Variable arginine vasopressin levels in neonatal congestive heart failure.

Arginine vasopressin levels in 17 neonates with cardiac disease were compared with control levels in 10 healthy newborn infants. Infants with congestive heart failure who were free of left ventricular outflow tract obstruction had a mean level of 80 +/- 18 pg/ml, which was significantly greater than the mean control level (p less than 0.001). Infants with congestive heart failure and left ventricular outflow tract obstruction had a mean vasopressin level of 3 +/- 0.7 pg/ml, which was lower than the mean control level of 6 +/- 0.7 pg/ml (p less than 0.05). The data suggest that impaired forward flow to high pressure sinoaortic and ventricular baroreceptors is necessary for vasopressin release in congestive heart failure. In left ventricular outflow tract obstruction with heart failure these receptors may be impaired or absent, leading to decreased vasopressin release. Low plasma arginine vasopressin may adversely affect circulatory homeostasis.

The folate in human milk.

In previous studies of the folate content of human milk, samples were prepared for assay by a method that resulted in a turbid solution that was then assayed by a turbidimetric microbiological method. We have used an improved microbiological assay in which the milks were treated with rennin to precipitate casein and heated in a buffered ascorbate to coagulate lactalbumin and lactoglobulin. Milks were obtained serially from nursing mothers for periods ranging from 1 day to 6 months postpartum. The results showed that the folate in human milk has few glutamate residues since treatment with a purified folate conjugase preparation release no additional folate activity for Lactobacillus casei. Colostrum is relatively low in folate, but milk folate increases as lactation proceeds. During each stage of lactation there was great variation in milk folate content among the women. In the case of a folate-deficient woman, supplementation with folic acid resulted in a prompt increase in milk folate level.

Health codes for newborn care.

A survey was conducted of the health departments in each of the 50 states, Washington, DC, and the Commonwealth of Puerto Rico to determine the present legal mandates for newborn care. Each of the 52 health departments were queried regarding birth certificates, identification procedures, prophylactic eye care, umbilical cord care, use of vitamin K, Apgar scoring, and metabolic screening. In each category, the departments were asked whether the procedures were mandatory or optional. Birth certificates are uniformly required within the health codes of all states. Although in-hospital identification of newborns is required in most states, four states specifically require arm banding, and only New York State requires footprinting. Eye prophylaxis with silver nitrate is required in 49 states, with erythromycin or tetracycline allowed as topical alternatives in 42 states. Clamping of the umbilical cord is addressed by eight states. Parenteral vitamin K administration is mandated by only five states. Apgar scoring is addressed by 25 states. Newborn metabolic screening is available in every health department, although significant variations exist in the tests available.

Feeding the low-birthweight infant: orally or parenterally?: II. Corrected bromide space in parenterally supplemented infants.

Previously published data suggested that the faster rate of weight gain observed in parenterally supplemented neonates compared to their orally fed peers might be attributable to water retention rather than to more rapid tissue accretion. The present study was designed to test that hypothesis by observing changes in extracellular water, estimated as corrected bromide space (CBS). Ten neonates with a mean birthweight of 1,250 gm (range, 800 to 1,980 gm) and a mean gestational age of 31 weeks (range, 24 to 38 weeks) were randomly assigned to a 67 cal/dl formula feeding or an oral 100 cal/dl formula feeding supplemented parenterally with dextrose and amino acids. CBS was estimated within 19 hours of birth and between the 7th and 28th postnatal days. Mean total daily water and protein intakes during the intervening period were similar for orally fed and supplemented neonates, but the latter took significantly less orally and received more parenterally. CBS increased in all but one of the supplemented neonates whereas two of four orally fed babies had decreasing values and one had stable values. Shorter times before regaining birthweight, faster rates of weight gain, and lower arterial pH were associated with larger CBS as well as with parenteral supplementation. These data suggest that parenteral supplementation may result in water retention and/or shifts from the intracellular to the extracellular space. Previously reported earlier and greater mean daily weight gains in supplemented babies may be related to water accumulation rather than tissue accretion, but definitive conclusions must await further studies, including concomitant estimates of total and extracellular body water.

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Epidemiology and control of vancomycin-resistant enterococci in a regional neonatal intensive care unit.

