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Biomedical subjects

B W Goetzman

Publications and source records attributed to B W Goetzman.

At least 37 records · Page 2Linked to original sources

Effect of blood sampling site on measurements of bilirubin-albumin binding.

Significant arterio-venous concentration gradients in metabolites such as lactate could result in sampling site differences in bilirubin binding measurements. Therefore, total bilirubin and apparent unbound bilirubin concentrations were determined on paired capillary and arterial serum samples from ten neonates with hyaline membrane disease. There were no significant arterial versus capillary differences in bilirubin binding in these infants. However, a small, statistically significant but clinically irrelevant, difference in total bilirubin concentration was found. Consistent blood sampling sites should be used for laboratory tests where arterial, venous, and capillary results differ or could conceivably differ.

Arteries↗

Nutritional practices and outcome of extremely premature infants.

We analyzed the records of 182 newborns with birth weights under 1000 g, who survived longer than seven days, to determine risk factors for subacute mortality and morbidity. Statistical analysis using logarithm-linear modeling was used to identify complex interactions and to minimize confounding. Nosocomial infection, necrotizing enterocolitis, male gender, and chronic lung disease (CLD) were identified as independent risk factors for subacute mortality. Male gender and CLD were associated with increased mortality only among patients who received parenteral nutrition (PN). Moreover, PN, rather than enteral nutrition (EN), was a risk factor for delayed growth, nosocomial infection, and CLD. Delayed initiation of EN was associated with decreased necrotizing enterocolitis risk only among male infants with birth weights under 775 g. Our results do not support elective withholding of EN in other groups of extremely low-birth-weight infants. We conclude that indications for PN and for withholding initiation of EN in very-very-low-birth-weight infants need to be established by prospective studies.

Body Weight↗

Ultrasound diagnosis of renal calcification in infants on chronic furosemide therapy.

We describe seven infants who developed renal calcification and bone demineralization following furosemide therapy with average daily doses of as little as 0.75 mg/kg per day. Renal calcifications were present in all seven cases and were more readily detected with ultrasonography than with plain films. Renal calculi were seen in four patients, sonographically demonstrated as echogenic foci in the dependent portion of the collecting system, usually accompanied by acoustic shadowing. One patient developed nephrocalcinosis, sonographically observed as echogenic medullary pyramids plus punctate, shadowing parenchymal calcifications. In two patients the location of the calcification could not be determined.

Bone Diseases↗

Changes in the auditory brainstem response associated with intravenous infusion of unconjugated bilirubin into infant rhesus monkeys.

The auditory brainstem response (ABR) was monitored in nine infant rhesus monkeys during the intravenous infusion of 50-168 mg/kg of unconjugated bilirubin. Sulfisoxazole (200 mg/kg) was sometimes given near the end of or just before the bilirubin infusion if no obvious ABR change had yet occurred. Five of the animals were term gestation, four were preterm, and they ranged from 1 to 40 days of age at the time of study. The three oldest term animals, studied at 20, 35 and 40 days of age, respectively, showed variable changes in the ABR waves during bilirubin infusion and these changes were not altered further by sulfisoxazole administration. The other two term infants, studied at 1 and 6 days of age, respectively, showed sulfisoxazole enhanced ABR wave latency increase and amplitude reduction followed by loss of the ABR. Both of these animals became apneic following ABR loss and eventually died. The ABR reappeared in one animal prior to death. Minimal gross and microscopic changes were present in the brain of the 6-day-old animal at autopsy. The four preterm animals all had a progressive wave amplitude decrease followed by loss of the ABR with bilirubin alone. These preterm animals were sacrificed shortly after the ABR loss with only one showing yellow staining of the basal ganglia at autopsy. The infant rhesus monkey may be a useful paradigm for bilirubin-induced ototoxicity as manifested by potentially reversible ABR changes. The changes are dependent on gestational and chronological age of the animal and appear to occur in the peripheral eighth nerve or cochlea as well as in brainstem pathways.

