Biomedical subjects
Publications and source records attributed to A J Rudolph.
This is a report of the histochemical and ultrastructural analysis of nevus cell aggregates in the placenta from a neonate with a giant pigmented nevus. Although the distinction between aberrant migration of neural crest elements and blood-borne metastasis from the giant pigmented nevus is not readily resolved, the authors favor the former as an explanation of this unusual placental lesion.
In a group of infants with hyaline membrane disease, the level of optimal constant positive airway pressure (CPAP) was assessed by raising CPAP in small steps from an initial low value, and after each change measuring the arterial alveolar difference for CO2 (aADCO2) and transmission of airway pressure to the esophagus. Below optimal CPAP there was a progressive increase in mixed alveolar partial pressure of CO2 (PACO2) and no change in arterial partial pressure of CO2 (PaCO2), so that aADCO2 declined and reached a lowest value at optimal CPAP. Correspondingly, transmission of airway pressure increased progressively and reached a highest value at optimal CPAP. Between 1 step below and optimal CPAP, PACO2 rose from 30.9 to 34.0 torr, and aADCO2 declined from 16.6 to 12.7 torr. Between optimal and 1 step above optimal CPAP, PaCO2 increased from 46.7 to 51.0 torr, PACO2 rose slightly, and aADCO2 increased from 12.7 to 15.6 torr. Thus, the aADCO2 was an excellent index of optimal CPAP. In five patients with measurements of PaO2 at constant fractional inspired oxygen, calculated values for arterial oxygen saturation changed from 80.8 to 91.5 to 92.2%, and calculated values for venous admixture changed from 0.61 to 0.48 to 0.46 as CPAP was raised from 1 step below through optimal to 1 step above optimal CPAP. The results are interpreted to mean a progressive improvement in perfusion of well ventilated lung units as CPAP increased to optimal levels, but a significant reduction of both ventilation and perfusion above optimal CPAP.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of newborn nutritional inadequacy is one of the major areas in perinatal medicine where intervention can influence outcome. An infant's failure to thrive may be the result of prenatal and/or post-natal causes. Management of failure to thrive in the newborn infant must include identification of the problem, establishment of an efficient therapeutic regimen and means of evaluating the morbidity which may occur.
Lung distension is associated with increased phospholipid secretion into the air spaces. Basal, lavage-induced, and inflation-produced phospholipid secretion, in postmortem in situ lungs of newborn rabbits, were examined at three different levels of maturity, with and without 10(-3) M dl-propranolol. Lungs were lavaged with saline at successive 3- and 15-min time intervals to separate basal from lavage-induced secretion. Inflation-produced secretion was studied after static inflation at 30 cmH2O for 30 min. At 27.5 days gestation, basal secretion was undetectable, and neither lavage-induced nor inflation-produced secretion were influenced by propranolol. At 29.5 days gestation, basal secretion was only just detectable. Distension-associated secretion was increased over that present at 27.5 days gestation, and propranolol had a significant inhibitory effect, especially on lavage-induced secretion, in which the inhibition was shown to be rapidly reversible. There was a significant increase of basal secretion at 2.5 days postterm, possibly inhibited by propranolol. In addition, there was a further substantial increase of distension-associated secretion, and the inhibitory effect of propranolol persisted. These changes were independent of the sedimentation behavior of lavaged phospholipid. Overall, the results are consistent with evidence, produced in other laboratories, that there is an increasing density of sympathetic neurons and beta-adrenergic receptors in whole lung preparations during late gestation in the rabbit and suggest that granular pneumocytes, the presumed source of secreted phospholipid, take part in this developmental change.
