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Biomedical subjects

L J Willmore

Publications and source records attributed to L J Willmore.

At least 19 recordsLinked to original sources
PubMed1979

Simultaneous determination of the anticonvulsants, cinromide (3-bromo-n-ethylcinnamamide), 3-bromocinnamamide, and carbamazepine in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for monitoring plasma concentrations of cinromide (3-bromo-N-ethylcinnamamide) and its de-ethylated metabolite. Carbamazepine levels can be easily measured by the same technique. The N-isopropyl analogue of cinromide is used as internal standard, and all compounds are easily separated on a reversed-phase column operated at 55 degrees with a small-diameter pre-column maintained at the same temperature. The extraction is rapid and generally applicable to plasma and urine samples that are to be analyzed by reversed-phase chromatography. Short- and long-term reproducibility studies show less than 4% relative standard deviation for replicate determinations for all drugs. Limits of quantitation are 10-20 ng/ml with an internal standard concentration of 3 micrograms/ml. Another metabolite of cinromide, 3-bromocinnamic acid, which may have some anticonvulsant effect, can be analyzed simultaneously by buffering the mobile phase and adding an ion-pairing reagent.

Anticonvulsants↗
PubMed1979

Epilepsy and pregnancy.

The management of the pregnant epileptic requires close cooperation between the neurologist and obstetrician. To prevent complications, knowledge is required about the natural history of epilepsy during pregnancy, the possible teratogenic effects of antiepileptic drugs, and changes in their absorption, biotransformation, and excretion. Close plasma antiepileptic drug monitoring is required because of the change in the handling of antiepileptic drugs during pregnancy. The treatment of status epilepticus with intravenous phenytoin is effective. Drug interactions which may lead to toxic plasma levels of some drugs and subtherapeutic plasma levels of others should be anticipated. The risk of problems resulting from antiepileptic drug therapy during pregnancy appears to be minor, provided that proper medical supervision is available. Newer antiepileptic drugs should not be administered to the pregnant epileptic until their safety in pregnancy is fully established.

Abnormalities, Drug-Induced↗
PubMed1979

Treatment of postanoxic intention myoclonus with valproic acid.

Valproic acid in therapeutic doses was used in the treatment of postanoxic intention myoclonus. Disappearance of the myoclonus occurred with marked improvement in the electroencephalogram. No significant side effects were noted. Hepatic function tests were monitored. Determination of valproic acid plasma levels was used to guide therapy. Levels above 55 micrograms were generally required. The patient remains free of myoclonus after four and one half months.

Humans↗
PubMed1979

Valproic acid and plasma levels of phenytoin.

Eight patients were treated concurrently with a constant dose of phenytoin and valproic acid for 1 year. During initial therapy with valproic acid, total plasma phenytoin levels decreased. The interaction was transient and was not observed at the end of 1 year. Total plasma phenytoin levels returned to pre-valproic-acid levels in seven patients.

Drug Interactions↗
PubMed1979

Epilepsy and pregnancy. Serum thyroxine levels during phenytoin therapy.

Blood levels of phenytoin, total thyroxine, and free thyroxine were determined in 10 epileptic women during and following pregnancy. Although total thyroxine concentrations of phenytoin-treated subjects were significantly lower than control values, pregnancy did not appear to diminish the relative increase in total thyroxine seen in normal pregnancy. Free thyroxine concentrations, which were equally depressed at all test times, remained at low euthyroid levels during pregnancy. Following delivery, 3 patients developed free thyroxine levels below 1.0 ng/100 ml. Phenytoin dosage was increased to improve seizure control but produced relatively low blood levels during pregnancy. Following delivery, phenytoin dosage was slightly decreased but produced a significant increase in phenytoin blood levels. The potential effects of phenytoin-related changes in maternal and fetal thyroxine levels are discussed.

Abnormalities, Drug-Induced↗
PubMed1978

Chronic focal epileptiform discharges induced by injection of iron into rat and cat cortex.

A single injection of 5 or 10 microliters of ferrous or ferric chloride into rat or cat sensorimotor cortex resulted in chronic recurrent focal paroxysmal electroencephalographic discharges as well as behavioral convulsions and electrical seizures. Recurrent focal epileptiform discharge caused by cortical injection of iron salts suggests that the development of human posttraumatic epilepsy may depend, in part, on the neurochemical alterations induced by the principal metallic ions found in whole blood.

Animals↗
PubMed1978

Identification of speech lateralization by intracarotid injection of methohexital.

Speech lateralization was assessed in 25 patients with epilepsy by direct carotid injection of carotid catheterization from a femoral approach. Hemispheric anesthesia was induced by intracarotid injection of the rapidly acting barbiturate methohexital. This technique allowed same-day study of both hemispheres, permitted repeated injection of either carotid artery without accumulation of methohexital sufficient to cause systemic effects, and added little to the total time required for three-vessel cerebral angiography. Unilateral seizures were induced by methohexital injection in 4 patients. No other complication secondary to the methohexital study was observed.

Adolescent↗
PubMed1978

Recurrent seizures induced by cortical iron injection: a model of posttraumatic epilepsy.

