Failure of Lasix to induce a fetal diuresis.
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Diuresis↗
Biomedical subjects
R D Leake
Publications and source records attributed to R D Leake.
Retinal hemorrhage in retinopathy of prematurity associated with tocopherol treatment.
Two hundred eighty-seven infants were enrolled in a double masked, randomized, placebo controlled trial of early parenteral tocopherol given from day one. Among the 232 survivors with ophthalmologic follow-up, retinal hemorrhages occurred more frequently in the tocopherol group (16/111; 14.4%) than in the placebo group (8/121; 6.6%). The development of retinal hemorrhages correlated strongly with plasma tocopherol levels from three weeks to three months (P less than 0.05). Future studies of tocopherol should be aware of potential bleeding diatheses, and study this prospectively.
Cerebral Hemorrhage↗
Water excretion in preeclampsia: behavior as nephrotic syndrome.
Decreased free water excretion and the development of interstitial edema are recognized characteristics of preeclampsia. However, the pathophysiology of decreased urine excretion in preeclampsia is presently controversial: diminished glomerular filtration, renal arteriolar spasm, elevated plasma vasopressin levels, and plasma volume contraction have been suggested as etiologies. We studied seven pregnant patients with a diagnosis of mild preeclampsia to assess the role of vasopressin, serum protein, and glomerular function in the renal excretion of water. The ability to excrete a water load was significantly and directly correlated with serum albumin (P less than 0.05) and protein (P less than 0.02) concentrations. Neither plasma vasopressin nor creatinine clearance correlated with water excretion. The similarity of preeclampsia and the nephrotic syndrome with regard to the renal excretion of water is discussed.
Anuria↗
Amniotic fluid ionic concentration in response to chronic fetal vasopressin infusion.
Chronically prepared, third trimester fetal lambs were administered 72-h intravenous infusions of arginine vasopressin (AVP) (65 or 130 mU/kg h) or 0.9% saline. Saline infusion preceding the AVP infusion did not change amniotic fluid (AF) composition. During the AVP infusion, there were significant increases in amniotic fluid osmolality (278.8 +/- 4.9 to 302.1 +/- 4.5 mosm) and in sodium (122.7 +/- 3.3 to 135.3 +/- 3.6 meq/l) and potassium (9.7 +/- 2.6 to 13.8 +/- 1.3 meq/l) concentrations. Saline infusion after the AVP infusion resulted in return of AF osmolality, sodium, and potassium toward normal levels. Fetal plasma and amniotic fluid AVP levels measured by radioimmunoassay significantly increased during AVP infusion and decreased during the subsequent saline infusion. There were no changes in maternal or fetal plasma osmolality in response to AVP. These results suggest that fetal AVP released in response to intrauterine stress may alter the composition and osmolality of amniotic fluid in a reversible manner.
Amniotic Fluid↗
Oxytocin release induced by melatonin in the ewe.
The pineal gland indolamine melatonin now appears to be a primary mediator of the timing of estrus in mammals. Because the neurohypophyseal nonapeptides arginine vasotocin and oxytocin have recently been identified in the pineal glands of several species, we sought to assess the possibility of an interaction between melatonin and the neurohypophyseal hormones. An acute melatonin infusion (216 mumol) was administered to pregnant and nonpregnant ewes. Although plasma arginine vasopressin and arginine vasotocin levels did not change, melatonin produced a significant increase in plasma oxytocin in the nonpregnant though not the pregnant ewe. These data suggest a possible interaction between melatonin and oxytocin in the integration of mammalian reproduction cycles.
Animals↗
Arginine vasotocin in ovine fetal blood, urine, and amniotic fluid.