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A total of 570 patients, aged less than 24 months, who were seen in the emergency room at Texas Children's Hospital for evaluation of acute febrile illness had a WBC count, differential count, and a blood culture obtained. Bacteremia occurred in 7.7% (n = 44) (22 Haemophilus influenzae; 17 Streptococcus pneumoniae; three Escherichia coli; one group B Streptococcus; one Staphylococcus aureus). The sensitivity, specificity, and positive predictive value of morphologic changes (vacuolization and toxic granulation) of polymorphonuclear neutrophils (segmented neutrophils plus band cells), WBC count greater than or equal to 15,000/microL and band cells greater than or equal to 500/microL were examined. Additionally, abnormalities in three of four tests (WBC count greater than or equal to 15,000/microL, band cells greater than or equal to 500/microL, segmented neutrophils greater than or equal to 10,000/microL, and/or total polymorphonuclear neutrophils greater than or equal to 10,500/microL) were evaluated. Morphologic changes of polymorphonuclear neutrophils were noted frequently in patients with culture-proven bacteremia (63% and 51% positive predictive value for vacuolization and toxic granulation, respectively) and were more predictive of bacterial infection than traditional tests. If both vacuolization and toxic granulation were present, the positive predictive value increased to 76%. Examination of the peripheral blood smear may provide important adjunctive information for the presence of bacteremia prior to bacteriologic confirmation.
Three clinical trials enrolling 418 infants (less than or equal to 1500 g birth weight) and an ultrastructural data base of 71 pairs of whole eye donations have elucidated the efficacy of vitamin E in suppressing the development of severe retrolental fibroplasia (ROP). Only continuous vitamin E supplementation to adult physiologic levels from the first hours of life suppresses the development of severe ROP. Supplementation does not increase the incidence of necrotizing enterocolitis, sepsis, intraventricular hemorrhage, or mortality. Only multivariate analysis, which considers all risk factors simultaneously, is appropriate when appraising the efficacy of supplementation since all the clinical risk factors uniquely impinge on the oxygen dynamics of the developing retina. Mesenchymal spindle cells are the cellular mediators of the induction of ROP by oxygen in which increased oxygen tension triggers extensive gap junction formation between adjacent spindle cells. This cellular event, which occurs as early as four days of life, halts the normal vasoformative process and triggers neovascularization, which becomes clinically evident some 8 to 12 weeks later.
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Hypoxic ischemic encephalopathy is a major cause of mortality in neonates. Studies in experimental subjects have shown differing responses of plasma arginine vasopressin to hypoxia. Plasma arginine vasopressin levels, serum osmolality, urine osmolality and fluid intakes were measured in thirteen asphyxiated and nineteen control newborn infants during the first seventy-two hours of life. In the asphyxiated infants plasma arginine vasopressin was found to be elevated as compared to control infants on days one (p less than 0.001) and two (p less than 0.007) but not on day three of life. Urine osmolality was also elevated in the study patients on days one (p less than 0.01) and two (p less than 0.001) but not on day three, in spite of equal intakes of fluid on day one in both groups and significantly diminished fluid intake on days two and three in the study patients. Serum osmolality was not different between the two groups on any day studied, and was felt to be on the basis of diminished intake in the study infants. The data presented in this study support the concept that arginine vasopressin release occurs following perinatal asphyxia in term newborn infants.
The steady-state pharmacokinetics, renal function and quantitative beta 2-microglobulin (beta 2-M) excretion were prospectively evaluated in 22 very low birth weight (VLBW) infants (700-1,470 g birth weight and 25-33 weeks gestational age) receiving 2.4 mg/kg gentamicin at randomly assigned 12- or 18-hour dosing intervals. Gentamicin trough concentrations were significantly lower in only those infants greater than 1,000 g birth weight on the 18-hour schedule (p less than 0.05). ESTRIP analysis of gentamicin disposition at steady state revealed a biexponential function with half-life (mean +/- SEM), 9.78 +/- 0.86 h, plasma clearance 0.64 +/- 0.06 ml/kg/min and volume of distribution 0.50 +/- 0.03 liter/kg. Serum creatinine at steady state correlated with half-life (p less than 0.01), plasma clearance (p less than 0.01), and trough levels (p less than 0.001). Despite the frequent occurrence of gentamicin trough levels persistently greater than 2.0 micrograms/ml, renal function matured normally as serum creatinine progressively decreased (p less than 0.001) and creatinine clearance progressively increased (p less than 0.001) with advancing conceptional age. Urinary excretion of beta 2-M, thought to be a marker of proximal tubular damage from gentamicin, did not correlate with elevated trough levels, and was in fact lower in those infants with the highest measured trough levels (p less than 0.001). Nephrotoxicity was suspected in only 2 infants both of whom had additional renal insult during the first few days of life. Despite the frequent occurrence of elevated gentamicin trough levels and prolonged elimination half-life in these VLBW infants, their renal function matured normally throughout therapy and nephrotoxicity from gentamicin, as evidenced by beta 2-microglobulinuria, did not occur.
