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Biomedical subjects

I R Holzman

Publications and source records attributed to I R Holzman.

At least 55 records · Page 3Linked to original sources

Neonatal intestinal oxygen consumption during arterial hypoxemia.

In 12 chronically catheterized neonatal lambs, we determined intestinal tract blood flow (Qi) and O2 consumption (VO2i) at O2 contents of arterial blood (CaO2) ranging from 15.3 to 3.2 ml O2/dl blood. We measured Qi with the radioactive microsphere technique and computed intestinal O2 delivery (DO2i), VO2i, and O2 extraction (VO2i/DO2i) using the Fick principle. In lambs breathing air, mean Qi = 214 ml X min-1 X 100 g intestine-1, DO2i = 27.0 ml O2 X min-1 X 100 g-1, O2 extraction = 21%, and VO2i = 5.6 ml O2 Xmin-1 X 100 g-1. During reductions in CaO2, Qi and DO2i decreased. Intestinal O2 extraction increased sufficiently, however, so that VO2i was maintained over the range of CaO2 from 15.3 to about 6.5 ml O2/dl blood. VO2i was independent of Qi at Qi greater than 160 ml X min-1 X 100 g-1. When CaO2 was reduced below values of 6.5 ml O2/dl blood, corresponding to Qi less than 160 ml X min-1 X 100 g-1, VO2i fell in association with increases in the H+ concentration difference between mesenteric venous and arterial blood. These data indicate that the intestinal tract of the neonatal lamb can meet its oxygen requirements when O2 supply varies over a wide range. When O2 availability reaches a critically low level, intestinal anaerobic metabolism develops as the O2 supply to the neonatal intestinal tract becomes inadequate for the O2 demand.

Animals↗

Responses of lymphocytes from human colostrum or milk to influenza antigens.

Paired samples of peripheral blood and colostrum or milk were obtained from women 1 to 6 days after delivery. After Ficoll-Hypaque centrifugation, peripheral blood lymphocytes (PBL) and colostrum or milk lymphocytes (COL) were examined for surface membrane characteristics and in vitro proliferative reactivity. As determined by sheep red blood cell rosetting and by immunoglobulin-coated beads, PBL showed an average of 54% T and 12% B lymphocytes, whereas COL showed 33% T and 22% B rosettes, respectively. Paired samples of PBL and COL were used for lymphocyte transformation with three distinct strains of influenza virus: A/USSR, A/Victoria, and B/Hong Kong. Of COL from nine subjects tested against all three strains of influenza virus, five samples (56%) gave positive responses to at least one. These studies indicate that COL contain cells responsive in vitro to several influenza antigens. Such sensitized cells may provide a mechanism for the transfer of antigen responsiveness and protection from the mother to the neonate.

Antigens, Viral↗

Results of feeding a special formula to very low birth weight infants.

Fifty-eight premature infants weighing less than 1,600 g at birth were fed a special formula. The formula contained nutrients in amounts recommended by the Committee ono Nutrition of the American Academy of Pediatrics for very low birth weight (VLBW) infants. The feeding studies were carried out at newborn nurseries in Tampa, Florida (study A, n = 25), Pittsburgh, Pennsylvania (study B, n = 20), and Oaklawn, Illinois (study C, n = 13). Study subjects were comparable in birth weight, gestational age, and in the duration of follow-up in the nurseries. All study subjects grew at rates of weight acquisition equivalent to the comparative fetal counterpart. Routine anthropometric measurements were similar to those of fetal development curves. Mean protein intake ranged from 2.3 to 3.7 g/kg/day and mean caloric intake from 105 to 150 kcal/kg/day. Late metabolic acidosis in association with prematurity was absent in all subjects studied as demonstrated by normal pH values, bicarbonate, and partial pressure of carbon dioxide. Serum sodium and serum chloride levels were normal. Serum calcium ranged from 8.3 to 10.1 mg/dl and serum phosphorus from 6.0 to 7.5 mg/dl. Total serum protein levels ranged from 4.5 to 5.1 g/dl. Blood urea nitrogen diminished progressively from 5.1 to 2 mg/dl in the course of the study. Serum glucose levels in samples taken prior to and 2 h after feeding did not demonstrate any evidence of reactive hypoglycemia.

