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Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 91 records · Page 5Linked to original sources
PubMed1990

Inhibition of photosensitive seizures in man by the beta-carboline, ZK 95962, a selective benzodiazepine receptor agonist.

A single-dose study of the beta-carboline, ZK 95962, on photosensitive generalized paroxysmal activity in the EEG was conducted in 6 patients with primary generalized epilepsy. Four of the patients were newly diagnosed and did not receive any antiepileptic drug or other medication during the study. Two were receiving current therapy with carbamazepine. A double-blind cross-over study with 2 injections of ZK 95962 (20 micrograms/kg body weight repeated 10 min after 1st injection) and 2 placebo injections were carried out in a randomized order, with 4 h intervals between the injections with active drug and placebo. On the day before the trial, the sensitivity range (standardized photosensitivity range, SPR) was determined hourly using flash frequencies of 2, 6, 8, 10, 15, 20, 30 and 40 Hz for 4 sec in ascending and descending order until generalized spikes or spike waves occurred. A significant reduction in photosensitivity was observed 2-12 min after injection of ZK 95962 in all patients, lasting 2-3 h. No change in the SPR was observed after placebo injections. The feelings of uneasiness and myoclonic jerks, provoked by photostimulation, were also abolished by ZK 95962, but not by placebo injections. Side effects, including sedation were not observed. The results suggest that benzodiazepine receptor ligands such as ZK 95962 may be potent antiepileptic drugs.

Adolescent↗
PubMed1990

The effects of propofol anesthesia on local cerebral glucose utilization in the rat.

The autoradiographic 14C-2-deoxy-D-glucose method was used to determine local cerebral glucose utilization (LCGU) during propofol anesthesia and recovery in 52 regions of the rat brain. Control rats intravenously received 5 ml.kg-1.h-1 of the egg-oil-glycerol emulsion that constitutes the vehicle for propofol. Anesthetized animals received an iv bolus of propofol (20 mg/kg) followed by continuous infusion of the anesthetic at 12.5, 25, or 50 mg.kg-1.h-1 for 1 h prior to injection of 14C-2-deoxy-D-glucose and for the following 45 min. In addition, a fifth group of animals were studied immediately after awakening from a 20 mg/kg bolus of propofol as indicated by the first reappearance of head lift. All rats were spontaneously breathing room air throughout the experimental procedure. The general pattern of the cerebral metabolic response to propofol anesthesia was a dose-related, widespread depression of LCGU. At the three infusion rates of propofol tested, overall mean LCGU was reduced by 33%, 49%, and 55%, respectively, and significant decreases were observed in 60%, 85%, and 90% of the regions assayed. These effects were rapidly reversible, since in the recovery group, LCGU returned to near control values in the majority of the brain areas. Although all of the anatomofunctional systems (sensorimotor, extrapyramidal, limbic, and reticular) were involved, forebrain structures showed a greater sensitivity to the depressant action of propofol than did hindbrain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1990

Children with epilepsy: the effect of seizures, syndromes, and etiological factors on cognitive functioning.

Overall, children with epilepsy have poorer concentration and mental processing and are less alert than age-matched controls. The relationship between cognitive functioning and epilepsy is complex, however, with widely differing degrees of intellectual impairment--ranging from minimal to severe and progressive--related to diverse types of epileptic seizures, syndromes, and etiological factors. Prolonged and frequently repeated seizures are typically associated with more severe effects on cognitive functioning, particularly if epilepsy is symptomatic, i.e., secondary to a demonstrable brain lesion. A combination of such factors may contribute to the mental deterioration seen in many children suffering from severe epilepsy.

Child↗
PubMed1990

Pharmacokinetic comparison of two carbamazepine slow-release formulations.

In a single-blind pharmacokinetic study patients being treated with conventional carbamazepine (CBZ) in a t.i.d. regimen were randomly allocated to identical doses of two CBZ slow-release formulations (Trimonil Retard and Tegretol Retard) administered once daily. Statistical analysis involved the following parameters: AUC, Cmin, Cmax and Fluctuation Index (FI). With regard to Cmin and FI statistically significant differences in favour of Tegretol Retard were observed.