Aminophylline treatment of pregnant rabbits for 2 days, beginning at 25.5 days gestation, produced a significant increase in total phospholipid in fetal lung tissue at 27.5 days gestation, 8.92 +/- 0.76 (mean +/- SEM) mg/g wet lung weight, compared with 5.46 +/- 0.83 in saline-injected control animals (p less than 0.005). Three lines of evidence suggest this was not related to the surfactant system: (1) there was no increase in disaturated phosphatidylcholine in fetal lung tissue, (2) there was no increase in total phospholipid harvested by lung lavage after static lung inflation, and (3) there was no change in the lung deflation pressure-volume curve or stability index. Aminophylline treatment produced no acceleration in general anatomic lung development, as reflected in the ratio of lung air-space capacity to lung tissue weight. Under similar experimental conditions, maternal caffeine treatment had no effect on fetal rabbit lungs.
A review was made of 195 peripheral blood smears of 157 neonates who required sepsis work-up in the first month of life. Degenerative changes of neutrophils including vacuolization and toxic granulation were observed frequently in infants with culture-proven bacterial sepsis. Of 21 peripheral blood smears from 20 neonates subsequently proven to have bacterial infection, 17 had vacuolization present in the neutrophils for a sensitivity of 81%, a specificity of 93%, and a positive predictive accuracy of 59%. Toxic granulation changes in neutrophils showed similar results. This simple test can be performed easily in all hospitals; it does not require special laboratory facilities. The test appears to provide a valuable adjunct in the early detection of neonatal bacterial infection.
To determine whether early intramuscular vitamin E supplementation influences the incidence of intraventricular hemorrhage (IVH) in infants with birth weight less than or equal to 1,500 g, data were analyzed from 134 infants enrolled on a protocol to evaluate the efficacy of intramuscular plus oral vitamin E v oral supplementation alone in the treatment of retrolental fibroplasia. All 134 infants received, via nasogastric tube, 100 mg/kg/d of vitamin E daily (dl-alpha-tocopheryl acetate in MCT [medium-chain triglyceride] oil; 150 mosM) for at least 8 weeks with the first dose administered within the first eight hours of life. Sixty-four patients received, in addition, intramuscular vitamin E on days 1, 2, 4, and 6 of life and 70 patients received placebo injections in a randomized double-blind fashion. In the first week, vitamin E plasma levels were significantly higher in the 64 patients given intramuscular vitamin E. In spite of this difference no change in the incidence of sepsis or necrotizing enterocolitis was observed. Both the incidence and severity of intraventricular hemorrhage were reduced significantly in the patients given intramuscular vitamin E as compared to the patients given placebo (P = .013 and P = .04, respectively). The data suggest that vitamin E, a natural antioxidant, may play an important role in protecting the CNS microcirculation from the effects of hypoxic/ischemic injury.
To evaluate the efficacy of four early intramuscular injections of vitamin E given in addition to continuous minimal oral vitamin E supplementation, 168 very low-birth-weight infants (less than or equal to 1,500 g) have enrolled in a randomized, double-masked, clinical study. All infants received vitamin E orally, 100 mg/kg/d. In addition, on days 1, 2, 4, and 6, seventy-nine infants received vitamin E intramuscularly, 15, 10, 10, and 10 mg/kg, respectively. On the same days, 89 control infants received placebo intramuscular injections. Multivariate analysis of the 135 infants who survived greater than or equal to 10 weeks showed no significant difference in the development of severe retrolental fibroplasia between these two supplementation schedules (P = .86). Plasma vitamin E levels never exceeded a mean of 3.3 mg/100 mL, and no toxicity was observed. Ultrastructural analyses of seven pairs of whole eye donations from infants receiving IM vitamin E demonstrated identical kinetics of gap junction formation between adjacent spindle cells as compared with 13 pairs of whole eye donations from control infants (P greater than .3). Therefore, oral vitamin E supplementation affords retinal protection against the development of severe retrolental fibroplasia when initiated on the first day of life and maintained continuously until retinal vascularization is complete.