Blood Glucose↗

Fetal intestinal oxygen consumption at various levels of oxygenation.

In seven chronically catheterized fetal lambs, blood flow and oxygen consumption (VO2) in the combined small and large intestines were determined at various oxygen concentrations in fetal arterial blood (CaO2). Intestinal blood flow (Qi) was measured with the radioactive-microsphere technique; intestinal oxygen delivery (DO2 = Qi X CaO2), VO2 [Qi X C(a-v)O2, where oxygen extraction [C(a-v)O2/CaO2] were computed with the Fick equation. Compared with normally oxygenated fetuses (CaO2 greater than 6.6 ml/dl), moderately hypoxemic fetuses (CaO2 = 4.4-6.6 ml/dl) had decreased intestinal DO2, increased oxygen extraction, and no change in intestinal VO2, Qi, or mesenteric-venous pH and base excess. During severe fetal hypoxemia (CaO2 less than 4.4 ml/dl), DO2 decreased further while oxygen extraction increased substantially. Intestinal VO2 dropped, however, because the rise in oxygen extraction could no longer completely compensate for the reduced DO2. With severe hypoxemia, Qi and mesenteric-venous pH and base excess also fell. These data indicate that the fetal intestinal tract is able to meet its oxygen needs during hypoxemia until a critically low level of oxygenation is reached. Below this level intestinal oxygenation becomes inadequate, and anaerobic metabolism ensures.

Animals↗

Intragastric feeding in the neonatal dog. Its effect on intestinal osmolality.

Hypertonic formulas have been implicated in the etiology of necrotizing enterocolitis. We measured the osmolality of neonatal canine intestinal contents one hour after intragastric feeding of isotonic breast milk, isotonic formula, or hypertonic formula in 1-day-old and 9-day-old puppies. Regardless of the formula tonicity, all intestinal contents were hypertonic in both segments. Hypertonic formula had been diluted, and isotonic feedings concentrated in the neonatal canine intestine. Gastric contents could be recovered only from hypertonic-fed puppies, which implies delayed gastric emptying to permit formula dilution. We conclude that any form of neonatal feeding can lead to hypertonic intestinal contents. Factors other than tonicity of a formula should be considered in the pathophysiology of necrotizing enterocolitis.

Animals↗

Oxygen consumption by the gastrointestinal tract and liver in conscious newborn lambs.

We determined blood flow to and O2 consumption (VO2) by the gastrointestinal tract (GI) and liver and also measured cardiac output and whole-body VO2 in nine chronically catheterized unanesthetized lambs (7-16 days of age). Blood flows were calculated with the radionuclide-labeled microsphere technique, and blood O2 contents were measured with an O2 content analyzer. During the fasting state, GI blood flow was 58 +/- 4 (means +/- SE) ml.min-1.kg body wt-1; GI VO2 was 1.4 +/- 0.1 ml O2.min-1.kg-1. Neonatal GI VO2 was linearly related to both GI blood flow and O2 delivery (DO2). GI O2 extraction [(VO2/DO2).100] averaged 28% and did not vary with blood flow or DO2. Liver blood flow was 73 +/- 4 ml.min-1.kg-1 (271 +/- 23 ml.min-1.100 g liver-1), and liver VO2 was 2.0 +/- 0.1 ml O2.min-1.kg-1 (7.3 +/- 0.5 ml O2.min-1.100 g-1). Hepatic O2 extraction varied from 18 to 81% . VO2 by the neonatal liver did not correlate with liver blood flow or DO2. Hepatic O2 extraction, however, was inversely related to liver DO2. Our data indicate that the gastrointestinal tract and liver of the unanesthetized newborn animal exhibit O2 demands 1.5-3 times those reported in the adult. The neonatal gastrointestinal tract meets its O2 demands with a comparatively large blood flow and O2 delivery, whereas the neonatal liver provides for its O2 requirements by varying its O2 extraction.

Animals↗

Gastrointestinal tract O2 uptake and regional blood flows during digestion in conscious newborn lambs.

