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Biomedical subjects

A Sherwin

Publications and source records attributed to A Sherwin.

16 recordsLinked to original sources
PubMed1992

Improved pregnancy outcome in epileptic women in the last decade: relationship to maternal anticonvulsant therapy.

The prevalence of abnormal pregnancy outcomes in the offspring of 103 epileptic women, followed prospectively during pregnancy between 1982 and 1989, was compared with that in the previous study of 119 pregnancies by Dansky et al from the same institution. Our results have shown a significant decrease in the prevalence of major malformations, as compared with the previous study: 8.8% vs 24.1% (P < 0.01). Monotherapy was more frequent and the mean number of drugs used during pregnancy was significantly smaller in the present study. Phenytoin, phenobarbital and primidone were prescribed less frequently in the present study, whereas carbamazepine and valproic acid were used more frequently. Plasma levels of valproic acid during pregnancy were higher in mothers of malformed babies. In the present study, plasma folate levels were significantly higher, and more patients were taking folate supplements during pregnancy. In conclusion, the type and number of drugs used during pregnancy, as well as the plasma concentrations and serum folate levels, may determine the frequency of abnormal outcomes.

Abnormalities, Drug-Induced↗
PubMed1991

Phenytoin toxicity due to interaction with clobazam.

The benzodiazepine antiepileptic drug clobazam can be added to existing AED treatment, usually without clinical toxicity. We report 3 patients in whom the addition of clobazam led within several weeks to clinically obvious phenytoin (PHT) intoxication in patients who had been taking maximum tolerable PHT doses. Symptoms and high PHT levels resolved with lowering the PHT dose. Clobazam and norclobazam levels were not elevated. This interaction is probably related to interference with hepatic degradation of PHT. Clinicians should be aware of possible PHT intoxication in patients starting clobazam.

Adult↗
PubMed1991

Developmental anterobasal temporal encephalocele and temporal lobe epilepsy.

The authors describe the association between an antero-basal temporal lobe encephalocele and medically intractable temporal lobe epilepsy in three patients treated successfully by surgery. Two men and one woman, aged 26 to 37 years (mean 31 years), had onset of complex automatism and generalized seizures in their second and fourth decades (mean age 22.7 years). They had been epileptic for 6 to 14 years (mean 8.3 years) before surgery. Preoperative electroencephalograms localized ictal epileptic activity to the left mesial temporal lobe in all cases, and neuropsychological testing revealed dominant temporal lobe dysfunction. Magnetic resonance (MR) imaging demonstrated an anteromedial basal temporal encephalocele extending into the pterygopalatine fossa through a bone defect at the base of the greater sphenoid wing in the region of the foramen rotundum and pterygoid process, a discrete center of embryonal chondrification. At surgery, the encephaloceles were found in front of the uncus, and an area of gliosis extended from the encephalocele to the amygdalohippocampal region. All patients have been seizure-free following anterior temporal resection and amygdalohippocampectomy including the encephalocele. These three cases delineate a condition of disordered embryogenesis wherein a developmental anterobasal temporal encephalocele acts as the substrate for temporal lobe epilepsy. This lesion may be diagnosed preoperatively with MR imaging and should be considered in the differential diagnosis of late-onset temporal lobe epilepsy.

Adult↗
PubMed1990

Add-on trial of clobazam in intractable adult epilepsy with plasma level correlations.

Clobazam, a novel benzodiazepine, was used as an add-on agent in 47 adult patients with intractable epilepsy and a variety of seizure types. A greater than 75% reduction in seizure frequency was observed in 42% (18) of the patients and a greater than 50% reduction in 65% (29) of the patients which was sustained over a mean follow-up period of 13.3 (+/- 5.6) months. Nine patients had to discontinue the drug due to minor adverse effects or increased seizures. Possible tolerance developed in 6 patients. Plasma levels of the active metabolite N-desmethylclobazam were linearly related to dosage and appeared to correlate with both therapeutic and toxic responses. Clobazam appears to be a safe and effective add-on antiepileptic for a wide variety of seizure types in intractable epilepsy.

Adult↗
PubMed1989

In vivo quantification of blood-brain transfer and binding of [125I]HEAT, an alpha 1-adrenoceptor antagonist.

