Showing papers in "Pediatric Research in 1986"
TL;DR: The lack of invasive bacterial infections in this small group of preterm infants after discharge from the nursery suggests that further studies will be necessary to determine whether the hypogammaglobulininemia places these very low birth weight infants at risk for serious infection.
Abstract: Plasma immunoglobulin concentrations of premature infants of birth weight less than 1500 g were measured longitudinally from birth to 10 months chronological age. Infants were divided into two groups based on gestational age (group I: 25-28 wk; group II: 29-32 wk). In the 1st wk of life, plasma IgG levels correlated with gestational age (r = 0.5, p less than 0.001). At 3 months chronological age, the geometric mean plasma IgG levels were 60 mg/dl in group I and 104 mg/dl in group II infants. Most infants remained hypogammaglobulinemic at 6 months with seven of 11 infants in group I and 13 of 21 infants in group II having plasma IgG levels below 200 mg/dl. In the 1st wk of life, plasma IgM concentrations were 7.6 and 9.1 mg/dl in groups I and II, respectively. They rose to 41.8 and 34.7 by 8 to 10 months of life. Plasma IgA concentrations were comparable for groups I and II in the 1st wk of life (1.2 and 0.6 mg/dl, respectively), but at 1 month of age group I infants had a transient increase in IgA which was not seen in the group II infants (4.5 versus 1.9 mg/dl, respectively, p less than 0.02). This transient elevation in IgA did not correlate with type or route of feeding or amounts of transfused blood. Group I and group II infants had comparable rates of infections prior to discharge from the nursery (p = 0.27). After discharge, the 43 preterm infants followed until 10 months chronological age had a significantly higher incidence of infections than 41 term infants (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
247 citations
TL;DR: It is suggested that effective lipolysis mediated by high GH and possibly low IGF levels, is an important adaptive mechanism to assure fuel (fatty acids) supply for metabolism of brain and peripheral tissues during nutritional deprivation.
Abstract: Serum insulin, growth hormone (GH), insulin-like growth factors (IGFs) I and II, cortisol, and albumin concentrations were measured in 15 children with kwashiorkor, 15 with marasmic-kwashiorkor, and 21 with marasmus, before and in the survivors, after nutritional rehabilitation, as well as in 10 underweight and eight normal Egyptian children. We also evaluated arginine-induced insulin and GH secretion. IGF-I concentrations were reduced in the three severely malnourished groups (0.07 ± 0.03, 0.05 ± 0.03, and 0.09 ± 0.09 U/ml, respectively) but returned to normal after refeeding. IGF-II concentrations were low in the kwashiorkor (175 ± 79 ng/ml), marasmic-kwashiorkor (111 ± 57 ng/ml), and marasmic children (128 ± 70.9 ng/ml) and returned to normal after nutritional rehabilitation. Basal GH levels were high in the three severely malnourished groups (21.9, 28.8, and 16.6 ng/ml, respectively) and returned to normal after refeeding (8.1, 6.5, and 6.0 ng/ml, respectively). GH responses to arginine were depressed in the three malnourished groups and improved significantly in marasmic-kwashiorkor and marasmic children after nutritional rehabilitation. Insulin responses to arginine were impaired in kwashiorkor, and marasmic-kwashiorkor children and improved significantly after refeeding. IGF-I levels correlated significantly with percent of expected weight (r=0.52, p<0.001), percent of expected height (r=0.42, p<0.001), and weight/ (height)2 index (r=0.34, p<0.01). IGF-I levels correlated positively with insulin levels (r=0.421, p<0.001) and negatively with cortisol concentrations (r=—0.400, p<0.001). It is suggested that effective lipolysis mediated by high GH and possibly low IGF levels, is an important adaptive mechanism to assure fuel (fatty acids) supply for metabolism of brain and peripheral tissues during nutritional deprivation.
232 citations
TL;DR: Low molecular weight, hydrophobic, surfactant- associated protein, SAP 6-14, was distinguished from SAP-35, the major glycoprotein in mammalian surfactants by amino acid composition, peptide mapping, and by resistance of SAP-14 to digestion by endoglycosidase F, collagenase, trypsin, and other proteases.
Abstract: . Hydrophobic protein of 6,000 and 14,000 daltons was isolated from mammalian pulmonary surfactant obtained from canine, human, and bovine alveolar lavage material. Low molecular weight, hydrophobic, surfactant- associated protein (SAP), herein referred to as SAP 6-14, was distinguished from SAP-35, the major glycoprotein in mammalian surfactants (the 35,000 dalton glycoprotein A or apolipoprotein A) by amino acid composition, peptide mapping, and by resistance of SAP 6-14 to digestion by endoglycosidase F, collagenase, trypsin, and other proteases. The amino acid composition of SAP 6-14 was found to be highly enriched in leucine and other hydrophobic amino acids. The characteristics of protein isolated from bovine replacement surfactant extracts utilized for the treatment of hyaline membrane disease in humans were also studied. SAP 6-14 isolated from calf lung surfactant replacement extracts (CLSE) and surfactant- TA were found to be identical to SAP 6-14 isolated from ether/ethanol extracts of various mammalian surfactants. By contrast, SAP-35, the major surfactant-associated glycoprotein of molecular weight=35,000, and other higher molecular weight proteins were not detected in significant quantities in the CLSE or surfactant-TA replacement surfactants, either by highly sensitive silver stain analysis or by immunoblot using monospecific antisera generated against bovine SAP-35. Biophysical studies of the CLSE replacement surfactant containing only SAP 6-14 and native phospholipids demonstrated full surface activity compared to natural lung surfactant. Dynamic surface tension lowering and adsorption properties of CLSE were essentially identical to those of freshly isolated bovine whole surfactant. Thus, hydrophobic SAP 6-14 is the only protein detected in bovine lung extract surfactants with full biophysical activity. The major surfactant associated protein, SAP-35, was not a significant component of either the CLSE or surfactant-TA replacement preparations.
