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Biomedical subjects

W J Cashore

Publications and source records attributed to W J Cashore.

At least 37 records · Page 2Linked to original sources
PubMed1985

The effects of brain blood flow on brain bilirubin deposition in newborn piglets.

Since kernicteric lesions are usually found in the subcortical regions of the brain and these areas also receive the highest blood flow during asphyxia and hypercapnia, we hypothesized that increases in brain bilirubin deposition may be related to increases in brain blood flow. Fourteen piglets underwent a 3-h infusion of bilirubin to maintain total serum bilirubin at approximately 8 mg/dl, during which time blood gases, hemodynamic variables, and brain blood flow were determined. After sacrificing the animals, regional brain bilirubin content was determined. Ten piglets underwent the same protocol; in addition, hypercapnia was induced during the last hour of study (PaCO2 approximately 70 mm Hg). The regional brain blood flow and bilirubin deposition were significantly increased over control values (p less than 0.05) following hypercapnia in the subcortical region and significantly so in the midbrain and cerebellum. In separate groups of control (n = 6) and hypercapnia (n = 6) piglets, 125I-labeled albumin was infused and demonstrated that hypercapnia was not associated with increased regional brain albumin content. We conclude that hypercapnia-induced augmentation in regional brain blood flow is associated with increased deposition brain blood flow is associated with increased deposition of unbound bilirubin. Although the causal relationship between these two observations has not been firmly established, the findings deserve future investigation to clarify the role of brain blood flow, brain bilirubin deposition, and the production of kernicterus in high risk infants.

Albumins↗
PubMed1984

The management of hyperbilirubinemia.

When pre-established "safe" limits of serum bilirubin are exceeded, or when hyperbilirubinemia is present in association with other conditions such as prematurity with respiratory distress, asphyxia, or neonatal infections, the need to lessen the risk of bilirubin encephalopathy requires specific and effective interventions to lower the unconjugated or indirect-reacting bilirubin level in infants at risk. To this end the authors examine the criteria for intervention, the means of decreasing serum bilirubin levels, phototherapy, exchange transfusion, and the problem of jaundice in breast-fed infants.

Blood Volume↗
PubMed1984

Effect of acidosis on bilirubin deposition in rat brain.

The effect of metabolic and respiratory acidosis on bilirubin and albumin entry into the brain was studied in 24 awake and unanesthetized rats. Hyperbilirubinemia was established by infusion of unconjugated bilirubin at a rate of 30 mg/kg/h for three hours. After two hours, metabolic acidosis was produced in eight rats by infusion of 0.5 N hydrochloric acid at a rate of 0.02 mL/g/h. This reduced the pH level to 7.03 +/- 0.01 (mean +/- SEM) with a normal value for PCO2. Respiratory acidosis was produced in another group of eight animals who breathed 20% CO2 in a balanced gas mixture for the last hour of the study period. This resulted in a reduction of pH to 7.04 +/- 0.01 with PCO2 of 100.4 +/- 2.3 mm Hg. A third group of eight rats served as controls and were given equal volumes of saline infusion. No increase in brain bilirubin or brain albumin was found in the group with metabolic acidosis, but in the group with respiratory acidosis both bilirubin and albumin concentrations in the brain increased significantly. No significant differences were found between the groups in serum total or apparent unbound bilirubin, albumin, or osmolality. The results indicate that a brief period of acidosis per se does not increase bilirubin entry into the brain, but hypercarbia does so by opening of the blood-brain barrier.

Acidosis↗
PubMed1983

Reserve albumin and bilirubin toxicity index in infant serum.

Reserve albumin concentration (the concentration of albumin available for binding of unconjugated bilirubin) was determined in 95 sera from 76 subjects by dialysis with 14C-monoacetyl diamino diphenyl sulfone (MADDS). An index, I of bilirubin toxicity in the plasma was calculated for each subject, based on the bilirubin and reserve albumin concentrations, the affinity of bilirubin for serum albumin, and the pH-dependent solubility of bilirubin in the plasma. The values of reserve albumin and of I varied significantly with gestational age, clinical condition (whether sick or well), and serum bilirubin level. The value of reserve albumin was decreased and I was increased in association with clinical factors (e.g., hyperbilirubinemia, hypoxia, acidosis, or sepsis) recognized as increasing the risk for bilirubin encephalopathy. The lowest values of reserve albumin and the highest values of I were found in the least mature and sickest infants.

