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Biomedical subjects

R E Weitzman

Publications and source records attributed to R E Weitzman.

At least 19 recordsLinked to original sources
PubMed1987

Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients.

Elevated plasma vasopressin concentrations have been documented in antipsychotic drug-treated patients as well as a drug-free acutely psychotic patients. To evaluate the effects of antipsychotic drugs on plasma vasopressin, we measured vasopressin response to a single dose of intramuscular chlorpromazine or intravenous haloperidol in normal individuals and to 2 weeks of oral antipsychotics in patients with acute schizophrenia. Neither intramuscular chlorpromazine nor intravenous haloperidol affected plasma vasopressin in normals, except in one subject who developed high plasma vasopressin concentrations coincident with marked hypotension following chlorpromazine. Prior to antipsychotics, two acute schizophrenia patients had elevated plasma vasopressin concentrations, which normalized during antipsychotic drug treatment. We conclude that antipsychotics do not directly stimulate vasopressin release, but may indirectly stimulate vasopressin release by well-described baroreceptor reflex mechanisms if hypotension occurs. Also, acute schizophrenia may be associated with increased plasma vasopressin levels in some patients.

Adult↗
PubMed1984

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↗
PubMed1984

Relationship between plasma arginine vasopressin and renal water handling in decompensated cirrhosis.

Although an impairment in renal water excretion is a commonly encountered clinical problem in cirrhotic patients, the mechanisms responsible for this abnormality are uncertain. ADH levels are elevated in some patients with decompensated cirrhosis, but a causal relationship between these levels and impaired water excretion has not been established. Since in normal man, water immersion to the neck (NI) results in a preferential central hypervolemia (CV), without plasma compositional change, and a resultant suppression of AVP, we designed the present study to determine if the diuretic response of cirrhotic patients to NI is mediated by a decrease in AVP. 17 cirrhotic patients with ascites were studied following 14 h of dehydration on two occasions: during a seated control study (C) and during 4 h of NI. AVP, determined by RIA, was measured every 30 min. 12 of the 17 patients manifested a diuresis that equalled or exceeded that documented in normal hydropenic subjects during immersion. NI did not alter mean AVP as compared with either the pre-study hour or those of the corresponding control study. Furthermore, peak V and CH2O varied independently of prestudy AVP (r = -0.116), mean change in AVP (r = -0.060), as well as nadir AVP levels (r = -0.122). The demonstration of a diuresis in some of the subjects, occurring without concomitant suppression of plasma AVP, suggests that ADH may constitute a permissive rather than pivotal factor in the impaired water excretion of many patients with advanced liver disease.

Adult↗
PubMed1982

Pindolol: effects on blood pressure and plasma renin activity.

The influence of pindolol, other antihypertensive agents, or placebo upon plasma renin activity (PRA) was examined in five separate studies involving 249 subjects (pindolol), n = 149; propranolol, n = 43; methyldopa, n = 13; chlorthalidone, n = 16; placebo, n = 28). In addition, the subjects were stratified in for studies into low (n = 104), medium (n = 96), or high (n = 15) PRA categories according to baseline PRA and sodium excretion measurements. The response to antihypertensive therapy was analyzed in each PRA category. Pindolol and propranolol lowered PRA comparably at equivalent dosages, although this effect was not consistently observed in all studies or at all dosage levels. Methyldopa therapy was not associated with a decline in PRA and chlorthalidone elevated PRA. Pindolol and propranolol lowered both supine and erect diastolic blood pressure (BP) comparably. This effect was similar in subjects categorized as having low or medium PRA. Too few patients were studied with high PRA to derive statistically meaningful data. Pindolol lowered standing systolic BP to a greater extent than did propranolol, especially in the medium PRA category. It was concluded that pindolol, like other beta-adrenergic blockers, lowers PRA, that the effect of pindolol on diastolic BP is independent of the baseline PRA category, and that pindolol is more effective than propranolol in lowering standing systolic BP, at least in the medium PRA category.