Administration, Oral↗
PubMed1990

Regional cerebral blood flow study with 99mTc-hexamethyl-propyleneamine oxime single photon emission computed tomography in Alzheimer's and multi-infarct dementia.

Thirty-four demented patients, 19 with Alzheimer's and 15 with multi-infarct dementia, were studied using single photon emission computed tomography, and 99mTc-hexamethyl-propylenemine oxime as a tracer of regional cerebral perfusion. Tracer activity ratios, determined in cortical and subcortical regions, were compared with those of 11 age-matched controls. In both groups of demented patients, most of the cortical regions showed significant declines in tracer uptake from control values, with the greatest reductions in the parietal cortex. Significantly lower parietal indexes were found in the Alzheimer's patient group as compared both to the control values and to the group of multi-infarct dementia patients. A positive correlation was found between the magnitude of the parietal deficits and the severity of dementia.

Aged↗
PubMed1989

Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy.

1. A meta-analysis has been performed on nine placebo controlled trials of vigabatrin (GVG) administered as add-on therapy to patients suffering from drug resistant epilepsy. 2. There were two pilot placebo-controlled dose ranging studies, six double-blind crossover studies and a multicentre response controlled study. 3. There were a total of 398 patients entered and 390 have been evaluated for safety and 337 for efficacy. 4. In spite of the difficulties in the clinical evaluation of new antiepileptic drug, a reduction in seizure frequency was reported following the addition of vigabatrin to the concomitant medication in all studies. This was statistically significant in the larger of the two pilot studies, the multicentre study and three of the six double-blind studies. 5. There was a statistically significant reduction in seizures of in all six double-blind studies when the 98 patients suffering from complex partial seizures with or without generalisation were considered. Seventy two percent of these patients showed a greater than 25% reduction in seizure frequency. 6. Vigabatrin was well tolerated. The frequency of adverse events was similar to that reported elsewhere.

Aminocaproates↗
PubMed1989

Long-term evaluation of vigabatrin (gamma vinyl GABA) in epilepsy.

In studies spanning more than 5 years, more than 1,100 patients with epilepsy have been treated with vigabatrin (gamma vinyl GABA, GVG). Sixty-two patients with partial seizures with secondary generalization took part in this trial: 41 patients continued in the trial after 19 months of treatment. After 36 months, the median percentage of baseline seizures was less than 20%. GVG is a very potent antiepileptic drug. It is well tolerated in humans. The side effects are few. Skin rash and other allergic reactions have rarely been seen. Tolerance to the sedative effect is in contrast to the lack of tolerance to the anti-epileptic effect.

Adult↗
PubMed1989

Single-photon emission computed tomography studies with 99mTc-hexamethylpropyleneamine oxime in dementia: effects of acute administration of L-acetylcarnitine.

The acute effects of intravenously administered L-acetylcarnitine (LAC) were evaluated with single-photon emission computed tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime in 30 demented patients (21 with a clinical diagnosis of Alzheimer's dementia and 9 with mixed-type dementia). Two SPECT scans were performed: in basal conditions, and 30 min after the administration of 500, 1,000, 1,500, or 2,000 mg LAC intravenously. Tracer activity ratios were determined in 10 pairs of cerebellar, cortical and subcortical regions. After administration of the lowest dose of LAC, no changes from the basal values were observed in any of the regions examined. The higher doses of the drug significantly elevated the tracer activity in cortical regions, particularly in the parietal lobe, which showed an impaired regional cerebral blood flow in the basal study. These effects of LAC and their relation with the cholinomimetic properties of the drug are discussed.

Acetylcarnitine↗
PubMed1989

[Medical treatment of epilepsy].

The most important single factor in achieving control of epileptic seizures is a correct diagnosis of seizures and syndromes. It is essential to realise that treatment should be directed against the rate of seizures, not the plasma levels. Monotherapy with the new retarded formulations of carbamazepine or valproate should be the first drugs chosen. The most promising new antiepileptic drugs are oxcabazepine and vigabatrin, which should be made available to all neurologists.

