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Biomedical subjects

M J Novy

Publications and source records attributed to M J Novy.

At least 73 records · Page 4Linked to original sources
PubMed1985

Relationship of uteroplacental blood flow to the placental clearance of maternal dehydroepiandrosterone through estradiol formation in the pregnant baboon.

The theory that maternal intervillous blood flow is a major determinant of the rate at which the placenta clears androgenic steroid precursors through estrogen formation has never been tested by direct experimentation. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the placental clearance (PC) of dehydroepiandrosterone (D) through estradiol (E2) formation in pregnant baboons near term. A continuous iv infusion of [7-3H]D and [4-14C]E2 was administered to four pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min (t0-t270). Maternal Qda was continuously recorded by electromagnetic flow transducer at the aortic bifurcation and altered with an aortic snare device. A 50% reduction in Qda was imposed at t60 and released at t180. Blood samples were collected at 10-min intervals from t30-t60 (control interval), t120-t180 (occlusion interval), and t240-t270 (release interval). All four animals were later studied after pregnancy with an identical infusion for 90 min, with blood samples obtained at 10-min intervals from t30-t90. Equilibrium concentrations of [3H]D, [3H]E2, and [14C]E2 in plasma were determined and the MCR of D (MCR-D), the transfer constant of conversion of D to E2 (rho DE2), and the PC of D through E2 formation (PCDE2) were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals in pregnant animals and under conditions of existing Qda in the nonpregnant state. Control MCR-D during pregnancy (mean +/- SE, 740 +/- 74 liters/day) exceeded MCR-D after pregnancy (500 +/- 40 liters/day). MCR-D fell significantly during occlusion (P less than 0.05). Both rho DE2 and PCDE2 decreased uniformly when Qda was reduced by 50% and returned toward the control level with release of the aortic constriction. The mean rho DE2 in pregnant animals was 0.068 +/- 0.0073 (+/- SE), 0.039 +/- 0.0020, and 0.059 +/- 0.0063 during control, occlusion, and release intervals, respectively, all exceeding rho DE2 in the nonpregnant state (0.013 +/- 0.0004). Control mean PCDE2 was 46.3 +/- 8.24 (+/- SE) ml/min; it decreased to 18.9 +/- 2.68 with 50% reduction in Qda and was 35.6 +/- 5.43 when Qda was restored to 75% of the control value. PCDE2 was directly proportional to Qda (r2 = 0.98; P less than 0.01; n = 12) and remained a constant fraction (0.13 +/- 0.002) thereof in all four animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Fetal cardiovascular responses to asphyxia induced by decreased uterine perfusion.

Cardio-respiratory responses to asphyxia produced by decreased uterine perfusion were studied in 15 sheep fetuses. In chronic (spinal-anesthetized) and acute (inhalation-anesthetized) preparations, we measured fetal PO2, PCO2, pH, heart rate, arterial and umbilical venous pressures at rest and 5 min after controlled reductions of maternal aortic blood flow. Umbilical blood flow was determined by electromagnetic flow transducer on the fetal descending aorta with the iliac arteries ligated, in conjunction with radionuclide-labelled microspheres. In contrast to previous studies in which fetal hypoxaemia was produced by decreased maternally inspired O2 concentrations, decreasing degrees of uterine perfusion were associated with increasing degrees of hypercapnea and acidemia, as well as hypoxaemia. In chronic experiments, heart rate and umbilical blood flow fell significantly in response to decreased uterine perfusion with all degrees of hypoxaemia studied. In acute experiments, during the control period, PO2 values were similar to those of chronic experiments while values for pH and umbilical blood flow were lower and those for umbilical vascular resistance were higher. In the acute experiments, hypoxic stresses identical to those in the chronic studies failed to produce significant hemodynamic changes, except for bradycardia in response to severe hypoxaemia. These differences were apparently due to the pharmacologic effects of halothane and the operative stresses.

Anesthesia↗
PubMed1984

Circadian hormonal interactions among the mother, fetus, and amniotic fluid.