Adult↗
PubMed1982

Pathogenesis of dialysis-induced hypoxemia.

Patients undergoing hemodialysis with acetate-containing dialysis solutions develop hypoxemia. To determine the cause of the hypoxemia, we studied and compared the ventilatory, gas-exchange and blood-gas responses in chronic renal failure patients undergoing hemodialysis with acetate and bicarbonate dialysis solutions. Seven stable chronic dialysis patients were dialyzed against acetate and bicarbonate solutions in a random order. Dialysis was carried out using a 1.5 m2 hollow fiber dialyzer at a blood flow rate of 200 ml/min and a dialysate flow rate of 500 ml/min. During acetate dialysis, PaO2 fell within 15 minutes from a mean control predialysis concentration of 84 = 6 (SEM) mmHg to a mean of 70 +/- 7.5 mmHg (P less than 0.05), and remained low throughout the study. PaO2 did not change significantly during bicarbonate dialysis. Total ventilation fell from a predialysis level of 7.2 +/- 0.7 L/min to 5.7 +/- 0.6 L/min within 15 minutes (P less than 0.05). PaCO2 was not significantly changed from predialysis levels with either acetate or bicarbonate dialysis. Measurement of blood concentration of CO2 and bicarbonate across the dialyzer indicated that the total CO2 loss (as CO2 and bicarbonate) through the dialyzer was 3 millimoles per minute or the equivalent of approximately 60 ml of CO2 per minute, i.e., about one third of the patient's metabolic production of CO2.

Acetates↗
PubMed1981

Oxytocin concentrations during the neonatal period.

Plasma oxytocin levels in the umbilical artery (UA) exceeded umbilical venous levels in newborn infants delivered by cesarean section (without maternal labor) (p less than 0.05) and following labor (NS). There was an initial rapid decrease in oxytocin concentration from UA levels to those in peripheral venous blood by 30 min of page. Plasma oxytocin levels for breast-fed and formula-fed infants remained elevated over adult basal levels (1.7 +/- 0.3 mu U/ml) throughout the 4-day study period. Mean oxytocin concentration measured in breast milk from 10 mothers 2-4 days following vaginal delivery was 10.0 +/- mu U/ml. The stimulus for fetal and neonatal oxytocin secretion remains obscure, but continues beyond the period of birth.

Bottle Feeding↗
PubMed1981

Developmental aspects of the renal response to hypoxemia in the lamb fetus.

The effects of fetal hypoxemia on renal hemodynamics and renal function were studied in two groups of chronically catheterized young (< 120 days of gestation) and near-term lamb fetuses (> 130 days). Fetal hypoxemia produced, in both groups, a significantly decrease in renal blood flow (RBF) and a significant increase in the filtration fraction. However, the glomerular filtration rate (GFR) did not change significantly suggesting that the renal vasoconstriction associated with fetal hypoxemia was more important at the efferent than at the afferent arteriolar level. In the group of near-term fetuses, the decrease in RBF correlated closely with changes in plasma renin activity (PRA) (r = 0.77). No changes in PRA were observed during hypoxemia in the group of young fetuses. After hypoxemia, reactive hyperemia associated with a significant increase in urinary prostaglandin excretion (PGE and PGF2 alpha) was observed in near-term fetuses but not in young fetuses. It also was demonstrated that fetal hypoxemia produced a significant increase in fetal plasma concentrations of vasopressin associated with an antidiuresis in all but one near-term fetus and in 50% of the young fetuses, suggesting that the ability of the fetal kidney to reabsorb free water is more developed in near-term fetuses. Finally, fetal hypoxemia had no effect on mean arterial pressure and heart rate in young fetuses; however, in near-term fetuses, a significant increase in blood pressure and a decrease in heart rate were observed. In summary, it appears that the response of the fetal kidney to hypoxemia depends on the degree of fetal maturation.

Animals↗
PubMed1981

Ovine maternal and fetal plasma oxytocin concentrations before and during parturition.