228 citations
TL;DR: The results show a progressive increase of red blood cells and hemoglobin and no significant modification of hemostasis was observed over a 12-wk intrauterine gestation, which provides useful reference values for future investigations.
Abstract: Utilizing an easy and safe procedure for fetal blood sampling in utero we have studied 409 fetuses for prenatal diagnosis of rubella, toxoplasmosis, hemophilia, and hemoglobinopathies. Retrospectively we selected 163 fetuses confirmed as normal at birth and tested between 18 and 30 wk of gestation to establish normal hematological parameters and to follow the evolution of erythropoiesis, differential counts, hemoglobin synthesis, and hemostasis. Total white blood cell and platelet counts did not change during this period. The lymphocytes represented the main population and we observed a decrease of normoblasts during gestation. The results show a progressive increase of red blood cells and hemoglobin. This evolution is demonstrated by the ratio hemoglobin A to acetylated hemoglobin F. No significant modification of hemostasis was observed over a 12-wk intrauterine gestation. These results provide useful reference values for future investigations.
222 citations
TL;DR: Short-term oral treatment of human volunteers and rats with S.b. is associated with a marked increase in the activity of disaccharidases without morphological alteration of the intestinal mucosa, and the findings do not suggest an effect of S.B. on the incorporation rate of enzymes into the brush border membrane.
Abstract: To evaluate the response of the small intestinal mucosa to Saccharomyces boulardii (S.b.), a yeast widely used in some countries as an adjuvant drug with oral antimicrobial therapy, seven healthy adult volunteers were treated with high doses of lyophilized S.b. (250 mg four times per day) for 2 wk. A peroral jejunal suction biopsy was performed on days 0 and 15 of the study. Compared to the initial biopsy, histological examination of the posttrial biopsy revealed no morphological alteration nor change in villus height or crypt depth. After treatment, the specific activity (per U protein) of sucrase, lactase, and maltase was, respectively, increased by 82% (p less than 0.05) 77% (p less than 0.05), and 75% (p less than 0.05) over the basal activity of the enzymes measured on day 0, whereas mucosal protein content remained unchanged. Similar findings were found in the jejunum of adult rats treated for 5 days with either viable or killed S.b. cells. The changes in total enzyme activity (per jejunal segment) paralleled the changes in specific enzyme activity. In vitro assays on freshly prepared suspensions of S.b. (6.0 X 10(8) viable cells/ml) evidenced a high activity for sucrase (mean +/- SE: 8 364 +/- 1280 U X g X protein-1) but no maltase, neutral lactase, acid beta-galactosidase, or aminopeptidase activity. To determine whether treatment with S.b. could influence the incorporation rate of neutral lactase into the brush border membrane, 14-day-old sucklings treated either with saline or with S.b. were given intraperitoneally a dose of 20 microCi D-[1(14)C] glucosamine 3 hours before sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)
163 citations
TL;DR: It is concluded that the higher nonimmunoglobulin enterotoxin-inhibitory activity in human milk compared to bovine milk is associated with the differences in the ganglioside fraction.
Abstract: Milk gangliosides inhibit Vibrio cholerae enterotoxin and Escherichia coli heat-labile enterotoxin. Human milk gangliosides showed considerably higher enterotoxin-inhibitory activity compared to bovine and formula milk gangliosides as measured in vitro by enzyme-linked immunosorbent assay and in vivo in rabbit small bowel loops. While gangliosides from less than 1 ml human milk inhibited 0.1 microgram choleratoxin in vitro and in vivo, five to 10 times higher amounts of bovine milk gangliosides were necessary to achieve similar results. Analysis of the ganglioside composition in human, bovine, and bovine milk-based formula milk showed that the ganglioside patterns in human and bovine milk differed markedly. The ganglioside patterns of bovine milk and formula milk appeared identical. In human or bovine milk, the total amount of gangliosides was 11 mg/liter compared to 6 mg/liter in formula milk. The predominating ganglioside in human milk, monosialoganglioside 3 (74% of total gangliosides), was only a minor component (3%) of bovine milk gangliosides. Disialoganglioside 3 represented 80% of bovine milk gangliosides compared to 25% of the human milk gangliosides. Trace amounts of monosialoganglioside 1 were detected in human, as well as in bovine, milk by a sensitive high performance thin-layer chromatography immunoassay. The monosialoganglioside 1 content in human milk was 10 times higher than in bovine milk. We conclude that the higher nonimmunoglobulin enterotoxin-inhibitory activity in human milk compared to bovine milk is associated with the differences in the ganglioside fraction.
115 citations
TL;DR: Findings suggest that Sm- C/IGF I is synthesized in many human fetal tissues from as early as the 1st trimester and provide further evidence for an autocrine/paracrine role of this peptide growth factor.
