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Biomedical subjects

W H Theodore

Publications and source records attributed to W H Theodore.

134 records · Page 8Linked to original sources
PubMedDate not supplied

Seizure frequency in intractable partial epilepsy: a statistical analysis.

We examined the seizure records of 13 patients (nine men and four women, ages 27-50 years) with intractable partial epilepsy, maintained with steady anti-epileptic drug dosages. Patients recorded daily seizure frequency on calendars. Periods of outpatient observation ranged from 99 to 1,710 days and the number of observed seizures ranged from 18 to over 400, with daily seizure rates of 0.1-4.3 per day. We used the quasi-likelihood regression model to examine the following four departures of the daily seizure counts from a Poisson (random) model: (1) linear increasing or decreasing time trends in expected seizure rates; (2) clustering, where the expected seizure rate on a given day depends on the number of seizures observed on the immediate prior days; (3) monthly cyclicity; and (4) increased variability (overdispersion). Linear time trends were seen in six patients (four increasing and two decreasing), clustering was seen in 10 patients, and a near-monthly cycle appeared in four patients (two of nine men and two of four women). A significant amount of extra variation (overdispersion) relative to a Poisson distribution was observed in all but one of the 13 patients. Departures from a Poisson (random) model appear more common in this population of patients with medically intractable epilepsy than is commonly recognized, and have clinical importance as well as implications for the design of clinical studies.

Adult↗
PubMedDate not supplied

Effect of felbamate on plasma levels of carbamazepine and its metabolites.

Felbamate (FBM) is a novel antiepileptic drug (AED) currently undergoing clinical evaluation in the United States. During a controlled clinical trial conducted at the National Institutes of Health Clinical Center, FBM was added to constant carbamazepine (CBZ) monotherapy. CBZ total concentrations were reduced during active FBM treatment (mean reduction 25%, range 10-42%, p less than 0.001). The effect was evident after the first week of treatment and reached a plateau in 2-4 weeks. To clarify the interaction mechanism, free and total concentrations of CBZ and its plasma metabolites were determined by high-performance liquid chromatography (HPLC) and ultrafiltration in four patients. In these patients, FBM treatment reduced CBZ concentrations and increased CBZ-epoxide (CBZ-E) concentrations (p less than 0.01). Free fractions of all compounds were unmodified. FBM appears to be capable of inducing CBZ metabolism. CBZ-FBM interaction may be clinically relevant.

Anticonvulsants↗
PubMedDate not supplied

Cerebrospinal fluid and serum levels of dopa, catechols, and monoamine metabolites in patients with epilepsy.

We measured CSF and serum concentrations of monoamines and monoamine metabolites in normal control subjects and in patients with partial epilepsy between and less than 2 h after complex partial seizures (CPS) or secondarily generalized tonic-clonic seizures (SGTCs). After SGTCs, concentrations of norepinephrine in CSF were significantly higher (p less than 0.05) than interictal concentrations, concentrations after PSs, and concentrations in control subjects. Serum epinephrine levels also were significantly higher after SGTCs than interictal and control subjects' levels. CSF HVA levels were significantly higher after PSs than interictal or control subjects' levels. CSF concentrations of norepinephrine and its intraneuronal metabolite, dihydroxyphenylglycol, were highly correlated, both interictally and following SGTCs, whereas correlations between serum and CSF levels of these catechols generally were not statistically significant. The results indicate that seizures are associated with release of catecholamines in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Cerebrospinal fluid levels of neuropeptides, cortisol, and amino acids in patients with epilepsy.

We measured lumbar cerebrospinal fluid (CSF) levels of somatostatin, cholecystokinin, neurotensin, atrial natriuretic factor, vasoactive inhibitory peptide, neuropeptide Y, adrenocorticotrophic hormone, corticotropin releasing hormone, beta-endorphin, metenkephalin, cortisol, alanine, glycine, aspartate, glutamate, taurine, and gamma-aminobutyric acid in 25 inpatients with epilepsy at known interictal and postictal times and in 11 neurologically normal volunteers. There were no significant differences between interictal or postictal complex partial seizures (CPS), postictal generalized tonic-clonic seizures (GTC), and control CSF neuropeptide, cortisol, and amino acid (AA) levels. However, there were nonsignificant trends for CSF levels of several neuropeptides to be increased after CPS and GTC as compared with interictal baseline levels. There were significant correlations between levels of certain CSF neuropeptides or (AAs) and serum antiepileptic drug (AED) levels. Several correlations were noted between CSF levels of AAs, including a correlation between the excitatory neurotransmitters aspartate and glutamate identified only after CPS.

