Biomedical subjects
Publications and source records attributed to K Voeller.
The computed tomography findings are discussed in four cases of neuronal ceroid lipofuscinosis. When this severely progressive inherited disease of lipid metabolism is suspected, confirmation may be obtained with electron microscopy of peripheral lymphocytes and certain tissues. Some physiologic-pathologic features are discussed.
The application of a Bayesian feedback algorithm for phenytoin (PHT) dosing adjustments was modified empirically to take advantage of measurements of plasma unbound PHT concentrations in the estimation of Km values. Doses were calculated to achieve steady-state unbound PHT nadirs of 1.2 mg/L with an allowable range of 0.9-1.5 mg/L. The success of this approach was compared with that of a routine strategy encompassing the use of monitored total plasma PHT concentrations and no estimates of kinetic parameters. Allowing up to a double feedback of monitored values, the Bayesian approach was better than the routine procedure in predicting doses that led to PHT concentration within the targeted range (p less than 0.005). The approach to optimizing PHT dosing described herein offers the advantage of rapidly converging on near-optimal therapy for those patients who are already on PHT but whose seizures are not suitably controlled, and may be useful even for patients who exhibit abnormal PHT plasma protein binding, such as those who also must take valproic acid.
The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a gas-liquid chromatography procedure. The phenytoin free fraction among pediatric epilepsy patients not taking valproic acid was normally distributed with a mean (+/- SD) of 9.2 +/- 1.8%. The mean (+/- SD) free phenytoin fraction among patients also taking valproic acid was 13.2 +/- 4.5%. Salivary ultrafiltrates exhibited a close correspondence with plasma ultrafiltrate concentrations, and the ratio of salivary to plasma ultrafiltrate concentrations was 1.06 +/- 0.15. Substantial intraindividual variation in the phenytoin free fraction and the increase in free fraction among patients on valproic acid emphasize the importance of using plasma unbound levels for monitoring phenytoin. The close agreement between plasma and salivary ultrafiltrate concentrations suggests that the latter will provide a practical noninvasive means of monitoring phenytoin.
Lead-chelating medication was used to treat 13 hyperkinetic school children whose blood and urine lead levels were in an elevated but "nontoxic" range. Six children with histories of etiologically relevant perinatal or developmental complications showed relatively little improvement. Seven other children with unremarkable histories, and for whom a lead etiology could thus be entertained, showed marked improvement. The authors conclude that lead may play an important role in the etiology of some cases of hyperactivity; lead-chelating agents may have a major place in the treatment of hyperactivity; and the medical workup of hyperactivity should include lead level measurements and careful consideration of other possible etiological factors.
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