PubMed Health⌕ Search

Biomedical subjects

W H Theodore

Publications and source records attributed to W H Theodore.

At least 91 records · Page 5Linked to original sources
PubMed1992

Effects of carbamazepine on pituitary-adrenal function in healthy volunteers.

Carbamazepine (CBZ) is a widely used therapeutic agent in seizure, pain, and mood disorders. Although CBZ has been shown to inhibit hypothalamic CRH secretion in vitro, limited data suggest that systemic CBZ induces pituitary-adrenal activation. Few data are available to reconcile these effects or clarify their mechanism(s), particularly in healthy human subjects. We report here a study of basal ACTH and cortisol secretion and their responses to ovine CRH administration in nine healthy volunteers, studied both during repeated (2-3 weeks) administration of CBZ and while medication free. CBZ significantly increased mean 24-h urinary free cortisol (mean +/- SE, 197 +/- 17 vs. 137 +/- 24 nmol/day; P less than 0.02) and evening basal total plasma cortisol (113 +/- 17 vs. 83 +/- 14 nmol/L; P less than 0.05) as well as cortisol-binding globulin-binding capacity (497 +/- 36 vs. 433 +/- 28 nmol/L; P less than 0.01). Despite the CBZ-induced hypercortisolism, plasma ACTH responses to CRH during CBZ treatment remained robust, rather than being suppressed by basal hypercortisolism. In fact, during CBZ treatment, we noted a positive correlation between the increase in basal plasma cortisol and the increase in the plasma ACTH response to CRH (r = 0.65; P less than 0.05). We also observed a reduction in cortisol-binding globulin-binding capacity after CRH administration (315 +/- 25 vs. 433 +/- 28 nmol/L; P less than 0.001), which was accentuated by CBZ treatment (342 +/- 19 vs. 497 +/- 36 nmol/L; P less than 0.001; magnitude of fall, -155 +/- 22 nmol/L on CBZ vs. -118 +/- 11 nmol/L off CBZ; P less than 0.05). We conclude that CBZ increases plasma cortisol secretion in healthy volunteers independent of its effect on plasma cortisol-binding capacity. This pituitary-adrenal activation seems to reflect a pituitary, rather than a hypothalamic, effect of CBZ. Hence, despite CBZ-induced hypercortisolism, the ACTH response to CRH remained robust in direct proportion to the CBZ-induced rise in basal plasma cortisol. Thus, we propose that the increased cortisol secretion observed during CBZ treatment reflects a relative inefficacy of glucocorticoid negative feedback at the pituitary. This pituitary-driven increase in cortisol secretion combined with the expected reduction in centrally directed CRH secretion could contribute to the anticonvulsant properties of CBZ.

Adrenocorticotropic Hormone↗
PubMed1990

Pathology of temporal lobe foci: correlation with CT, MRI, and PET.

Twenty-six patients with medically refractory complex partial seizures had temporal lobectomy after evaluation, which included prolonged scalp EEG recordings, positron emission tomography (PET), MRI, and x-ray CT. PET showed a region of focal interictal temporal hypometabolism corresponding to electrographic localization of seizure onset in 21. Five patients had a region of increased MRI signal intensity on the spin echo image in the region of the EEG focus, 2 had an abnormality ipsilateral to but distinct from the EEG focus, and 1 had bilateral findings. CT was abnormal in 3 cases; 2 had tumors. Three patients had low grade tumors (1 with a normal PET). PET can detect metabolic dysfunction associated with mild pathologic changes in epileptic foci, but increased signal intensity on MRI does not necessarily correlate with the degree of pathologic abnormality. Tumors may be less likely when both CT and MRI are normal.

Adolescent↗
PubMed1990

Basic principles of clinical pharmacology.

This article reviews basic principles of clinical pharmacology and their therapeutic application. The effects of drug absorption, distribution, protein binding metabolism, and excretion are discussed. Models for repetitive oral and intravenous dosing are presented, and the difference between pharmacokinetic and pharmacodynamic analysis emphasized. The final section reviews the effects of physiologic and pathologic processes on clinical pharmacology.

