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Biomedical subjects

C E Ahlfors

Publications and source records attributed to C E Ahlfors.

At least 19 recordsLinked to original sources
PubMed2001

Bilirubin-albumin binding and free bilirubin.

The relevance of plasma bilirubin-albumin binding and, in particular, the nonalbumin-bound or "free" bilirubin concentration to neonatal bilirubin toxicity is controversial. The pivotal role that "free" bilirubin played in the bilirubin toxicity that occurred following administration of sulfisoxazole or benzyl alcohol to jaundiced newborns, and the correlation of "free" bilirubin with bilirubin-induced changes in the auditory brainstem response are strong support for measuring "free" bilirubin when evaluating neonatal jaundice. Reliable methods for measuring "free bilirubin" are available, and population reference values are needed to help determine its proper clinical use.

Anti-Infective Agents↗
PubMed2001

Benzyl alcohol, kernicterus, and unbound bilirubin.

A prospective study in 1983 demonstrated no significant relationship between serum unbound bilirubin levels and kernicterus. The presence of benzoate (a bilirubin-binding competitor) in the serum along with sample dilution, however, may have rendered the unbound bilirubin measurements in that study inaccurate.

Anesthetics, Local↗
PubMed2001

Auditory brainstem response and unbound bilirubin in jaundiced (jj) Gunn rat pups.

The role of plasma bilirubin-albumin binding in the pathogenesis of kernicterus in human newborns is controversial. Kernicterus in the jaundiced (jj) Gunn rat pup, an animal model for kernicterus, prolongs interwave intervals and decreases wave amplitude in the auditory brainstem response (ABR). Plasma total bilirubin concentration (TBC), albumin concentration, and unbound bilirubin concentration (UBC), a measure of bilirubin-albumin binding, were measured in 16-day-old jj Gunn rat pups (n = 21) and compared with ABR wave latencies, interwave intervals, and wave amplitudes by linear correlation. The UBC, but not the TBC or TBC/albumin ratio, correlated positively and significantly with ABR I-II and I-III interwave intervals (r = 0.55, p = 0.009, and r = 0.60, p = 0.004, respectively). The UBC, but not the TBC or TBC/albumin ratio, predicts bilirubin toxicity, as measured by bilirubin-induced ABR changes in jj Gunn rat pups.

Animals↗
PubMed2000

Measurement of plasma unbound unconjugated bilirubin.

A method is described for measuring the unconjugated fraction of the unbound bilirubin concentration in plasma by combining the peroxidase method for determining unbound bilirubin with a diazo method for measuring conjugated and unconjugated bilirubin. The accuracy of the unbound bilirubin determination is improved by decreasing sample dilution, eliminating interference by conjugated bilirubin, monitoring changes in bilirubin concentration using diazo derivatives, and correcting for rate-limiting dissociation of bilirubin from albumin. The unbound unconjugated bilirubin concentration by the combined method in plasma from 20 jaundiced newborns was significantly greater than and poorly correlated with the unbound bilirubin determined by the existing peroxidase method (r = 0.7), possibly due to differences in sample dilution between the methods. The unbound unconjugated bilirubin was an unpredictable fraction of the unbound bilirubin in plasma samples from patients with similar total bilirubin concentrations but varying levels of conjugated bilirubin. A bilirubin-binding competitor was readily detected at a sample dilution typically used for the combined test but not at the dilution used for the existing peroxidase method. The combined method is ideally suited to measuring unbound unconjugated bilirubin in jaundiced human newborns or animal models of kernicterus.

Adult↗
PubMed2000

Unbound bilirubin associated with kernicterus: a historical approach.