To study the relationships between fetal and maternal oxytocin (OT) levels and the initiation of labor in sheep, paired maternal and fetal plasma OT concentrations (microunits per ml) were measured by RIA. Samples were obtained daily from pregnant ewes and their fetuses for 5 days before spontaneous delivery and frequently during the first and second stages of labor and during the 3 h after delivery. The mean maternal plasma OT concentration during the first stage of labor was not different from that preceding labor. In contrast, the mean maternal plasma OT level during stage 2 of labor was significantly higher than the earlier baseline maternal values or the mean paired fetal concentration. There was no significant increase in the mean fetal plasma OT concentration before delivery. The newborn plasma OT concentration was elevated 15 min after delivery. From these data, we conclude that in the sheep, 1) the onset of labor is not associated with increased maternal plasma OT levels, 2) cervical or vaginal distension may be the stimulus for maternal OT release during stage 2 of labor, 3) an increase in the fetal plasma OT concentration does not occur before the initiation of labor or during the course of labor, and 4) stress in the final moments of labor or in early neonatal life may be responsible for elevated cord and early neonatal plasma OT levels.

Animals↗
PubMed1981

Isoosmotic central blood volume expansion suppresses plasma arginine vasopressin in normal man.

Despite numerous studies which have characterized the regulation of antidiuretic hormone (ADH), the role of volume in governing ADH release remains incompletely defined. Most studies have examined the quantitative effects of hypovolemia on arginine vasopressin (AVP). In contrast, few have assessed the role of hypervolemia on AVP regulation. Furthermore, there are no data to date on the effect of acute isoosmotic volume expansion on plasma AVP in man. The successful characterization of the water immersion model (NI) and the demonstration that it induces an acute central volume expansion without changes in plasma composition commended its utilization in the present study. Twelve normal subjects were studied after 14 h of dehydration on two occasions: control and during 4 h of NI. Blood was obtained every 30 min for AVP. AVP was unaltered during the control period. In contrast, there was a prompt and sustained suppression of AVP throughout NI (P < 0.05 vs. control). There were no concomitant changes in plasma osmolality. Since the changes in AVP occurred consequent to central volume expansion but in the absence of concomitant changes in plasma composition, the current data support the concept that acute isoosmotic central volume expansion in man results in a suppression of plasma AVP.

Adult↗
PubMed1981

Plasma oxytocin concentrations in men, nonpregnant women, and pregnant women before and during spontaneous labor.

Baseline plasma oxytocin (OT) concentrations were measured in 25 healthy men, 102 nonpregnant women, and 59 pregnant women from 15-42 weeks gestation. In addition, plasma OT levels were measured at the onset, peak, and immediately after a single uterine contraction in 6 women in the latent phase and 14 women in the active phases of labor, as well as in 19 women at initial presentation of the fetal head on the perineum (+3 station) and 11 women at the time of delivery of the head during a normal vaginal delivery. Baseline plasma OT concentrations did not vary significantly among men (1.5 +/- 0.2 microunits/ml), nonpregnant women (1.4 +/- 0.2 microunits/ml), or pregnant women before labor (1.3 +/- 0.1 microunits/ml) and did not differ in an additional subgroup of 20 women receiving oral contraceptive medication (1.8 +/- 0.7 microunits/ml). In studies conducted during labor, plasma OT concentrations did not correlate with uterine pressure measurements and did not increase significantly over baseline pregnancy concentrations during the latent (1.3 +/- 0.2 microunits/ml) or active (1.6 +/- 0.2 microunits/ml) phases of labor. There was a significant increase in plasma OT levels from the time of initial visualization of the fetal head to the time of delivery of the head (1.1 +/- 0.1 to 4.2 +/- 1.1 microunits/ml, respectively; P less than 0.05). These data support the view that maternal plasma OT levels remain low during pregnancy until late in the second stage of labor.

Female↗
PubMed1980

Effect of osmolality on arginine vasopressin and renin release after hemorrhage.