Animals↗

Pulmonary vascular responses to nitrous oxide in newborn lambs.

The hemodynamic effects of N2O and N2O plus hypoxia were studied in six lambs (0-3 days of age) that were instrumented with pulmonary artery flow probes and catheters, as well as aortic and left atrial catheters. N2O was administered to the awake lambs through a mask in mixtures of 75% N2O:25% O2 and 75% N2O:11% O2:14% N2. Pulmonary arterial pressure and resistance increased significantly upon exposure to N2O both during normoxia and hypoxia, and nitrous oxide also significantly elevated left atrial pressure and decreased pulmonary artery blood flow during normoxia. Aortic pressure was essentially unchanged by nitrous oxide. The data indicate that in newborn lambs the pulmonary vasculature responds to N2O with vasoconstriction.

Animals↗

Effect of pulmonary artery distention on systemic vascular resistance in newborn lambs.

Balloon distention of the left pulmonary artery (PA) was produced in 14 lambs (aged 1 to 3 days) to assess whether an increase in systemic vascular resistance results from such distention. The lambs were anesthetized with chloralose and instrumented to enable measurement of systemic blood flow, PA pressure, aortic pressure, heart rate and right atrial pressure. PA distention resulted in an increase in systemic vascular resistance and aortic pressure (p less than 0.05). This result was probably due to a systemic vasoconstrictor response, since systemic blood flow and right atrial pressure did not change significantly. Limited trials using autonomic blocking agents suggested that the response is either a reflex under autonomic control or a response to humoral release of alpha-adrenergic substances. In conclusion, some interdependence appears to exist between the systemic and pulmonary vascular beds. It is postulated that such changes may be important in fetal life when they may affect redistribution of cardiac output during adaptation to hypoxemia.

Adrenergic alpha-Antagonists↗

Gram's stains of tracheal secretions predict neonatal bacteremia.

The presence of bacteria in tracheal secretions stained by the Gram method was evaluated as a method of predicting neonatal bacteremia. The presence of bacteria had a 74% sensitivity and a 47% predictive accuracy in identifying neonates with bacteremia before 12 hours of age. The specificity in predicting newborns without bacteremia was 98%. In the same neonates, an immature neutrophil-total neutrophil ratio of 0.2 or more had a 77% sensitivity in predicting neonates with bacteremia. Neonates with bacteria in their blood and tracheal aspirates, who died shortly after birth, had pneumonia on postmortem examination. In newborns who have respiratory distress and a risk of infection at birth, Gram's stains of tracheal secretions are a practical and useful method of predicting congenital bacteremia.

Bacteria↗

Effects of fetal-maternal exchange transfusion on fetal oxygenation and blood flow distribution.

The effect of reducing hemoglobin affinity for O2 on fetal oxygenation was assessed in seven fetal lambs in which fetal blood was almost completely replaced by maternal blood 2-3 days postoperatively. Measurements of fetal blood gases and organ blood flow (radionuclide-labeled microsphere technique) were obtained before and 1 h after the exchange transfusion. Umbilical venous blood PO2 increased from 29 +/- 5 to 35 +/- 6 (SD) Torr (P less than 0.001) but hemoglobin O2 saturation decreased from 78.2 +/- 10.3 to 39.8 +/- 8.8% (P less than 0.001), resulting in a 46% decrease in umbilical venous blood O2 content. Since umbilical-placental blood flow also decreased (P less than 0.002), O2 delivery to the fetus decreased by 64% (P less than 0.002). Although O2 extraction increased from 32.5 +/- 6.8 to 50.9 +/- 9.0% (P less than 0.002), fetal O2 consumption fell from 7.28 +/- 1.97 to 4.10 +/- 1.20 ml X min-1 X kg-1 (P less than 0.02), and metabolic acidemia developed. No significant change in fetal cardiac output was observed. Blood flow increased significantly to the myocardium and adrenals but fell in the placenta, carcass, and lungs and was maintained in other organs. This resulted in a significant decrease in the amount of O2 delivered to all fetal organs except to the myocardium in which it was maintained. In the sheep the higher affinity of fetal blood hemoglobin for O2 helps maintain normal oxygenation during fetal life by facilitating O2 uptake at the placenta and unloading O2 in the tissues.