We determined gastrointestinal tract O2 uptake, cardiac output, regional blood flows, and whole-body O2 uptake before and for 1-6 h after feeding in 10 chronically catheterized unanesthetized lambs (9-15 days of age). Total gastrointestinal blood flow (sum of blood flows to the stomach, small intestine, and colon, as calculated with the radioactive microsphere technique) increased 23% at 1 h postprandially. This increased flow at 1 h was due to a large increase in blood flow to the stomach, whereas blood flows to the small intestine and colon did not change significantly. By 2 h, stomach blood flow and thus total gastrointestinal blood flow had returned to fasting values. In contrast, total O2 uptake by the gastrointestinal tract organs (stomach, small intestine, and colon) increased 65% at 1 h, 51% at 2 h, and 28% at 3 h postprandially in association with increases in O2 extraction (O2 uptake/O2 delivery) of 41% at 1 h, 45% at 2 h, and 27% at 3 h. There were no digestion-related changes in whole-body O2 uptake or in cardiac output and its distribution to the brain, heart, kidney, liver (hepatic artery), and carcass. Our data indicate that postprandial increases in O2 demand by gastrointestinal tract organs of the newborn animal are met primarily by enhanced tissue O2 extraction, rather than by metabolic hyperemia, because the postprandial hyperemia observed in the neonate is of short duration and is confined to the stomach.

Animals↗

Sequential changes in placental blood gases and pH during the hour following delivery.

We studied the effect of a delay in blood sampling on the measurement of placental blood gases, pH and calculated bicarbonate. Blood was sampled serially at 15-minute intervals during the hour following delivery from placentas and attached umbilical cords of unasphyxiated term neonates. Placentas and attached cords were stored at room temperature. When blood was sampled exclusively from the segment of the umbilical vein lying within the umbilical cord, there were no statistically significant changes during the time of study in pH, PCO2 or PoO2. When some or all of the serial samples were taken from vessels on the surface of the placenta, there was a statistically and biologically significant decrease in the pH and increase in the PCO2 values of the blood. Our results indicate that the validity of the measurements of umbilical venous blood gases and pH is not affected by up to an hour's delay in blood sampling.

Bicarbonates↗

Glucose polymer tolerance in premature infants.

Some formulas designed for premature infants contain glucose polymer (GP) as part of their carbohydrate content. GP tolerance tests and lactose tolerance tests were performed on 11 healthy premature infants at 2 to 3 weeks of age to compare their ability to digest and absorb GP and lactose. Total plasma reducing substances (TPRS), plasma insulin (PI), and plasma glucose were measured 10 minutes before and 30, 60, and 120 minutes after the oral carbohydrate test meal. Lactose and GP stimulated a significant increase in TPRS at 30 and 60 minutes and produced similar glycemic responses. However, GP stimulated PI response whether measured as the area under the PI response curve or as the PI/TPRS ratio. It was concluded that although GP and lactose evoke similar glycemic responses, they differ in their abilities to stimulate insulin secretion. The mechanism controlling this differential insulin response is unknown.

Administration, Oral↗

Fluid administration and bronchopulmonary dysplasia. The lack of an association.

The fluid intake of 38 surviving infants with severe respiratory distress syndrome was evaluated. There were no substantial difference in fluid administration between those in whom bronchopulmonary dysplasia (BPD) developed and those in whom it did not. The factors that were associated with the development of BPD were the degree of prematurity, patent ductus arteriosus, pulmonary air leak, exposure to high concentrations of oxygen, and use of ventilation at faster rates.

Ductus Arteriosus, Patent↗

Hyaline membrane disease. A controlled study of inspiratory to expiratory ratio in its management by ventilator.

Sixty-nine neonates with severe hyaline membrane disease (HMD) were mechanically ventilated using either a 1:2 or a 2:1 inspiratory to expiratory (I/E) ratio. Survivors in the 2:1 group required a lower fraction of oxygen in the inspired air (FiO2) and lower end-expiratory pressure to achieve satisfactory oxygenation. During the first week of life, time of exposure to FiO2 greater than 0.60 while being mechanically ventilated was 29.7 +/- 7.5 hours for the 1:2 group and 6.6 +/- 2,7 hours for the 2:1 group, while time of exposure to end-expiratory pressure greater than 3 cm H2O was 49.4 +/- 7.9 hours for the 1:2 group and 13.4 +/- 7.4 hours for the 2:1 group. Mortality and the incidence of air leak, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, and pulmonary hemorrhage were not different for the two groups. Using an increased I/E ratio during the acute phase of HMD improved oxygenation but did not alter morbidity or mortality.

