of the cervix occurring with PGF2alpha-induced contractions may possibly lead to cervical incompetence with later pregnancies. Although the efficacy of PGF2alpha as an abortifacient is confirmed, the large complication rate with the procedure cannot be ignored.

Abortion, Induced↗

Further observations on the nature of pressor responsivity to angiotensin II in human pregnancy.

The pressor dose of infused angiotensin II was determined before and after rapid volume expansion with 800 to 1075 ml of high-hematocrit blood. There was no remarkable change in sensitivity to infused angiotensin demonstrated except in two instances in which transient volume overload developed. The data support the hypothesis that increased angiotensin sensitivity observed in patients with pregnancy-induced hypertension is the consequence of increased vascular responsivity.

Anemia, Sickle Cell↗