Arginine vasotocin ([8-arginine]-oxytocin) (AVT), the primary antidiuretic principle in submammalian vertebrates, has been reported to be present in mammalian pituitary and pineal glands. Although the most phyletically ubiquitous of the known neurohypophysial peptides, AVT is still not recognized as a mammalian hormone. We examined plasma, urine, and amniotic fluid from fetal lambs by radioimmunoassay (RIA) for evidence of AVT to assess the possibility of its being such a hormone. Measureable quantities of AVT-like immunoreactivity (irAVT) were observed in fetal plasma (2.4 +/- 0.2 pg/ml), urine (1.4 +/- 0.2 pg/ml), and amniotic fluid (1.9 +/- 0.2 pg/ml). Since the AVT antiserum shows minimal cross-reactivity with arginine vasopressin (AVP) and oxytocin (OT), measurements of AVP and OT concentrations in the same biological fluids also were conducted with specific antisera. The results suggest that the irAVT was not accountable on the basis of cross-reaction. To further verify the identity of the irAVT, a high pressure liquid chromatography system using RIA as a means of detection was developed. This system is sufficiently sensitive to allow the separation and quantitation of picogram quantities of the synthetic peptides AVT, AVP, and OT. In this system, the irAVT in fetal plasma, urine, and amniotic fluid appeared as a single peak coeluting with synthetic AVT. These results indicate that AVT is present in ovine fetal plasma and support the view that the fetus secretes this peptide. The physiological significance of circulating AVT remains to be defined.
Amniotic Fluid↗
Ovine fetal-maternal water transfer is independent of fetal prolactin levels.
To examine the effect of prolactin (PRL) on transplacental water flow, we infused mannitol (500 ml; 20% solution) over 10 min into five chronically catheterized ewes (121-134 days' gestation), producing a peak maternal plasma osmolality by 10 min and fetal osmolality by 20 min. One day before or after, an identical amount of mannitol was infused into the same ewe during the 2nd h of a 2-h infusion of PRL (40 +/- 2.2 micrograms/h) into a fetal leg vein. Mean (+/- SE) fetal plasma PRL levels were 6.9 +/- 3.2 ng/ml at baseline. Steady state fetal PRL levels were 17.7 +/- 7.4 ng/ml during PRL infusion. Maternal mannitol infused without administration of PRL to the fetus evoked a rise in fetal plasma osmolality similar to that following maternal mannitol during PRL administration to the fetus. Thus, as shown previously, PRL affects water permeability across the membranous chorioamnion, whereas results of the present study indicate that the hormone does not affect water transfer across the ovine chorionic villi (placenta).
Animals↗
A novel oxytocin-like and vasotocin-like peptide in human plasma after administration of estrogen.
Using three antisera to oxytocin (OT Pitt Ab-1, OT Pitt Ab-2, and TOR OT Ab), we found comparable levels of OT in response to infant suckling and during infusion of synthetic OT, and identical standard curves with biological and synthetic standards of OT. Pitt Ab-1, but not Pitt Ab-2 or TOR OT Ab, measured increased OT in response to estrogen. Using an arginine vasotocin RIA (TOR AVT Ab), we found an increase in AVT immunoreactivity after estrogen treatment. Mean basal OT levels measured with OT Pitt Ab-2 in plasma of men [0.75 +/- 0.06 (+/- SEM) microU/ml] and women (0.8 +/- 0.09 microU/ml) were lower than OT measured with Pitt Ab-1 (1.7 +/- 0.09 microU/ml in men and 1.7 +/- 0.07 microU/al in women; P less than 0.001). Mean OT measured with Pitt Ab-2 in the plasma of women given estrogen chronically (0.8 +/- 0.04 microU/ml) and acutely (0.6 +/- 0.15 microU/ml) were not significantly different from basal levels. OT levels measured with Pitt Ab-1 in the same samples were 4.6 +/- 0.5 and 4.3 +/- 0.5 microU/ml, respectively, both significantly increased from basal levels (P less than 0.001) and significantly higher than OT measured with Pitt Ab-2 (P less than 0.001). Mean OT measured with Pitt Ab-1 in the plasma of pregnant women was 8.6 +/- 1.02 microU/ml, significantly higher than OT measured with Pitt Ab-2 (1.0 +/- 0.3 microU/ml; P less than 0.001). Men given 25 mg diethylstilbestrol had significant increases in OT measured with Pitt Ab-1 and in AVT measured with TOR AVT (P less than 0.01), but not in OT measured with Pitt Ab-2. Plasma from a man given diethylstilbestrol was prepared for high performance liquid chromatography and applied to a C18 muBondapak reverse phase column. The plasma contained two peaks of immunoreactivity detected as OT with Pitt Ab-1 and as AVT using TOR AVT Ab. The material was not detected by Pitt Ab-2 or TOR OT Ab and did not coelute with standards of OT, AVT, or AVP. Pregnancy plasma, thioglycolic acid, chymotrypsin, and trypsin reduced Pitt Ab-1, Pitt Ab-2, and TOR OT immunoreactivity of synthetic OT. The percent recovery of OT immunoreactivity was not significantly different with Pitt Ab-1 vs. Pitt Ab-2. A novel peptide, which is increased in response to administered estrogen, is present in human plasma and is detected by some antisera to OT and AVT. The observation explains the wide variability in OT levels in the estrogen-primed state and provides a new mechanism to study estrogen-related physiology and pathophysiology.