Abstract: To investigate the possible role of somatomedin- C/insulin-like growth factor I (Sm-C/IGF I) in early human development, we measured this peptide by radioimmunoassay in extracts of multiple tissues and in plasma from fetuses during the first half of gestation (9-19 wk) All tissues contained Sm-C/IGF I far in excess of that which could be accounted for by Sm-C/IGF I derived from blood entrapment Lung and intestine had the highest concentrations (166 ± 35 mU/g, n=25 and 160 ± 20 mil/ g, n=19, respectively; mean ± SEM) and liver the lowest (67 ± 16 mU/g, n=26) Plasma concentrations were 270 ± 20 mU/ml (n=20) Neither fetal weight (6-258 g) nor gestational age correlated with Sm-C/IGF I concentrations in any tissue or in plasma These findings suggest that Sm- C/IGF I is synthesized in many human fetal tissues from as early as the 1st trimester They also provide further evidence for an autocrine/paracrine role of this peptide growth factor
109 citations
TL;DR: The present experiments have attempted to define the minimal hypoxic insult which impairs autoregulation in the newborn Iamb and to assess the time to recovery and found that cerebral autoreGulation was abolished after 20 min of hypoxia and recovered within 7 h.
Abstract: Autoregulation of cerebral blood flow has been demonstrated in both fetal and newborn animal models under normoxic conditions. In the present experiments we have attempted to define the minimal hypoxic insult which impairs autoregulation in the newborn lamb and to assess the time to recovery. We measured cerebral blood flow by the intracarotid 133Xe method in fifteen 4- to 9-day-old lambs and tested autoregulation of cerebral blood flow by increasing blood pressure 20-30% with phenylephrine. Autoregulation was tested in the control state and at successive time intervals after an hypoxic stress (PaO2 of 30 mm Hg) of 10 or 20 min. We found that cerebral autoregulation was abolished after 20 min of hypoxia and recovered within 7 h. Since this model identifies the minimal hypoxic insult to abolish autoregulation it might be used to study means to protect autoregulation or to hasten its recovery after hypoxia.
108 citations
TL;DR: Lung effluent phospholipids were studied in 29 small preterm infants with severe RDS and the saturated phosphatidylcholine/ sphingomyelin ratio increased during the surfactant-induced remission of respiratory failure, decreased during the relapse of respiratory Failure, and increased again during the recovery.
Abstract: . The turnover and pool size of surfactant has been studied in animals, but there is little similar information in humans. In the present investigation lung effluent phospholipids were studied in 29 small preterm infants with severe RDS. Thirteen were treated with mechanical ventilation, and 16 additionally received natural human surfactant. The first dose (60 mg surfactant/kg body wt) was given between 2 and 10 h of age, and the surfactant was given again if there was an insufficient response. Together 260 aspirates, recovered during routine suctioning of the airways, were analyzed for phospholipids. Phosphatidylglycerol, present only in exogenous surfactant, was used as a specific marker to estimate the apparent pool size and the half-life of surfactant phospholipid. In addition, the saturated phosphatidylcholine/sphingomyelin ratios were correlated with the ventilatory index (mean airway pressure x fractional inspiratory oxygen/arterial oxygen tension). There was a linear correlation between the ventilatory index and the saturated phosphatidylcholine/ sphingomyelin (r ~ -0.70) but no consistent correlation between the ventilatory index and the amount of phospholipids in the aspirate. The saturated phosphatidylcholine/ sphingomyelin ratio increased during the surfactant-induced remission of respiratory failure, decreased during the relapse of respiratory failure (present among 50% of the surfactant-treated infants), and increased again during the recovery. The control infants tended to have lower saturated phosphatidylcholine/sphingomyelin ratios during the first week than the surfactant-treated infants. The recipients of surfactant had slightly more severe lung disease than the controls, when the results were adjusted by covariance to remove the differences in the saturated phosphatidylcholine/ sphingomyelin ratio. Exogenous surfactant increased the apparent endogenous pool size at least fivefold. The apparent half-life of phosphatidylglycerol was 30 h (20–36 h). The half-life was independent of the amount of exogenous surfactant (60 versus 120 mg/kg). Therefore, the apparent turnover rate after 120 was higher than after 60 mg/kg surfactant (p<0.01).
108 citations
TL;DR: It is concluded that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed, qualitatively similar to that observed in adult animals, thus demonstrating developmental maturity of the fetus.
Abstract: . Acute hypoxemia was produced in chronically catheterized sheep fetuses to determine the response time necessary to increase plasma immunoreactive erythropoietin (Ep) concentration. Sodium nitrite (0.2 mM) was infused via a fetal vein to induce fetal hypoxemia. The resultant fetal methemoglobinemia was associated with a predictable, incremental decrease in arterial oxygen content. Twelve nitrite infusions were performed in eight fetal sheep preparations (gestational ages 115-146 days). Mean methemoglobin level increased to 33% of total Hb after 1- 2 h of NaNO2 infusion. These results were compared to those obtained in nine control studies in eight fetuses in which no change was observed for plasma Ep, arterial oxygen content, Pao2, pHa, or whole blood lactate. In the nitrite infused group, however, a significant and progressive increase in mean plasma Ep level over baseline levels was observed during the 4th and 5th h of hypoxemia (p<0.01). This change in Ep was significantly greater compared to the control group. These results, however, were confounded by the concomitant development of a lactic acidemia secondary to the fetal hypoxemia. To examine the theoretic possibility that lactic acidemia may primarily affect fetal Ep levels, an additional group of five fetuses was infused with L-lactic acid for the same time period. Although the decrements in pHa and whole blood lactate levels achieved in these fetuses were in excess of those observed during the nitrite infusions, this possibility was ruled out since no change in fetal plasma Ep levels occurred. We conclude that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed. This response of plasma Ep to hypoxemia in late gestation fetal sheep is qualitatively similar to that observed in adult animals, thus demonstrating developmental maturity of the fetus.