Adult↗
PubMedDate not supplied

Interictal aggression in epilepsy: the Buss-Durkee Hostility Inventory.

Adult patients with left, right, or bilateral temporal lobe epilepsy or absence epilepsy, and normal controls completed the Buss-Durkee Hostility Inventory (BDHI), a standardized questionnaire of aggressive tendencies. Patients with left temporal lobe seizure foci scores higher on the Suspicion scale than did other patients or controls (p < 0.05). Factor analysis scale scores identified three factors: hostile feelings, covert aggression, and overt aggression. The groups differed on their pattern of factor scores (p < 0.01): patients with left temporal lobe epilepsy scored higher than other groups on hostile feelings, normal controls scored higher on Covert aggression, and bitemporal patients scores higher on Overt aggression. Patients with absence seizures did not differ from controls. Lateralization of the seizure focus in patients with temporal lobe epilepsy may alter expression of aggressive behavior.

Adult↗
PubMedDate not supplied

Interictal autonomic nervous system function in patients with epilepsy.

We studied 24 patients with partial seizures receiving carbamazepine (CBZ) monotherapy and 40 normal controls, 17 of whom were tested with and without CBZ therapy. Autonomic nervous system assessment included baseline heart rate (HR) and blood pressure (BP); BP and HR changes during orthostasis and cold pressor test (CPT); and HR changes during sinus arrhythmia, Valsalva maneuver, and cold face test with apnea (CFTA). Our study demonstrated normal interictal autonomic function in patients with epilepsy, but, variations in BP and HR during orthostasis and CPT were significantly (p < 0.05) higher in epilepsy patients than in controls with or without CBZ. Epilepsy patients had higher initial increases in BP and greater subsequent decreases in BP than did nonmedicated controls during CPT. Controls with CBZ had higher HR during orthostasis and CFTA than did those without CBZ. CBZ levels correlated with baseline and orthostatic BP and HR during deep breathing (sinus arrhythmia). Our results showed that patients with epilepsy have greater BP and HR variability and reactivity than controls, attributable in part to CBZ levels.

Adolescent↗
PubMedDate not supplied

Assessment of whole-brain vasodilatory capacity with acetazolamide challenge at 1.5 T using dynamic contrast imaging with frequency-shifted burst.

PURPOSE: To determine whether whole-brain acetazolamide-induced changes in regional cerebral blood volume (rCBV) can be assessed on a conventional gradient 1.5-T MR system using 3-D dynamic susceptibility contrast-enhanced MR imaging. METHODS: A 3-D frequency-shifted (FS) burst technique was used to assess the intravascular first pass of contrast agent. Changes in rCBV were calculated in 40 volunteers before and after acetazolamide (n = 30) or saline (n = 10) injection using customized analysis software on an independent workstation. A single-section gradient-echo technique with better spatial resolution was used in one additional volunteer to examine the effect of partial volume averaging on calculation of absolute rCBV. RESULTS: A statistically significant increase in rCBV (gray matter = 23%, white master = 32.5%) was noted after acetazolamide compared with saline. Baseline fractional CBVs were 22% +/- 3% for gray matter and 12% +/- 2% for white matter. Partial volume averaging was probably responsible for a systematic but linear overestimation of absolute rCBV. CONCLUSION: Acetazolamide-induced changes in rCBV can be assessed using 3-D dynamic susceptibility contrast-enhanced MR imaging with FS-burst on a conventional gradient 1.5-T MR system. Values obtained with this technique overestimate absolute rCBV but are systematically biased and can be used for intersubject and intrasubject ratio comparisons.

Acetazolamide↗