Adult↗
High pressure liquid chromatographic separation of an oxytocin/arginine vasotocin-like peptide from the plasma of patients with chronic renal failure.
Levels of a novel oxytocin (OT)- and arginine vasotocin (AVT)-like peptide detected by one antiserum to OT (Pitt Ab-1) and one antiserum to AVT (Tor AVT) were recently found to rise in human plasma in response to administration of estrogen. The novel peptide rose in parallel with the estrogen-stimulated neurophysin (ESN). The mean level (+/- SEM) of ESN in plasma of 11 individuals with altered renal function (nondialyzed) was significantly higher than the level in individuals with normal renal function (4.2 +/- 0.9 vs. 1.1 +/- 0.04 ng/ml; P less than 0.01). In patients treated with hemo- or peritoneal dialysis, mean (+/- SEM) levels of ESN were 18.1 +/- 3.2 and 16.8 +/- 3.7 ng/ml, respectively. Levels of estradiol and estrone were not elevated and did not correlate with high levels of ESN. Levels of OT Pitt Ab-1, AVT, and ESN immunoreactivity were measured in plasma form nine patients undergoing hemodialysis and eight patients undergoing peritoneal dialysis. Mean (+/- SEM) levels of all three peptides were elevated (12.9 +/- 1.5 microU/ml, 32.1 +/- 6.7 pg/ml, and 13.5 +/- 4.0 ng/ml, respectively). ESN was significantly correlated with OT Pitt Ab-1 and AVT (R2 = 0.80; P less than 0.001). Plasma samples from the same patients were pooled, treated, and separated by reverse phase HPLC. The plasma contained a peak of immunoreactivity detected by Pitt Ab-1 and Tor AVT Ab. The position of the material was distinct from that of synthetic OT, AVT, or AVP and corresponded to the position of the novel OT-like peptide found in plasma of individuals given estrogen. The findings support parallel secretion of the OT-like peptide with ESN and represent the first disease state characterized by high levels of this OT- and AVT-like peptide.
Adult↗
Fetal lung liquid regulation by neuropeptides.
The fetal lung, filled with fluid during intrauterine life, is recognized as a site of fluid production, significantly contributing to amniotic fluid volume. To assess possible hormonal control of lung liquid production, we studied the effect of intravenous vasopressin or vasotocin on lung liquid production in chronically catheterized fetal sheep. Both vasopressin and vasotocin infusion resulted in a significant decrease in lung fluid production (38% and 40%, respectively) when compared to that in control animals receiving saline infusion. There was no significant change in lung fluid osmolality, sodium, or potassium. These findings suggest that lung liquid production in utero may be regulated by the fetus and that vasopressin or vasotocin may be of physiologic importance in lung fluid dynamics during the third trimester of ovine pregnancy and perhaps during parturition.
Animals↗
The oxytocin secretory response to breast stimulation in women during the menstrual cycle.
