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Biomedical subjects

R D Leake

Publications and source records attributed to R D Leake.

At least 73 records · Page 4Linked to original sources

DDAVP (1-desamino-8-D-arginine vasopressin) clearance rate.

Utilizing a highly sensitive radioimmunoassay (RIA) for 1-desamino-8-D-arginine vasopressin (DDAVP) and a constant infusion kinetic protocol we measured DDAVP clearance rates (CR) in 6 non-pregnant ewes. Despite mean (and SEM) plasma DDAVP levels as high as 5349 (+/- 151) pg/ml, no changes in blood pressure or heart rate were observed. The CR of DDAVP was 3.6 (+/- 0.2) ml/kg X min. This CR is only 23% of the mean arginine vasopressin (AVP) CR measured in similar animals in an earlier study. The relatively decreased CR of DDAVP appears to account largely for the approximately 5-fold prolongation of antidiuresis of this synthetic derivative relative to AVP.

Animals↗

Immunologic response to early and routine DTP immunization in infants.

The effect of early immunization, prior to discharge from the newborn nursery, on subsequent immunity as determined by enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig) M and IgG antibody titers to filamentous hemagglutinin and lymphocytosis-promoting toxin (LPT) of Bordetella pertussis and by standard pertussis agglutinin titers was investigated. Eighteen infants received routine diphtheria-tetanus-pertussis (DTP) immunization at 2, 4, and 6 months of age; 17 other infants received routine immunization and an additional DTP immunization in the newborn nursery. Antibody was determined on samples of cord blood and whole blood obtained at 4, 6, and 9 months of age. IgM anti-filamentus hemagglutinin was significantly higher at 4 and 6 months of age in the group that received early immunization (P less than .05). There was no significant difference in IgM anti-LPT, IgG anti-filamentus hemagglutinin, IgG anti-LPT, or pertussis agglutinin antibodies. Six control infants had high cord IgG anti-LPT titers. These six infants had significantly lower antibody titers to LPT at 6 and 9 months of age when compared with control with control infants with lower cord titers. Thirteen infants in the early immunization group with lower cord IgG anti-LPT titers achieved significantly lower titers at 9 months of age than the 12 comparable infants in the control group.

Bacterial Toxins↗

Bulk flow of amniotic fluid water in response to maternal osmotic challenge.

Amniotic fluid volume is regulated by a complex system of fluid exchanges with fetal and maternal fluid compartments. To assess possible hormonal control of amniotic fluid water exchange with the maternal vascular compartment, we studied the effect of intra-amniotic injections of prolactin, vasopressin, or vasotocin on the amniotic to maternal water flux induced by the acute intravenous infusion of mannitol to the pregnant ewe. This mannitol stimulus increased amniotic fluid osmolality secondary to a shift of free water to the maternal vascular/extracellular compartments. Prior intra-amniotic injection of prolactin but not vasopressin or vasotocin blunted the amniotic fluid osmolar response to maternal mannitol infusion. These results suggest that resorption of amniotic fluid water may occur at the chorioamnion and that amniotic fluid prolactin may have a regulatory function in amniotic fluid volume and osmolar homeostasis.

Amniotic Fluid↗

Serological response to filamentous hemagglutinin and lymphocytosis-promoting toxin of Bordetella pertussis.

Serum antibody responses to the filamentous hemagglutinin and the lymphocytosis-promoting toxin of Bordetella pertussis after vaccination with diphtheria and tetanus toxoids and pertussis vaccine, adsorbed, were assayed by using the enzyme-linked immunosorbent assay. The effect of early immunization, during the first week of life, on the antibody response also was determined. After vaccination, immunoglobulin G (IgG) and IgM directed against both the filamentous hemagglutinin and the lymphocytosis-promoting toxin were detected. Generally, antibody titers increased with subsequent injections and the age of the children. Maternal antibodies against filamentous hemagglutinin and lymphocytosis-promoting toxin were detected in cord blood. The ability of an infant to produce serum IgG anti-lymphocytosis-promoting toxin after vaccination with pertussis vaccine was inversely related to the cord blood serum IgG anti-lymphocytosis-promoting toxin titer at birth. A good antibody response was observed in infants with low cord blood titers, and a poor antibody response was seen in infants with high cord blood values. The IgM anti-lymphocytosis-promoting toxin response was good in groups with both low and high cord blood titer, with no significant difference observed between the two groups. No IgA anti-lymphocytosis-promoting toxin or IgA anti-filamentous hemagglutinin titers were observed in vaccines. IgA antibodies were observed in convalescent sera from two adults and may be presumptive evidence of infection with B. pertussis.