108 citations
TL;DR: The increased quantity of selected immune factors in the feces of very low birth weight infants fed FM may have resulted not only from passive ingestion and persistence of these factors throughout the gastrointestinal tract but also from endogenous synthesis induced by the feeding of human milk.
Abstract: . The amounts of lactoferrin, lysozyme, total IgA, secretory IgA (SIgA), and specific SIgA antibodies to a pool of Escherichia coli O antigens were measured in 96- h collections of feces obtained from 28 very low birth weight infants, 28-30 wk of gestation, studied at 2.5 and 6 wk of age. Eighteen of these infants were fed their mothers' milk fortified with fractions of skim and cream derived from pasteurized, lyophilized, mature human milk (FM) and 10 infants were fed commercial cow's milk-based formula. The concentrations of these selected immune factors in the FM and formula also were measured. Specific SIgA antibodies to E. coli O antigens were detected in the feces of 90% of the FM-fed infants, but in none of the feces of the formula-fed infants. The feces obtained from FM-fed infants had markedly greater quantities of lactoferrin (j><0.001), lysozyme (p=0.006), and IgA (p<0.001) than those of cow's milk formula-fed infants. The concentrations of total and secretory IgA were correlated significantly (r=0.88, p<0.001) and 95% of total IgA was SIgA. The fecal concentration of specific SIgA antibodies to E. coli O antigens in FM-fed infants correlated with the concentration of these antibodies in their milk (p<0.001). However, there were no direct relationships between the milk concentrations or the infants' intakes of the other selected immune factors and the excretion of these factors in the feces. Significant relationships were noted among the immune factors in the feces, but not among the concentrations of these factors in the fortified human milk. The increased quantity of selected immune factors in the feces of very low birth weight infants fed FM may have resulted not only from passive ingestion and persistence of these factors throughout the gastrointestinal tract but also from endogenous synthesis induced by the feeding of human milk.
TL;DR: The results suggest that glucose supply to the fetus may be limited in times of maternal hypoglycemia and that placental mechanism(s) may serve to buffer glucose transfer to the unborn child in conditions of hyperglycemia.
Abstract: The impact of varying maternal glucose concentrations on glucose uptake, transfer, and metabolism was investigated in the human placenta perfused in vitro. The rates of placental glucose uptake from the maternal perfusate and transfer to the fetal perfusate were significantly correlated with maternal glucose concentration up to 20 mM. Placental glucose utilization was also dependent upon maternal glucose concentration up to 17 mM. Between 3 and 53 mM maternal glucose, lactate production increased 3-fold while no change in oxygen consumption could be demonstrated. Correlatively, glucose storage was shown to increase dramatically above 10 mM maternal glucose. These results suggest that glucose supply to the fetus may be limited in times of maternal hypoglycemia and that placental mechanism(s) may serve to buffer glucose transfer to the fetus in conditions of hyperglycemia.
TL;DR: The distributions of lymphocyte subsets and monocytes in the peripheral blood mononuclear leukocytes of 72 normal children from 2 months to 135/12 yr were examined using quantitative immunofluorescence analysis with monoclonal antibodies.
Abstract: The distributions of lymphocyte subsets and monocytes in the peripheral blood mononuclear leukocytes of 72 normal children from 2 months to 135/12 yr were examined using quantitative immunofluorescence analysis with monoclonal antibodies. Distinct decreases with age were found in the total leukocyte counts, the percentages and the absolute numbers of peripheral blood mononuclear leukocytes. The percentages of Leu-2a+ cells, Leu-7+ cells, and Leu-M3+ cells significantly increased with age, whereas the percentages of Leu-3a+ cells, Leu-4+ cells, and 2H7+ cells significantly decreased with age. As a result, ratios of Leu-3a+/Leu-2a+ decreased with age. No prominent differences with age were found in the proportions of Leu-10+ cells and HLA-DR+ cells.
TL;DR: Tissue from CF patients consumed oxygen at a rate that was two to three times that of non- CF tissues and had 60% more ouabain binding sites than non-CF epithelium, which support recent findings that the sodium conductance of the apical cell membrane and net sodium absorption by CF nasal epithelia are greater than those ofnon-CF nasal epithellium.
Abstract: . Ion transport by the epithelium lining the airways of patients with cystic fibrosis (CF) is characterized by a raised transepithelial PD and an increased amiloride sensitivity (1). These properties could arise from normal sodium transport across an epithelium with decreased cell chloride permeability and limited chloride secretion. Alternatively, a higher than normal rate of sodium absorption could contribute to these abnormalities. We investigated the latter possibility by measuring oxygen consumption and specific ouabain binding of CF and atopic polyp epithelia and normal turbinate epithelium. Tissue from CF patients consumed oxygen at a rate that was two to three times that of non-CF tissues and had 60% more ouabain binding sites than non-CF epithelium. These results are not consistent with an isolated defect in chloride permeability but support recent findings that the sodium conductance of the apical cell membrane and net sodium absorption by CF nasal epithelium are greater than those of non-CF nasal epithelium.
