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Biomedical subjects

K B McCormick

Publications and source records attributed to K B McCormick.

5 recordsLinked to original sources

Antiepileptics and the development of congenital anomalies.

We are conducting a prospective cohort study of epilepsy and pregnancy to determine the nature and extent of adverse pregnancy outcomes in infants of mothers with epilepsy (IME). Women with epilepsy were enrolled no later than the first trimester and were matched with controls; their infants were examined at 8 weeks by pediatricians blinded to maternal status. A number of variables were compared between case and control infants: birth weight, length, gestational age, head circumference, Apgar scores, feeding difficulties, neonatal irritability, and presence of major malformations and minor anomalies. The number of minor anomalies per infant was greater for IME than for controls (mean, 5.05 and 3.65, p less than 0.0001 per infant, respectively). Prominent occiput was the only anomaly seen significantly more often in IME than in controls (p less than 0.05).

Abnormalities, Drug-Induced↗

Use of unbound drug concentrations to determine neonatal anticonvulsant exposure.

Unbound and total concentrations of several anticonvulsant drugs were measured by liquid chromatography in maternal and neonatal cord serum collected at birth from 16 women being treated for epilepsy and their newborns. Maternal and neonatal unbound drug concentrations agreed closely for phenobarbital (n = 6), phenytoin (n = 7), carbamazepine (n = 8), and its epoxide metabolite. Mean maternal total drug concentrations were higher than neonatal concentrations in the cases of phenobarbital, carbamazepine, its epoxide and diol metabolites. The differences were due to greater protein binding in maternal serum. Measurement of total anticonvulsant concentrations in newborns may be misleading, because of altered protein binding in the neonate. For the medications tested, neonatal and maternal exposures to unbound drug appear to be equivalent.

Adult↗

Pregnancy and epilepsy: nursing implications.

Pregnant women with epilepsy have a greater risk for complications of pregnancy and adverse pregnancy outcomes. Problems that may arise during the course of pregnancy include an increase in seizure frequency, reduction of serum antiepileptic drug levels, and an increase in bleeding during pregnancy and after delivery. The infant of an epileptic mother is at twice the risk of infants in the general population to have a major malformation, and the risk for perinatal death is 1.2 to 3 times greater. Despite these facts, at least 90% of women with epilepsy have a normal pregnancy and deliver a normal infant. The pregnant woman with epilepsy may minimize the risk of adverse outcome by taking measures to ensure an optimal prenatal course. The neuroscience nurse can provide these clients with accurate information regarding pregnancy and epilepsy and can review measures that may be taken to reduce chances of an unfavorable outcome.

Abnormalities, Drug-Induced↗

Zonisamide in epilepsy: a pilot study.

We compared zonisamide monotherapy (12 weeks) to carbamazepine monotherapy (12 weeks) after phenytoin baseline monotherapy (8 weeks) in an open crossover pilot study of eight adults with uncontrolled partial seizures. Zonisamide had definite antiepileptic activity in five subjects. In two of these, response to zonisamide was superior to that to either phenytoin or carbamazepine. A third subject became seizure free on zonisamide, but had to be withdrawn after 18 days because of mild Stevens-Johnson syndrome. The other three subjects were withdrawn from the study because of drug toxicity, manifested mainly by impaired higher mental function and increased seizures. The best response to zonisamide was at doses approximating 6 mg/kg/day, with plasma levels of 20-30 mg/L. Plasma levels of greater than 30 mg/L usually were associated with toxicity. The pharmacokinetics of zonisamide are complex and nonlinear, with steady-state plasma levels being approximately three times higher than those predicted from a single-dose study.

Adolescent↗

Efficacy of nafimidone in the treatment of intractable partial seizures: report of a two-center pilot study.

Nafimidone is a potential new antiepileptic drug with a therapeutic profile in experimental animal seizure models similar to that of phenytoin (PHT). We report here the first clinical trial of nafimidone in epileptic patients. Twelve adult male patients with a mean of four or more medically intractable seizures per month were enrolled in a 14-week pilot study. Patients were stabilized on therapeutic levels of PHT and carbamazepine (CBZ) (nine patients) or on PHT alone (three patients) before entering a 4-week baseline period. Nafimidone, to a maximum dose of 600 mg/day, was added during 2 weeks in hospital. Patients were then evaluated weekly for 8 weeks. Eight patients experienced 33-98% improvement in seizure control. Three others did not show significant change in seizure frequency but experienced sufficient subjective improvement that they continued into long-term follow-up. One patient, who had a 63% improvement in mean weekly seizures during the pilot study, declined to continue. Thus, 10 patients entered long-term follow-up. Six of the 10 sustained 53 to greater than 99% improvement in seizure control compared with baseline over the course of 46-53 weeks of follow-up. Nafimidone had a marked inhibitory effect on the clearance of CBZ and PHT, resulting in higher plasma levels in nine patients. The possible role of the elevated CBZ levels in the apparent efficacy of nafimidone is discussed.

Adult↗