Eugene W. Adcock

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A,D, and E and riboflavin

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.

Diversity of Bile Acids in the Fetus and Newborn Infant

Summary The bile acids found in the fetus and newborn are more numerous and diverse than has generally been appreciated. The four conventional bile acids, cholic, chenodeoxycholic, deoxycholic, and lithocholic acids, are found. In addition, however, stereoisomers of the conventional bile acids, bile acids with functional groups at different positions or in greater number than found in conventional bile acids, and “short-chain” and “long-chain” bile acids are found. The site of origin, pathways of synthesis, metabolism, and excretory routes of these unconventional bile acids are largely unknown. Their effects on the function of the liver and other tissues have not yet been established. It is uncertain which of these compounds is peculiar to the fetus and newborn, and which will be found in normal or abnormal adults. This review is an early look at a field bound to advance rapidly in the next several years.

Cyclopentolate (Cyclogyl) toxicity in pediatric patients

Summary The clinical features of Cyclogyl toxicity from ocular instillation of the 2.0 per cent solution have been described in a 4 6/12-year-old boy. Previously undescribed systemic signs of postganglionic cholinergic blockade resembling atropine intoxication were also noted. Occlusion of the punctum at the time of instillation may prevent all of these effects. It is recommended that the use of Cyclogyl for routine funduscopic examination of pediatric patients be limited to one drop of the 0.5 per cent solution in each eye, to be repeated only once after unequivocal failure of cycloplegia and mydriasis.

Syndrome of inappropriate antidiuretic hormone secretion in neonates with pneumothorax or atelectasis

Nine episodes of the syndrome of inappropriate antidiuretic hormone secretion occurred in five newborn infants following atelectasis or pneumothorax. All infants had pre-existing lung disease and were being treated with positive pressure ventilation. The mean interval between acute atelectasis or pneumothorax and the development of diagnostic hyponatremia, hypo-osmolal serum, hyperosmolal urine, and oliguria was 13.4 hours. Fluid restriction and removal of the triggering event resulted in resolution of the abnormalities within 1.5 to 4 days. Infants who develop atelectasis or pneumothorax should be evaluated for the subsequent occurrence of SIADH; the administration of a water load to them may result in dilutional hyponatremia, for which fluid restriction, not sodium infusion, is the proper therapy.

Polymorphonuclear leukocyte function in newborn infants

PHAGOCVTOSIS and killing of bacteria by human polymorphonuclear leukocytes is accompanied by a number of oxidative alterations, including increases in hexose monophosphate shunt activity, oxygen consumption, and hydrogen peroxide production. I The purposes of this study were (1) to investigate H MPS activity in resting and phagocytizing PMNL obtained from infected and healthy infants, (2) to determine the bactericidal activity of PMNL obtained from healthy control infants and adults in the presence of either adult or infant serum, using Staphylococcus aureus and Escherichia coli as the test organisms, and (3) to compare bactericidal activity with HMPS activity in healthy control infants and adults.

Effect of Uterine Artery Insulin Infusions on Umbilical Glucose Uptake in Sheep

Summary: Although glucose is an important fuel for fetal oxidative metabolism, regulation of its availability to the mammalian fetus is poorly understood. This study was performed to determine the effect of infusions of insulin into the uterine arterial circulation on umbilical uptake of glucose in chronically instrumented, unstressed sheep. Twenty-eight determinations of umbilical glucose uptake and diffusion clearance of glucose by the placenta were made in four ewes. Immediately following a control study during which saline was infused into the uterine artery, porcine regular insulin diluted in saline was infused at 0.05 to 8.1 mU/min · kg uterine weight for 20–30 min and the determinations were repeated. Subsequent studies were performed at the conclusion of additional infusions of insulin to a maximum of 21.6 mU/min · kg.There was a significant increase in umbilical glucose uptake during initial insulin infusions (4.47 ± 0.6 mg/min · kg fetus) compared to the control studies (3.08 ± 0.6 mg/min · kg) associated with an increase in diffusion clearance (13.8 ± 1.9 ml/min · kg fetus vs. 8.99 ±1.8 ml/min · kg). When the total cumulative dose of exogenous insulin, It, was 162 mU/kg uterine weight or less, the umbilical uptake of glucose, Q, may be expressed as a function of maternal arterial blood glucose concentration in milligrams per dl, [A], and of It.Speculation: Exogenous insulin infused at physiologic rates into the ovine uterine artery increases the permeability of the placenta to glucose by increasing the initial rate of glucose transport by a carrier system into cells which comprise the placenta until insulin receptor sites are saturated.