TL;DR: It is concluded that even a short period of oligohydramnios interferes with lung development, and that the extent of this interference depends to a large extent on the time of onset and to a lesser extent on its duration.
Abstract: We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45, delta of -0.047 mg, p = 0.004; period B, days 45 to 50, delta of -0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, delta of -0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one-way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, delta of -0.072 mg, p = 0.001; period E, days 45 to 55, delta of -0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: CF lung fluids contain markedly increased levels of elastolytic activity which are closely linked to the extent of CF lung disease and which are capable of proteolytically generating C5a, an important mediator of inflammation by proteolysis of the C5 component of the complement system.
Abstract: Experiments performed in vitro have demonstrated that leukocyte neutral proteases produce an important mediator of inflammation, C5a, by proteolysis of the C5 component of the complement system. Cystic fibrosis (CF) lung fluids were characterized by high levels of neutrophils (39% of total cells versus 2% in normals) and contained significantly elevated amounts of elastolytic activity (mean 17.7 ng/micrograms total protein) compared to the lung fluids obtained from normal volunteers (0.2 ng elastolytic activity/micrograms protein, p = 0.001). The objective of these studies was to determine if complement activation and complement-derived chemotactic activity are present in CF lung fluids. C3c peptide representing activation of C3 could not be identified in the bronchial-alveolar lung lavage fluids of normal subjects but was readily identified by means of crossed immunoelectrophoresis in CF lung fluids (n = 9, mean 49% of C3); the mean level of C3 was decreased in CF lung specimens. Chemotactic activity was significantly elevated in lung fluids of the CF patients when compared to normal lung fluids. Using gel-filtration chromatography and a sensitive radioimmunoassay the chemotaxin present in CF specimens was identified as the anaphylatoxin C5a. C5a levels in the bronchial-alveolar lavage fluids of CF patients was inversely related to volume in liters expired in 1 s of a forced expiratory maneuver expressed as a percent of vital capacity determined from a forced expiratory maneuver (r = -0.72). Because there was a direct relationship between the total elastolytic activity present in CF airways and the concentration of C5a (r = 0.97, p = 0.03), it was postulated that airway proteases with elastolytic activity also cleave C5, nonimmunologically producing C5a. Detailed inhibition assays revealed that much of the total elastolytic activity had the inhibition profile of a serine proteinase. The levels of the serine proteinases were closely correlated with the numbers of neutrophilic leukocytes present per ml of lavage fluid (r = 0.7, p = 0.05). However, inhibitors of leukocyte serine proteases did not prevent the generation of additional chemotactic activity and the proteolysis of radiolabeled C5 substrate was not prevented by inhibitors of neutrophil elastase. Although the purified metalloelastase of Pseudomonas aeruginosa was active on cell-bound and free C5 yielding C5a, inhibition of this bacterial protease in CF lung fluids only partially blocked cleavage of the alpha- and beta-chains of C5.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: The data resolve the issue as to whether or not pure SM-C/IGF-I will induce growth in length and demonstrate the usefulness of recombinant IGF-I in the studies of growth regulation.
Abstract: . An Escherichia coli derived somatomedin-C/IGF-I preparation (rec-IGF-I) with an amino acid sequence identical to the natural IGF-I derived from human plasma, increases body length and weight, as well as the growth of several organs of Snell dwarf mice, when administered for 4 wk. After 2 wk of treatment rec-IGF-I (22.2 μ/day) induced a significant increase over buffer treated controls, to a comparable degree as obtained with bacterially synthesized human growth hormone (bhGH; 8.4 μ/day). The weight/length ratio of rec-IGF-I and bhGH-treated dwarf mice after 4 wk of treatment were not significantly different. A significant increase over controls was obtained with both preparations. Organs with increased weights after bhGH treatment (brain; submandibular salivary glands; heart, liver, kidneys, thymus, and spleen) were also heavier after rec-IGF-I. Significance was only reached for the kidneys and the spleen and the musculus quadriceps femoris. Organs weights expressed as a percentage of body weight of bhGH and rec-IGF-I treated dwarfs were similar except for the relative weight of the heart of the bhGH group, which was significantly increased compared to the controls and the rec-IGF-I group. These data resolve the issue as to whether or not pure SM-C/IGF-I will induce growth in length and demonstrate the usefulness of recombinant IGF-I in the studies of growth regulation.
TL;DR: The study suggests that the intradaily variation in energy expenditure in premature infants nursed according to present day techniques is almost equally due to the thermogenic effect of feeding and muscular activity, and to variations in muscular activity both representing a small fraction of the total energy expenditureIn premature infants.