The secretion of total phospholipid in postmortem in situ lungs of newborn rabbits was examined using the technique of lung lavage after an initial lavage procedure, and then after a period of static air inflation at 30 cm H2O pressure for 45 min. There was a significant reduction in the phospholipid yield with 10(-3) molar DL-propranolol used as the initial lavage fluid, both immediately after the initial lavage procedure (experimental group, 0.29 +/- SE 0.04 mg/g dry lung weight; control group, 0.57 +/- SE 0.09; p less than 0.01) and after static inflation with air (experimental group, 1.14 +/- SE 0.15; control group, 2.22 +/- SE 0.24; p less than 0.001). Preinjection of the breathing newborn rabbit with DL-propranolol was not necessary for this inhibitory effect. There was no significant reduction when 10(-3) molar atropine, lidocaine, D-propranolol, or 10(-5) scopolamine were substituted as the initial lavage fluid, nor was there any reduction when the concentration of DL-propranolol was decreased to 10(-4) or 10(-5) molar. Because D-propranolol has all the properties of DL-propranolol, except 100-fold less beta-adrenergic antagonist activity, the inhibition by propranolol was due to specific beta-adrenergic blockade. In the absence of an intact circulation or a functional central nervous system, it is concluded that surfactant phospholipid secretion is partly controlled by an intrapulmonary neurogenic reflex.
Soft tissue calcification has been reported following the intramuscular injection of calcium salts and the intravenous administration of calcium gluconate. The present case report describes a neonate in whom calcification of the superficial scalp veins developed following administration of calcium chloride and sodium bicarbonate through a scalp vein needle.
To further evaluate the efficacy of oral vitamin E in preventing the development of severe retrolental fibroplasia (RLF) in very low-birth-weight infants, 100 infants treated with 100 mg/kg/d of vitamin E (dl-alpha-tocopheryl acetate) were compared with 75 infants treated with 5 mg/kg/d of vitamin E (dl-alpha-tocopherol) in the same nursery during the previous year. All 175 infants weighed less than or equal to 1,500 g at birth and required supplemental oxygen. A total of 120 infants (69 treatment; 51 control) survived greater than or equal to 10 weeks. Multivariate analysis of the control population identified five risk factors (P less than or equal to .10): gestational age, level and duration of oxygen administration, intraventricular hemorrhage, sepsis, and birth weight. When multivariate analysis was applied to both control and treatment groups, the severity of RLF was found to be significantly reduced in infants given the treatment dose of vitamin E (P = .003). Ultrastructural analyses of 58 pairs of whole-eye donations from high-risk infants surviving less than 10 weeks suggest that the initial morphologic event is gap junction increases between the plasma membranes of adjacent spindle cells of the van-guard retina. Such extensively gap junction-linked spindle cells are apparently removed from the vasoformative process as early as 4 days of life, forming a barrier to further normal vascular development and triggering retinal and vitreal neovascularizations approximately 8 weeks later. These events are maximally suppressed by elevated plasma vitamin E levels in infants greater than or equal to 27 weeks gestational age.
A large retrospective clinical study is reported confirming pathologic studies upon the effect of hyaline membrane disease on the occurrence of intraventricular hemorrhage in very low birth weight infants. Two hundred and twenty infants with birth weight less than or equal to 1 500 g and gestational age less than or equal 32 weeks were studied. Infants with hyaline membrane disease (112) had 56% incidence of intraventricular hemorrhage whereas of those without hyaline membrane disease (108) only 31% developed intraventricular hemorrhage (p less than 0.001). When controlled for gestational age, the more immature infants (less than or equal to 1 000 g) exhibited no difference in the occurrence of intraventricular hemorrhage whether hyaline membrane disease coexisted or not. In the 1 001-1 500 g group, the occurrence of hyaline membrane disease with intraventricular hemorrhage was significant (p less than 0.001). The association of lower Apgar scores and the influence of intermittent positive pressure ventilation in infants with intraventricular hemorrhage is discussed. Extreme immaturity negates all perinatal clinical expertise in determining neonatal outcome. Therefore, carrying pregnancies beyond 28 weeks gestation is mandatory. Beyond 28 weeks, pulmonary maturity and the influence of therapeutic modalities and maternal transport become increasingly important.