Adult↗
PubMed1983

Bilirubin-displacing effect of furosemide and sulfisoxazole. An in vitro and in vivo study in neonatal serum.

Sulfisoxazole and furosemide, 0.1-1.0 mM, both decreased reserve albumin concentration for bilirubin binding in pooled cord serum as estimated by rate of dialysis of 14C-monoacetyl-diamino-diphenylsulfone (MADDS) in undiluted serum at 37 degrees C. Peroxidase oxidation at a bilirubin:albumin ratio of 0.5 also showed that both drugs were capable of displacing bilirubin in vitro when added in molar excess of the albumin present. However, when aliquots of the same treated sera which had been used undiluted in the MADDS assay were diluted 40-fold and titrated with bilirubin and peroxidase, no drug-related increase in free bilirubin or decrease in reserve albumin could be shown. In vivo administration of 1 mg/kg furosemide showed no change in total bilirubin or reserve albumin by the MADDS technique in 8 infants. Estimation of the peak plasma level theoretically achievable with 1 mg/kg of furosemide suggests that peak plasma levels achieved with that dose are probably not high enough to produce significant reduction of reserve albumin, in agreement with the in vivo findings. In testing neonatal serum for bilirubin displacement by drugs, the choice of method, drug concentration, and dilution of the sample may influence the interpretation of results.

Bilirubin↗
PubMed1983

Effect of serum hyperosmolality on opening of blood-brain barrier for bilirubin in rat brain.

The effect of hyperosomolality on the blood-brain barrier for bilirubin was studied in rats. Hyperbilirubinemia was induced in the chronically catheterized rat by infusion of bilirubin at a rate of 30 mg/kg/h for three hours. After two hours of bilirubin infusion, three levels of hyperosmolality were induced by bolus of urea at three different doses: 50, 75, and 100 mmol/kg, respectively. The serum osmolality rose from 297 mosm/L in the control group to 345, 383, and 400 mosml/L in the three respective groups. No significant differences were found between the groups in levels of total or free serum bilirubin, serum albumin, blood pH, and blood gases. A significant dose relationship was found in both brain bilirubin and brain albumin content with reference to the serum hyperosmolality. The results indicate that hyperosmolality causes opening of the blood-brain barrier for bilirubin in the rat. It may be speculated that this adverse phenomenon (hyperosmolality) may play a role in the pathogenesis of kernicterus in infants whose serum bilirubin levels are below the range of saturated bilirubin binding capacity.

Animals↗
PubMed1982

Unbound bilirubin and kernicterus in low-birth-weight infants.

Unbound bilirubin, bilirubin binding capacity, and bilirubin binding affinity were determined by the horseradish peroxidase method at the time of maximum hyperbilirubinemia and/or before exchange transfusions in 13 preterm infants who later died and had autopsies performed. Five of the 13 infants had kernicterus at autopsy. There were no significant differences in weight, gestational age, highest indirect bilirubin level, albumin concentration, severity of acidosis, use of assisted ventilation, sepsis, or other major clinical complications between the five infants with kernicterus and the eight infants without kernicterus. Compared with the eight nonkernicteric infants, the five kernicteric infants had significantly higher unbound bilirubin concentrations (13 +/- vs 27 +/- 9 nmoles/liter, respectively, P less than .05) and significantly lower bilirubin binding capacity and affinity. The data suggest an association between low bilirubin binding capacity and affinity, increased unbound bilirubin, and kernicterus in preterm infants with severe clinical complications.

Bilirubin↗
PubMed1980

Free bilirubin concentrations and bilirubin-binding affinity in term and preterm infants.