OBJECTIVE: To determine the unbound bilirubin concentration (UBC) associated with kernicterus with the use of clinical data from clusters of kernicterus after sulfisoxazole and benzyl alcohol administration. DESIGN: Sulfisoxazole at 12 mg/dL and benzoate at 10 mmol/L are associated with kernicterus at total bilirubins near 12 and 10 mg/dL, respectively. The concurrent UBC was estimated by first measuring the drug-induced increases in UBC in plasma and artificial sera (peroxidase-diazo method). The increases were then applied to baseline UBC, determined by linear regression analysis of binding data (peroxidase method) from 86 newborns, at total bilirubins of 12 mg/dL for sulfisoxazole and 10 mg/dL for benzoate. Sensitivity and specificity were determined with existing data. RESULTS: Sulfisoxazole and benzoate increased UBC in artificial sera 2.1-fold and 4.1-fold, respectively, and in plasma (sulfisoxazole) 2.4-fold. Benzoate would increase baseline UBC from 0.29 to 1.19 microg/dL and sulfisoxazole from 0.36 to 0.86 microg/dL. The sensitivity and specificity of a UBC of 0.86 microg/dL for predicting kernicterus are 79% and 92% and for 1.19 microg/dL, 50% and 98%, respectively. CONCLUSION: Historic data predict that the unbound bilirubin above which kernicterus becomes likely lies between 0.86 and 1.19 microg/dL, in good agreement with existing information.

Benzyl Alcohol↗
PubMed1995

Plasma fluorescein binding and transcapillary fluorescein escape rate in renal failure associated with diabetes.

Microvascular damage, often resulting in renal failure, is a common complication of diabetes. Transcapillary fluorescein escape rate (TCFER) as monitored by intravital microscopy has been used as an indicator of the extent of capillary damage in diabetes and to assess improvement in microvascular function after combined kidney-pancreas transplant. However, fluorescein anion binds to plasma albumin, and albumin-ligand binding may be altered in the presence of renal disease. The purpose of this study was to compare fluorescein binding by plasma from diabetics with renal failure with plasma from healthy nondiabetics. Fluorescein binding by plasma from seven type I diabetics awaiting kidney-pancreas transplant and seven healthy adults of similar age and sex was studied using ultrafiltration and dialysis. There was no significant difference in the apparent albumin binding of fluorescein at physiologically relevant fluorescein concentrations, even though the TCFER was significantly increased in the diabetics as compared with the controls. Hippurate, a ligand that accumulates in renal failure, did alter fluorescein binding in a defatted albumin solution but not sufficiently to account for the differences in TCFERs. These data indicate that impaired albumin binding of fluorescein does not contribute significantly to the TCFER in diabetics with renal failure.

Adult↗
PubMed1994

Criteria for exchange transfusion in jaundiced newborns.

OBJECTIVE: A widely published set of exchange transfusion criteria lowers critical bilirubin concentrations when the serum albumin falls to < 2.5 g/dL. Although acknowledging the role of bilirubin-albumin binding in bilirubin neurotoxicity, this approach may inadvertently produce two critical bilirubin concentrations. This study investigates using the bilirubin/albumin ratio instead of the single albumin concentration to eliminate this potential ambiguity in the criteria. DESIGN AND PARTICIPANTS: The bilirubin/albumin ratio was defined as a reliable indicator of bilirubin-albumin binding if the frequency curves of specific unbound bilirubin concentrations are normally distributed functions of the ratio. Therefore the bilirubin/albumin ratios at which the unbound bilirubin reached 10, 15, and 20 nmol/L were determined by the peroxidase method in 35 well full-term, 10 ill full-term, and 19 ill preterm neonates. The frequency curves for each unbound bilirubin concentration plotted against the bilirubin/albumin ratio were tested for normality. RESULTS: The frequency of each unbound bilirubin concentration was a normally distributed function of the bilirubin/albumin ratio. Furthermore, the mean ratio at which each unbound bilirubin occurred did not differ significantly among the groups of neonates. CONCLUSION: The bilirubin/albumin ratio is a simple, nonambiguous way of incorporating the serum albumin concentration into exchange transfusion criteria.

Bilirubin↗
PubMed1991

Neonatal bilirubin exposure and psychoeducational outcome.

The association between neonatal bilirubin exposure and psychoeducational outcome was investigated in a group of grade school children 9 to 11 years old who required neonatal intensive care between 1977 and 1980. Seventy-four children were evaluated with four measures of psychoeducational outcome, including the Kaufman Mental Processing and Achievement Scales, the Beery Visual Motor Integration Test, and the Vineland Adaptive Behavior Scale. A measure of bilirubin binding calculated directly from the albumin concentration correlated significantly with the Kaufman Mental Processing Composite, although other more direct measures of bilirubin exposure (such as maximum serum bilirubin, direct measures of binding, and cumulative bilirubin exposure) did not. Thus, it is possible that the impact on psychoeducational outcome is the result of some other effect of low serum albumin itself, in addition to its ability to bind bilirubin. The correlation of the calculated albumin-determined binding value with the Kaufman Mental Processing Composite suggests that this level, rather than total serum bilirubin, may be more appropriate in determining clinical management.

