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Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 109 records · Page 6Linked to original sources
PubMed1987

Alterations in local cerebral glucose utilization induced by phencyclidine.

The effects of phencyclidine (PCP; 0.5, 1,5, 10 mg/kg, i.v.) on local cerebral glucose utilization (LCGU) in the rat were studied with the 2-deoxy-D-[1-14C]glucose method. Significant findings were obtained in 41 of 87 brain regions of PCP-treated rats (25-270% of control). Rates of LCGU increased throughout the limbic system, except the habenula. Although LCGU increased in most sensory structures, it decreased in specific layers of the somatosensory and auditory cortices and the inferior colliculus. Evidence was seen for dissociation between LCGU responses of specific thalamic relay areas and their terminal fields in the cortex. Increases in LCGU occurred throughout the motor system, manifesting a striking pattern of columnar activity in the motor cortex. However, LCGU was reduced in the frontal cortical pole. Elevated LCGU was observed in the pontine nuclei and the nuclei and the nucleus solitarius. Effects of 5 mg/kg PCP diminished with time although 8 regions maintained a metabolic alteration at 180 min. PCP induced several behaviors, including stereotypies, which varied with the dose and time after drug administration. The results demonstrate a PCP-induced activation of various functional circuits in the brain, especially the limbic system, and may provide a physiological basis for PCP's psychotomimetic properties.

Animals↗
PubMed1987

Vigabatrin: no microvacuoles in a human brain.

Vigabatrin (gamma-vinyl-GABA) has been shown to be an effective antiepileptic drug. However, clinical investigations have been hampered by the finding of intramyelin edema (microvacuoles) in rats and dogs. In an autopsy study of a 38-year-old woman with astrocytoma, treated with vigabatrin 80 mg/kg body weight per day for over 6 months and 125 mg/kg body weight per day for the last 2 months as add-on therapy because of drug-resistant epilepsy, we did not find any microvacuoles in the brain. So far microvacuoles have never been observed in primates, warranting continued investigations of this promising antiepileptic drug.

Adult↗
PubMed1987

Metabolic aspects of aging brain and related disorders.

In this report we summarize some of our findings obtained with single photon emission computed tomography (SPECT) in man and with 19F nuclear magnetic relaxation (19FNMR) and (14C) deoxyglucose ([14C]DG) techniques in animals. 99Tc-hexamethyl-propyleneamineoxime (99Tc-HM-PAO) SPECT showed a pattern of decreased cerebral perfusion in Alzheimer and Parkinson patients without clinical and instrumental signs of cerebrovascular diseases. Rat cerebral cortex superoxide dismutases (SODs) concentrations, as detected with 19FNMR, increased in an age-related fashion. These increases may constitute a self-protecting mechanism of the brain against the parallel elevations of free radical reactions observed during aging. The specific neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) elevated ([14C]DG) uptake in catecholaminergic regions of the mouse brain. These effects could be prevented by pretreatment with l-deprenyl. Our results suggest that excitotoxic mechanisms may participate in the neurotoxic effect of MPTP and they can be abolished by the monoamine-oxidase B (MAO-B) inhibitor.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Effects of isoflurane anesthesia on local cerebral glucose utilization in the rat.

The effect of isoflurane anesthesia on local rate of glucose utilization was investigated in the rat brain by means of the autoradiographic 14C-2-deoxyglucose method. Local cerebral glucose utilization (LCGU) was measured in 26 neuroanatomic structures of awake and isoflurane-anesthetized rats. Isoflurane anesthesia (1.5% inspired) caused both increases and decreases in LCGU. Significant reductions were found in all cortical areas examined and in primary sensory relay nuclei of central visual and auditory pathways. Among regions of the extrapyramidal motor system, LCGU was increased in substantia nigra pars compacta, and decreased in cerebellum, red nucleus, and ventral thalamus. Large increases in LCGU were observed in some structures of the limbic system such as the medial habenulo-interpeduncular system and the CA3 field of hippocampus. LCGU was significantly reduced by isoflurane in the CA1-CA2 field and dentate gyrus of hippocampus. These results are similar to previous findings on the LCGU response to other inhaled and intravenous anesthetics and further confirm the regional specificity of the effects of anesthetics on brain metabolism.

Anesthesia, Inhalation↗
PubMed1985

gamma-Vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy.

The antiepileptic effect of gamma-vinyl gamma-aminobutyric acid (GABA), an irreversible GABA-transaminase inhibitor, was investigated in an add-on, placebo-controlled, double-blind, cross-over, fixed-dose trial. Twenty-one patients suffering from difficult to control complex partial seizures participated; 18 patients completed the trial. Serum levels of concomitant antiepileptic drugs were kept constant throughout the trial. Three patients (17%) experienced a 75% reduction in seizure frequency and in 8 (44%) the seizures were reduced by at least 50%. Two patients developed a moderate and 1 patient a marked increase in seizure frequency during treatment with gamma-vinyl GABA. Except for 2 patients who had to discontinue the trial because of adverse effects of gamma-vinyl GABA, the participants were unable to discriminate between treatment regimens with regard to side effects. gamma-vinyl GABA seems to be a promising new antiepileptic drug, and the first one to present convincing evidence of a GABAergic mechanism of action.