Animals↗

Fetal adaptations to spontaneous hypoxemia and responses to maternal oxygen breathing.

Circulatory adaptations to spontaneous hypoxemia were assessed with the microsphere method at 119-123 days gestation in ovine fetuses who were subsequently found to be growth retarded. Combined ventricular output tended to be increased and it was redistributed so that oxygen delivery to the heart was increased by over 50%, oxygen delivery to the lung and placenta were decreased, and that to other organs, including the brain, were maintained. Maternal oxygen breathing for 1 h not only reversed these adaptations, but also produced an augmented lung blood flow. Umbilical blood flow was not affected. These findings have clinical implications for the growth-retarded fetus about to undergo the stress of labor.

Animals↗

Elevated ratios of type I/III collagen in the lungs of chronically ventilated neonates with respiratory distress.

Increased synthesis of type I collagen, leading to increased ratios of type I to type III collagen in the lungs, has been observed in the lungs of animals with experimental pulmonary fibrosis. Similar changes in collagen type ratios have been observed in lungs of humans dying of idiopathic pulmonary fibrosis and of adult respiratory distress syndrome. In this study, lung collagen type ratios were examined in infants with acute and chronic lung disease. Tissue from the right lower lobes of neonates was obtained post mortem. Specific collagen types were quantitated by solubilization of lung collagen with CNBr and fractionation of the resulting mixture of peptides by column chromatography and polyacrylamide gel electrophoresis. Ratios of type I/III collagen were calculated for each lung sample using two independent pairs of marker peptides for these determinations. In some cases the ratio of type V to type III collagen in these same lung samples was also quantitated. We observed a significant increase in the ratio of type I/III collagen in infants with a premortem diagnosis of chronic lung disease, usually preceded by respiratory distress syndrome. We also observed two infants with large changes in collagen type ratios who might have had pulmonary fibroplasia secondary to intrauterine lung disease. These data suggest that there may be several subsets of infants with respiratory distress syndrome, each having a different prognosis.

Chronic Disease↗

Pulmonary vascular response to digoxin in newborn lambs.

The effects of digoxin on pulmonary vascular resistance (PVR) were evaluated in normoxic (N) and hypoxic (H) newborn lambs with normal and elevated PVR, respectively. Lambs were anesthetized and instrumented to enable continuous measurement of mean pulmonary arterial pressure (PPA), mean left atrial pressure (PLA), mean pulmonary blood flow (Qp), and mean aortic pressure (PAO). Digoxin (10-20 micrograms/kg) was injected via central venous catheters in 11 N lambs and 4 H lambs. Under N conditions, baseline PVR was equal to 0.12 mm Hg/ml/min/kg, PPA was 33 mm Hg, PLA was 6 mm Hg, Qp was 235 ml/min/kg, and PAO was 69 mm Hg. Following digoxin, mean PVR increased by 24% (P less than 0.001) and PPA increased by 23% (P less than 0.001) for an average duration of 199 sec while QP increased by 5% (P less than 0.02) and PLA was constant suggesting a direct vasoconstrictive effect. Under H conditions, baseline PVR was equal to 0.26 mm Hg/ml/min/kg, PPA was 58 mm Hg, PLA was 4 mm Hg, Qp was 208 ml/min/kg, and PAo was 65 mm Hg. Following digoxin, mean PVR, Qp, PLA, and PAo did not change appreciably although PPA had a uniform increase of 5% (P less than 0.001). The blunted response may suggest that either the pulmonary vascular bed was maximally constricted or that digoxin and hypoxia share a common mechanism. In conclusion, digoxin has a direct pulmonary vasoconstrictor action in newborn lambs. Because of its short duration, this action probably should not alter the clinical use of this drug in newborn humans.

