The removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy.
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Biomedical subjects
Publications and source records attributed to R J Porter.
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Listeners display extremely short latencies when asked to reproduce (shadow), a random series of vowel-vowel sequences. The latency of the shadowing response is as fast or faster than that obtained when the same subjects are asked simply to produce a predetermined vowel-vowel gesture as rapidly as possible. The speed of the shadowing response suggests a fast and direct linkage of the speech-analysis and speech-production mechanisms.
Developmental changes in the plasma insulin response to milk ingestion have been determined in neonatal lambs fed by bottle and in naturally suckled infant rabbits. In lambs at 4 days of age and older plasma insulin increased within 5 min of suckling and declined again before increasing to a second peak 60 to 120 min after the feed. The early insulin peak was not associated with any change in plasma glucose and was absent in lambs at 1 day of age. When the early insulin peak was absent the increase in plasma glucose following the meal was greater. The early, apparently reflex, release of insulin also occurred in some 'sham-fed' lambs. Atropine administration before feeding abolished the early peak in insulin. A marked early peak of insulin release, not accompanied by any consistent change in plasma glucose, was also observed in naturally-suckled infant rabbits at 1, 5, 10 and 15 days after birth.
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Pitch judgments for dichotic chords composed of two pure tones often show a bias in favor of the chord-component going to one ear. This "ear-advantage for pitch" (EAP) varies between subjects, but is very stable within subject and is thought to reflect differences in spectral "sensitivity" of the two auditory pathways. The present study explored this hypothesis by examining pitch judgments of complexes composed of tones dichotically paired with frequency-varying signals. The direction and strength of EAP was first established using pure tones, then rising tone glides were introduced into the channel going to thenondominant ear. Since a glide possesses less energy at a given frequency than a pure tone of equal duration, an increase in EAP was expected. An increase in EAP was consistently observed for only one subject; three subjects showed small, variable effects; and six subjects displayed a decrease in EAP. The results suggested that factors other than relative spectral sensitivity affect observed EAP.
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The clinical efficacy of phensuximide and methsuximide was studied in relation to plasma concentrations of these compounds and their desmethyl metabolites. Single- and chronic-dose studies of each drug were carried out in five patients with intractable seizures. Patients were evaluated before and during treatment by 6-hour simultaneous video and telemetered electroencephalographic recordings to characterize the seizure type and by daily determinations of plasma antiepileptic drug concentrations. Phensuximide had a mean half-life of 7.8 hours and accumulated to an average fasting level of only 5.7 micrograms per milliliter. Desmethylphensuximide averaged only 1.7 micrograms per milliliter with a similar half-life. Methsuximide had an even shorter half-life, averaging 1.4 hours, but its desmethyl metabolite had a mean half-life of 38 hours and therefore accumulated to levels in excess of 40 micrograms per milliliter. The addition of phensuximide to their regimens benefited none of the patients, but two had an excellent response to methsuximide. The failure of phensuximide and its desmethyl metabolite to accumulate to reasonable levels is the likely explanation for the relatively weak antiepileptic effect of phensuximide as compared with methsuximide.
A 26-year-old woman with intractable seizures and fluctuating plasma phenytoin concentrations is described. Noncompliance with prescribed drug regimens was suspected. Phenytoin was first given as a capsule and then as an elixir. Ingestion of the capsule was monitored, and active non-compliance was proved and admitted by the patient. The causes of inadequate plasma phenytoin concentrations are few and can be determined either by specific laboratory methods or by changing the form of the drug.
Intensive monitoring techniques were used to improve seizure diagnosis and control in 23 patients with intractable epilepsy: (1) Video recording of clinical seizures and the ictal EEG, (2) long-term telemetered EEG recordings, and (3) frequent determination of plasma antiepileptic drug concentrations. Patients were monitored in the hospital for an average of 8 weeks and after discharge were followed for an average of 8 months. At follow-up, 70 percent of the patients continued to have improved seizure control as compared with baseline studies, 83 percent had decreased toxicity, and about half had made gains in social adjustment. Use of the techniques described can make a significant contribution to patients previously considered intractable to therapy.
