Leonore Ballowitz

Phototherapy in Gunn Rats

A new mathematical analysis is done with data from animal tests published 1977 in this journal. For the phototherapy-induced serum bilirubin decrease, reliable concentration-time functions can be asce

Mathematical description of the temporal changes in serum bilirubin concentration during phototherapy in newborn infants.

Deriving from experiments in Gunn rats, an equation is developed which allows one to calculate and predict the photoeffect in human babies, when phototherapy begins between days 3 and 5. The serum bilirubin level at the start, the illuminated body surface and the effective irradiance applied are taken into consideration.

Sephadex-Gel Filtration (SGF) in Infant and Adult Gunn Rats

SGF was compared in infant and adult homozygous Gunn rats. Without any drug application, the test was negative in the adult animals, whereas a remarkable percentage of positive SGF was obtained in 5-7-day-old rats, especially in those undernourished and/or intensely icteric. Unexpectedly, in infant rats the rate of positive SGF after sulfadimethoxine injection was lower than in the untreated control group. Moreover, in 9-10-day-old animals who had positive SGF before the injection, the test became negative 15-20 min after sulfadimethoxine application in vivo. No convincing explanation could be given, but drug interference with the binding capacities of the Sephadex column could be excluded by appropriate in vitro tests.

The influence of various aminoglycoside preparations on bilirubin/albumin binding

The effect of antibiotics of aminoglycoside structure on the albumin binding of bilirubin has been tested in homozygous (jaundiced) Gunn rats aged 3-5 days. The following drugs were investigated: different preparations of gentamycin, kanamycin, tobramycin and sisomicin. The animals received 50-75% of the LD50 of heterozygous (non-jaundiced) Gunn rats. Mortality, weight gain and changes in the plasma bilirubin concentration were recorded. It was found that the displacement of bilirubin from albumin is caused by the different stabilizers used and not by the antibiotic itself. With the exception of lyophilized preparations of gentamycin for intrathecal application all vials contain different amounts of these preservatives. Special preparations used during the newborn period contain relatively more of these stabilizers. The toxicity of the additives has already a negative influence on the LD50 for heterozygous Gunn rats when the low dosed Refobacin and Sulmicin vials are given. For Refobacin (production 1973/74) the tolerance is reduced by nearly 50%. The toxicity caused by the stabilizer alone is even more marked when given to homozygous (jaundiced) Gunn rats. It becomes evident that benzylalcohol is the substance responsible for the displacement of bilirubin from albumin. The serum concentration of bilirubin decreases for 3-24 hrs depending on the doses given to the animal. This offers the opportunity to measure the competitive displacement of bilirubin easily and exactly. The free unbound, unconjugated bilirubin tends to diffuse into the lipid of the brain with resultant kernicterus. This was shown in histochemical preparations of the cerebellum of young homozygous Gunn rats. Using enzyme reactions for lactic acid dehydrogenase and NADH2-tetrazolium reductase the cytotoxic effect of bilirubin on PURKINJE cells could be demonstrated. The effect of the stabilizers used in the other antibiotic drugs tested can be neglected under clinical conditions. Finally the steepness and duration of the decrease of plasma bilirubin after injection of the dangerous stabilizers was studied in animals of different age (3-5 days; 3-4 weeks). Different results observed can be explained by the more rapid metabolism of benzoates in older animals. However, it remains an open question at what age Gunn rats reflect most precisely the human situation in premature and newborn babies.

The Gunn Rat — A Model for Phototherapy

For more than 15 years, neonatologists, a pediatric neurologist, illumination engineers as consultants and later on a pediatrician, formerly trained in mathematics and chemistry — are using in our hospital the Gunn rat strain as a model. phototherapv (PT) was one of the main topics. Today, the succeeding steps of research shall be listed in short and completed by new data.*

Bilirubin encephalopathy: Changing concepts

This overview begins with a discussion of clinical approaches to prevent brain damage in jaundiced newborns. Results of longitudinal follow-up studies are given. The main part deals with pathogenesis, whereby bilirubin albumin binding, competition by drugs, bilirubin distribution and equilibration in the body, the increased sensitivity of the infantile nervous system, the mechanism of bilirubin entry into nerve cells and the resulting intracellular damage are emphasized.