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Biomedical subjects

E A Rodin

Publications and source records attributed to E A Rodin.

At least 19 recordsLinked to original sources

Dipole sources of the human alpha rhythm.

Dipole sources were investigated in 22 normal subjects with a variety of strategies available through the BESA program. When all the data were summed one regional source, located near the midline in the basal portions of the occipital lobe, explained 92% of the variance. Two regional sources, initially constrained for symmetry but subsequently freed from constraint placed them also in the occipital regions near the midline and reduced the residual variance to 4%. Pooled data obscure, however, the marked individual differences especially in regard to lateralization. In the individual case the major source was also always in one occipital area but its location, especially the degree of separation from the midline depended upon alpha distribution and the strategy used in the workup of the data. The orientation of the major components of the regional sources was usually in the posterior-anterior direction, fairly parallel to the midline and while the other one pointed to the upper convexity. Because of the considerable variability of the alpha rhythm in given subjects and even within the same individual a model which requires symmetry constraints is not optimal for all instances, even when constraints are lifted thereafter. The study demonstrated the feasibility of distinguishing predominantly mesial sources from those which are bihemipheric with more lateral origins but several different models may have to be used to reach the most realistic conclusions.

Adult

Some problems in the clinical use of topographic EEG analysis.

The correct clinical use of topographic EEG analysis is labor intensive, time consuming and does not bypass the problems involved in conventional EEG interpretations. The physician interpreting maps needs not only to be fully cognizant of all the aspects of clinical electroencephalography but also of the special issues inherent in this methodology. Certain problems that are specific to topographic EEG analysis and that can lead to wrong interpretations are presented.

Brain Mapping

Derivation and evaluation of an equation for prediction of free phenytoin concentration in patients co-medicated with valproic acid.

The relationship between free phenytoin fraction (F-PHT-F) and valproic acid (VPA) was studied under two conditions: (a) in serum samples from 43 institutionalized patients (212 serial data points) at plateau steady state, and (b) in plasma samples from 50 outpatients coming for regular visits to our clinic throughout the day. Results for both groups led to identical linear regression equations relating F-PHT-F to VPA: F-PHT-F = 0.095 + 0.001 (VPA). Nevertheless, as expected, the resulting equation gave an unreliable prediction of F-PHT-F due to a variable physiological matrix. Substituting the parameter F-PHT-F by its equivalent (F-PHT/PHT) gave the equation F-PHT = [0.095 + 0.001 (VPA)] PHT. The predictive power of this equation was evaluated by the comparison of obtained and predicted F-PHT concentrations. For the combined patient group (n = 93), an excellent agreement (r = 0.972 and F = 999.9; p less than 0.001) was obtained. Although the empirically derived constants of the equation are not unique and may vary depending on the conditions of different methodologies, the fundamental relationship has been established and can be used to reliably predict F-PHT concentration from plasma VPA and PHT concentrations.

Adult

Derivation and evaluation of an equation for prediction of free carbamazepine concentrations in patients comedicated with valproic acid.

The relationship between free carbamazepine fraction (F-CBZ-F) and valproic acid (VPA) was studied in 50 outpatients coming for regular visits to our clinic throughout the day, and was compared with 50 patients without VPA comedication under similar conditions. F-CBZ-F was found to be significantly (t = 3.5, df = 98, p less than 0.001) higher for VPA comedicated patients (0.291 +/- 0.024) when compared with patients without VPA (0.247 +/- 0.016). Linear regression analysis for total plasma VPA concentration versus F-CBZ-F gave the equation: F-CBZ-F = 0.247 + 0.00062 (VPA); n = 50, r = 0.697, p less than 0.001, indicating unreliable prediction of F-CBZ-F from VPA concentration. Substituting the parameter F-CBZ-F by its equivalent (F-CBZ/CBZ) yielded the equation F-CBZ = [0.247 + 0.00062 (VPA)] CBZ. The predictive power of this equation was evaluated by the comparison of obtained and predicted F-CBZ concentrations. An excellent agreement (n = 50, r = 0.981, p less than 0.001) was obtained. Although the empirically derived constants of the equation are not unique and may vary depending on the conditions of different methodologies, the fundamental relationship has been established and can be used to reliably predict F-CBZ concentration from plasma VPA and CBZ concentration.