A patient with Von Hippel-Lindau's disease was followed from the time of diagnosis to the time of his death 13 year later. He was asymptomatic when the diagnosis was made, although a hemangioblastoma of the medulla was found on angiography. The patient's course and autopsy are described and the features of this disease are reviewed.
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The plasma protein binding of diphenylhydantoin sodium was determined in 26 patients who had been taking diphenylhydantoin regularly for more than two weeks. The free (unbound) diphenylhydantoin level was found to vary from 5.8% to 12.6% of the total drug concentration. This range of variation may be clinically important, if it can be established that the binding of diphenylhydantoin to plasma proteins limits entry of the drug into the brain. The binding of diphenylhydantoin was directly proportional to the plasma albumin concentration, which thus appeared to be the most important determinant of diphenylhydantoin binding. Diphenylhydantoin binding was independent of the plasma concentration of the drug in the usual therapeutic range. In vitro studies showed little effect by phenobarbital sodium or penicillin G; therapeutic levels of acetylsalicylic acid, however, increased free diphenylhydantoin by nearly 50%.
Sixteen adult, right-handed, moderate-to-severe atutterers (12 males, 4 females) and 20 nonstuttering controls (10 males, 10 females) were given a dichotic nonsense-syllable test to determine hemispheric lateralization for speech. Both male and female stutterers evidenced right-ear advantages in syllable identification similar in magnitude to those found for normals. These data confirm other reports of no difference in cerebral speech lateralization for stutterers and nonstutterers and, therefore, lend no support to theories that relate stuttering to abnormalities in cerebral lateralization. Acknowledgments. This study was conducted while the authors were at the University of Connecticut, Storrs. The assistance of Dr. R. L. Webster, the staff of the Institute for Behavioral Research, and the Departments of Psychology and Linguistics at the University of Connecticut is gratefully acknowledged.
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Forty-eight patients, 4 to 24 years of age, with recurring absence seizures were studied prospectively for twenty-seven months. Each patient and his EEG were recorded simultaneously by a multicamera videotape technique and each recording was repeatedly viewed and described in writing by two observers who subsequently resolved any differences by joint viewing. From the 48 patients, 374 clinical absence seizures were recorded and classified according to the International Classification of Epileptic Seizures. Automatisms accompanied at least one attack in 88 per cent of the patients. Mild clonic components occurred in 71 per cent, and decreased postural tone in 41 per cent. Only one patient experienced an attack comprising only "blank staring" accompanied by unawareness and amnesia, but 40 per cent of patients exhibited this type of attack in addition to more complex absence attacks. Seizures of ten seconds or less in duration occurred among 85 per cent of patients. Each of the 374 seizures were readily classified according to the International Classification, but simple absence constituted only 9-4 per cent of the seizures. The others most often contained, in order of prevalence, either automatisms, mild clonic components, or decreased postural tone, or a combination of two or more of these features. The relationship between increased duration of the seizures and the occurrence of automatisms was significant. The findings are discussed in relation to differential diagnosis and mechanisms of automatisms. Absence seizures differ from complex partial (temporal lobe, psychomotor) seizures because an aura does not precede the abruptly beginning absence attack, the seizure usually lasts less than ten seconds, and mental clarity returns instantly at the end of the seizure.
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Thirty-seven patients with previously untreated absence seizures were treated with ethosuximide. Seizures were completely controlled in 7 patients (19 percent); 90 to 100 percent control was achieved in 18 patients (49 percent) and 50 to 100 percent control in 35 (95 percent). Plasma ethosuximide concentration increased with dose, but variability in the plasma concentration produced by a given ethosuximide dose made it impossible to predict a patient's plasma concentration from the dose. The therapeutic range of plasma ethosuximide concentration was 40 to 100 mug per milliliter. Patients with evidence of structural central nervous system abnormalities responded as well or better to the drug as patients without such evidence. Ethosuximide did not impair psychometric performance, but rather resulted in improved performance in 17 cases. The side effects of ethosuximide were minor, and rarely required withdrawal of the drug.