The effects of alterations of plasma osmolality on plasma arginine vasopressin (AVP) and renin activity (PRA) following graded hemorrhage were studied in conscious dogs who were either euhydrated, dehydrated, water loaded, or infused with hypertonic saline. Base-line plasma osmolality and AVP were significantly different in the four treatment groups; however, following hemorrhage the increases in log AVP did not significantly differ. An unexpected finding was that water loading resulted in significant elevations in PRA and plasma aldosterone concentrations, whereas plasma osmolality and AVP were reduced. Prior to hemorrhage, PRA was significantly greater in the water-loaded and dehydrated groups than in the euhydrated or saline-infused groups; following hemorrhage the increases in log PRA were not significantly different in all four treatment groups. The data suggest that, although alterations in osmolality influence base-line levels of AVP, they have no effect on relative (logarithmic) rises in AVP following hemorrhage. Similarly, alterations in AVP may influence base-line PRA, but do not influence relative rises in PRA following hemorrhage.

Animals↗
PubMed1980

Effects of furosemide and acute salt loading on vasopressin and renin secretion in the fetal lamb.

Circulating arginine vasopressin (AVP) and plasma renin activity responses to furosemide (2 mg/kg) and acute hypertonic saline (10 mEq/kg) were studied in the fetal lamb from 100 days gestation to term. The baseline to peak plasma AVP response (delta 3.7 +/- 1.2 uU/ml) and area under the response curve (209 +/- 57 uU/ml/65 min) in the fetal lambs > 123 days were greater than in those < 106 days gestation (delta 1.8 +/0 1.1 and (171 +/- 61, respectively), P < 0.02. The plasma renin activity/AVP ratio after furosemide was similar in the two gestational groups. The log plasma AVP responses corrected for rise in plasma osmolality (0.090 +/- .01 uU/ml) 30 min after infusion, and the area under the response curve (253 +/- 49 uU/ml/30 min) was greater (P < 0.02) in the fetal lambs > 120 days than in those under 115 days gestation (.035 +/0 0.01 and 88 +/0 29, respectively), P < 0.02. These results confirm that the fetal lamb responds to an osmotic stimulus with increased plasma AVP levels and documents that this response significantly matures during the last trimester of gestation. The fetal lamb also manifests a hypothalamus-posterior pituitary AVP response to furosemide that is proportional to the maturing renal renin response.

Animals↗
PubMed1980

Metabolic clearance rate and transplacental passage of oxytocin in the pregnant ewe and fetus.

The MCR and placental permeability to oxytocin were determined in chronically catheterized pregnant sheep. Simultaneous maternal and fetal plasma oxytocin (OT) concentrations were measured by RIA before and during continuous infusion of synthetic OT to steady state conditions. Baseline fetal plasma OT concentrations were significantly higher than simultaneously collected maternal concentrations (1.6 +/- 0.13 vs. 1.1 +/- 0.13 muU/ml, respectively; P less than 0.01). Mean fetal OT MCRs were 12.0 +/- 1.35 and 12.1 +/- 1.09 ml/kg . min at OT infusion rates of 64 and 640 muU/kg . min. Mean maternal MCRs were 12.1 +/- 2.64 and 12.4 +/- 1.38 ml/kg . min at OT infusion rates of 80 and 800 muU/kg . min. Uterine contractions were induced by maternal OT infusion of 800 muU/kg . min but not by lower infusion rates; no uterine contractions were induced by fetal OT infusion. OT did not appear to cross the placenta in either direction under the present study conditions.

Animals↗
PubMed1980

The effect of nursing on neurohypophyseal hormone and prolactin secretion in human subjects.