Circadian rhythms and hormonal interactions among the maternal, fetal, and amniotic fluid compartments were studied in long-term catheterized rhesus macaque monkeys between days 127 and 138 of gestation (term = 167 days). Blood samples were collected at 3-hour intervals for 48 hours and analyzed by radioimmunoassay for estrone, estradiol, cortisol, progesterone, dehydroepiandrosterone sulfate, and prolactin. Distinct circadian rhythms were present for cortisol and progesterone in the maternal circulation and for progesterone and dehydroepiandrosterone sulfate in the fetal circulation (p less than 0.05). Although maternal and fetal estrogen levels were higher in AM samples than in PM samples, a statistically significant circadian rhythm was not present (p greater than 0.10). Fetal levels of progesterone and dehydroepiandrosterone sulfate and maternal levels of progesterone were highest between 9:00 PM and 3:00 AM and lowest between 9:00 AM and 3:00 PM. Maternal levels of cortisol were highest between 6:00 AM and 9:00 AM and lowest between 6:00 PM and 12 midnight. The circadian patterns of maternal cortisol and progesterone were inversely related to each other (r = -0.68; p less than 0.01). Amniotic fluid cortisol levels were highest between 9:00 AM and 12 noon and lowest between 6:00 PM and 3:00 AM (p less than 0.10). With the possible exception of cortisol, amniotic fluid steroid hormones did not demonstrate distinct diurnal fluctuations, nor did they correlate with steroid changes in maternal or fetal blood. Because the rhesus placenta is permeable to glucocorticoids it is likely that transplacental passage of maternal cortisol influences the activity of the fetal pituitary and adrenal so that the circadian rhythm in the fetal axis is 180 degrees out of phase with that of the maternal axis. The circadian rhythms in fetal dehydroepiandrosterone sulfate and progesterone in late gestation parallel the biorhythm in uterine contraction frequency and amplitude, with peaks during periods of darkness between 9:00 PM and 3:00 AM.

Amniotic Fluid↗
PubMed1984

Prostaglandin synthase inhibitory activity in the plasma of rhesus monkeys during late pregnancy: effect of dexamethasone.

Plasma from rhesus monkeys during late pregnancy contained a factor(s) that was inhibitory of prostaglandin synthase activity. There was no consistent trend in the inhibitory activity of plasma obtained between 120 days of gestation and term (approximately 167 days of gestation). Administration of dexamethasone (0.125 to 1.0 mg twice daily) consistently increased inhibitory activity in plasma after an initial treatment period of 5-10 days. Administration of dexamethasone for several weeks is associated with prolongation of gestation in rhesus monkeys. We suggest that the action of dexamethasone, to delay parturition is related, in part, to an enhancement of the activity of a circulating factor(s) that is inhibitory of prostaglandin synthase activity.

Animals↗
PubMed1984

Daily hormonal changes in the maternal, fetal, and amniotic fluid compartments before parturition in a primate species.

The daily hormonal fluctuations that occur simultaneously in the fetus, mother, and amniotic fluid during late gestation and before preterm parturition were studied in long term catheterized rhesus macaques. Blood and amniotic fluid samples were collected twice daily and analyzed by RIA for estrone, estradiol, dehydroepiandrosterone sulfate (DHEAS), progesterone, cortisol, and prostaglandin F2 alpha metabolite (PGFM). Vaginal delivery in monkeys with live fetuses was preceded by rising concentrations of DHEAS in fetal, but not maternal, blood. Parallel increases in fetal plasma estrone, maternal plasma estrone and estradiol, and amniotic fluid estrone preceded the rise in amniotic fluid PGFM (P less than 0.005, by analysis of variance). Cortisol levels remained stable in maternal blood and amniotic fluid, but increased before delivery in fetal blood. Nocturnal progesterone peaks in both fetal and maternal blood increased progressively in magnitude in fetuses before parturition. Rising concentrations of fetal DHEAS, estrone, and progesterone indicated an increase in adrenal activity before parturition in the rhesus fetus. PG production, reflected in amniotic fluid PGFM concentrations, was temporally related to increasing amniotic fluid concentrations of estrone. Although progesterone withdrawal may occur at a local tissue level, parturition occurred without an apparent decrease in circulating maternal, circulating fetal, or amniotic fluid progesterone concentrations.