The uptake and binding constants of [125I]iodo-2-[beta-(4-hydroxyphenyl)-ethyl-amino-methyl]tetralone ( [125I]HEAT) in rat brain were determined in vivo. The initial clearance of the radioligand from blood to brain, K1, was calculated from the initial uptake of the radioligand; it averaged 0.21 +/- 0.01 (SD) ml g-1 min -1, consistent with an initial extraction of 25% (i.e., one-quarter of the blood flow). The most strongly binding regions included the olfactory bulb, thalamic nuclei, medial geniculate body, and cerebral cortical layers. We identified saturable, specific binding in frontal cortex layers 1, 5a, and 5c (motor region), frontal cortex layers 3+4, ventral thalamic nuclei, medial geniculate body, striatum, cerebellum, and olfactory bulb. Addition of unlabeled ligand depressed binding in all regions to the same low level (partition coefficient) of 0.8 ml g-1. Displacement of [125 I]HEAT binding by unlabeled HEAT yielded a global affinity constant (KDVd) of 34 +/- 8 pmol g-1 and receptor densities (Bmax) that varied from 50 pmol g-1 in cerebellar cortex and caudate nucleus to 200 pmol g-1 in the region of highest specific binding, the medial geniculate body.

Adrenergic alpha-Antagonists↗
PubMed1989

Metabolism of prostaglandin D2 by human cerebral cortex into 9 alpha, 11 beta-prostaglandin F2 by an active NADPH-dependent 11-ketoreductase.

In homogenates of rat cerebral neocortex prostaglandin D2 (PGD2) was found to be quantitatively the main PG biosynthesized by a cytosolic PGD synthetase from endogenously released arachidonic acid. Amounts of 628 ng/g wet weight were found after 30-min incubation periods compared with basal levels of 2.3 ng/g wet weight. In human cerebral cortex, whether obtained at biopsy or postmortem, only small amounts of PGD2 (4.5-11.7 ng/g wet weight/30 min) were formed. Furthermore, PGD2, added to homogenates of human biopsy temporal cortex, was converted efficiently into 9 alpha,11 beta-PGF2 by a NADPH-dependent 11-ketoreductase as has been reported in other human tissues (liver and lung). PGF2 alpha was determined directly as the n-butylboronate derivative. It became clear that 9 alpha,11 beta-PGF2 was formed in considerably greater amounts than PGF2 alpha and that other metabolites are also formed. These results can account for the low amounts of PGD2 found in incubations of human brain tissue. The rat brain does not contain 11-ketoreductase activity. The present results indicate that the 9 alpha,11 beta-PGF2 must be considered along with other eicosanoids in pathophysiological situations in brain.

Adolescent↗
PubMed1988

Excitatory amino acids are elevated in human epileptic cerebral cortex.

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)--epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)--temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (mumol/g protein, mean +/- SEM): glutamate--spiking 109.8 +/- 1.8, nonspiking 87.4 +/- 2.0 (p less than 0.001); aspartate--spiking 15.2 +/- 0.9, nonspiking 12.2 +/- 0.5 (p less than 0.05); GABA--spiking 15.0 +/- 1.0, nonspiking 13.9 +/- 1.4 (NS); taurine--spiking 14.5 +/- 0.8, nonspiking 12.2 +/- 0.8 (NS); and glycine--spiking 11.5 +/- 0.8, nonspiking 7.4 +/- 0.6 (p less than 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.

Adolescent↗
PubMed1986

Stability of alpha-1 adrenoceptors in surgically excised human brain.

Alpha-1 adrenoceptor sites were measured in membranes prepared from nonepileptic superficial cortex following temporal lobectomy for lesions in deep medial structures. There was no significant change in receptor density (Bmax) or affinity (Kd) when paired samples were either frozen immediately or kept at room temperature for 24 hours before freezing and storage at -70 degrees C. Regional variability in the Bmax or Kd of alpha-1 adrenoceptor binding was not observed in serial samples from lateral temporal cortex. We previously reported a localized decrease in alpha-1 adrenoceptors in epileptic foci when compared to adjacent nonepileptic tissue obtained from the same patient. As nonepileptic control tissue from an adjacent gyrus is frequently not available in the same specimen, the stability of alpha-1 adrenoceptors justifies the use of postmortem brain for comparative studies.

Adolescent↗
PubMed1984

Enzyme changes in actively spiking areas of human epileptic cerebral cortex.

Five enzymes involved in glutamic acid, GABA, and catecholamine metabolism were measured in epileptic human brain. Electrocorticographically defined areas of focal spiking were compared with samples from surrounding nonspiking cortex. Comparative enzyme activities were as follows (mumol/h/g wet wt): glutamic acid dehydrogenase (GDH)--spiking 135.77 +/- 10.22 (mean +/- SEM), nonspiking 118.58 +/- 9.42 (p less than 0.001, N = 17); glutamic acid decarboxylase--spiking 10.63 +/- 0.95, nonspiking 9.96 +/- 1.10 (NS, N = 13); GABA-aminotransferase--spiking 36.49 +/- 1.05, nonspiking 36.46 +/- 1.48 (NS, N = 12); glutamine synthetase--spiking 96.94 +/- 3.81, nonspiking 96.52 +/- 4.10 (NS, N = 20); and tyrosine hydroxylase (TH; nmol/h/g)--spiking 16.23 +/- 2.39, nonspiking 10.67 +/- 1.95 (p less than 0.001, N = 14). Increased activity of GDH and TH may prove useful to characterize further areas of active spiking in human focal epilepsy.