Carbon Dioxide↗

Nonimmunologic hydrops fetalis: a review of 19 cases.

Nineteen cases of nonimmunologic hydrops fetalis occurring during a nine-year period were reviewed. The pregnancies were complicated by hydramnios (78%) and preterm delivery (84%). Hydramnios appears to be the most useful indicator of the pregnancy at risk; its occurrence should prompt ultrasonographic investigation for evidence of hydrops. Modalities available for antenatal diagnosis of underlying fetal abnormalities include amniocentesis, serologic tests, fetal cardiac monitoring, radiography, hemoglobin electrophoresis and glucose tolerance testing. A specific cause for the hydrops may not be detectable (42% of our cases were idiopathic). Management of affected pregnancies is influenced by the frequent occurrence of fetal asphyxia and premature delivery. Outcome is poor: only 32% of the babies survived beyond the neonatal period. Symptomatic treatment for the neonate includes fluid restriction, maintenance of blood sugar, support of ventilation and attention to the complications of asphyxia.

Adult↗

Nutritional rickets in 2 very low birthweight infants with chronic lung disease.

Two very low birthweight infants with rickets are described; one had a low serum 25-hydroxy-vitamin D3 concentration. Similarities in their clinical courses included low birthweights, low calcium intakes, uncertain vitamin D intakes, and chronic administration of frusemide and sodium bicarbonate--all potential aetiological factors in the development of bone undermineralisation. Both infants had a resolution of their chronic lung disease before their treatment for rickets. This experience has led us to the more cautions use of frusemide and sodium bicarbonate in infants at risk for rickets, and shows the need to ensure daily vitamin D supplements.

Bicarbonates↗

Catheterization of the posterior tibial artery in the neonate.

Catherization of the posterior tibial artery provides an alternative to cannulation of other arteries. We successfully catheterized this artery 17 times in 15 neonates whose weights ranged from 800 to 3,000 g. The catheters were placed percutaneously 13 times and by cutdown four times, and they remained in place for as long as 12 days (mean, 96 hours). Compromise of distal circulation was found in only two babies, both of whom had had umbilical artery catheters removed because of cyanosis of the toes that had resolved itself prior to posterior tibial artery cannulation. Our patients experienced no short-term complications from this procedure.

Arteries↗

Glucose metabolism, lactate, and ammonia production by the human placenta in vitro.

Fifteen human placentas were obtained at term. Placental fragments were incubated in a bicarbonate-buffered Earle's solution. Additions of glutamate (1 mM) or glutamine (1 or 2 mM) were made. All incubations showed a net utilization of glucose. There was a striking variability among placentas in the net glucose utilization rate (1.27 mumoles/g/hr-11.44 mumoles/g/hr, coefficient of variation = 62%). The intraplacental coefficient of variation in glucose utilization was only 14%. All placental incubations showed a net production of both lactate (mean = 7.5 mumoles/g placental wet weight/hr) and ammonia (mean = 3.5 mumoles/g placental wet weight/hr). There was no correlation between lactate of ammonia production and glucose utilization. The addition of sodium glutamate (1 mumole/ml) produced no change in glucose utilization or ammonia production. The addition of glutamine (1 and 2 mumoles/ml) produced a significant increase in ammonia production over that found in the controls, but no change in glucose utilization. Incubation with 2 mumoles glutamine/ml demonstrated an increase in lactate production. All incubations showed a striking increase in ammonia concentration after 45 min of incubation. Individual placentas may differ markedly in their ability to utilize glucose in an in vitro system. Ammonia production may be a normal metabolic endproduct in a tissue lacking an active urea cycle or a byproduct of the purine nucleotide cycle.

Ammonia↗