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Biomedical subjects

R D Leake

Publications and source records attributed to R D Leake.

At least 91 records · Page 5Linked to original sources

Glucose perturbation in experimental hyperviscosity.

Hyperviscosity was produced in one member of each of 7 sets of twin newborn lambs by an exchange transfusion with 500 ml maternal packed red blood cells. The remaining seven control twin lambs underwent an identical exchange with maternal whole blood. Postexchange hematocrits were 63 +/- 6 and 29.0 +/- 3% (mean +/- S.E.), respectively (P less than 0.01). Whole blood viscosity measured at 3 rpm increased from 3.2 +/- 0.4 centipoise (cps) to 14.4 +/- 6.1 cps in the lambs made hyperviscous (P less than 0.01) and remained unchanged in the control lambs (2.2 +/- 0.1 versus 2.8 +/- 0.3 cps). A 2-hr steady state glucose infusion was performed on each lamb before and after the packed cell or whole blood exchange transfusion. Mean steady state plasma glucose concentrations were significantly decreased from pre-exchange steady state glucose infusion levels in the same lambs made hyperviscous (P less than 0.05), whereas steady state glucose levels increased from preexchange levels in the twin lambs exchanges with maternal whole blood. Mean plasma insulin and glucagon values for the hyperviscous and control lambs remained unchanged during the glucose infusion.

Animals↗

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↗

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↗

Basal and pentagastrin-stimulated acid secretion in newborn human infants.

Basal and pentagastrin-stimulated gastric acid secretion was measured in 26 healthy newborn infants on the 1st and 2nd days of life. Basal acid outputs (BAO) on day 1 (0.378 mEq/hr) and day 2 (0.388 mEq/hr) were similar and not significantly different from the maximal acid outputs (MAO) on day 1 (0.413 mEq/hr) and day 2 (0.452 mEq/hr). When calculated on a mEq/kg/hr basis, BAO on day 1 was 0.110 with an MAO of 0.122. The BAO on day 2 was 0.114 with an MAO of 0.133. Fasting serum gastrin levels obtained before the acid studies on each day were elevated (mean, day 1 = 100 pg/ml; mean, day 2 = 108 pg/ml). These findings suggest that either gastric acid secretion in the newborn is maximal under basal condition or that newborn parietal cells are unresponsive to pentagastrin on day 1 and 2 of life.

Female↗

Control of vasopressin secretion in the newborn lamb.

The plasma sodium, osmolality, and arginine vasopressin (AVP) responses to phlebotomy, hypertonic saline, water loading and fluid restriction were studied in 2--49 day old lambs. Phlebotomy of 10 and 20% of the lamb's estimated blood volume produced 37- and 44-fold increments in plasma AVP, without a concomitant change in plasma sodium or osmolality. The infusion of 10 mEq/kg sodium chloride produced a 12% rise in plasma sodium concentration accompanied by a 7-fold rise in plasma AVP. Water loading with 100 ml/kg hypotonic fluid produced a significant fall in plasma sodium concentration (10.7%) and a decrease in plasma AVP. Eighteen hr of water deprivation evoked a 7-fold increase in AVP. These results indicate that the newborn lamb is capable of responding appropriately to known stimuli for AVP secretion. The stimulus response ratio (SRR): (formula: see text) of newborn lambs was nearly identical after hypertonic saline and water loading and was also quite similar to that of the adult ewe after a saline challenge. The SRR of water deprived lambs was greater than that after the other stimuli, presumably reflecting combined volume and osmolar stimuli. We conclude that the neurohypophysis and the volume receptor systems of the newborn lamb are capable of appropriate, mature AVP responsiveness during the first days of extrauterine life.

Animals↗

Development pharmacokinetics of the posterior pituitary hormones.

Arginine vasotocin, arginine vasopressin, and oxytocin play a critical role in the stimulation of labor and delivery and in salt and water homeostasis in the newborn infant. The authors present information on their chemistry, secretion, and metabolism, and discuss the clinical effects upon target organs of their presence or absence.

Animals↗

Osteomyelitis as a complication of umbilical artery catheterization.