Aptitude↗
PubMed1990

Taurine depletion in very low birth weight infants receiving prolonged total parenteral nutrition: role of renal immaturity.

In a prospective, controlled study, plasma and urinary taurine concentrations were determined weekly, between postnatal weeks 3 and 18, in (1) seven sick infants (gestational age less than 28 weeks, birth weight less than or equal to 1000 gm) who received a taurine-free total parenteral nutrition solution for 32 to 49 days (group P) and who subsequently were formula fed and (2) eight sick infants matched by gestational age and birth weight, who received formula or human milk from day 3 to 4 of life (group E). Ten healthy full-term infants ranging in age from 1 to 18 weeks and fed with formula provided normal values (group C). Significantly lower mean plasma taurine values (range 1.59 to 3.43 mumol/dl) were found between postnatal weeks 3 and 7 in group P compared with group E (range 5.54 to 6.97 mumol/dl) and with group C (5.6 +/- 0.34 mumol/dl). After initiation of feeding, plasma taurine concentrations in group P increased to normal. Markedly elevated values of mean fractional excretion of taurine, 38% to 56%, were found between weeks 3 and 5 in group P and E compared with group C (15.5 +/- 3.2%). In contrast, during the same period, low urinary taurine values (4.9% to 6.7%) were found in two larger, older infants receiving total parenteral nutrition whose plasma taurine values were in the normal range. After week 5, urinary taurine values were in the control range in all groups. We conclude that the absence of taurine in total parenteral nutrition solutions administered to very low birth weight infants and the limited ability of the immature kidney to adapt to low taurine intake by "up-regulation" of tubular taurine reabsorption may result in depleted taurine body pools during the first weeks of life. This inability to conserve taurine by the immature nephron could potentially have a deleterious effect on the developing brain and retina in these infants, and indicates a possible need for taurine supplementation.

Enteral Nutrition↗
PubMed1988

Renal calcification in preterm infants: pathophysiology and long-term sequelae.

We examined the clinical course of 17 preterm infants with chronic lung disease who received loop diuretics and developed nephrocalcinosis; nine of them were followed for up to 4.5 years. The mean gestational age was 26.8 weeks (SD 2.2 weeks), and mean birth weight was 830 gm (SD 276 gm). The diagnosis of renal calcification was made at a mean age of 12 weeks (SD 6.5 weeks) by abdominal x-ray examination, screening abdominal ultrasound studies or, both. Calcification was associated with both furosemide therapy and the presence of multiple potential risk factors. Renal calcification, length, and function were subsequently evaluated in nine patients at a mean age of 21.3 months (SD 15.3 months). Improvement in calcification occurred in five patients, with total resolution in four. Renal length, determined by ultrasound examination and corrected for body length, was normal in 17 of 18 kidneys. Serum creatinine values and calculated glomerular filtration rates were abnormal in four of nine patients. We conclude that renal calcification in preterm infants is associated with multiple risk factors, including furosemide usage, and tends to diminish during the first year of life. However, renal function may remain compromised in some patients.

Birth Weight↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1985

Bilirubin binding by the fractionated alternate allelic components of heterozygous monkey albumin.

Analysis of bilirubin-binding parameters for purified albumin of nine rhesus monkeys heterozygous for albumin MacA and albumin MacB was performed after separating these two albumin forms by fast protein liquid chromatography (FPLC). The binding capacity (n) for MacA-enriched samples was lower than that for the MacB variant in eight of nine fraction pairs analyzed, while the affinity constant (K) was higher in all nine MacA-enriched samples. The values for n X K were higher in MacA-enriched samples in eight of nine pairs tested. These data, together with previous studies, geographic specificity of the MacB variant, and the presence of dietary competitors for the primary bilirubin binding site on the albumin molecule, suggest an evolutionary advantage for the MacB variant only in areas where the dietary competitors are present.

Alleles↗