The effect of nursing on plasma levels of oxytocin (OT), arginine vasopressin (AVP), and PRL was studied in six normal women 2-3 days post partum. Maternal blood samples were obtained for measurement of OT, AVP, PRL, sodium, and osmolality 3 and 0 min before suckling, at 3-min intervals for 15 min during suckling, and 5 min after completion of suckling. Plasma OT rose during suckling from a mean (+/- SEM) baseline value of 1.1 +/- 0.2 to 3.6 +/- 0.6 microU/ml by 3 min (P < 0.001), reached a peak level of 6.4 +/- 1.5 microU/ml by 6 min (P < 0.005), and remained elevated for the entire 15-min period of suckling. Serial measurements of plasma OT during suckling failed to show a pattern consistent with episodic secretion. The baseline plasma AVP concentration was 0.4 +/- 0.1 microU/ml and was not significantly altered by suckling. Plasma sodium and osmolality remained unchanged during the suckling period. The baseline serum PRL level was 268 +/- 24 ng/ml and rose to 362 +/- 31 ng/ml after 15 min of suckling (P < 0.05). The data suggest that suckling is a specific stimulus for OT and PRL secretion but has no effect on AVP release.

Arginine Vasopressin↗
PubMed1980

The clinical physiology of water metabolism. Part III: The water depletion (hyperosmolar) and water excess (hyposmolar) syndromes.

Hyperosmolality occurs when there are defects in the two major homeostatic mechanisms required for water balance-thirst and arginine vasopressin (AVP) release. In this situation hypotonic fluids are lost in substantial quantities causing depletion of both intracellular and extracellular fluid compartments. Patients with essential hypernatremia have defective osmotically stimulated AVP release and thirst but may have intact mechanisms for AVP release following hypovolemia. Hyperosmolality can also be seen in circumstances in which impermeable solutes are present in excessive quantities in extracellular fluid. Under these conditions there is cellular dehydration and the serum sodium may actually be reduced by water drawn out of cells along an osmotic gradient. Hyposmolality and hyponatremia may be seen in a variety of clinical conditions. Salt depletion, states in which edema occurs and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may all produce severe dilution of body fluids resulting in serious neurologic disturbances. The differential diagnosis of these states is greatly facilitated by careful clinical assessment of extracellular fluid volume and by determination of urine sodium concentration. Treatment of the hyposmolar syndromes is contingent on the pathophysiology of the underlying disorder; hyponatremia due to salt depletion is treated with infusions of isotonic saline whereas mild hyponatremia in cirrhosis and ascites is best treated with water restriction. Severe symptomatic hyponatremia due to SIADH is treated with hypertonic saline therapy, sometimes in association with intravenous administration of furosemide. Less severe, chronic cases may be treated with dichlormethyltetracycline which blocks the action of AVP on the collecting duct.

Adenocarcinoma↗
PubMed1980

Pharmacokinetics of oxytocin in the human subject.

Oxytocin (OT) metabolic clearance rates (MCR) were measured during the constant infusion of 4 mU/min synthetic oxytocin (Pitocin) in 22 healthy adult subjects: 6 men, 6 nonpregnant women, and 10 pregnant women. Pregnant subjects were at term and undergoing OT induction of labor. Mean (+/- SEM) baseline plasma OT concentrations were similar for men, pregnant women, and nonpregnant women. OT MCR was 27 +/- 1.8 ml/kg/min in men; 20.6 +/- 2.8 ml/kf/min in nonpregnant women; and 23.1 +/- 2.6 ml/kg/min in pregnant women. These values were statistically similar. The OT MCR corrected to prepregnancy weight was 25.4 +/- 2.0 ml/kg/min. This value is also statistically similar to the values in men and nonpregnant women. OT degradation was studied in vitro in pooled plasma of men, nonpregnant women, pregnant women, and cord blood. No significant degradation was observed in men, nonpregnant women, or cord plasma. There was an 85% per hour decrease in OT concentration in plasma of pregnant women, confirming earlier reports. These results suggest that the cystine amino peptidase enzyme mediating OT degradation in pregnancy plasma is preferentially secreted by trophoblast cells into maternal plasma and does not seem to cross the placental barrier.

Cystinyl Aminopeptidase↗