Free bilirubin concentration, bilirubin-binding capacity, and bilirubin-binding affinity were determined by peroxidase oxidation in 66 newborn infants. Twelve healthy term infants whose unconjugated bilirubin concentration was 15.8 +/- 3.7 mg/dl (mean +/- SD) had a binding capacity of 31.9 +/- 3.7 mg/dl (bilirubin: albumin molar ratio = 0.89 +/- 0.07) and Ka = 28 +/- 11 x 10(7)/M. Twelve term infants with clinical complications of asphyxia, acidosis, respiratory distress, or sepsis, and 17 preterm infants with no complications had lower serum albumin concentrations and slightly reduced binding capacity and affinity compared to the healthy term infants. Free bilirubin concentrations were similar in these three groups, averaging 8 to 9 nmol/l in each group. Twenty-five preterm infants with complications had significantly higher free bilirubin (19 +/- 11 nmol/l), lower binding capacity, and lower binding affinity than any of the other three groups (P less than 0.01 for all comparisons). Five of the 25 sick preterm infants had kernicterus at autopsy. These five infants were similar to the other 20 in birth weight, gestational age, serum bilirubin, and serum albumin level, but had significantly higher free bilirubin and significantly lower binding capacity and affinity. The data suggest that serious neonatal illness is associated with a marked reduction in bilirubin-binding capacity and affinity and an increased risk of kernicterus in preterm infants. The mechanism by which neonatal morbidity decreases bilirubin binding is not known.

Bilirubin↗
PubMed1980

Rapid fluorometric assay of bilirubin and bilirubin binding capacity in blood of jaundiced neonates: comparisons with other methods.

The concentrations of total blood bilirubin, albumin-bound bilirubin, and the reserve and total bilirubin binding capacities of 35 neonatal blood samples (28 patients) were determined by automated front-face fluorometry ((hematofluorometer). These values were compared to results of diazo determinations, Sephadex gel filtration, and peroxidase-oxidation methods. Total blood bilirubin level by fluorometry agreed well with the total plasma bilirubin level by diazotization (r = .96, sigma = 1.7 mg/100 ml). Albumin-bound bilirubin concentrations by fluorometry also correlated well with diazo values (r = .95, sigma = 1.9 mg/100 ml) and were slightly lower than the total blood bilirubin concentrations. Values for total bilirubin binding capacity determined by fluorometry agreed well with results obtained for the same specimens by Sephadex gel filtration (n = 28, r = .97, sigma = 1.8 mg/100 ml) and by peroxidase-catalyzed oxidation (n = 25, r = .97, sigma = 1.7 mg/100 ml). The agreement among the results obtained by the three methods indicates a well-defined in vitro end point at which available primary or "tight" binding sites on albumin are saturated with bilirubin. In this clinical experience the coefficient of variation of results with the hematofluorometer was 8.4% for total blood bilirubin and 6.5% for total binding capacity. A comparison of "sick" with "well" infants revealed that the fraction of bilirubin not bound to albumin was significantly different for these two groups. The assays made with the hematofluorometer are quick (10 to 15 minutes) and require only a small quantity (approximately 150 microliters) of blood.

Bilirubin↗
PubMed1979

Kinetics of bilirubin oxidation with peroxidase, as applied to studies of bilirubin-albumin binding.

In the determination of unbound bilirubin by rate of oxidation with peroxidase, errors may be caused by (1) phenol, propylparaben, and phenothiazines (free radical acceleration), (2) haemoglobin (peroxidase effect), and (3) ascorbate (inhibition). Such errors may be diminished by dilution 1:40, or with an anti-oxidant, tert-butyl-p-hydroxyanisole, and ascorbate oxidase.

Ascorbate Oxidase↗
PubMed1979

Increase in bilirubin binding to albumin with correction of neonatal acidosis.

Twenty-six serial measurements of free bilirubin concentration and apparent association constant of bilirubin for albumin (Ka) at a bilirubin: albumin molar ratio of 0.8 were performed and compared with baseline values in 11 newborn infants with acidosis before treatment and during recovery from acidosis. When arterial pH was corrected from 7.12 +/- 0.02 (Mean +/- S.EM.) to 7.34 +/- 0.02, there was a significant decrease in serum free bilirubin concentration and a significant increase in the Ka at molar ratio 0.8. The data offer in vivo evidence that correction of acidosis in the neonate results in an improvement of the apparent bilirubin binding affinity of albumin.

Acid-Base Equilibrium↗