Plasma oxytocin concentrations were measured during 12 minutes of mechanical pump stimulation in nine healthy women during the follicular and luteal phases of the menstrual cycle. In the follicular phase (and in five healthy male subjects), plasma oxytocin values did not increase above baseline levels with breast pump stimulation. In contrast, pump stimulation evoked a significant increase in plasma oxytocin levels during the luteal phase of the menstrual cycle. These observations suggest that oxytocin secretion is modulated by hormones involved in the menstrual cycle in women.
Adult↗
Oxytocin secretory response to breast stimulation in pregnant women.
Plasma oxytocin levels were measured serially in 10 pregnant women prior to labor and 16 women during labor in response to 12 minutes of Egnell breast pump stimulation. There was no increase in plasma oxytocin concentrations during either the second or third trimesters in 24 of the 26 subjects studied. Five minutes of manual autostimulation of the breast in 10 additional women at term also had no effect on plasma oxytocin levels.
Breast↗
Perinatal bacterial infection after prolonged rupture of amniotic membranes: an analysis of risk and management.
Chi-square and logistic stepwise multiple regression analysis of perinatal determinants of infant bacterial infection following prolonged rupture of amniotic membranes for 24 hours or more prior to delivery was applied in 33 infected infants and 66 matched control infants from the NINCDS Collaborative Project. In order of statistical significance, the most important variables were placental inflammation (P = 0.002), gestational age less than 34 weeks (P = 0.008), gestational age 34 to 37 weeks (P = 0.013), male sex (P = 0.015), Apgar score less than 6 at 5 minutes (P = 0.023), and clinical amnionitis (maternal fever, fetal tachycardia, or amniotic or gastric fluid leukocytes or bacteria) (P = 0.044). Duration of labor during PROM, race, and maternal age and parity were insignificant. Using these predictive variables, identification of infected infants for either microbial surveillance (superficial and systemic cultures) or microbial surveillance and anticipatory antibiotic therapy (discontinued after 3 days of negative cultures) was highly significant (P = 0.0001). Incorporating these variables and derived coefficients from multivariate analysis, a mathematical model was used for evaluation and prediction of perinatal bacterial infection with a sensitivity of 82% and specificity of 70%. Analysis of 46 infants prior to and 310 infants after implementation of this process at Harbor-UCLA Medical Center indicated significant improvement in the appropriate management of these infants at risk (from 59% to 87% of the population, P less than 0.05). Inappropriate antibiotic therapy decreased from 35% to 10% (P less than 0.05). In the absence of a shift in the median days of hospitalization of non-PROM infants, determination of the grand median days of PROM infant hospital stay showed a decrease (P less than 0.01) after initiation of this evaluation and management scheme.
Amnion↗
Radioimmunoassay of vasotocin, vasopressin, and oxytocin in human neonatal cerebrospinal and amniotic fluid.
Arginine vasotocin (AVT) has been measured in neonatal cerebrospinal fluid (CSF) and human amniotic fluid using a newly developed specific radioimmunoassay system. There were significant amounts of AVT in all samples. Vasopressin and oxytocin also were measured in the samples and could not account for the levels of vasotocin found. The source and function of these neurohypophyseal peptides in CSF and amniotic fluid remains speculative.
Adult↗
Arginine vasopressin metabolic clearance and production rates in fetal sheep, pregnant ewes, and lambs.
Arginine vasopressin (AVP) metabolic clearance rates (MCR) and production rates (PR) were measured in chronically catheterized fetuses, maternal ewes (130-135 days of gestation), and 1- to 6-month-old sheep using constant infusion noncompartmental kinetic methodology. No significant differences in mean basal plasma AVP levels, MCR rates or PR were found among the fetuses, maternal ewes or lambs. MCR of AVP did not change with steady-state plasma AVP levels varying from 2 to 68 micronmicron/ml. Neither the placenta nor the fetal kidney appear to play a significant role in AVP metabolic clearance.
Animals↗
Permeability of the sheep placenta to 125I-arginine vasopressin.