Adolescent

Chronic antiepileptic drug therapy: classification by medication regimen and incidence of decreases in serum thyroxine and free thyroxine index.

Results are described on the association of decreased serum total thyroxine (T4) and free thyroxine index (FTI) with antiepileptic drug therapy in a group of randomly selected chronically medicated outpatients (n = 291). For monotherapy subgroups (n = 164), the highest incidence (T4, 23.9%; FTI, 25.4%) of below normal values occurred in patients medicated with carbamazepine (CBZ), followed by phenytoin [(PHT) T4, 13.2%; FTI, 7.9%], and phenobarbital [(PB) (T4, 3.4%; FTI, 0%]. No T4 and FTI values below normal were detected in any patients (n = 30) on chronic valproic acid (VPA) monotherapy. For CBZ monotherapy (n = 67), women (n = 37) had a higher frequency of below normal values of T4 (p less than 0.05) and FTI (p less than 0.001) than men (n = 30). Therefore, the order of decreasing T4 and FTI effect was as follows: CBZ (women) greater than CBZ (men) greater than PHT greater than PB greater than VPA. For polytherapy subgroups (n = 127), the highest incidence (T4, 51.9%; FTI, 48.1%) was found in patients medicated with PHT and CBZ, followed by PHT and VPA (T4, 37.0%; FTI, 23.9%), and PHT and PB (T4, 17.2%; FTI, 10.3%). For PHT and CBZ poly-therapy (n = 52), women (n = 21) had a higher frequency of below normal values of T4 (p less than 0.05) and FTI (p less than 0.001) than men (n = 31). The magnitude of the decreasing T4 and FTI effect was greater for polytherapy subgroups (versus monotherapy subgroups) and in order as follows: PHT + CBZ (women) greater than PHT + CB (men) greater than PHT + VPA greater than PHT + PB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Intellectual functions of patients with childhood-onset epilepsy.

The intellectual functions of 64 epileptic patients who had had an initial evaluation between five and 16 years of age, including the WISC, were re-evaluated after a period of at least five years. In general the seizure states had improved, and 50 per cent were in remission for between two and eight years. All but four were still taking at least one anticonvulsant drug. WISC IQ estimates showed a slight decrease. Verbal and performance areas could be differentially affected, and a gain in one could be offset by a loss in the other, so the Full-scale IQ might not be a reliable measure of day-to-day performance. Those whose seizures remained uncontrolled had a statistically significant decrease in performance IQ, whereas in general it was stable or increased for patients in remission. There was evidence that decreased IQ indicated slower mental growth rather than loss of previously acquired function. Phenobarbital but not phenytoin levels were inversely correlated with IQ, suggesting that the upper limit of the 'therapeutic range' of phenobarbital may already be toxic with regard to learning abilities. To optimize an epileptic child's functioning in school and to prevent long-term intellectual problems, it is advisable that IQ testing should be part of the routine initial evaluation, and that drug levels should be checked at regular intervals.

Adolescent

Chronic valproic acid therapy and incidence of increases in venous plasma ammonia.

Results are described on the association of elevated ammonia (NH3) with valproic acid (VPA) therapy in a large group (n = 157) of randomly selected, chronically medicated (greater than 2 years) outpatients. The highest incidence (45.5%) of elevations occurred in patients comedicated with VPA-phenobarbital (PB)-phenytoin (PHT) combinations, followed by VPA-PB (33.3%) and VPA-PHT (15.4%). No NH3 elevations were detected in all patients (n = 38) on chronic VPA monotherapy. Considering the total sample (n = 157), NH3 concentrations were found to be linearly and directly correlated with VPA plasma concentration (n = 125, r = 0.249, p less than 0.001), PB concentration (n = 86, r = 0.411, p less than 0.001), sum of VPA-PB concentration (n = 60, r = 0.721, p less than 0.001), and sum of VPA-PB-PHT concentration (n = 33, r = 0.802, p less than 0.001). When patients in the subgroups (n = 73) that included all the patients with elevated NH3 were separated into one group (n = 47) with normal NH3 (less than or equal to 0.70 micrograms/ml) and one group (n = 26) with elevated NH3 (greater than or equal to 0.71 micrograms/ml), Student's t tests for equality of means showed that the group with elevated NH3 had a significantly higher mean plasma concentration for VPA, PB, sum of VPA-PB, and sum of VPA-PB-PHT (all at p less than 0.001) when compared with the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Effect of phenothiazines on serum antiepileptic drug concentrations in psychiatric patients with seizure disorder.