Amniotic Fluid↗
PubMed1983

Dexamethasone and estradiol treatment in pregnant rhesus macaques: effects on gestational length, maternal plasma hormones, and fetal growth.

To determine the effects of suppressing fetal and maternal adrenal activity on parturition, we treated pregnant rhesus macaques with dexamethasone (0.25 to 4.0 mg, twice a day) from gestation day 130 until delivery (term = 167 days). Long-term dexamethasone treatment increased gestation length: 71% of fetuses were born postmaturely (after day 175 of gestation; X2 = 52.6; P less than 0.001). The dexamethasone decreased basal levels of maternal estradiol and cortisol, but not progesterone, and abolished the prepartum estrogen and prolactin surges; doses greater than 0.16 mg/kg per day resulted in fetal death but not premature delivery. That vaginal delivery was induced by estradiol benzoate in monkeys with prolonged pregnancy and dead fetuses, but not in those with live fetuses, suggests active fetal inhibition of prostaglandin synthesis. The dexamethasone retarded fetal growth (410 +/- 16 gm versus 501 +/- 5 gm for controls; P less than 0.001) and decreased thymus, spleen, and adrenal weights (P less than 0.01). A less significant decrease in brain weight was noted (P less than 0.1), as were decreases in biparietal diameter, occipitofrontal diameter, and head circumference (P less than 0.05). These results indicate that corticosteroids do not induce premature labor in primates. On the contrary, long-term dexamethasone administration is associated with prolonged pregnancy and suppression of estrogen biosynthesis.

Animals↗
PubMed1983

Circadian patterns and dexamethasone-induced changes in uterine activity in pregnant rhesus monkeys.

Five monkeys with amniotic pressure catheters were placed in restraining chairs on days 127 to 131 of gestation (term = 167 days) for examination of circadian patterns in uterine activity. Uterine activity (total area under the contraction curve) was recorded continuously for 3- to 9-day intervals while the animals were exposed to a 16-hour:8-hour light:dark photoperiod. A ratio of hourly contraction area to mean hourly contraction area was established for each individual, and a circadian pattern was observed, with the occurrence of peak uterine activity between 2200 and 0200 hours (analysis of variance, P less than 0.01). An unrestrained animal equipped with a telemetry device and monitored for 23 days demonstrated a similar pattern. Four other catheterized, chair-restrained, pregnant monkeys were used to examine the effects of dexamethasone on uterine activity rhythms. After a 48-hour control period, dexamethasone (0.1 mg/hr) was infused via a maternal venous catheter for 48 hours. Fetal and maternal estrone and estradiol levels and total uterine activity were significantly reduced during dexamethasone infusion (P less than 0.05). In the 48 hours after dexamethasone infusion, mean uterine activity returned to preinfusion levels but the nocturnal peak remained ablated. Therefore, dexamethasone, alters the magnitude, as well as the circadian pattern, of uterine activity in association with reduced estrogen biosynthesis by the fetoplacental unit. Since the effect on uterine activity is biphasic, dexamethasone probably acts by more than one mechanism.

Animals↗
PubMed1983

Current status of the molecular structure and function of the plasma sex steroid-binding protein (SBP).

