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Biomedical subjects

W B Karp

Publications and source records attributed to W B Karp.

At least 37 records · Page 2Linked to original sources

Vitamin E in neonatology.

It is difficult to maintain an objective attitude toward the use of vitamin E in neonatology. On the one hand, the desire to ameliorate iatrogenic diseases, such as BPD and ROP, makes one grasp hopefully at any theory or clinical trial that suggests a role for vitamin E in decreasing the handicaps that patients take with them from the intensive care nursery. On the other hand, when the question of toxicity arises, one tends to be negative, remembering the unfortunate experiences with oxygen, chloramphenicol, sulfisoxazole, and now, E-Ferol Aqueous Solution. We like to think that if this review had been written 2 years ago, our conclusions, based on the analysis of the data, would have been the same. But, probably, in the absence of data on the severe toxicity of one vitamin E preparation, we would have been more liberal in our recommendations for the use of vitamin E in neonatology. At this time, however, any use of supplemental vitamin E beyond the guidelines of the American Academy of Pediatrics cannot be recommended. Nor can the monitoring of blood Vitamin E levels be recommended as an assurance of nontoxic tissue concentrations in sick, premature infants. All physicians caring for premature infants are urged to review their nursery policies to make sure that excessive doses of vitamin E are not being administered. It is hoped that additional clinical trials will provide more definite answers to the questions about the efficacy of vitamin E in ROP and IVH.

Humans↗

Binding of dapsone and its analogues to human serum albumin.

The binding of dapsone, 4,4'-sulfonylbis(aniline)(1), and its diacetylated derivative, 4,4"'-sulfonylbis(acetanilide)(2), to human serum albumin is reported. To assess the ability of these compounds to displace 4'-[(4-aminophenyl)sulfonyl]acetanilide (3) from albumin, a dialysis rate technique was used. Competition for the bilirubin binding site on albumin was measured with the peroxidase assay. Compounds 1 and 2 strongly displaced both 3 and bilirubin from human serum albumin. The association constants for 1 and 2 with respect to bilirubin binding were 1.29 X 10(3) and 1.15 X 10(4) M-1, respectively. These results suggest that the binding site for 3 and the bilirubin binding site are similar with respect to 1 and 2 and that the binding of dapsone and its derivatives probably does not involve the amino function.

Dapsone↗

The effect of mercuric acetate on selected enzymes of maternal and fetal hamsters at different gestational ages.

This study establishes levels of activity of glucose-6-phosphate dehydrogenase (G6PD), glycogen phosphorylase (GP), and cytochrome c oxidase (cyt c ox) in maternal, placental, and fetal tissues at Days 9, 12, and 15 in the 16-day gestation period of the hamster, and following a single dose of either 8 or 15 mg/kg mercuric acetate on the eighth gestational day. Mercury significantly elevated maternal kidney G6PD activity and decreased GP activity. The increase in kidney G6PD strongly correlated with observed urine and kidney abnormalities.

Animals↗

Drugs affecting bilirubin uptake by human erythrocyte ghosts.

Drugs known to affect the red blood cell membrane and used clinically in neonates were tested for their ability to cause increased 14C-bilirubin uptake by erythrocyte ghosts. The additional uptake of bilirubin by ghosts in the presence of penicillin G, phenobarbital, furosemide and theophylline may be explained by the effect of these drugs on free bilirubin levels as measured with a horseradish peroxidase assay. In contrast, the effect of chlorpromazine in causing increased bilirubin uptake by ghosts could not be totally explained by either ghost lysis or increased free bilirubin levels, as measured by light scattering, and was due to a direct effect of chlorpromazine on the ghost membrane. Our results demonstrate that drugs may act through different mechanisms in causing increased bilirubin uptake by erythrocytes.

Bilirubin↗

Hematin and bilirubin binding to human serum albumin and newborn serum.