The intrapatient effect of starting (group A, n = 16), increasing (group B, n = 19), decreasing (group C, n = 23), and discontinuing (group D, n = 34) the phenothiazines (PHZs) thioridazine, chlorpromazine, or mesoridazine on serum phenytoin (PHT), phenobarbital (PB), and primidone (PRI) was studied at a constant antiepileptic drug regimen and between two consecutive steady-state concentration determinations in 92 institutionalized epileptic patients with psychiatric disorders. For PHZ initiation or dosage increase (groups A and B), serum PHT and PHT concentration-to-dose ratio (C/D) decreased by 44 (p less than 0.001) and 41.6% (p less than 0.001) in group A, and 32.9 (p less than 0.001) and 35.3% (p less than 0.005) in group B, respectively. For PHZ dosage decrease or discontinuation (groups C and D), serum PHT and C/D ratio increased by 54.8 (p less than 0.001) and 51.3% (p less than 0.01) in group C, and 71.2 (p less than 0.001) and 69.2% (p less than 0.001) in group D, respectively. The changes for PB were in the same direction, although to a lesser extent. No statistically significant differences were noted for PRI. For groups A and B, the clinical trend was for increase in number of seizures when PHZs were started or dosage increased. For groups C and D, a clear trend for PHT intoxication was evident when PHZ dosages were decreased or discontinued.

Adolescent

Monitoring free valproic acid in epilepsy patients medicated with coanticonvulsants.

Methodology for monitoring free valproic acid (VPA) and experimental proof of intrapatient in vivo diurnally and disproportionately variable free VPA fractions has recently been reported. An inherent assumption in accepting therapeutic VPA plasma levels to be 50-100 micrograms/ml is that free fractions remain constant. This assumption is no longer tenable. Therefore, monitoring only VPA plasma levels could be misleading. The serial 9-h time-course (7 a.m. 0 10-1-4 p.m.) of free versus plasma VPA levels was investigated in 24 patients. Limits for diurnal fluctuations were (mean +/- SD): Group A (n = 14); 49.0 mg/kg; multiple equal dosing: Free VPA (micrograms/ml) 6.06 (1.55 to 12.62 (4.89), plasma VPA (micrograms/ml) 52.9 (11.6) to 84.2 (21.3), percent free VPA 11.5 (1.8) to 14.9 (2.5). Group B (n = 10); 30.6 mg/kg; b.i.d.: 12.0 (2.4) mg/kg a.m. and 18.7 (3.3) mg/kg p.m.: Free VPA 5.53 (1.04) to 9.92 (1.51), plasma VPA 52.0 (7.3) to 79.2 (9.6), percent free VPA 10.7 (1.6) to 12.5 (0.8). Reducing the dosage by 19 mg/kg (A to B) decreased VPA plasma levels by 6.9% nd free VPA levels by 28.9%. For B: y = 8.15 + 4.03 x; n = 10, r = 0.954, Sy.x = 1.38, when x = steady-state (7 a.m.) free VPA concentration and y = VPA mg/kg/day. The findings suggest that multiple dosing is unnecessary. Similar plasma levels with far less diurnal fluctuations of free levels are achievable by a smaller drug dose with approximately two-thirds of total daily dose being administered in the evening and one-third in the morning.

Adult

Dissociation between free and bound phenytoin levels in presence of valproate sodium.

A dissociation of free vs bound phenytoin levels is frequently observed in the presence of therapeutic doses of valproate sodium. This leads at times to symptoms and signs of phenytoin intoxication despite "therapeutic" plasma levels. The importance of supplementing bound levels with free levels is stressed when combined therapy of this type is used in epileptic patients.

Adult

Serial free and plasma valproic acid and phenytoin monitoring and drug interactions.