Purification and characterization of the sex steroid-binding protein (SBP) from human, macaque, baboon, and rabbit sera indicate that the protein is composed of two polypeptide chains which associate noncovalently to yield a native structure having molecular weight distributions of about 88,000 for primate SBPs, and 80,000 for rabbit SBP. The subunit molecular weight distributions are 44,000 for human SBP, 47,000 for macaque and baboon SBP's, and 40,000 for rabbit SBP. Isoelectric focusing show extensive microheterogeneity for all four SBPs. The patterns appear to be unique for each species and reveal the presence of at least twelve bands of different colour intensity reflecting a specific spectrum of active SBP molecules. The existence of the large number of dimeric forms of SBP arises through the combination of many variants of the same two subunits containing different amounts and types of carbohydrate sidechains. Physiological studies on the intravenous infusion of pure rhesus SBP, human SBP, and purified monospecific SBP-antibodies into the rhesus reveal an inverse relationship between SBP and the metabolic clearance rate of testosterone. The effect is complex and depends on the concentration of SBP, albumin, and testosterone which in turn influences the distribution of testosterone between albumin and SBP.

Animals↗
PubMed1982

Transabdominal cervicoisthmic cerclage for the management of repetitive abortion and premature delivery.

The indications for a transabdominal approach for cervicoisthmic cerclage (TCIC) included traumatic laceration, congenital or surgical shortening of the cervix, previously failed transvaginal cerclage, and advanced cervical effacement with intact membranes. The frequency of all cerclage procedures was 1 in 260 deliveries; one TCIC was performed for each six vaginal procedures in the period from 1966 to 1980. A 0.5-cm Mersilene band was applied at the level of the anatomical internal os in an avascular space between branches of the uterine artery. Prior to this operation, the 16 patients had had 55 pregnancies (excluding first-trimester abortions) and had experienced 42 fetal losses (24% salvage rate). After TCIC, 22 pregnancies in 16 patients resulted in 19 term births, two premature births with favorable outcomes, and one fetal loss (95% salvage rate; chi 2 = 46.5, P less than 0.001). All infants were delivered by cesarean section. Postoperative morbidity and the incidence of premature labor or rupture of the membranes were low. Transabdominal cerclage is effective in selected patients with poor obstetric histories that show anatomically defective cervices, or when marked effacement has precluded high vaginal placement of the cerclage.

Abortion, Habitual↗
PubMed1981

Regulation of placental growth and chorionic somatomammotropin in the rhesus monkey: effects of protein deprivation, fetal anencephaly, and placental vessel ligation.

An isocaloric protein-deficient diet (0.5 gm/kg of body weight) was administered throughout pregnancy to 10 rhesus monkeys (Macaca mulatta). Ligation of the fetal interplacental bridging vessels (n = 6) and functional fetal hypophysectomy (experimental induction of anencephaly) (n = 10) were performed at midgestation. Monkey chorionic somatomammotropin (mCS) concentrations were measured serially in maternal plasma and in fetal plasma at birth. Fetal weight, trimmed placental weight, and placental DNA content were determined near term in the experimental groups and in controls matched for gestational age. Maternal mCS concentrations rose steadily until term and this rise paralleled the increase in placental weight (mCS at term = 16.5 +/- 0.90 microgram/ml in maternal plasma and 0.024 +/- 0.001 microgram/ml in fetal plasma). At term, maternal mCS correlated with placental DNA (r = 0.61, P less than 0.01) and placental weight (r = 0.49, P less than 0.01), but not fetal weight. Maternal mCS levels were not affected by protein deprivation, fetal anencephaly, or ligation of the interplacental bridging vessels. Maternal protein deprivation had a negative effect on fetal birth weight (409 +/- 22 versus 472 +/- 18 gm for controls, P less than 0.05) and maternal weight gain during pregnancy but had no effect on placental DNA or trimmed placental weight. Fetal anencephaly resulted in a 23% reduction in trimmed placental weight, no change in placental DNA, a 40% reduction in fetal body weight, and a reduced fetal/placental weight ratio. Ligation of interplacental bridging vessels resulted in atrophy of the secondary placental disc, an increase in weight and DNA content of the primary placenta, and normal fetal weight. We have concluded that the hemochorial placenta of the rhesus monkey responds to interruption of the fetal villous circulation in the first half of gestation by initiating compensatory hyperplasia. Placental cellular replication in the second half of rhesus pregnancy in minimally regulated by the fetal central nervous system or the pituitary gland. Secretion of mCS is primarily controlled by the mass of functioning trophoblast.