A single injection of 5 or 10 microliters of ferrous or ferric chloride into rat or cat sensorimotor cortex resulted in chronic recurrent focal paroxysmal electroencephalographic discharges as well as behavioral convulsions and electrical seizures. Iron-filled macrophages, ferruginated neurons, and astroglical cells surrounded the focus of seizure discharge. Recurrent focal epileptiform discharges caused by cortical injection of iron salts suggests that the development of human posttraumatic epilepsy may depend, in part, on neurochemical alterations induced by the principal metallic ions found in whole blood.

Animals↗
PubMed1978

Steady-state kinetics of valproic acid in epileptic patients.

Pharmacokinetic evaluation and prediction were carried out in 20 epileptic patients. Using conventional pharmacokinetic techniques and a one-compartment model, predicted and observed valproic acid plasma concentrations were compared. Valproic acid assay was performed by gas-liquid chromatography. There was good agreement between predicted and observed plasma concentrations. Most patients had predicted half-lives (t1/2s) of 6 to 8 hr, independent of the plasma concentration of valproic acid. Five patients had predicted t1/2s of 12 hr. The correlation between dose and plasma level was poor. Most patients had valproic acid plasma levels between 55 and 100 microgram/ml. Administration of valproic acid three times a day with determination of individual plasma concentrations offers a reliable method of monitoring. Constant levels are maintained in individual patients, but there is substantial intersubject variation.

Adolescent↗
PubMed1978

Clinical efficacy of valproic acid in relation to plasma levels.

Valproic acid is a new antiepileptic drug recently introduced in the United States for the treatment of absence seizures. In this study on patients with absence and other seizure types, the majority of patients achieved optimal control within four weeks of therapy. No patient responded to valproic acid who did not show an initial clinical response by four weeks of active therapy. Optimal response was generally achieved when plasma levels were greater than 55 microgram/ml. Excellent clinical response was observed in the treatment of absence and myoclonic seizures. Twenty-two patients continued in a long term study have maintained the same degree of seizure control as observed at the time of optimal control.

Adolescent↗
PubMed1978

Status epilepticus in pregnancy: effect of phenytoin malabsorption on seizure control.

In the second trimester of pregnancy in a 26-year-old woman, marked exacerbation of epileptic seizures occurred with somatomotor status epilepticus. The oral requirement of phenytoin varied, and up to 1,200 mg per day were needed to maintain a therapeutic plasma concentration during the second trimester. Intestinal malabsorption was shown to be a causal factor; 56 percent of the daily oral dose of phenytoin was found in the stool. Late in pregnancy and postpartum, therapeutic plasma concentrations of phenytoin were maintained with decreased daily oral doses. Intestinal absorption improved postpartum.

Administration, Oral↗
PubMed1978

Effect of valproic acid on spike and wave discharges in patients with absence seizures.

Twenty-five patients with absence seizures were treated with valproic acid in doses from 17 to 62.5 mg per kilogram per day. Nineteen patients experienced reduction of spike and wave discharges; in 11 it was greater than 75 percent. Twenty-one patients had a reduction of the total time of spike and wave discharge. Four patients had increase of spike and wave discharges. Nineteen patients had fewer absence seizures. There was no correlation between plasma concentration of valproic acid and EEG change, but clinical improvement occurred when plasma levels of valproic acid reached 50 to 60 microgram per milliliter.

Adolescent↗
PubMed1978

Valproic acid: interaction with other anticonvulsant drugs.

The interaction of valproic acid and other antiepileptic drugs was studied in 25 patients for 5 to 9 months. Clinical evaluations, seizure records, and antiepileptic drug levels were followed regularly. Eleven of the 13 patients required a reduced phenobarbital dose when concurrently treated with valproic acid. This reduction was prompted by sedation. An average dose reduction of 46 percent resulted in an average serum phenobarbital decrease of 15 percent. Ten of 15 patients had decreased phenytoin concentrations during concurrent administration with valproic acid. No definitive conclusion was reached about other antiepileptic drugs. Decreased phenobarbital excretion because of urine acidification and displacement of phenytoin from protein binding sites may account for the observations. Careful monitoring of anticonvulsant levels is required in anticipation of the documented interactions.

Adolescent↗
PubMed1978

Effect of valproic acid on hepatic function.

Altered hepatic function tests occurred in four of 25 patients treated with valproic acid. An average dose reduction in three patients of 10 mg per kilogram per day resulted in reversion of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) to normal. The drug was discontinued in one patient. Careful monitoring of hepatic function is required of patients being treated with valproic acid, but our experience suggests that dose reduction alone may be effective in preventing untoward hepatic side effects.

Adolescent↗
PubMed1978

Hematologic effects of phenytoin therapy during pregnancy.

Serum folate and plasma phenytoin concentrations were measured in 10 epileptic gravidas who did not receive folate supplementation. Mean serum folate concentration averaged 5.0 ng/ml during the second and third trimesters of pregnancy but significantly decreased to 2.9 ng/ml during nonpregnant evaluation 1 to 12 months following delivery. No patient exhibited anemia or macrocytosis suggestive of cellular folate deficiency either during or following pregnancy. Although phenytoin dosage remained relatively constant, plasma phenytoin concentrations during pregnancy were significantly lower than nonpregnant concentrations. The improvement in folate status observed during pregnancy may be related to lowered plasma phenytoin concentrations.

Carotenoids↗