BACKGROUND: After the occurrence of two cases of bloodstream infection with vancomycin-resistant enterococci (VRE) in our regional neonatal intensive care unit, we studied the epidemiology of VRE and applied extensive infection control measures to the unit to control VRE transmission. METHODS: Infection control measures applied to the unit included weekly surveillance for VRE colonization; education; cohorting of VRE-positive, VRE-negative and VRE-exposed babies with separate personnel and equipment for each group; use of gowns and gloves on room entry; and hand washing before and after each patient contact. Risk factors for VRE colonization were determined with a stepwise logistic regression model. RESULTS: Thirty-three (40.2%) babies became colonized with VRE. The VRE colonization rate was reduced from 67% to 7% after implementation of infection control measures. Prolonged antimicrobial treatment and low birth weight were significantly associated with an increased risk of VRE colonization. CONCLUSION: VRE can spread rapidly among newborns in a regional neonatal intensive care unit. Strict infection control measures can reduce the rate of VRE colonization among neonates.

Specificity of glycosaminoglycan suppression of endothelin-1 production by human umbilical vein endothelial cells.

Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide found in nature. Its production is stimulated by thrombin. By inhibiting thrombin we have previously shown that heparin, a highly negatively-charged glycosaminoglycan (GAG), suppresses the production of ET-1 by cultured human umbilical vein endothelial cells (HUVEC). The purpose of our study is to determine the effect of other GAGs and related compounds on ET-1 production. The GAGs and related compounds used in the study were: chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C, fucoidin, low molecular weight dextran sulfate, high molecular weight dextran sulfate, and hyaluronan. HUVEC were incubated for 48 hr with media containing these GAGs and related compounds and with media without GAG as control. ET-1 levels were measured by radioimmunoassay. GAGs and related molecules with higher sulfate content, heparin, chondroitin sulfate B, low and high molecular weight dextran sulfates significantly suppressed ET-1 production by HUVEC. Fucoidin also suppressed ET-1 production despite its lower sulfate content, probably because of its structural similarity to heparin. These compounds may be useful for future in vivo studies.

Release of superoxide dismutase activity from human umbilical veins by heparin.

OBJECTIVE: This study evaluated superoxide dismutase activity released from human umbilical veins incubated with different doses of heparin and examined at different time points. STUDY DESIGN: Umbilical veins of fresh cords from full term babies were incubated with 175 or 1 U/ml of heparin at one end while the other end was incubated without heparin as control. Specimens were obtained at 10 minutes and 24 hours (high-dose) or at 10 minutes and 60 minutes (low-dose). Superoxide dismutase activity was measured by the cytochrome c method. Results were analyzed using Student's paired t test. RESULTS: A time-dependent release of superoxide dismutase activity into the buffer was observed in both heparin specimens as well as in control specimens. The difference in release in the presence of heparin was of statistical significance, compared with the controls. CONCLUSION: Because heparin is routinely used as an anticoagulant to maintain the patency of umbilical catheters, we conclude that this usage may alter a newborn's response to oxygen free radical damage by changes in superoxide dismutase activity.

Perinatal glucose homeostasis: the unique character of hyperglycemia and hypoglycemia in infants of very low birth weight.

Tiny babies have the potential problem of hypoglycemia due to diminished hepatic glycogen stores, which can be potentiated by conditions frequently present in this birth weight group: asphyxia, cold stress, hypoxia, polycythemia. Despite the early administration of fluid and feeding, tiny babies are still at risk for developing hypoglycemia. Their immaturity, expressed by their limited ability to tolerate parenteral glucose infusions, puts them at risk for becoming hyperglycemic as well. Hence careful glucose administration and frequent monitoring of blood glucose are essential during the first several days after birth, in anticipation of hypoglycemia as well as hyperglycemia.

Neonatal hypoglycemia and hyperglycemia: two unique perinatal metabolic problems.

Hypoglycemia is a frequent, potentially morbid disease in the newborn. Most infants who are at risk can be identified either prior to or immediately after birth. A knowledge of those factors that cause or potentiate the development of hypoglycemia can alert the physician as to which infants require close observation and frequent monitoring of blood glucose. Care in interpretation of laboratory data is important in establishing the diagnosis. Prompt treatment can prevent permanent damage and promote intact survival in these infants. Hyperglycemia has been reported with the use of parenteral glucose in infants of very low birth weight. Rate of glucose infusion appears to be a critical factor in the development of hyperglycemia in these infants. The hazards of allowing fasting hypoglycemia to develop by inappropriate withholding of early calories and of causing hyperglycemia by injudicious use of parenteral glucose infusions in the tiny neonate show the critical need for constant monitoring of blood glucose both by screening techniques and by laboratory determinations.

The nitric oxide donor S-nitroso-N-acetyl-D,L-penicillamine degrades heparan sulfate and heparin.