Anencephaly↗
PubMed1980

Reversal of Kroener fimbriectomy sterilization.

Sterilization by fimbriectomy has been thought to be irreversible. The present report describes the surgical approach and results in nine patients after microsurgical tubal reconstruction and indicates that repeated pregnancy is possible after fimbriectomy reversal. Preoperative radiographic studies were used to document cornual patency and to evaluate the length, width, and rugal pattern of the ampullary segment. A new ostium was created by transverse salpingostomy and a cuff-eversion technique by means of microsurgical methods. A tubal patency rate of 83% and an intrauterine pregnancy (IUP) rate of 44% was achieved. The mean interval from operation to conception was 6 months. There were no ectopic pregnancies. The ideal candidate for fimbriectomy reversal has tubal remnants 8 cm or longer, an ampullary width of 1 cm or greater, rugal patterns on x-ray film, and minimal peritubal adhesions. Successful reversal was associated with protrusions of the endosalpinx to form a neofimbria. The success of fimbriectomy sterilization probably depends more on complete ampullary occlusion than on absence of the infundibulum with fimbria. The role of the fimbria in ovum pickup is discussed. The IUP rate after microsurgical fimbriectomy reversal compares favorably with the IUP rate after macrosurgical end-to-end anastomosis and exceeds the reversibility rate of laparoscopic electrocoagulation sterilization.

Adult↗
PubMed1980

Pulmonary lamellar bodies in human amniotic fluid: their relationship to fetal age and the lecithin/sphingomyelin ratio.

We investigated the appearance of pulmonary lamellar bodies (LBs) in human amniotic fluid as a function of fetal age. We also studied their relationship to the lecithin/sphingomyelin (L/S) ratio and to the results of the rapid surfactant test (RST). LBs observed in amniotic fluid generally ranged in diameter from 1.5 to 2.0 mu and were seen as single structures or in clusters. When patients were grouped by gestational age, there was a significant difference (P less than 0.001) in the distribution of amniotic fluid LBs. No LBs were observed in amniotic fluid before 26 weeks' gestation, but 50% of specimens at 28 to 32 weeks' gestation and 85% of specimens at term had LBs. Patients with amniotic fluid LBs had higher L/S ratios and intermediate or mature RST values when compared to patients without LBs, but a statistically significant relationship between the presence of LBs and the L/S ratio or RST was not found. We conclude that qualitative examination of amniotic fluid LB content by conventional electron microscopy is unlikely to reflect fetal lung maturation in a precise manner. However, direct quantification of LBs may provide a more specific index of fetal lung maturity and the risk of respiratory distress syndrome.

Amniotic Fluid↗
PubMed1980

Materno-fetal pharmacokinetics and fetal distribution of valproic acid in a pregnant rhesus monkey.

Chronic indwelling catheters in the maternal femoral artery and vein, fetal carotid artery and jugular vein, and amniotic cavity of a pregnant rhesus monkey permitted administration of sodium valproate (NaVPA) and collection of timed samples of maternal and fetal blood and amniotic fluid. After a single IV dose (50 mg/kg) to the mother, a rapid distribution phase (t1/2 alpha = 0.5 minute) was followed by a biphasic decline in concentration in maternal blood (t1/2 beta = 31 minutes, t1/2 gamma = 390 minutes). VPA appeared rapidly in fetal blood, reached a concentration slightly higher than in maternal blood by 15 minutes, and thereafter declined in parallel with the concentration in maternal blood. Terminal fetal/maternal ratios of blood concentration of VPA were about 1.3. Similar patterns of decline were observed after NaVPA was given IV to the fetus. A multicompartment first-order materno-fetal pharmacokinetic model is presented. Tissue distribution studies in the fetus showed that VPA concentration was highest in blood; moderate in heart, liver, spleen, kidney, and skeletal muscle; and low in brain.

Amniotic Fluid↗