Aminocaproates↗
PubMed1988

Nicotine enhances cerebral glucose utilization in central components of the rat visual system.

The effect of nicotine in visual system components of the rat brain was examined using the 2-deoxy-D-[1-14C]-glucose ([14C]DG) technique. Nicotine was administered subcutaneously (SC) at doses of 0.1, 0.3, and 1.0 mg/kg 2 min before the infusion of the radiotracer. Local cerebral glucose utilization (LCGU) was stimulated by nicotine in a dose-dependent manner in many brain regions associated with the visual system. Increases of over 100% were seen in the superior colliculus, nucleus of the optic tract, and portions of the accessory optic system (medial and dorsal terminal nuclei, and the inferior fasciculus). Statistically significant increases were also observed in the lateral geniculate nucleus, the lateral terminal nucleus and the cerebellum. The effects were blocked by pretreatment with mecamylamine and by enucleation. The findings lend support to the involvement of the nicotinic cholinergic system in the processing of visual information or visual-motor function.

Animals↗
PubMed1988

[99mTc]-HM-PAO SPECT in Parkinson's disease.

Thirty-six patients affected by Parkinson's disease were studied using single photon emission computed tomography (SPECT) and [99mTc]-HM-PAO as a tracer. The scanning procedure was performed 16-24 h after discontinuation of specific therapy. Tracer activity ratios were determined in 10 pairs of cerebellar, cortical, and subcortical regions. Data were compared with those of 10 age-matched controls. Most of the regions examined did not show any relevant change between parkinsonian and control subjects. Notably, mean activity in striatal regions were similar in the two groups. Increased activity in caudate-putamen was found in patients who were on chronic DOPA therapy. Side-to-side asymmetries in the basal ganglia increased with the severity of the disease. Significant reductions of tracer uptake, from control values, were observed bilaterally in the parietal cortex. These deficits were more pronounced in patients with mental deterioration and in subjects who had been chronically treated with anticholinergic drugs. Parietal perfusion deficits in parkinsonian patients resemble those described in Alzheimer's dementia. These findings suggest that the heterogeneous alterations of regional cerebral blood flow (rCBF) in parkinsonian patients reflect the multifactorial pathophysiology of the disease.

Adult↗
PubMed1988

Effects of nicotine on local cerebral glucose utilization in the rat.

We used the autoradiographic 2-deoxy-D-[1-14C]glucose (14C-DG) method of Sokoloff to identify brain areas with altered rates of local cerebral glucose utilization (LCGU) in vivo in response to peripheral I-nicotine administration (0.1, 0.3, 1.0, and 1.75 mg/kg, s.c.). Nicotine stimulated LCGU primarily in areas reported to contain nicotine binding sites, indicating that the sites are true receptors. Increases in LCGU of 100% or more over control were obtained in the medial habenula, fasciculus retroflexus, superior colliculus, and median eminence. Substantial stimulation (50-100% increases) also was obtained in the cerebellar vermis, interpeduncular nucleus, and anteroventral and interanteromedial thalamic nuclei. Moderate increases (20-50%) were observed in the reticular nucleus of the medulla, paramedian lobule, nucleus of the spinal tract of the trigeminal nerve, presubiculum, subiculum, red nucleus, ventral tegmental area, substantia nigra, nucleus ambiguus, nucleus tractus solitarius, dorsal lateral geniculate nucleus, mammillothalamic tract, and fornix. The greatest stimulation in most affected areas was obtained with 0.3 mg/kg nicotine administered at 2 min, but not longer, before 14C-DG. Effects of nicotine on LCGU were antagonized by mecamylamine. The findings indicate that the interaction of nicotine with specific binding sites is coupled to cerebral energy metabolism. The distribution of in vivo cerebral metabolic effects of nicotine implicates various brain regions in the behavioral and physiological effects of nicotine.

Animals↗