Clifford J. Sells

Pharmacokinetics of anticonvulsants in pregnancy: Alterations in plasma protein binding

Anticonvulsant levels decline as pregnancy progresses, even in the face of constant and, in some cases, increased dosages of medications. It has been suggested that this decline is responsible for the increase in seizure frequency seen in approximately one-third of the women with epilepsy who become pregnant. Changes in plasma protein binding may explain the declines in anticonvulsant concentrations during pregnancy. A prospective cohort study was designed to test this hypothesis. Carbamazepine, phenytoin and phenobarbital were studied. The mean total concentrations of all 3 drugs declined as pregnancy progressed, rising in the postpartum period. Free concentrations also declined, but did so significantly only for phenobarbital. The free fraction for all anticonvulsants studied rose significantly throughout pregnancy. Protein binding is significantly altered during pregnancy for all 3 drugs studied and appears to account for much of the decline in anticonvulsant concentrations seen in this condition. It is suggested that free rather than total drug concentrations be monitored in pregnant women with epilepsy.

Neuromotor Development of Graduates of the Neonatal Intensive Care Unit: Patterns Encountered in the First Two Years of Life

The neurodevelopmental course of 219 Neonatal Intensive Care Unit graduates followed prospectively over 2 years was determined on retrospective chart review. Mild neuromotor abnormalities during the first year were identified in 50%, three-quarters of which proved transient with normal development at 2 years of age. Moderate abnormalities were identified in 7%, half of which proved transient. Severe neuromotor abnormalities were identified in 20%, two-thirds of whom had cerebral palsy at 2 years. Persistent noncerebral palsy neuromotor abnormalities remained in one-third of those in the severe abnormality group, one-half of those in the moderate abnormality group, and one-quarter of those in the mild abnormality group. As birthweight decreased, the incidence of always normal development and transient neuromotor abnormalities decreased while the incidence of persistent neuromotor abnormalities increased. Small for gestational age infants demonstrated a slightly higher incidence of persistent abnormalities than their appropriate for gestational age counterparts. No significant sex differences were observed.

Predictive validity of the “movement assessment of infants”

Early identification of neuromotor deficits, cerebral palsy or other neurological handicaps, is a focus of concern for neurologists, pediatricians, and developmental therapists. Among infants at risk for developing these handicaps are those with low birthweight, idiopathic respiratory distress syndrome, and early central nervous system insults. The Movement Assessment of Infants (MAI), a neuromotor assessment tool, was developed for the purpose of evaluating high-risk infants participating in the University of Washingtons Neonatal Intensive Care Unit Followup Clinic. The predictive validity of the MAI was evaluated for 246 infants for whom assessments had been completed at four months and for whom at least one set of followup data was available at either one or two years of age. Correlations between the MAI total risk score and all five of the outcome measures at one and two years were highly significant. The clinical relevance of this study in the use of the MAI as an evaluation tool for identifying infants with neuromotor dysfunction is discussed.

Physical and Occupational Therapy: Effects Related to Treatment, Frequency, and Motor Delay.

Issues related to occupational and physical therapy services for handicapped students are outlined. Among the issues addressed are the efficacy of therapy treatments, who should receive therapy, the frequency of services, and the effects of therapy on non-motor domains. Results of an experiment are reported which tested hypotheses about several of these issues. Findings suggest that the developmental therapy treatment affected gross motor gains for preschool children who exhibited moderate but not mild motor delays, and that one treatment per week was as effective as three treatment sessions per week.Issues related to occupational and physical therapy services for handicapped students are outlined. Among the issues addressed are the efficacy of therapy treatments, who should receive therapy, the frequency of services, and the effects of therapy on non-motor domains. Results of an experiment are reported which tested hypotheses about several of these issues. Findings suggest that the developmental therapy treatment affected gross motor gains for preschool children who exhibited moderate but not mild motor delays, and that one treatment per week was as effective as three treatment sessions per week.

Measuring Effects Of Psychoactive Medication In A Child With A Learning Disability

There is little information showing that specific psychoactive medications generally have predictable effects on children with learning disabilities. Thus, the need often arises to have a simple, but objective, method for determining whether a drug has effected a desired behavior change. Three types of behavioral measurement are presented, along with the results of these techniques, as they were applied to a child placed on psychoactive medication. In this instance, the obtained data did not demonstrate any drug effects on the behaviors for which the medication was prescribed.

Psychoactive Medication and Learning Disabilities

A seven-year-old emotionally disturbed boy with some features of the hyperkinetic syndrome was placed on a double-blind placebo control program to assess the effects of psychoactive medications (Ritalin and Dexedrine) on academic and social behaviors. Academic and social behaviors were generally improved with medication, but the beneficial effects varied depending upon the specific drug, dosage, and time of day. Some adverse side effects were noted with specific drug dosages. The importance of careful monitoring of children treated with psychoactive medications is stressed.

Reducing the Institutional Waiting Lists for the Mentally Retarded

Twenty-nine families who had children on the admission waiting list of a Washington State Institution for the retarded were studied. These parents and their retarded children had very little knowledge of possible outpatient services and had received little, if any, ongoing supportive primary care. Most parents were seeking institutionalization for their child to obtain relief for themselves and their family. Admission to the institution generally was not timed to meet either the needs of the individual or his family. Expansion of community services for the retarded can be important in reducing the number of candidates for admission to state institutions for the retarded.

Central Nervous System Stimulants — Their Use in the "Non-Classical" Hyperkinetic Syndrome: A Case-Controlled Study

From: The Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195. ALTHOUGH A VARIETY of pharmacologic agents have been developed for children with learning impediments over the past 35 years, the lack of uniform terminology and methods of investigation, the imprecision of diagnostic criteria, and the paucity of wellcontrolled studies makes critical evaluation ‘