Search PubMed⌕ Search

Biomedical subjects

K Silverstein

Publications and source records attributed to K Silverstein.

5 recordsLinked to original sources
PubMed1992

Disposition of antineoplastic agents in the very young child.

Maturation of physiologic process which govern the disposition of pharmacologic agents can yield significant changes in absorption, distribution, metabolism, and elimination of drugs in neonates, infants and children. However, there are very little data concerning the disposition of anticancer drugs in young children. Pharmacokinetic data for six anticancer agents were compared in infants less than 1 year of age and children greater than 1 year of age treated at St Jude Children's Research Hospital. No pharmacokinetic data were available for infants less than 2 months of age. Median methotrexate clearance tended to be lower in four infants (0.26-0.99 years) vs 108 children (1-19 years): 80 vs 103 ml min-1 m-2, respectively (P = 0.01). There was no difference in the median 42 h methotrexate concentration. Teniposide systemic clearance and terminal half-life and cytarabine systemic clearance were not different between the two groups. There was no significant difference in etoposide systemic clearance when normalised to body surface area (ml min-1 m-2), however a significantly lower systemic clearance relative to body weight (ml min-1 kg-1) was observed in two infants, 0.5 to 1 year of age, vs 23 children, 3-18 years of age. Doxorubicin systemic clearance was not significantly different between the two groups when systemic clearance was expressed in ml min-1 kg-1. However, there was a trend toward a lower rate of systemic clearance in ml min-1 m-2 in infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1984

Sequence-determined DNA separations.

The variation in electrophoretic mobility of DNA under conditions of marginal helix stability provides a useful means for investigation of the relation between the helix-random chain transition and base sequence in natural DNA and a powerful procedure for separation of DNA molecules according to sequence. The use of statistical mechanical theory for analysis of the transition equilibria together with new, simplified theoretical considerations on the effect of strand unravelling on mobility have shown that the gel behavior is predictable for known sequences. A number of the distinctive consequences of the theory and their correspondence with the properties of real molecules have been demonstrated. These include the extremely close cooperative linkage of large blocks of bases into domains, the existence of sharp boundaries between domains, the major role of nearest-neighbor interaction in determining stability, the dependence of domain structures on neighboring and more remote sequences, and the depression of domain melting temperature if the sequence lies at the end of a molecule. New and unusual applications derive from the possibility of separating DNA molecules by properties of their sequence. Exceedingly complex mixtures, such as the sum of all fragments produced by the action of a sixbase specific restriction endonuclease on a complete bacterial genome, can be resolved completely. Additional inserted sequences are easily discerned. The difference of a single base pair in a molecule permits detection and isolation of mutant sequences. The need for full sequential analysis of long molecules for characterization of mutants can be reduced by localizing a change within a small fragment.

Bacteriophage lambda↗