A retrospective study of 400 infants requiring umbilical artery catheterization performed from 1969 to 1971 at Indiana University Medical Center and Marion County General Hospital disclosed six cases of associated osteomyelitis. A similar review of approximately 550 cases of umbilical artery catheterization at Harbor General Hospital from 1972 to 1974 revealed an additional case. The causative organism was Staphylococcus aureus in each instance. Mean onset of symptoms following catheter removal was ten days. In all instances osteomyelitis occurred on the side ipsilateral to insertion and distal to the catheter tip. Postulated mechanisms include bacterial contamination of the catheter, thrombus formation, and local hypoxia from partial occlusion of the vessels by a large catheter.

Catheterization↗

Infraumbilical entry into the peritoneal cavity through a small incision for the identification and cannulation of an umbilical artery.

An infra-umbilical entry into the peritoneal cavity through a small incision, without anesthesia, for the identification and cannulation of an umbilical artery was employed for monitoring and therapy in five prematurely born neonates. The extra-peritoneal approach to umbilical artery identification and cannulation had been unsuccessful in all of these cases. The operations were carried out in the neonatal intensive care unit under strict surgical asepsis. Microsurgical techniques with 2.5 times magnification and microsurgical instruments were employed and found to be quite useful. In all five cases, an umbilical artery was readily identified and cannulated and there were no postoperative complications attributed to this approach.

Blood Gas Analysis↗

Glomerular filtration rate during the period of adaptation to extrauterine life.

Inulin clearance (Cin) was measured in 20 infants of 27--43 weeks of gestation during the first 24 hr of their extrauterine life. Cin ranged from 0.7--4.7 ml/min and correlated with gestational age (P less than 0.05). In 18 infants of similar gestational ages studied after 2--3 days of extrauterine adaptation, the Cin ranged from 1.1--17.9 ml/min and also correlated with gestational age (P less than 0.01). By day 2--3, the infants of near term gestational age achieved a greater increase in Cin than did the markedly preterm infants, as reflected by a significantly different slope of the regression line for Cin and gestational age for the infants studied at 1 vs. 2--3 days of age (P less than 0.001).

Gestational Age↗

Measurement of "true" glucose production rates in infancy and childhood with 6,6-dideuteroglucose.

"New" glucose production has been measured in 54 infants and children for the first time by continuous three-to-four-hour influsion of the safe, nonradioactive tracer 6,6-dideuteroglucose. The use of combined gas chromatography--mass spectrometry with monitoring of selected ions allowed deuterium enrichment in blood glucose to be measured on microliter samples with an error of less than 2 per cent. In the young child, glucose production increased in a slightly curvilinear manner from 1 kg. to 25 kg. body weight, when it reached 140 mg. per minute, almost the adult value of 173 mg. per minute (2.28 +/- 0.23 mg./kg.-min., mean +/- S.E.). Normalized for weight, glucose production in premature infants was 5.46 +/- 0.31 mg./kg.-min., in term neonates averaged 6.07 +/- 0.27 mg./kg.-min., in children below the age of six years was 7.1 +/- 0.27 mg./kg.-min., and in late childhood averaged 5.4 +/- 0.28 mg./kg.-min. Relative to estimated brain weight, however, glucose production was essentially linear from the 1-kg. premature infant to the 80-kg. adult. These data, the first measurements of "new" glucose production in childhood, suggest that brain size may be a principal determinant of those factors that regulate hepatic glucose output throughout life.

Blood Glucose↗

The effects of large volume intravenous fluid infusion on neonatal renal function.

Twenty healthy infants weighing less than 2,000 gm were studied at low (3.6 ml/kg/hr) or high (10.3 ml/kg/hr) rates of intravenous infusion. Inulin clearance determined by the constant infusion method was greater at the high rate of infusion (p = less than 0.05). Inulin clearance in two groups of infants over 2,000 gm studies at the same low or high rates of infusion did not increase at the higher rate of infusion. Since the GFR in infants less than 2,000 gm depends partially on the rate of intravenous infusion, small, healthy preterm infants may benefit from a rate of fluid administration greater than the low rate. When studies at low and high rates of infusion were compared in the 20 infants less than 2,000 gm, the fractional urinary sodium excretion increased with the increased fluid load. Delivery of fluid from the proximal tubule (CH2O =Na per dl GFR) increased (p less than 0.005). Free-water clearance and the absolute volume of urine increased at the high rate of infusion. These data indicate that the healthy preterm infant less than 2,000 gm, like the adult, compensates by increasing free-water clearance and urine volume when challenged with a large fluid load. Although fluid changes of short duration are appropriately handled, the effect of continuous rapid infusion on water and sodium balance in infants of this size remains to be determined.

Body Fluids↗