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Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 127 records · Page 7Linked to original sources
PubMed1983

Effects of cholinomimetics on glucose utilization in rat brain optic systems.

Physostigmine and oxotremorine effects on local cerebral glucose utilization (LCGU) in rat brain optic systems were examined by the [14C]2-deoxy-D-glucose procedure. Both drugs significantly stimulated LCGU in the superior colliculus (superficial layer) and nucleus of the optic tract, but not in the visual cortex. Physostigmine, but not oxotremorine, stimulated LCGU in components of the accessory optic system. The effects in the accessory optic system apparently result from nicotinic actions of physostigmine.

Animals↗
PubMed1983

Progabide: a controlled trial in partial epilepsy.

Progabide (SL 76002) was studied in a randomized double-blind crossover trial using 20 outpatients suffering from partial complex seizures. Progabide was added to the concomitant antiepileptic treatment in a fixed dosage schedule. The design included an open therapy control unit. No significant difference was established between the number of partial seizures during treatment with progabide and placebo. A trend was observed for lower seizure frequency of secondary generalized seizures during treatment with progabide. Only mild and transient side effects were observed. There was no difference between the side effects of progabide and placebo.

Anticonvulsants↗
PubMed1983

Practical aspects in the treatment of epilepsy.

The different forms of epilepsy require different treatment, and drug choice depends on certain pharmacological and pharmacokinetic principles. Optimal treatment is based on single drug therapy, if possible, and monitoring of plasma antiepileptic drug levels. Such treatment, together with clinical observations and the cooperation of a well-informed patient, will achieve the best seizure control. Nevertheless, seizure recurrence or increased seizure frequency is a possibility. When withdrawal of treatment is indicated, it must be done according to certain principles. The possibility of pregnancy must be considered when choosing antiepileptic drugs for fertile women. Drug kinetics are different during pregnancy, and frequent monitoring and adjustment of the regimen are essential. Special care is necessary during delivery because of a higher risk of complications and apparently increased perinatal mortality. Plasma half-life of antiepileptic drugs may be increased or decreased in newborns. Slow elimination of diazepam contributes a special risk. Breast feeding is safe in most cases, but phenobarbital and diazepam may cause sedation of the infant.

Adult↗
PubMed1983

THIP: a single-blind controlled trial in patients with epilepsy.

In an early phase-2 study, THIP (4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol) was investigated in a single-blind controlled trial comprising 9 outpatients suffering from epilepsy. THIP was added to the concomitant antiepileptic treatment with increasing doses (15 to 120 mg/day) based on therapeutic effect or side-effects. The blood levels of concomitant therapy were kept constant. No significant difference was established between the number of seizures during treatment with maximal doses of THIP and placebo. A trend was observed for lower seizure frequency during a period on submaximal dose of THIP.

Adult↗
PubMed1983

Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy.

The anti-epileptic effect of gamma-vinyl-GABA (GVG) was studied using a placebo-controlled, single-blind design in 15 patients with therapy-resistant epilepsy, the majority experiencing complex partial seizures. GVG was added to concomitant treatment, which was kept at constant serum levels. Following administration of 1 g, 2 g and 3 g per day, significant reductions in seizure frequency were observed. A poor correlation was found between GVG serum levels and clinical effect. Only mild and transient side-effects were observed.

Adolescent↗
PubMed1982

[The epileptic mother and her child (author's transl)].

Antiepileptic drugs are thought to be responsible for an abnormally high incidence of post-partum haemorrhages. Data on perinatal mortality of epileptic patients are discordant. Children of epileptic mothers are frequently undersized. Although they have an incidence of malformations 1.25 times higher than average, these may be associated with the severity of seizures and with the disease itself, since there is no evidence that anticonvulsants are teratogenic. The influence of pregnancy on epileptic attacks is extremely variable. Seizures occurring during a pregnancy need not necessarily occur during subsequent pregnancies. There seems to be a positive correlation between eclampsy, late epilepsy, familial epilepsy and abnormal EEGs. Status epilepticus is unusual in child-bearing women. The dosage of several antiepileptic drugs needs to be increased during pregnancy, probably because of accelerated metabolism and reduced intestinal absorption. Decrease in plasma protein levels seems to be of little significance. Antiepileptic drugs which cross the placenta are usually excreted by the newborn within a week, but children of mothers who are given diazepam during delivery may be intoxicated. Drug concentrations in milk are low, but the child must be supervised if the mother takes phenobarbitone or diazepam. However, in most cases breast-feeding is safe. Pregnant epileptic women should be carefully examined throughout pregnancy and post-partum for obstetrical reasons and because the drugs they absorb may give abnormal blood levels.

Anticonvulsants↗
PubMed1982

Effects of oxotremorine on local glucose utilization in the rat cerebral cortex.