We studied the permeability of the ovine placenta to AVP. 125I-AVP (9.3 +/- 1.9 mU) with approximately 82 (+/- 17.3) X 10(6) counts per 5 min were infused intravenously in 6 pregnant ewes. Six blood samples were collected at 10-min intervals over a 1-hour period from chronically catheterized maternal and fetal sheep. 125I-AVP in maternal and fetal plasma samples (1 ml each) were counted in a gammacounter for 5 min. Maternal counts decreased from 9,300 to 2,500 counts per 5 min over the hour following infusion but no increase in radioactivity could be measured in fetal blood, indicating that the sheep placenta is impermeable to 125I-AVP.
Animals↗
The effect of hypoxia on neurohypophyseal hormone release in fetal and maternal sheep.
The effect of hypoxemia on arginine vasopressin (AVP) and oxytocin (OT) release was investigated in the chronically catheterized fetus and ewe. During 30 min of 10% maternal oxygen delivery, mean (+/- SEM) arterial PO2 decreased from 105 +/- 10.6 to 48 +/- 3.5 mm Hg in the ewe and from 21 +/- 1.3 to 12 +/- 0.8 mm Hg in the fetus (each P less than 0.001). Arterial PCO2 decreased from 35 +/- 4.4 to 29 +/- 1.0 mm Hg in the ewe, whereas fetal PCO2 decreased from 43 +/- 2.3 to 35 +/- 3.5 mm Hg (P less than 0.05). Blood pH increased from 7.44 +/- 0.03 to 7.56 +/- 0.04 in the ewe (P less than 0.01) and from 7.36 +/- 0.004 to 7.40 +/- 0.006 in the fetuses (P less than 0.01). Baseline mean AVP levels were identical in ewes and fetuses (0.7 +/- 0.1 microU/ml). After 30 min of hypoxia, plasma AVP levels remained unchanged in the ewes (0.9 +/- 0.1), but increased dramatically in the fetuses (47 +/- 21 microU/ml) (P less than 0.001). There was a highly significant correlation between the duration of hypoxia and log fetal AVP concentrations (r = 0.85). The log fetal plasma AVP also was inversely correlated to the log fetal PO2 values (r = 0.83). Mean baseline fetal and maternal plasma OT levels were 2.6 +/- 0.5 microU/ml and 2.2 +/- 0.5 microU/ml, respectively. After 30 min of hypoxia fetal and maternal OT values were 2.9 +/- 0.8 microU/ml (not significant).
Animals↗
Cortisol facilitates ovine fetal/maternal water transfer.
After the infusion of 500 ml 20% mannitol to 12 pregnant ewes, we studied fetal plasma osmolality responses in chronically catheterized fetal lambs at 129-140 days' gestation. To compare the effects of arginine vasotocin (AVT) alone and AVT plus cortisol on fetal/maternal water transfer, the mannitol infusion was repeated during a 2-h fetal infusion of AVT alone (7 microU/kg/min) and during infusion of AVT with cortisol (50 micrograms/h) (eight and six animals, respectively). The fetal osmolar response to maternal mannitol administration was compared to the response following the baseline mannitol study in the same sheep. In four of the ewes, an identical (sham) study was performed substituting 500 ml normal saline for the mannitol infusion to the ewe. Fetal AVT infusion significantly obtunded the fetal osmolality increment induced by maternal mannitol alone [P less than 0.001, analysis of variance (ANOVA)]. Fetal AVT administered concurrently with cortisol produced an increment in fetal plasma osmolality in response to maternal mannitol that was significantly enhanced compared with that during fetal AVT infusion alone (P less than 0.001, ANOVA). The response to AVT with cortisol was similar to that following mannitol alone. Normal saline (sham protocol) produced no change in maternal or fetal osmolality. These results indicate that fetal AVT inhibits fetal to maternal water transfer following an osmotic stimulus to the ewe, while cortisol (infused with AVT) tends to counteract the inhibitory effect of AVT on fetal/maternal water transfer.
Analysis of Variance↗