In 12 institutionalized epilepsy patients who had been treated 19 months (SD +/- 5) with valproic acid, 27.0 mg/kg (SD +/- 11.9), phenytoin, 6.33 mg/kg (SD +/- 1.36), and co-anticonvulsants, the mean percentage of daily free valproic acid was 11.72 (SD +/- 2.10) and of phenytoin 20.39 (SD +/- 3.32). By serial within-day blood samplings for a.m., noon, and p.m. periods, the diurnal variation of percentage free valproic acid and phenytoin was determined for each patient. For morning and noon periods the variations in the percentages of free valproic acid and phenytoin were independent of each other, correlation coefficients (r) being zero for each period. In contrast, for early p.m. the correlation coefficient was highly significant at r = 0.894 (p less than 0.01). It is apparent that diurnal variations in the percentages of free valproic acid and phenytoin occur even in patients who have been treated with these compounds for more than a year.

Adolescent

Clorazepate therapy for refractory seizures.

We treated 61 patients with seizures refractory to conventional anticonvulsants by adding clorazepate to their regimen. There was some improvement of seizure control, but no overall improvement in the electroencephalogram. Improvement of seizure control was not significantly related to seizure type. No significant side effects, drug interactions, or laboratory abnormalities were noted with doses up to 3 mg per kilogram per day.

Adolescent

The reality of death experiences. A personal perspective.

In recent years, there has been a marked increase in reports of the subjective experience of individuals in severe life-threatening circumstances. These have been used to suggest that scientific facts are now in agreement with religious beliefs as to the survival of the personality after physical death. This paper presents a personal death experience viewed by the author as a "subjective reality". This is contrasted with "shared subjective reality," i.e., commonly held beliefs among groups of individuals which do not necessarily lend themselves to scientific verification and scientifically derived objective reality. Subjectively real death experiences are regarded as corollary to a toxic psychosis. The content of the psychosis, which is not under voluntary control, determines the subjective experience of having entered either heaven or hell.

Attitude to Death

Monitoring clorazepate dipotassium as desmethyldiazepam in plasma by electron-capture gas--liquid chromatography.

We describe a procedure for determing clorazepate dipotassium as its decarboxylated, pharmacologically active metabolite, desmethyldiazepam, in 100 microL of plasma, with use of electron-capture gas--liquid chromatography and with methylnitrazepam as the internal standard. The procedure is a one-tube, one-step extraction without derivative formation and is accurate, reproducible, and rapid. The sensitivity limit is 20 micrograms/L. Within-run and between-run CV's (concentration, 3.5 mg/L) were 2.9 and 3.5%, respectively. Within-run CV's for 1.5 and 1.0 mg/L concentrations were 3.9 and 4.3%, respectively. For a 1.0 mg/kg per day dose of clorazepate dipotassium, the mean steady-state concentration of desmethyldiazepam in plasma was 1.037 mg/L.

Anti-Anxiety Agents

Monitoring 2-ethyl-2-phenylmalonamide in serum by gas-liquid chromatography: application to retrospective study in epilepsy patients dosed with primidone.

We describe a procedure for determining 2-ethyl-2-phenylmalonamide (I) in serum of epilepsy patients dosed with primidone (II) for seizure control, by extracting the sample with chloroform under basic conditions, with use of an internal standard, 2-ethyl-2-(p-tolyl)malonamide, and without derivative formation. The sensitivity limit is 1.0 mg/L. Within-run CVs for 5, 10, and 30 mg/L concentrations were 3.5, 2.5, and 0.7%, respectively. For a 1.0 mg/kg body wt per day dose of II in patients co-medicated with phenytoin (Group A), the mean steady-state concentrations of I, II, and phenobarbital (III) were 0.72, 0.62, and 2.24 mg/L, respectively. For patients co-medicated with carbamazepine and phenytoin (Group B), I, II, and III concentrations were 0.68, 0.44, and 2.12 mg/L, respectively. Between these groups, only for II were the concentrations statistically different (t = 2.762; p < 0.01). For Group A no correlation was found between II and III. For Groups A and B, the coefficients of correlation between I and III were 0.626 and 0.826, respectively.

Adult