Antibodies, Bacterial↗

Does DDAVP (1-desamino-8-D-arginine-vasopressin) cross the blood-CSF barrier?

Plasma and CSF 1-desamino-8-D-arginine-vasopressin (DDAVP) levels were measured by radioimmunoassay following the infusion at constant rates of various amounts of DDAVP (12.5-20 ng/kg/min) into the jugular veins of 4 adult sheep prepared with chronic, indwelling cisterna magnum catheters, as well as jugular vein and carotid artery catheters. The mean steady-state CSF DDAVP concentration did not vary significantly from zero. Thus, DDAVP does not cross the blood-CSF barrier when administered intravenously.

Animals↗

Lymphocyte-derived chemotactic factor production by neonatal lymphocytes.

We examined neonatal lymphocyte production of the lymphokine, lymphocyte-derived chemotactic factor (LDCF). Supernatants from 1 neonatal lymphocyte cultures were paired with the supernatants from 10 adult lymphocyte cultures. Chemotactic activity was defined as the number of adult monocytes migrating toward phytohemagglutinin-stimulated supernatants minus the number of monocytes migrating toward nonstimulated control supernatants using a blind well chamber assay. Eight of the 10 neonatal lymphocyte cultures showed LDCF and five of the 10 adult lymphocyte cultures showed LDCF activity. The mean number of monocytes migrating toward neonatal supernatants was 13.0 +/- 1.5 and toward adult supernatants was 14.1 +/- 2.1. To determine if a quantitative difference in LDCF production did exist, six additional experiments were performed assaying multiple dilutions of supernatants. No evidence was found for a quantitative difference in neonatal LDCF production compared to adult production. Our studies show that neonatal mononuclear cells are functionally as competent as adult mononuclear cells to produce LDCF in response to a mitogen challenge.

Adult↗

Radioimmunoassay of arginine vasopressin in urine: development and application.

A sensitive and specific RIA system for measurement of urinary arginine vasopressin (AVP) was developed. RIA sensitivity was 0.4 microU/l (approximately 0.8 pg/ml). Urine samples were extracted using columns of octadecasilyl-silica. The mean (+/- SEM) recovery of P after extraction (77.7 +/- 1.4%) was independent of urinary osmolality. The extracted immunologically active material migrated similarly to synthetic AVP on high pressure liquid chromatography. AVP immunoreactivity was found to be stable in urine stored for 24 h at room temperature and stable for 3 months when acidified promptly and stored at -20 C. Using the RIA system, we measured urinary AVP excretion as a percentage of total body AVP clearance. For this study, AVP (3.7 microU/min . kg) was infused in into four healthy nonsmoking adults in whom endogenous AVP was suppressed by oral water loading. The mean urinary AVP excretion rate was 14.7 +/- 2.1%. There was a highly significant positive correlation between log urinary AVP concentration and urinary osmolality (r = 0.97).

Arginine Vasopressin↗

Neonatal metabolic effects of oral ritodrine hydrochloride administration.

Neonatal hypoglycemia and hyperinsulinemia have been reported following maternal ritodrine administration, but no prospective controlled study of the neonatal metabolic and cardiovascular effects of maternal ritodrine is available. We conducted a double-blind prospective study in 35 patients with preterm labor and/or ruptured membranes. Patients in premature labor received ritodrine (max dose, 350 mcg/min) or a placebo intravenously for 12 hours, and then orally (20 mg every 4 hours) until labor ensued. Patients with ruptured membranes received only oral therapy. Only patients who were maintained on oral therapy for a minimum of 12 hours and who were within 6 hours of their last dose of oral therapy were included in the analysis. Glucose and insulin values in cord blood at 6 and 12 hours of age were not significantly different between the ritodrine and placebo groups. There were no hypoglycemic infants in the ritodrine group. Mean systolic and diastolic blood pressure, heart rate and blood volume were similar for ritodrine and control infants. Although premature infants are at high risk for hypoglycemia it appears from this study that chronic oral ritodrine therapy does not significantly affect neonatal glucose homeostasis.

Adult↗

Oxytocin and prolactin responses in long-term breast-feeding.

Plasma levels of oxytocin and prolactin were measured before and during 12 minutes of breast pump stimulation in five healthy, lactating, amenorrheic women on three occasions: ten to 90 days post partum, 90 to 180 days post partum, and 180 days to one year post partum. Baseline mean (+/- SEM) plasma oxytocin levels were similar in the three study periods. Mean stimulated plasma oxytocin levels increased in the three study periods (each P less than .001; mean baseline versus stimulated). Stimulated plasma oxytocin values were significantly greater at ten to 90 than at 90 to 180 days (P less than .05; analysis of variance). Baseline serum prolactin levels were 61 +/- 9.5, 36 +/- 8.6, and 33 +/- 10.8 ng/ml, respectively (not significant; one-way analysis of variance). Mean stimulated prolactin levels were 71 +/- 8.1, 43 +/- 4.5, and 43 +/- 2.8 ng/ml, respectively (not significant). Thus, the oxytocin secretory reflex continues in long-term lactation for the first year post partum. In addition, breast stimulation in long-term lactating women continues to produce a slight increase in serum prolactin levels.