Age Factors↗
PubMed1990

Clinical pharmacology of antiepileptic drugs. Selected topics.

This article illustrates basic principles of clinical pharmacology presented in article 1 with specific examples from the treatment of seizure disorders. The discussion includes protein binding, the role of a major carbamazepine metabolite, alterations in pharmacology of AEDs in the elderly, and AED withdrawal. The last topic, in particular, is a good example of the interaction of pharmacokinetic and pharmacodynamic considerations in explaining the clinical effects of a drug.

Age Factors↗
PubMed1989

Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorders.

We report the cases of 3 patients with medically intractable seizures in whom withdrawal of treatment with a long-acting benzodiazepine (clorazepate dipotassium, 2 patients; clonazepam, 1 patient) was followed by delirium with catatoniclike features. While an increase in seizure frequency occurred during withdrawal and prior to the onset of behavioral changes, electroencephalograms did not show epileptiform activity during the delirium. We compared these 3 patients with 10 others with intractable seizures in whom antiepileptic therapy was withdrawn without subsequent behavior changes. High-dose benzodiazepine therapy and a history of viral encephalitis may be risk factors for withdrawal delirium.

Adult↗
PubMed1989

Carbamazepine and its epoxide: relation of plasma levels to toxicity and seizure control.

We studied the relation of plasma levels of carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ-E), and their ratio to drug toxicity and seizure control in 7 patients with complex partial seizures. CBZ-E/CBZ increased with increasing CBZ levels and was higher when patients were taking phenytoin or valproic acid. There were weak correlations between CBZ, CBZ-E levels, toxicity scores, and seizure control when patients were taking CBZ alone, but not when other drugs were given as well. There were no significant differences in the correlation with toxicity score or seizure frequency between CBZ, CBZ-E, or their sum. Measurement of CBZ-E levels did not provide additional information useful for monitoring clinical response to CBZ therapy.

Carbamazepine↗
PubMed1989

The effect of carbamazepine on cerebral glucose metabolism.

We used positron emission tomography with 18F-2-deoxy-D-glucose to study the effect of carbamazepine on local cerebral metabolic rate for glucose (lCMRGlc) in 9 patients with complex partial seizures. Twenty regions of interest were evaluated. Seven control patients had serial scans without a drug change. Metabolic rates were significantly (p less than 0.05) lower in patients on carbamazepine in 6 of 20 regions of interest (3 left cerebral hemisphere, 3 right). Mean lCMRGlc was 7.4 +/- 2.0 mg/min/100 in patients on carbamazepine and 8.8 +/- 2.5 in patients off carbamazepine (p less than 0.00005; cutoff level for 180 comparisons: 0.00027). The mean (+/- SEM) difference in lCMRGlc between scans was 12 +/- 2%. No significant changes in lCMRGlc on serial scans were detected in any of the 20 regions for the control group. The mean (+/- SEM) variation for control regions of interest was 1 +/- 1%. This study showed that carbamazepine depresses cerebral glucose metabolism as much as phenytoin does, but much less than phenobarbital does. The difference in effect on lCMRGlc may be related to drug mechanisms of action, as well as to effects on memory, learning, mood, and behavior.

Brain↗
PubMed1989

Electroencephalographic studies of simple partial seizures with subdural electrode recordings.

We used subdural electrodes to study the EEG features of simple partial seizures in 7 patients. We detected epileptiform discharges in 61 of 68 subdurally recorded simple partial seizures compared with 6 of 55 simple partial seizures recorded with scalp electrodes (p less than 0.0001). The onset of 36 nonmotor simple partial seizures was detected only by the medial and basal temporal subdural electrodes, and the onset of 25 simple partial seizures with motor manifestations was recorded by subdural electrodes only from the lateral cortex of the posterior frontal lobe. There was a close correspondence between the area first involved in the epileptiform discharge during simple partial seizures and the area first involved during complex partial and secondary generalized tonic-clonic seizures. Subdural electrodes may be effective in localizing the onset and spread of simple partial seizures, including those that arise from the medial temporal lobe.