Development of gluconeogenic enzymes in fetal sheep liver and kidney.

In the sheep, the system of enzymes necessary for conversion of nonhexose substrates to glucose becomes active during late fetal life. Glucose-6-phosphatase and fructose-1,6-diphosphatase, two of the four key gluconeogenic enzymes, appear in significant amounts between 100 and 120 days gestation. Phosphoenolpyruvate carboxykinase activity is comparable to mature animals as early as 45 days gestation. Two aminotransferases, necessary to allow amino acid access to the gluconeogenic pathway, likewise have substantial activity as early as 45 days gestation. Hence, the surge of glucose-6-phosphatase and fructose-1,6-diphosphatase at 100-120 days gestation makes possible the endogenous production of new glucose by fetal sheep at a time when the amount of glucose transferred from the maternal circulation is less than the total aerobic substrate utilized by the fetus. Both renal cortex and liver have similar developmental patterns for the gluconeogenic enzymes, although renal cortex generally shows greater activity than liver. This observation holds true for tissue from both fetal and mature animals.

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants.

Introduction: Very-low–birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. Methods: Preterm infants with birth weight ≤1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid®. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, χ2, and analysis of variance. Results: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 ± 29 g and 25.5 ± 0.3 weeks (mean ± SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 ± 0.009 mg/kg/day), 35% more vitamin A (318.3 ± 11.4 μg/kg/day), and 14% more vitamin E (3.17 ± 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 ± 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 ± 0.022 μg/mL) and vitamin E (22.26 ± 1.61 /mL) concentrations were greater in the modified group. Conclusions: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.

Congenital torsion of the penis in father-son pairs.

Congenital torsion of the penis was observed in 5 newborns, 3 of whom had fathers with torsion of the penis. We believe that this common benign condition may be transmitted as an autosomal dominant trait.

Hydrolysis of dipeptides by human and ovine placentas.

Summary: Human and ovine placental tissue homogenates were assayed for dipeptidase activity in vitro. Glycyl-L-leucine, L-leucyl glycine, glycyl-L-lysine, and L-lysyl glycine were hydrolyzed by placental homogenates. The pH optimum for the reaction was 8.0. The relationship between enzyme activity and concentration was linear for placental homogenate concentrations between 0.01 and 0.10 mg protein/ml of reaction mixture. Enzyme activities were 1.92 ± 0.12 (S.E.) μoles/min/mg protein for hydrolysis of glycyl-L-leucine, 0.34 ± 0.06 (S.E.) μmoles/min/mg protein, for hydrolysis of glycy-L-lysine by human placenta, and 2.79 ± 0.8U μmoles/min/mg protein and 0.41 ± 0.25 μmoles/min/mg protein, respectively, by ovine placenta. The infusion of glycyl-L-lucine into the uterine artery of unstressed catheterized pregnant ewes yielded increased concentrations of both component amino acids in uterine venous blood and of leucine in umbilical venous blood.Speculation: The presence of dipeptidase activity in placental homogenates and the observation that glycyl-L-leucine when infused into the main uterine artery is hydrolyzed to its component amino acids support the hypothesis that leucine and possibly glycine extracted from the placenta by the umbilical circulation may be provided by placental hydrolysis of dipeptides which arise within the placenta from the degradation of larger peptides and proteins.