Abstract: . In order to assess the contribution of the thermogenic effect of feeding and muscular activity to total energy expenditure, nine premature infants were studied for 2 consecutive days during which time repeated measurements of energy expenditure by indirect calorimetry were performed throughout the day, combined with a visual activity score based on body movement. The infants were growing at 16.6 ± 4.0 g/kg/day (mean ± SD) and received 110 ± 8 kcal/kg/day metabolizable energy (milk formula) and 522 ± 40 mg N/kg/day. Their total energy expenditure was 68 ± 4 kcal/kg/day indicating that 41 ± 7 kcal/kg/day was retained for growth. Based on the combination of energy + N balances it was estimated that 80% of the weight gain was fat-free tissue and 20% was fat tissue. The rate of energy expenditure measured minute-by-minute was significantly and linearly correlated with the activity score in both the premeal (r = 0.75; p < 0.001) and the postmeal periods (r = 0.74; p < 0.001) with no difference in the regression slope, but with a significant difference in intercept. In preset feeding schedules the latter allowed an estimation of the thermogenic effect without the confounding effect of activity. This was found to be 3.1 ± 1.8% when expressed as a percentage of metabolizable energy intake. However when the “classical‘’ approach was used as a comparison (integretation of extra energy expenditure induced by the meal), the thermogenic effect was found to be greater, i.e. 9.5 ± 3.8% of the meal's metabolizable energy, due to the superimposed effect of physical activity in the postprandial state. The study suggests that the intradaily variation in energy expenditure in premature infants nursed according to present day techniques is almost equally due to the thermogenic effect of feeding (3.2 kcal/kg/day), and to variations in muscular activity (3.6 kcal/kg/day) both representing a small fraction of the total energy expenditure in premature infants.
TL;DR: The data indicate that EGF enhances fetal rat lung phospholipid synthesis in a dose-dependent manner and suggest that this is a direct effect on the lung tissue mediated by specific receptors.
Abstract: . Epidermal growth factor (EGF) has been shown to enhance cell multiplication or differentiation in a number of developing tissues. We have examined the effects of this growth factor on the biochemical development of explants of fetal rat lung, cultured in serum-free medium for 48 h. EGF enhanced the rate of choline incorporation into phosphatidylcholine and disaturated phosphatidylcholine in a dose dependent fashion. Half maximal stimulation occurred at a concentration of 1.0 nM, similar to the Kd for EGF binding to rat lung cell membranes. There was also significant stimulation of acetate incorporation into all phospholipids, particularly phosphatidylglycerol (539%), and increased distribution of radioactivity from acetate in this phospholipid fraction. Exposure to EGF stimulated PC synthesis in 18- and 19-day explants (term is 22 days) whereas maximal enhancement of DNA synthesis occurred after this time. This sequence differs from that observed during early embryonic development when EGF initially enhances cell multiplication. An additive interaction with regard to enhancement of PC synthesis was observed with EGF and thyroid hormone, but not EGF and dexamethasone. EGF had no effect on the activity of the enzymes of the choline incorporation pathway of phosphatidylcholine synthesis or on the activity of enzymes involved with acidic phospholipid synthesis. Fetal lung EGF content and EGF binding capacity were not increased by glucocorticoid treatment and similarly glucocorticoid binding capacity was not increased by EGF. These data indicate that EGF enhances fetal rat lung phospholipid synthesis in a dose-dependent manner and suggest that this is a direct effect on the lung tissue mediated by specific receptors.
TL;DR: Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products as well as decreasing first-order kinetics with t1/2s of 273 and 254 min, respectively.
Abstract: Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products. We studied metabolic changes caused by these substances and their pharmacokinetics in a biochemically different urea cycle disorder, lysinuric protein intolerance (LPI), under strictly standardized induction of hyperammonemia. Five patients with LPI received an intravenous infusion of 6.6 mmol/kg L-alanine alone and separately with 2.0 mmol/kg of benzoate or phenylacetate in 90 min. Blood for ammonia, serum urea and creatinine, plasma benzoate, hippurate, phenylacetate, phenylacetylglutamine, and amino acids was obtained at 0, 120, 180, and 270 min. Urine was collected in four consecutive 6-h periods. Alanine caused hyperammonemia: maximum increase 107, 28-411 microM (geometric mean, 95% confidence interval); ammonia increments were nearly identical after alanine + benzoate (60, 17-213 microM) and alanine + phenylacetate (79, 13-467 microM) (NS). Mean plasma benzoate was 6.0 mM when extrapolated to the end of alanine + benzoate infusions; phenylacetate was 4.9 mM at the end of alanine + phenylacetate. Transient toxicity (dizziness, nausea, vomiting) occurred in four patients at the end of combined infusions, and we suggest upper therapeutic plasma concentrations of 4.5 mM for benzoate and 3.5 mM for phenylacetate. Benzoate and phenylacetate then decreased following first-order kinetics with t1/2S of 273 and 254 min, respectively. Maximal plasma hippurate (0.24, 0.14-0.40 mM) was lower than maximal phenylacetylglutamine (0.48, 0.22-1.06 mM, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.
Abstract: . An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2–4 days of life, significantly higher plasma ANP plasma levels (range 129–356 pg/ml, mean 227) were found compared with older infants and children (p<0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.
TL;DR: The data demonstrate that FRC can be measured easily and accurately in preterm and older infants using a N2washout technique and are in the same range as values obtained by other investigators using the N2 washout or He-dilution techniques.
Abstract: Functional residual capacity (FRC) was determined in 50 infants by a simplified N2 washout method. Fourteen infants were preterm, four full-term newborns and the rest were 1 month to 5 yr of age. Weight ranged from 1.19 to 25.8 kg. The method gave well reproducible values with a mean coefficient of variation of 3.9%. The FRC values are equally well correlated to weight and length (r = 0.98). The correlation with weight is linear, intercepting the x axis (FRC = 0) at a weight of 480 g, the one with length is best described by a power curve. The course of the regression lines reflects the observation that FRC per kg weight or per cm length is lower in neonates than in larger infants. The FRC measurements are in the same range as values obtained by other investigators using the N2 washout or He-dilution techniques. The values are significantly smaller than thoracic gas volume measurements obtained by plethysmography. This difference may be due to air trapping or to possible methodological problems with the plethysmographic technique. The data demonstrate that FRC can be measured easily and accurately in preterm and older infants using a N2 washout technique.