Animals↗

Corticosteroid response in chronic lung disease of prematurity.

The medical records of 23 infants with stable chronic lung diseases of prematurity who were treated with corticosteroids during the second month of life were reviewed. Thirteen (56.5%) had significant improvement in lung function as evidenced by a mean decrease in delta AaPO2 of 49.5% and a mean decrease in PaCO2 of 15.4%. These proved to be long-lasting effects. Infants who responded to corticosteroids had significantly lower mean gestational age, birthweight, and percent loss of birthweight when compared with the infants who did not improve with this treatment. In addition, the number of days they required supplemental oxygen were fewer. Thus, corticosteroids may be beneficial therapeutically for some premature infants with chronic lung disease. Alternatively, corticosteroid responsiveness may differentiate types of chronic lung disease with improved prognoses. Controlled clinical trials are necessary before corticosteroids can be recommended in treating or evaluating chronic lung disease of prematurity.

Adrenal Cortex Hormones↗

The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs.

The responses of fetal heart rate and blood pressure to a transient reduction in uterine blood flow were studied in normoxemic and chronically hypoxemic lambs. In normoxemic fetuses, a reduction in uterine blood flow, if prolonged sufficiently, produced reflex bradycardia mediated through chemoreceptors and was associated with a decrease in carotid arterial PO2 to below 20 torr. The bradycardia was associated with a marked decrease in left ventricular output as measured by electromagnetic flowmeter; both were abolished by atropine. In chronically hypoxemic fetuses, a reduction in uterine blood flow produced a delayed deceleration of the heart rate which consisted of three components: reflex bradycardia due to chemoreceptor stimulation; baroreceptor-mediated reflex bradycardia which involved the slow and late recovery of the heart rate; and nonreflex bradycardia which was probably secondary to hypoxic myocardial depression. Quantitative analysis revealed a relationship between the components of delayed deceleration and the status of fetal oxygenation prior to the reduction in uterine blood flow. The lower the carotid arterial PO2, the shorter was the delay in the onset of bradycardia, the greater the decrease in heart rate, and the more prolonged the duration of bradycardia. The conclusion is that the response of fetal heart rate to a transient reduction in uterine blood flow is related to the duration of the reduction and to the status of fetal oxygenation prior to the decrease in uterine blood flow.

Animals↗

Effects of hemorrhage on umbilical venous return and oxygen delivery in fetal lambs.

The effect of acute hemorrhage (21.7 +/- 1.6%, mean +/- SE of the estimated blood volume) on the distribution of the umbilical venous return (UVR) and oxygen delivery to fetal organs (radionuclide microsphere technique) was studied in 10 chronically catheterized fetal lambs. Hemorrhage decreased UVR and total oxygen delivery to the fetus by 23 and 28%, respectively (P less than 0.001). A greater proportion of the UVR bypassed the liver through the ductus venosus (DV) (P less than 0.01). Consequently, DV blood flow was relatively maintained, and liver blood flow and oxygen delivery derived from the UVR decreased by 41 and 45%, respectively (P less than 0.002). The proportion of cardiac output constituted by DV blood increased by 30% (P less than 0.01). The changes in the distribution of the DV blood were similar to the changes in the distribution of cardiac output. As a result the proportion of organ blood flow and oxygen delivery derived from DV blood increased by 30% in both the upper and lower body organs. These studies show that fetal hemorrhage has a marked effect on the distribution of the UVR to the liver. The preferential distribution of the DV blood to the heart and brain is maintained but not enhanced. Our results indicate that changes in distribution of the DV-derived blood and oxygen following fetal hemorrhage is determined primarily by the responses of the arterial circulation, i.e., circulatory afterload.

Animals↗