Adolescent↗
PubMedDate not supplied

Transient changes in cortical alpha 1 adrenoceptors and seizure threshold following electroconvulsive seizures in rats.

Alpha 1 adrenoceptor density (Bmax) is consistently decreased in actively spiking human cortical epileptic foci. Interpretation of these unique human data is limited because all surgical excisions are completed shortly after a period of active seizure discharge. To determine the temporal profile of seizure-induced changes in cortical alpha 1 adrenoceptors we examined rats primed by 15 daily electroconvulsive seizures (ECS). Since the noradrenergic system has an inhibitory effect on epileptic activity, we also measured the postictal rise in minimal ECS seizure threshold. Animals were sacrificed immediately before or at intervals after the last scheduled seizure. Cortical membranes were assayed using [3H]prazosin as specific radioligand. Repeated ECS produced an increase in the number of cortical alpha 1 sites from 4 to 24 h postictally, but following the last seizure there was a transient 'normalization' of alpha 1 receptor density which persisted for 3 h. The postictal ECS seizure threshold also remained elevated for a 2 h period. Both these transient postictal changes may in part result from activation of the central NA system. Decreased alpha 1 adrenoceptors in surgical specimens of spiking cerebral cortex may also be a secondary response to focal seizure activity.

Animals↗
PubMedDate not supplied

Prolonged focal cerebral edema associated with partial status epilepticus.

Following several days of partial status epilepticus, three patients developed striking focal cerebral edema as demonstrated by computed axial tomography (CT) scan. An angiogram done in one patient showed a capillary blush and early cortical draining veins in the corresponding area. All patients developed severe focal neurological deficit which resolved as the edema improved, and this was demonstrated on serial CT scans (at 6 months, 1 month, and 2 months, respectively). In the first patient, an underlying tumor, and in the second and third, vascular occlusions, were suspected because we were not aware that edema due to status epilepticus could produce changes of such intensity and duration. The neurological disability after the partial status was long-lasting but reversed completely in our patients. Maximal radiological changes occurred in the area of maximal epileptic discharge. Minimal atrophic changes persisted in two of the three patients. The clinical, CT scan, and angiographic findings suggest that partial status epilepticus can be associated with abnormal vascular permeability leading to prolonged focal cerebral edema. Similar pathophysiology of lesser intensity may be responsible for shorter postictal neurological deficits. Awareness of this clinical and radiological entity should avoid misdiagnosis of cerebral tumor or infarction.

Adolescent↗
PubMedDate not supplied

Excitatory amino acids modulate phosphoinositide signal transduction in human epileptic neocortex.

Stimulation of phosphoinositide (PI) hydrolysis by norepinephrine (NE), carbachol (Carb), and excitatory amino acids (EAAs) was measured in slices prepared from neocortex excised during epilepsy surgery. NE and Carb markedly enhanced PI turnover (EC50: NE, 12 microM; Carb, 661 microM) as reflected by [3H]inositol monophosphate (IP1) accumulation in tissue slices prelabeled with [3H]myoinositol. These effects were dose-dependent, saturable, and five to six times higher than basal IP1 accumulation. A weaker stimulation (twofold) was observed with quisqualate (QUIS; EC50, 1.1 microM) and glutamate (GLU; EC50, greater than 1 mM), while minimal or no stimulation was seen with kainate (KA) and N-methyl-D-aspartate (NMDA). Agonist-stimulated PI turnover was significantly reduced in samples from actively spiking epileptic neocortex versus nonspiking areas as defined by electrocorticography (NE, -23%, p less than 0.05; Carb, -44%, p less than 0.01). Preincubation of slices with various EEAs inhibited Carb-induced IP1 formation. The maximal extent of inhibition (1 mM) was both amino acid-dependent (IC50: NMDA, 5 microM; KA, 3.3 microM; QUIS, 47 microM; GLU, greater than 1 mM). These data suggest that epileptic activity modulates PI metabolism and alters receptor-effector coupling. As important mediators of epileptogenesis, EAAs may interfere++ with the efficiency of this second messenger system.

Carbachol↗