Nitric oxide (NO) is a powerful vascular and neural regulator. One of the breakdown products of nitric oxide is nitrite which converts to nitrous acid, a reagent routinely used for the degradation of heparin and heparan sulfate. We have recently shown that nitric oxide gas degrades heparin and heparan sulfate through a nitrous acid mechanism (Vilar et al, 1997, Biochemical Journal, 324, 473-479). The purpose of the present study is to confirm these findings using the nitric oxide donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) under conditions that are close to those found in vivo. The results show that 2 mM SNAP releases a steady-state level of nitrite of over 200 microM. This level substantially degrades heparin and heparan sulfate at a pH of up to 5.0. This reaction may be important in breakdown of the glycosaminoglycan components of the extracellular matrix during normal and pathological conditions.

Suppression of endothelin-1 production in cultured human umbilical vein endothelial cells by heparin fractions separated by strong anion exchange chromatography.

Heparin has been shown to lower the production/secretion of the vasoconstrictive peptide endothelin-1. Endothelin-1 production is stimulated by thrombin, and it has been proposed that heparin binds to the anion-binding exosite of thrombin, preventing it from stimulating endothelin-1 production. To further test this proposal, heparin was fractionated by strong anion exchange chromatography (QAE-Sephadex A-25) into four fractions. These fractions had anticoagulant activities that increased linearly with charge, as defined by the median salt concentration needed for elution from the column. The fractions also differed in the total number of sulfates per mole of heparin, which was dependent on the molecular mass of the fractions rather than charge density. The fractions were found to significantly differ fron each other in their ability to suppress endothelin-1 production. The fraction eluting from the ion exchange column at the highest salt concentration had the greatest suppressive effect. Addition of sodium or potassium chloride to the media interfered with the ET-1 suppressive effect of unfractionated heparin, whereas lithium chloride had no effect. These data show that charge interactions between heparin and thrombin may be important in regulating the production of endothelin-1 and in regulating other thrombin-dependent functions.

Specific heparin fractions suppress endothelin-1 production in cultured human umbilical vein endothelial cells.

Vascular endothelial cells produce endothelin-1, a peptide with potent vasoconstrictor and mitogenic properties. Heparin suppresses thrombin-stimulated endothelin-1 production in endothelial cells; this is consistent with its reported effect of lowering blood pressure. Since heparin is a heterogeneous mixture of glycosaminoglycans, we examined the effects of different fractions of heparin in suppressing endothelin-1 production in cultured endothelial cells. Heparin fractions differing in size and in antithrombin III affinity were prepared. The results show that the suppressive effect of heparin is independent of these properties of size and antithrombin III affinity. Heparin sulfate suppressed endothelin-1 production to a similar level as heparin. These experiments were conducted in a complete culture medium in the absence of added thrombin. To assess the role of endogenous thrombin in the medium on this process, we tested the effects of hirudin, a specific thrombin inhibitor peptide, on suppression of endothelin-1. Hirudin, like heparin, binds to the anion-binding exosite of thrombin. Hirudin alone, and combined with heparin, suppressed endothelin levels to the same extent as heparin. These experiments demonstrate that the suppressive effect of heparin is the result of its binding to the traces of thrombin in the culture medium, preventing stimulation of endothelin-1 production. This study supports the hypothesis that the functional thrombin receptor may participate in the stimulation of endothelin-1 by thrombin.

Nitric oxide products degrade chondroitin sulfates.

Nitric oxide (NO) is a potent endogenous vasodilator that is elevated in response to inflammation. Inflammation also produces high levels of superoxide, which combines with NO to produce peroxynitrite (PN). We have previously reported that NO degrades heparin and heparan sulfate under acidic conditions and that PN degrades hyaluronan (HA) at neutral pH. Heparin and HA are glycosaminoglycans (GAGs) widely distributed in the extracellular matrix of tissues. Disruption of intestinal GAGs, particularly the chondroitin sulfates, were linked to inflammatory bowel diseases. Chondroitin sulfate A (CSA), chondroitin sulfate B (CSB), and chondroitin sulfate C (CSC) are constituents of the basement membranes of many tissues, including the intestine. The purpose of this study is to determine whether the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and PN can degrade chondroitin sulfates in vitro. The NO donor SNAP (2 mM, pH 4.0) or PN (5 mM, pH 7.4) was incubated for at least 1 week at 37 degrees C with CSA, CSB, or CSC. Breakdown of CSA, CSB, and CSC was assessed by gel filtration chromatography and compared with untreated controls. Percentage degradation was calculated based on the change in peak height compared to the control. SNAP treatment partially degraded CSB and CSC, whereas PN partially degraded all three chondroitin sulfates. Nitric oxide mediated degradation of GAGs, and particularly chondroitin sulfates, may be an important pathway of inflammatory tissue damage.