Studies in Kernicterus. I. The Protein Binding of Bilirubin*

Odell, Gerard B.

doi:10.1172/jci103864

Cited by 309 publications

(90 citation statements)

References 29 publications

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“…A 10 to 20 mg/kg loading dose of bilirubin was given followed by a continuous or intermittent (every 15-30 min) infusion of the bilirubin solution until either a total dose of about 150 mg/kg was given (usually 3-4 h) or obvious ABR abnormalities developed. If no ABR changes were apparent, the infant was given 200 mg/kg of sulfisoxazole intravenously (15). Periodic blood samples were obtained from a site remote from the bilirubin administration site, for measurement of the total and direct serum bilirubin concentration and, in some animals, the serum albumin and unbound bilirubin concentrations (I 6, 17).…”

Section: Methodsmentioning

confidence: 99%

Changes in the Auditory Brainstem Response Associated with Intravenous Infusion of Unconjugated Bilirubin into Infant Rhesus Monkeys

et al. 1986

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ABSTRACT'. 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. (Pediatr Res 20: 51 1-515, 1986) Abbreviation ABR, auditory brainstem response Hearing loss occurs in about half of the infants surviving bilirubin encephalopathy (1), and the ABR measured months or years following the bilirubin injury is often absent or present only at increased stimulus intensity suggesting auditory nerve injury (2, 3).Recent reports have documented a variety of acute, usually reversible ABR wave latency changes, amplitude changes, and

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Section: Methodsmentioning

confidence: 99%

Changes in the Auditory Brainstem Response Associated with Intravenous Infusion of Unconjugated Bilirubin into Infant Rhesus Monkeys

et al. 1986

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“…The sulfisoxazole experience alerted clinicians to the role of UCB binding in the pathogenesis of ABE, and methods for measuring UCB binding were pursued in hopes of better identifying babies truly needing a potentially lifesaving but also very risky exchange transfusion (4 ). Measuring B f directly proved elusive, however, and the early tests measuring plasma "saturation" with UCB (i.e., plasma UCB-binding capacity) ultimately proved unsuitable for routine clinical laboratory use (39,40 ).…”

Section: Where's the B F ? A Brief Clinical History Of Abe B T Andmentioning

confidence: 99%

Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

et al. 2009

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Background: The serum or plasma total bilirubin concentration (BT) has long been the standard clinical laboratory test for evaluating neonatal jaundice, despite studies showing that BT correlates poorly with acute bilirubin encephalopathy (ABE) and its sequelae including death, classical kernicterus, or bilirubin-induced neurological dysfunction (BIND). The poor correlation between BT and ABE is commonly attributed to the confounding effects of comorbidities such as hemolytic diseases, prematurity, asphyxia, or infection. Mounting evidence suggests, however, that BT inherently performs poorly because it is the plasma non–protein-bound (unbound or free) bilirubin concentration (Bf), rather than BT, that is more closely associated with central nervous system bilirubin concentrations and therefore ABE and its sequelae. Content: This article reviews (a) the complex relationship between serum or plasma bilirubin measurements and ABE, (b) the history underlying the limited use of Bf in the clinical setting, (c) the peroxidase method for measuring Bf and technical and other issues involved in adapting the measurement to routine clinical use, (d) clinical experience using Bf in the management of newborn jaundice, and (e) the value of Bf measurements in research investigating bilirubin pathochemistry. Summary: Increasing evidence from clinical studies, clinical experience, and basic research investigating bilirubin neurotoxicity supports efforts to incorporate Bf expeditiously into the routine evaluation of newborn jaundice. .

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“…Although a serum bilirubin concentration of 20 mg/ 100 ml (Hsia, Allen, Gellis and Diamond, 1952) is often taken as that at which treatment should be undertaken, other factors, including albumin binding capacity (Darrow and Cary, 1933;Odell, 1959) and blood pH (Keay and Boyle), must be taken into consideration. The proper assessment of the situation depends upon repeated determinations of serum bilirubin concentration.…”

Section: Fig I-absorption Spectra Of Bilirubin ( ---) and Haemoglobmentioning

confidence: 99%

A Critical Assessment of a New Instrument Designed for Rapid Measurement of Bilirubin in Microsamples of Neonatal Sera

1971

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Studies in Kernicterus. I. The Protein Binding of Bilirubin*

Cited by 309 publications

References 29 publications

Changes in the Auditory Brainstem Response Associated with Intravenous Infusion of Unconjugated Bilirubin into Infant Rhesus Monkeys

Changes in the Auditory Brainstem Response Associated with Intravenous Infusion of Unconjugated Bilirubin into Infant Rhesus Monkeys

Unbound (Free) Bilirubin: Improving the Paradigm for Evaluating Neonatal Jaundice

A Critical Assessment of a New Instrument Designed for Rapid Measurement of Bilirubin in Microsamples of Neonatal Sera

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