In jaundiced newborn infants, hemolytic disease is considered a risk factor for kernicterus due to the suspected competition between bilirubin and other hemoglobin breakdown products for albumin binding. We have studied the effect of hematin on bilirubin-albumin binding using the peroxidase assay and a light-scattering technique for measuring unbound bilirubin. Our results show that hematin does not affect bilirubin-albumin binding. To determine if other albumin binding functions are affected by hematin, we used a microdialysis rate technique employing two ligands, diazepam and monoacetyldiaminodiphenyl sulfone (MADDS). Hematin does not utilize the diazepam binding function of albumin, but does decrease the albumin binding of MADDS. The results of this study indicate that the MADDS and bilirubin binding functions are not identical. The clinical usefulness of reserve albumin equivalent determination using MADDS is discussed.

Bilirubin↗

Relationship of unbound bilirubin concentration to reserve albumin-binding concentration for bilirubin in human neonatal plasma.

We examined the relationship of plasma unbound bilirubin concentration and reserve albumin-binding concentration for bilirubin in a sample of 545 neonates. Plasma unbound bilirubin concentration and total bilirubin-binding concentration were determined with the peroxidase assay. Contrary to published reports, we found that plasma unbound bilirubin concentration and plasma reserve albumin for bilirubin-binding concentration are highly correlated (r = -0.706; p less than 0.001) and that the relationship between these two parameters is dependent upon the total bilirubin-binding concentration. That these measured parameters correlate in the same manner as predicted for free bilirubin and free albumin by the law of mass action, suggests that these measurements may be meaningful.

Bilirubin↗

Predicting the need for exchange transfusion in newborn infants. A comparison of five methods.

The need for exchange transfusion was analyzed retrospectively using several different methods (total bilirubin binding capacity, birth weight, plasma protein level, and two published charts). These predictive methods were applied to 175 jaundiced infants for whom all the data were available and to 19 infants who were actually exchanged. Most of the patients were sick, premature infants. This study demonstrates the lack of agreement among the predictive methods.

Bilirubin↗

Relationship of plasma total bilirubin, apparent unbound bilirubin and total albumin with cerebellar glycogen and abnormal Purkinje cells in the Gunn rat.

Total plasma bilirubin, apparent unbound plasma bilirubin, cerebellar glycogen and Purkinje cells were quantified in heterozygous Gunn rats, homozygous Gunn rats and normal Wistar rats. Our results indicated that, in the Gunn rat, total bilirubin, apparent unbound bilirubin, and the bilirubin/albumin molar ratio are highly correlated with each other and with alterations in cerebellar Purkinje cells and accumulation of cerebellar glycogen. In addition, cerebella of heterozygous Gunn rats contained many abnormal Purkinje cells without intramitochondrial glycogen and cerebella of homozygous Gunn rats showed many Purkinje cells with intramitochondrial glycogen. Our results demonstrate previously unreported differences between heterozygous Gunn rats and controls. We suggest that population of Purkinje cells in the heterozygous Gunn rats may have received a cellular insult from fetal exposure to bilirubin.

Animals↗

Biochemical alterations in neonatal hyperbilirubinemia and bilirubin encephalopathy: a review.

This review article discusses some current questions concerning the measurement of bilirubin in the blood of newborn infants and the relationship of these blood parameters to the biochemical defects responsible for bilirubin encephalopathy. A discussion of numerous theories, which have been put forth to explain the specific biochemical mechanism by which bilirubin acts on brain metabolism, demonstrates that presently there is no unequivocal explanation for the molecular events leading to bilirubin encephalopathy.

Amino Acids↗

Placental transport of nutrients.

The fetus is dependent upon the placenta for transport to it of all nutrients for energy and growth. The primary nutrients crossing the placenta are glucose, lactic acid, free amino acids, free fatty acids, and ketone bodies. Under normal circumstances, it appears that glucose is the primary energy source. In abnormal conditions there is the possibility that energy requirements may be met also by protein-amino acid oxidation and ketone body metabolism. The fetal brain may be quite adept in the use of ketone bodies. In all transport phenomena, the placenta intervenes by diverting nutrients into its own intermediary metabolism. For a more extensive consideration of these factors, several in-depth reviews are recommended. To better understand abnormalities of intrauterine growth, we need much more specific information about the mechanisms of placental transport and the intermediary metabolism of the placenta and fetus. When these are adequately in states of normal and abnormal intrauterine growth, we can then consider methods of metabolic intervention which will correct intrauterine growth failure and, hopefully, eliminate its hazards to the fetus and child.

Amino Acids↗