Harry Bard

Correction of the malabsorption of the preterm infant with a medium-chain triglyceride formula

After receiving milk-based formula for one week, 16 preterm infants, weighing 1,300 to 1,800 gm, were fed two isocaloric formulas containing either medium-chain or long-chain triglycerides for 15 days; the alternate formula was given for a second period of identical duration. While receiving MCT, the infants had greater (P smaller than 0.01) percent fat absorption (83.4 leads to 97.1%) and weight gain (7.5 leads to 11.5 gm/kg/100 calories). Because metabolic acidosis occurred with the LCT formula, the chloride content was adjusted to that of the MCT were confirmed and, in addition, there was a higher (P smaller than .01) percent retention of nitrogen (67.3 leads to 82.1).

Nitric Oxide Signaling via Nuclearized Endothelial Nitric-oxide Synthase Modulates Expression of the Immediate Early Genes iNOS and mPGES-1

Stimulation of freshly isolated rat hepatocytes with lysophosphatidic acid (LPA) resulted in LPA1 receptor-mediated and nitricoxide-dependent up-regulation of the immediate early genes iNOS (inducible nitric-oxide synthase (NOS)) and mPGES-1 (microsomal prostaglandin E synthase-1). Because LPA is a ligand for both cell surface and intracellular receptor sites and a potent endothelial NOS (eNOS) activator, we hypothesized that NO derived from activated nuclearized eNOS might participate in gene regulation. Herein we show, by confocal microscopy performed on porcine cerebral endothelial cells expressing native LPA1-receptor and eNOS and on HTC4 rat hepatoma cells co-transfected with recombinant human LPA1-receptor and fused eNOS-GFP cDNA, a dynamic eNOS translocation from peripheral to nuclear regions upon stimulation with LPA. Nuclear localization of eNOS and its downstream effector, soluble guanylate cyclase, were demonstrated in situ in rat liver specimens by immunogold labeling using specific antibodies. Stimulation of this nuclear fraction with LPA and the NO donor sodium nitroprusside resulted, respectively, in increased production of nitrite (and eNOS phosphorylation) and cGMP; these separate responses were also correspondingly blocked by NOS inhibitor l-NAME and soluble guanylate cyclase inhibitor ODQ. In addition, sodium nitroprusside evoked a sequential increase in nuclear Ca2+ transients, activation of p42 MAPK, NF-κB binding to DNA consensus sequence, and dependent iNOS RNA. This study describes a hitherto unrecognized molecular mechanism by which nuclear eNOS through ensuing NO modulates nuclear calcium homeostasis involved in gene transcription-associated events. Moreover, our findings strongly support the concept of the nucleus as an autonomous signaling compartment.

OUTCOME AT SCHOOL AGE OF CHILDREN WITH BIRTHWEIGHTS OF 1000 GRAMS OR LESS

A follow‐up study was done of extremely low‐birthweight infants (≤ 1000g) born between 1976 and 1979, a períod when aggressive intervention was not routine practice. The survival rate was 19 per cent. 44 of the 46 survivors were followed to a mean age of 6 1/2 years. By five years of age 23 of the 44 children had been admitted to hospital, mainly for surgery and respiratory problems. Eight of 31 five‐year‐old children were growth‐retarded and five of 26 were microcephalic. Among 44 children, ophthalmological problems were found in nine cases and neurosensory impairments (cerebral palsy, deafness:) in seven. 12 children were mentally handicapped or had impaired intelligence (IQ or DQ < 85). Over‐all, 14 of the 44 children had impairments, severe in four cases and moderate in 10. Mean verbal IQ was significantly lower than mean performance IQ. Among 37 children in school or in remedial programs, nine required special education and another 12 in regular classes either failed or had very poor results, or needed extra professional help. Only 16 of the children had no significant problems in school. These findings indicate that extremely low birthweight (≤ 1000g) represents a major risk to life, health (hospital admissions), long‐term growth, neurosensory integrity, cognitive development and learning potential.

Myocardial, erythropoitic, and metabolic adaptations to anemia of prematurity

We determined the effects of anemia of prematurity on myocardial, metabolic, and erythropoietic functions. Twelve anemic (hemoglobin range, 65 to 78 gm/L) infants without symptoms (gestational age, (mean +/- SD) 28 +/- 2 weeks; birth weight, 1178 +/- 326 gm) were studied at a postconceptional age of 35 +/- 1.6 weeks. All measurements were done before and 36 to 48 hours after a transfusion of packed erythrocytes. Cardiac output, heart rate, and myocardial function were assessed. Oxygen consumption, carbon dioxide production, resting energy expenditure, arterial oxygen pressure for 50% hemoglobin saturation, and the concentrations of erythropoietin and 2,3-diphosphoglycerate were also determined. After transfusion, increased hemoglobin level (75 +/- 4 to 150 +/- 16 gm/L) and decreased oxyhemoglobin affinity (20.8 +/- 1.7 to 23.6 +/- 2.1 gm/L; p < 0.05) caused a decrease in plasma erythropoietin concentration (from 21.1 +/- 6.2 to 5.8 +/- 1.5 mU/ml; p < 0.01). There was a decrease in heart rate (from 155 +/- 10 beats/min to 146 +/- 7 beats/min) and cardiac output (from 281 +/- 73 ml/kg per minute to 199 +/- 62 ml/kg per minute; p < 0.05). Myocardial function indexes, weight gain, and metabolic demands were normal before and after transfusion. These results suggest that oxygenation is adequately maintained in symptom-free infants with anemia of prematurity.

Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity in infants with bronchopulmonary dysplasia ☆ ☆☆ ★ ★★

OBJECTIVES The effects of anemia of prematurity during bronchopulmonary dysplasia (BPD) as well as on the metabolic and erythropoietic functions were determined before and after a transfusion. Fourteen anemic (Hb range: 65-88 gm/L), oxygen dependent (fraction of inspired oxygen < or = 35%), nonventilated, preterm infants with BPD were studied at a postnatal age of 6 +/- 2 weeks. STUDY DESIGN Cardiac output, heart rate, mean velocity of circumferential fiber shortening, shortening fraction (SF), and stroke volume were assessed by pulsed and continuous wave Doppler echocardiography. Values for resting oxygen consumption, carbon dioxide production, and energy expenditure were obtained by indirect calorimetry. The affinity of oxygenated hemoglobin was determined by a blood oxygen dissociation analyzer. RESULTS An increased hemoglobin level resulted in a suppression of erythropoietin secretion (p < 0.001), whereas heart rate, cardiac output, stroke volume, and SF decreased (p < 0.05). Weight gain before and after transfusion were similar. Plasma lactate levels decreased from 1.6 +/- 0.3 to 1.2 +/- 0.3. Oxygen consumption, carbon dioxide production, and energy expenditure were not affected. CONCLUSIONS Anemia of prematurity and BPD increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic compensatory responses are normalized by transfusion.

THE ASSOCIATED ANOMALIES THAT DETERMINE PROGNOSIS IN CONGENITAL OMPHALOCELES

Cogenital abdominal wall defects such as omphaloceles can be recognized by fetal ultrasonography. To determine whether associated anatomic features may be useful in determining fetal prognosis, a retrospective study was performed over a 5-year period. There were 28 cases of omphalocele; 16 were larger than 5 cm and classified as giant, and the remainder were considered small. Eleven of the 12 infants with small omphaloceles survived with minimal neonatal complications. Ten of the 16 infants with giant omphaloceles died because of associated congenital anomalies. These were congenital heart disease, central nervous system malformations, and diaphragmatic hernias. This review suggests that the prognosis is good when a prenatal diagnosis of giant omphalocele is made and careful fetal ultrasonography, including echocardiography, does not identify heart, central nervous system, or diaphragmatic malformations, even when there is liver herniation into the omphalocele.

The life span of erythrocytes transfused to preterm infants

This study was made to determine the life span of adult red cells transfused to early preterm infants. Nineteen very preterm infants (birth weight, 878.7 ± 221 g; gestational age, 26.8 ± 1.5 wk at birth) were sampled weekly after their last blood transfusion to determine the level(%) of fetal Hb in their circulation. Two microliters of blood were subjected to reverse phase HPLC to separate the α, β, and γ globin components of their Hbs. The percent of fetal Hb (HbF) was calculated asγ/γ + β × 100. The life span of the adult erythrocytes transfused was defined as the time interval between the transfusion and when the percentage of HbF in the recipients circulation returns to the HbF levels that exist in the infants autologous red cells (the maximum post transfusion HbF level). Twelve of the 19 infants were followed until their autologus HbF levels were reached. Their mean adult red blood cell life span was 56.4± 7 d (range: 46-68 d). The results obtained in this study imply that the number of days after a transfusion at which half the cells infused remain in the circulation in a preterm infant is about 30 d.

The effect of placental insufficiency on fetal and adult hemoglobin synthesis

Abstract To explain the mechanism underlying the increased fetal hemoglobin synthesis in intrauterine growth-retarded infants, the proportion of fetal hemoglobin (Hb F) and adult hemoglobin (Hb A) synthesized at birth and postnatally was determined in 10 term infants small for gestational ages (TSGA). The results were compared to preterm infants appropriate in weight for gestational ages (PRAGA) having similar birth weights as the TSGA infants and infants appropriate in weight for gestational ages having the same length of gestation as the TSGA infants (TAGA). Hb F synthesis at birth was 81.8 ± 5.7 per cent (S.D.) in the TSGA group, 90.2 ± 5.4 per cent (S.D.) in the PRAGA group, and 59.1 ± 10 per cent (S.D.) in the TAGA infants. The difference between TSGA and TAGA infants was very significant (P

Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials☆☆☆★

Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.

Congenital atresia and stenosis of the duodenum: The impact of a prenatal diagnosis

This review was undertaken to determine the effects of prenatal diagnosis, on the basis of ultrasonographic evidence, of a duodenal obstruction on the care and morbidity of the newborn infant. The records of 46 cases of either atresia or stenosis of the small bowel in infants treated during the last six years in a tertiary perinatal center were reviewed retrospectively. A prenatal fetal diagnosis of obstruction was made in 13 patients (12 obstructions located in the duodenum and one in the jejunum). The mean gestational age at prenatal diagnosis was 33.7 weeks (range 27 to 37 weeks). The course of those infants with the prenatal diagnosis made by ultrasound was compared with that of those infants in whom the diagnosis was established after the onset of symptoms of obstruction appeared. Such a prenatal diagnosis resulted in earlier surgical intervention (1.8 versus 3.9 days). Metabolic complications secondary to repeated vomiting were found to be less frequent. The expectant mother in whom such a fetal prenatal diagnosis has been made can be transported to a tertiary level perinatal center where neonatal and specialized surgical expertise are available. After birth, the infant can undergo immediate operation without being separated from its mother.