Adolescent↗
PubMed1985

Long-term study of gamma-vinyl GABA in the treatment of epilepsy.

The purpose of this study was to investigate the long-term efficacy and tolerability of gamma-vinyl GABA (GVG) in the treatment of epilepsy. 36 patients with severe therapy resistant epilepsies participated, the majority exhibiting complex partial seizures. The mean follow-up period was 9.3 months. GVG was administered as add-on therapy, to keep serum levels of concomitant treatment constant. The mean dose of GVG was 2.6 g's per day. Fifty-six per cent of the patients, including three patients with juvenile myoclonic epilepsy, experienced more than a 50% reduction in seizure frequency. No signs of tolerance development to the antiepileptic effect of GVG was demonstrated. Two patients were withdrawn from GVG treatment due to increased seizure frequency, and two due to side effects in the form of vomiting and nausea. Incidentally, the side effects observed were harmless and transient. Fifty per cent of the patients experienced no side effects at all. GVG seems to be a valuable antiepileptic compound. The results of this long-term study confirm observations from several short controlled trials.

Adolescent↗
PubMed1985

Concentration of valproate during pregnancy, in the newborn and in breast milk.

The serum-valproate level of four patients with epilepsy was followed during pregnancy. A decrease in serum level occurred late in pregnancy and was followed by a pronounced increase in the first week after delivery. The maternal serum concentration of valproate was compared to that of the umbilical cord. The level in cord blood was 145-219% higher than that in maternal blood. The concentration of valproate in breast milk was found to be 5-10% of the maternal serum concentration. The serum concentration was measured in one breastfed child. The level was 7.6% of the maternal serum concentration. All children were healthy without any signs of intoxication or malformation. Based on our experience, pregnant patients treated with valproate must be carefully controlled especially during the last month of pregnancy and in the first two weeks after delivery. The amount of valproate excreted into the breast milk was negligible and should not prevent breast feeding.

Adult↗
PubMed1985

Sleep and epilepsy.

Sleep has a marked influence on local epileptogenicity. Sleep deprivation appears to have an independent activating effect. It is effective in provoking spike-wave paroxysms in primary generalized epilepsy. Sleep recordings help in differentiating between partial and generalized epilepsies. Anterior temporal lobe discharges and partial seizures are facilitated by non-rapid eye movement (NREM) sleep, which also has a facilitatory effect on generalized discharges. Rapid eye movement (REM) sleep may activate frontal lobe, amygdaloid and supplementary motor area seizures, whereas it de-activates partial seizures from other regions, often revealing an occult focus. REM sleep also deactivates generalized seizures. Specific epileptic syndromes are related to the sleep-wakening cycle, i.e. Rolandic epilepsy, other benign partial epilepsies in childhood, and awakening epilepsy. Patients with an uncertain or unknown type of epilepsy should always be examined with routine electroencephalography (EEG) recording, sleep deprivation and spontaneous or sedated sleep recordings.

Anticonvulsants↗
PubMed1984

[The epileptic mother and her child].

This study is a review of the literature on the influence of epilepsy and antiepileptic medication on the course of pregnancy and the foetus, as well as of the effect of pregnancy on the disease. Antiepileptic treatment is supposedly responsible for the increased rate of abnormal bleeding after delivery. Data on the perinatal mortality of epileptics are conflicting. The offspring of epileptic women are often smaller than normal neonates, indicating retarded growth, and the incidence of malformations is 1.25 times higher. Until now there has been no direct evidence of a teratogenic effect of the commonly used antiepileptic drugs, and the risk of malformations may possibly be correlated with the severity of the epilepsy. The effect of pregnancy on seizure frequency seems to be quite variable. Higher seizure frequency is seen during pregnancy, but this is not a universal phenomenon. The incidence of seizures in gestational epilepsy has no predictive value with respect to the course of later pregnancy. A positive correlation seems to exist between the development of eclampsia and later epilepsy, a family history of epilepsy and cerebral dysrhythmias. Status epilepticus is uncommon in pregnancy. The requirement of several antiepileptic drugs is increased during pregnancy. The metabolism of carbamazepine, primidone, and clorazepate is probably accelerated in the gestational period, but data on other antiepileptic drugs are inconclusive or lacking. The intestinal absorption of antiepileptic drugs may be impaired during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗
PubMed1984

Glucose utilization in the Papez circuit: effects of oxotremorine and scopolamine.

The [14C]2-deoxy-D-glucose technique was used to test the effects of central muscarinic stimulation or antagonism on local cerebral glucose utilization (LCGU) in the rat limbic system. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.05, 0.1 or 0.7 mg/kg, i.p.), increased LCGU in the pre- and postsubiculum, anterior nuclei of the thalamus, mammillary bodies, retrosplenial medial cortex, medial septum, postcommissural fornix and mammillothalamic tract. Scopolamine (2.5 mg/kg, i.p.) blocked these effects, and independently decreased LCGU in the pre- and postsubiculum, anterior thalamic nuclei, and retrosplenial medial cortex. The affected brain regions are components of, or are connected with, the Papez circuit.