TL;DR: It is indicated that increased arterial pH, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs and possibly the pulmonary vasodilation in newborn infants with persistent pulmonary hypertension syndrome.
Abstract: Mechanically induced hyperventilation is used in the treatment of newborn infants with persistent pulmonary hypertension syndrome to induce respiratory alkalosis, which may attenuate their pulmonary vasoconstriction. Whether this treatment is effective because of the increase in arterial pH or the decrease in Paco2 was investigated in nine sedated, mechanically ventilated newborn lambs with hypoxia-induced pulmonary vasoconstriction. We found that respiratory alkalosis and metabolic alkalosis were equally effective in attenuating hypoxia-induced pulmonary vasoconstriction, but that hypocapnia (low Paco2 with a normal arterial pH) was ineffective. These results indicate that increased arterial pH, not decreased Paco2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs and possibly the pulmonary vasoconstriction in newborn infants with persistent pulmonary hypertension syndrome.
TL;DR: Surfactant-associated proteins, present in bovine lung-based replacement surfactants, are immunologically identified as SAP-6 and its oligomers.
Abstract: Hydrophobic, small molecular weight, surfactant-associated protein of Mr = 6000 (SAP-6) was isolated from bovine, canine, and human alveolar lavage and identified by silver staining after sodium dodecyl sulfate polyacrylamide gel electrophoresis gels. Lesser amounts of protein of Mr = 14,000, 20,000, and 26,000 daltons also copurified with SAP-6, likely representing oligomers of the Mr = 6,000 dalton protein. In the absence of sulfhydryl-reducing agents, increased amounts of the larger forms of the protein were observed. Antisera generated against bovine SAP-6 were used to further characterize the protein and distinguish it from the more abundant surfactant-associated glycoprotein of Mr = 35,000 (SAP-35) present in mammalian surfactants. Rabbit antisera generated against the bovine hydrophobic protein recognized SAP-6 and lesser amounts of the proteins of Mr = 14,000, 20,000, and 26, 000 daltons. The SAP-6 antisera were reactive against the hydrophobic proteins from human, bovine, and canine surfactants as assessed by immunoblot analysis after sodium dodecyl sulfate polyacrylamide gel electrophoresis. SAP-6 antisera did not detect bovine SAP-35 the abundant surfactant-associated glycoprotein, by immunoblot analysis; however, some reactivity of the anti-SAP-6 was detected against purified bovine SAP-35 by a sensitive enzyme-linked immune-adsorbant assay. Anti-SAP-6-did not react with bovine serum components either by immunoblot or by enzyme-linked immune-adsorbant assay. Monospecific antisera generated against bovine SAP-35 did not detect SAP-6 by immunoblot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Discriminant analysis showed that EEG changes were best predicted by the degree of blood-brain barrier opening and by the quality of serum bilirubin binding, which was not an important discriminator of encephalopathy.
Abstract: Experimental Bilirubin Encephalopathy: Importance of Total Bilirubin, Protein Binding, and Blood-Brain Barrier
TL;DR: It is suggested that further impairment of PMN chemotaxis in stressed neonates helps account for their increased susceptibility to overwhelming bacterial infection.
Abstract: . Defects in polymorphonuclear neutrophil (PMN) adherence and chemotaxis in neonates are thought to be an important cause of their increased susceptibility to overwhelming bacterial infection. Few studies of these functions have been carried out in stressed neonates who are at even greater risk of infection. PMN adherence and chemotaxis were examined in 33 stressed neonates with acute lower respiratory illness, 13 healthy neonates, and 43 healthy adults using whole blood PMN adherence and chemotaxis assays. PMN chemotaxis was significantly decreased in stressed neonates (locomotion index of 38.4 ± 9.7 µm) compared with that of healthy neonates (48.9 ± 12.8 µm, p<0.01) or adults (61.6 ± 11.9 µm, p<0.001). PMN chemotaxis was studied during illness and recovery in 13 of the 33 stressed neonates and showed significant improvement during recovery (41.6 ± 9.9 and 53.2 ± 11.9 µm, respectively, p = 0.012). PMN adherence was decreased in stressed neonates (1.4 ± 1.6%) compared with that of adults (12.3 ± 11.4%, p<0.01) but was similar to that of healthy neonates (1.1 ± 1.4%). These findings suggest that further impairment of PMN chemotaxis in stressed neonates helps account for their increased susceptibility to overwhelming bacterial infection.
TL;DR: The findings suggest that the increased number of jejunal receptors in the immature rat may, in part, explain the increased sensitivity and secretory response observed in vivo.