Adult↗

Phagocyte chemotaxis in the perinatal period.

Cross-sectional and limited sequential studies of neutrophil and monocyte chemotaxis were done using cells isolated from cord blood and peripheral blood of 2- to 6-day-old neonates and infants at 4 and 6 months of age. These studies show that cord blood phagocyte chemotaxis is comparable to adult values, whereas phagocyte chemotaxis at 2-6 days of age is significantly lower than adult (P less than 0.01) or cord (P less 0.01) chemotaxis values. At 6 months of age, phagocyte chemotaxis is still low compared to adult values (P less than 0.01).

Adult↗

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↗

Rapid glucose disappearance in infants with infection.

Altered carbohydrate metabolism has been reported during episodes of neonatal infection. To document that there is more rapid glucose disappearance during infection, intravenous glucose tolerance tests (IVGTT) and serial plasma growth hormone and insulin levels were determined in eight full-term neonates during the first three days of an acute episode of infection and during convalescence, 5 to 15 days later. Eight healthy infants were each studied once using the same study protocol. Glucose disappearance rates, measured as K1 of glucose, were increased (p less than 0.01) during both the acute septic period (3.7 +/- 0.3% disappearance/min; mean +/- S.E.M.) and convalescent period (2.5 +/- 0.2% min) when compared with values in control infants (1.3 +/- 0.3%/min). Gram-negative, gram-positive, and viral infections were all associated with rapid glucose disposal. The abnormality in carbohydrate homeostasis persisted for at least 5 to 15 days after treatment was begun. Baseline and stimulated (20-minutes post bolus glucose infusion) plasma insulin and growth hormone levels did not differ among the groups. Thus, there is no evidence that hyperinsulinism produced the rapid glucose disappeared rate and enhanced glucose utilization. The reason for the disturbed carbohydrate metabolism in neonatal infections remains unknown.

Age Factors↗

Reduced concanavalin A capping of neonatal polymorphonuclear leukocytes (PMNs).

Neonatal polymorphonuclear leukocytes (PMNs) have previously been shown to be chemotactically deficient. To probe the mechanism(s) responsible for this deficiency, we have investigated the phenomenon of concanavalin A-induced capping in neonatal PMNs. PMNs from cord blood of 17 healthy, full-term infants and 17 normal adult volunteers were isolated by standard Ficoll-Hypaque and dextran sedimentation. After incubation with and without colchicine, the cells were reincubated with fluorescein isothiocyanate-Con A, fixed, and prepared in wet mounts. Using a fluorescence microscope, PMNs were identified, and percentage of the capped cells was counted. Upon treatment with colchicine, adult PMNs showed a significant increase in the percentage of capped cells. By contrast, the cord blood PMNs showed no significant increase in capping after colchicine treatment. The difference between percentage of PMNs showing colchicine-induced capping in adult and cord blood was highly significant (P less than 0.01; Student's t test).

Adult↗

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↗

Plasma catecholamine concentrations in infants at birth and during the first 48 hours of life.

A radioenzymatic assay was used to measure plasma concentrations of the catecholamines, norepinephrine, and epinephrine in the perinatal period. Samples were obtained at birth from the umbilical artery and vein of infants born by vaginal and by cesarean section delivery; from peripheral venous samples of normal infants during the first 48 hours of life; and from peripheral venous samples of mothers prior to delivery. Concentrations of NE and E were elevated in umbilical samples, with umbilical artery levels exceeding umbilical venous concentrations. Umbilical plasma CAT concentrations were similar in vaginal and cesarean section delivered infants. Plasma concentrations of NE consistently predominated over E in all samples from neonates. Plasma CAT concentrations rapidly fell from cord levels within 15 minutes of delivery and remained at a lower plateau during the first three hours of life. By 12 hours of age plasma CAT concentrations fell to the levels of supine adult resting concentrations. Maternal plasma CAT concentration prior to delivery demonstrated a predominance of E over NE. These elevations of plasma CAT in the early neonatal period may play a rola in nonshivering heat production as well as in cardiovascular alterations associated with birth.

Catechol O-Methyltransferase↗

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↗