Animals↗
PubMed1984

Decreased cortical glucose utilization after ibotenate lesion of the rat ventromedial globus pallidus.

Rats received unilateral injections of ibotenic acid (12 micrograms) or vehicle in the ventromedial globus pallidus to lesion the primary source of cortical cholinergic innervation. At 3 or 28-32 days postinjection, the regional cerebral metabolic rate for glucose (rCMRglu) was measured by the 2-deoxy-D-[14C]glucose technique in nine cortical areas, the anterior thalamus, and the dorsal hippocampus. Effects of oxotremorine (0.1 mg/kg i.p.) on rCMRglu in these areas were assessed in ibotenic acid-lesioned and sham-treated rats. Significant effects of ibotenic acid injections and hemispheric asymmetries in rCMRglu were observed in all cortical areas (p less than or equal to 0.05), but not in the anterior thalamus or hippocampus. Cortical rCMRglu generally was lower in the lesioned hemisphere 3 days after ibotenic acid injections, but not after sham treatments. Hemispheric asymmetries were not apparent 28-32 days after pallidal lesions. Oxotremorine produced significant effects in the frontoparietal cortex and anterior thalamic nuclei. In the frontoparietal cortex, rCMRglu was 32% lower in the ibotenate-lesioned hemisphere as compared with the contralateral hemisphere. Oxotremorine did not eliminate hemispheric asymmetry, but increased rCMRglu in the lesioned frontoparietal cortex by 38%. Results support the views that cortical metabolic decrements in Alzheimer's disease are due in part to loss of subcortical cholinergic innervation and that muscarinic agonists may partially reverse these decrements.

Alzheimer Disease↗
PubMed1984

Does seizure activity produce Purkinje cell loss?

Eight Wistar rats were exposed to 140 electroconvulsive seizures over 50 days. Ten rats served as controls. The density of Purkinje cells in cerebellum ranged from 15.3 to 18.5/mm in the treated rats and from 15.2 to 19.1/mm in the controls. No Purkinje cell loss was disclosed in the rats subjected to electroconvulsive seizures. Twenty-five Mongolian gerbils of the seizure-susceptible strain were selected according to seizure score with five animals in each group. Five Mongolian gerbils of a seizure-resistant strain served as controls. The density of the Purkinje cells ranged from 21.4 to 29.8/mm in the seizure-susceptible animals and from 27.6 to 31.5/mm in the controls, with a lower density in the gerbils with seizures compared with the controls (p less than 0.05). There was no relation to type or number of seizures. Eight gerbils of the seizure-susceptible strain were included as a supplementary group, to disclose any possible genetic trait as an explanation of the lower Purkinje cell density. The Purkinje cell density in these animals ranged from 24.8 to 30.9/mm and did not differ from the density in the seizure-resistant gerbils. Thus the lower density of Purkinje cells in the seizure-susceptible Mongolian gerbils is a result of seizure activity. The excessive epileptic input with stimulation of the glutamatergic innervation of the Purkinje cells resulting in a persistent elevated gamma-aminobutyric acid (GABA) tone may explain the damage to the Purkinje cells in the gerbils and the loss of Purkinje cells found in patients with severe epilepsy.

Animals↗
PubMed1984

Weight gain during treatment with valproate.

An analysis was made of weight changes during treatment with valproate in 63 adult epileptic patients. 36 patients (57%) gained more than 4 kg in weight during treatment, while 27 patients (43%) were stable in weight with weight changes of less than +/- 4 kg. There were no significant differences between weight gainers and weight-stable patients with regard to age, sex, pretreatment overweight, duration of treatment, dosage or serum levels of valproate. From structured patient interviews, it appeared that the 2 groups of patients differed only insignificantly with regard to appetite, thirst and familial predispositions to obesity and diabetes. Consequently, no factors predictive for weight gain could be outlined. Presumable pathogenic mechanisms of importance are discussed.

Adult↗
PubMed1984

The effects of carbamazepine and valproate on folate metabolism in man.

The effect of carbamazepine and valproate treatment on folate metabolism was studied in 11 epileptic patients. The absorption of folic acid and of Pteroyl-gamma-L-glutamyl-gamma-L-glutamyl-L-glutamic acid, a synthetic substrate for intestinal folate deconjugase , was measured prior to and after 2 months of antiepileptic therapy with either carbamazepine (5 cases) or valproate (6 cases). After 2 months' treatment, the area under plasma concentration versus time curve was significantly decreased and t-max (time when maximal plasma concentration is obtained) was significantly prolonged. No inhibition of intestinal folate deconjugation was observed and the liver metabolism of folic acid was found to be unaffected by the treatment. These findings are interpreted as an inhibition of intestinal folic acid absorption caused by the antiepileptic therapy.

Adolescent↗