Abstract: . Escherichia coli which elaborate heat stable enterotoxin (ST) are a major cause of endemic diarrhea in infants. The reason(s) for this increased susceptibility of infants to ST-mediated diarrhea is unknown. We investigated the possibility that the immature (14 and 21 day old) rat small intestine is more sensitive to ST than is the adult. Initially we found there was a 600-fold increased jejunal sensitivity to ST in the immature animals as measured by dose required for half maximal secretion. Also there was a greater jejunal secretory response in the immature animals (14 ≥ 21 days old > adult). To determine the cause for this increased sensitivity and secretory response to ST, we examined: 1) binding characteristics of 125I-ST to brush border membrane (BBM) receptors and 2) membrane bound guanylate cyclase activation by ST in both immature and adult rats. Our findings demonstrate that more ST receptors are present in jejunal BBM from 14- and 21-dayold rats than in jejunal BBM from adult rats (2.34 ± 0.18, 2.85 ± 0.82, and 0.79 ± 0.13 × 1012 receptors/mg BBM protein, respectively), while the affinity of the BBM receptor for ST is similar at all three ages in both jejunum and ileum. Furthermore, both the jejunum and ileum of the rats of all three ages revealed an equal sensitivity of guanylate cyclase to activation by ST. These findings suggest that the increased number of jejunal receptors in the immature rat may, in part, explain the increased sensitivity and secretory response observed in vivo.
TL;DR: Serial measurements of bone mineral content, bone width, and the ratio of BMC:BW by photon absorptiometry of the left radius through the first 10 wk of life in 38 very low birth weight premature infants indicate a disorder of formation and/or remodeling of growing cortical bone.
Abstract: We report serial measurements of bone mineral content (BMC), bone width (BW, a measure of appositional bone growth), and the ratio of BMC:BW by photon absorptiometry of the left radius through the first 10 wk of life in 38 very low birth weight premature infants (birth weight less than 1300 g, gestational age less than 32 wk) Fifteen of 38 infants developed bronchopulmonary dysplasia (BPD) and as a group they could not be distinguished from the 23 infants without BPD, despite the high association between BPD and metabolic bone disease As BPD occurred in the smaller patients, the BPD group had a significantly lower mean birth weight and mean gestational age as compared to controls (950 +/- 125 g versus 1119 +/- 149, and 280 +/- 08 versus 290 +/- 13 wk) For both control and BPD groups, BMCs did not differ and remained relatively unchanged throughout the first 10 wk of life, lagging significantly behind the intrauterine rate as defined by measuring BMC in 175 infants of varying gestational ages during the first few days of life BW also did not differ during this period between groups BW did increase significantly in both groups (from 32 +/- 03 to 39 +/- 04 mm in the controls and from 30 +/- 03 to 38 +/- 04 mm in the BPD group), but remained significantly delayed compared to the intrauterine rate In both groups, BMC remained relatively constant despite increasing BW and thus BMC/BW decreased during the first 10 wk of life (from 115 +/- 13 to 102 +/- 19 in the controls and from 110 +/- 13 to 86 +/- 22 in the BPD group)(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: In contrast to older infants and adults, respiration and heart rate variability were not strongly related through a high frequency region respiratory sinus arrhythmia but rather through a breath amplitude sinus arrhythmia which occurs in the low frequency region of the spectrum.
Abstract: . The relationship between heart rate variability and respiration patterns was investigated using spectral analysis techniques in nine full-term infants whose ages ranged from 39-75 h. All the infants were studied during sleep, although no attempt was made to classify rapid eye movement or nonrapid eye movement states prospectively. The data obtained were examined to determine which aspects of neonatal breathing patterns are correlated with heart rate variability. Three spectral regions of heart rate variability could be identified: a very low frequency region below 0.02 Hz; a low frequency region from 0.02-0.20 Hz; and a high frequency region above 0.20 Hz. The dominant heart rate variability activity in these neonates was seen in the very low and low frequency regions, with little activity in the high frequency regions. In contrast to older infants and adults, respiration and heart rate variability were not strongly related through a high frequency region respiratory sinus arrhythmia but rather through a breath amplitude sinus arrhythmia which occurs in the low frequency region of the spectrum. The prominent very low frequency activity and the low frequency activity ascribed to breath amplitude modulation may result from autonomic nervous system mediation of chemoregulation.
TL;DR: The data show that, as in human adults, the endogenous glucose production in the newborn infant is regulated by plasma glucose and that prematurity and intrauterine growth retardation do not appear to have any significant effect on this regulation.
Abstract: The role of plasma glucose concentration in the regulation of endogenous glucose production in the human newborn was examined by infusing glucose at 2.6-4.6 mg/kg . min as a continuous infusion to eight normal term appropriate for gestational age infants, five preterm, and six small for gestational age infants. All infants were healthy, had no overt clinical problems and were studied 6 h after their last feed. Glucose production rates were measured during the basal state and during glucose infusion by tracer dilution using [6,6(2)H2]glucose. The rate of glucose production during the basal state was similar in preterm and term appropriate for gestational age infants (appropriate for gestational age 3.53 +/- 0.32, preterm 3.49 +/- 0.38 mg/kg . min, mean +/- SD), while it was higher in the small for gestational age infants (4.25 +/- 0.98, p less than 0.03) as compared with appropriate for gestational age. During glucose infusion, the peak glucose concentration was related to the rate of glucose infusion. The endogenous glucose production rates during glucose infusion were variable in the three groups. However, a negative correlation between peak glucose concentration and endogenous glucose production rate was observed (r = 0.59, p = 0.006). The insulin response to glucose infusion was comparable in all infants. In addition, three small gestational age and one preterm infants, who had become hypoglycemic in the immediate newborn period, were studied while they were receiving parenteral glucose and their plasma glucose had stabilized at 55.5 +/- 10.25 mg/dl. Tracer kinetic studies showed persistence of endogenous glucose production in these infants even though they were receiving high rates of exogenous glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)