Adult↗
PubMed1989

Dissociative states and epilepsy.

Since symptoms of chronic dissociative disorders such as multiple personality disorder (MPD) may be shared by patients with seizure disorders, we investigated the possible relationship between dissociative states and epilepsy. We monitored 6 MPD patients with intensive video-EEG recordings to determine whether epileptic phenomena have any correlation to the dissociative symptoms experienced by these patients. Previously, physicians had diagnosed epilepsy in all 6 patients; however, none proved to have epilepsy. In addition, we studied dissociative symptoms in 71 epileptic patients with the aid of a standardized questionnaire, the Dissociative Experiences Scale, and compared them with age-matched controls. While the group median score of cases with complex partial seizures was higher than that of normal controls, it was significantly lower than that of the psychiatric patients with MPD. Partial seizure patients with dominant hemisphere foci had higher depersonalization subscale scores than those with nondominant foci. Our data suggest that epilepsy is not a primary pathophysiologic mechanism for developing dissociative symptoms.

Adult↗
PubMed1989

Phenytoin withdrawal and seizure frequency.

We withdrew phenytoin from 17 inpatients maintained on combination therapy with carbamazepine for complex partial seizures and analyzed seizure occurrence in relation to plasma levels and time from initiation of withdrawal. The ratio of maximum to mean weekly seizure frequency did not vary with initial level or rate of withdrawal. The week with most frequent seizures began a median of 10 days after phenytoin levels became undetectable, and mean daily seizure frequency was higher at undetectable than at falling levels for the entire 2- to 10-week study period. Four patients had a total of 6 clusters of generalized tonic-clonic seizures; only 2 occurred while levels were falling and the other 4 at 3, 9, 28, and 42 days after reaching undetectable levels. Our data argue against the occurrence of withdrawal seizures in these patients and suggest that worsening of seizures following phenytoin discontinuation more likely reflects loss of therapeutic drug effect than a true abstinence phenomenon.

Adult↗
PubMed1989

Fear episodes due to limbic seizures with normal ictal scalp EEG: a subdural electrographic study.

The authors present the case of a 13-year-old girl with episodes characterized by either staring with preserved consciousness or fear in whom functional illness was suspected. Video-EEG telemetry revealed no changes during 30 of 32 attacks. Subdural electrode recordings revealed epileptiform discharges in 30 of 37 episodes. The discharge was always localized to the electrodes recording from the inferomedial temporal region, with electrodes over the lateral convexity of the same temporal lobe showing no background changes. Although the detailed pathophysiology of panic attacks remains to be clarified, the authors point out that their case and other epileptic case studies are consistent with the possibility that excessive neuronal activity in medial temporal lobe structures is a necessary element of the underlying mechanism.

Adolescent↗
PubMed1988

Complex partial seizures. Correlation of clinical and metabolic features.

We compared metabolic patterns on 18F-2-deoxyglucose positron emission tomography (PET) with closed circuit television and simultaneous electroencephalographic ictal recordings of complex partial seizures in 48 patients. Closed circuit television and electroencephalographic data and PET scans were scored by "blinded" raters. Of the 48 patients, 26 had unilateral temporal; three, frontal; ten, ipsilateral frontotemporal; one, frontoparietal; and five, temporoparietal hypometabolism; and three had widespread hypometabolism affecting frontal, temporal, and parietal lobes. patients with frontal hypometabolism alone had shorter ictal and postictal durations, but involvement of multiple regions was associated with prolonged seizures. Auras were more likely to be present in patients with temporal hypometabolism alone, but an initial motionless stare did not distinguish this group. However, other metabolic patterns did not predict specific ictal clinical features. Vocalizations (formed or unformed) were not more closely associated with frontal involvement. When hypometabolism is multilobar, it may be difficult to use PET to distinguish between complex partial seizures of frontal and temporal origin.

Brain↗