The [14C]2-deoxy-D-glucose technique (Sokoloff, L., M. Reivich, C. Kennedy, M. Des Rosiers, C. Patlak, K. Pettigrew, O. Sakurada, and M. Shinohara (1977) J. Neurochem. 28: 897-916) was used to examine the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in the cerebral cortex of the unanesthetized rat. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.1 to 1.0 mg/kg, i.p.) increased LCGU in the neocortex, mesocortex, and paleocortex. In the neocortex, OXO was more potent in elevating LCGU of the auditory, frontal, and sensorimotor regions compared with the visual cortex. Within these neocortical regions, OXO effects were greatest in cortical layers IV and V. OXO effects were more dramatic in the neocortex than in the meso- or paleocortex, and no significant effect occurred in the perirhinal and pyriform cortices. OXO-induced LCGU increases were not influenced by methylatropine (1 mg/kg, s.c.) but were antagonized completely by scopolamine (2.5 mg/kg, i.p.). Scopolamine reduced LCGU in layer IV of the auditory cortex and in the retrosplenial cortex. The distribution and magnitude of the cortical LCGU response to OXO apparently were related to the distributions of cholinergic neurochemical markers, especially high affinity muscarinic binding sites.

Animals↗
PubMed1981

Effect of oxotremorine on local cerebral glucose utilization in motor system regions of the rat brain.

The [14C]2-deoxy-D-glucose technique was used to test the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in rats. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.7 mg/kg, ip) increased LCGU in brain regions involved in motor function: the sensorimotor cortex; the extrapyramidal motor system, including the striatum, globus pallidus, red nucleus, substantia nigra, subthalamus and ventral nucleus of the thalamus; the cerebellar vermis, fastigial nucleus and nucleus interpositus; and the vestibular nucleus. No effects were observed in the fibers of the pyramidal tract, internal capsule, cerebellar white matter and the dentate nucleus. Increases were not affected by methylatropine (1 mg/kg sc), but were completely antagonized by scopolamine (2.5 mg/kg, ip). The anatomic distribution and magnitude of the LCGU response to OXO were not simply correlated with the reported densities of muscarinic receptors.

Animals↗
PubMed1981

Carbamazepine: a clinical biopharmaceutical study.

In a biopharmaceutical study of carbamazepine, the F-CBZ, DAK preparation, which contained small particles with minor variation in size, had a more rapid dissolution rate than Tegretol, which contained larger particles of more variable size. Accordingly, carbamazepine had a more rapid absorption rate from F-CBZ, DAK than from Tegretol in a comparative absorption test involving single-dose administration of 200 mg to 8 healthy volunteers. The clinical significance of the difference in absorption rates for the steady state levels of carbamazepine and carbamazepine-10,11-epoxide, and the frequency of side-effects in relation to tablet intake, were evaluated in a double-blind, randomized, double-dummy cross-over trial of 35 days' duration, in 21 well-adjusted epileptic patients. 9 patients were treated with Tegretol alone and 12 with Tegretol combined with other antiepileptic drugs. A lower steady state plasma level of carbamazepine was found at 08.00 h during treatment with F-CBZ, DAK in comparison with Tegretol. The difference was small. There was no difference in the type and frequency of side-effects or seizures between the 2 preparations. The frequency of epileptic fits was not correlated with the plasma level of carbamazepine or the epoxide. Side-effects, however, had a tendency to be correlated with the concentration of the epoxide. Thus, the particle size influenced the absorption rate of carbamazepine, without having a significant correlation wih the frequency of side-effects. The difference in the minimum plasma level of carbamazepine between treatments with the two preparations was modest, and appeared to be without clinical significance.

Adult↗
PubMed1981

Differences in single dose phenytoin kinetics between Greenland Eskimos and Danes.

Phenytoin (PHT) disposition was studied in Greenland Eskimos and in Caucasians (Danes) in order to reveal possible ethnic differences in the pharmacokinetics. PHT was administered i.v. as a single, subsaturation does to healthy adult volunteers and determined in plasma by thin-layer chromatography. Based on the time/concentration curves obtained, the half-life, volume of distribution, the area under the curve, and the total body clearance were calculated. The protein binding was measured by ultrafiltration. Three groups were studied: Group 1 were Eskimos living in East Greenland, group 2 were Eskimos living in Denmark, and group 3 were comparable Caucasians, as a reference group. The total body clearance of PHT per kg body weight was almost twice as high in Eskimos, irrespective of place of living or sex, compared with the Danish group. The volume of distribution was larger in the Eskimo group, but the protein binding did not differ. The reason for the differences in clearance and volume of distribution between the two ethnic groups is not clear, but the results emphasize that ethnic differences in pharmacokinetics can be of significance. The total body clearance values for PHT in Caucasians found in the present study agreed with results from other European investigations that used the same dose, but different analytical assays.

Adolescent↗
PubMed1981

Influence of disulfiram on the serum concentration of carbamazepine in patients with epilepsy.

Treatment of alcoholics with phenytoin and disulfiram (DI) simultaneously is complicated and inexpedient because of the marked drug interaction. The aim of this study was to investigate whether an interaction exists between DI and carbamazepine (CBZ). The serum levels of CBZ and the metabolite CBZ-10, 11-epoxide were measured by high-pressure liquid chromatography in seven out-patients with epilepsy, on monotherapy with CBZ, before and during two weeks administration of DI. Five patients completed the investigation. None were alcoholics. The changes in the serum levels were insignificant, i.e. without clinical important. Moreover, uncontrolled clinical experience has not indicated any interaction between DI and CBZ. Thus the influence of DI on the metabolism of CBZ is probably negligible. CBZ is suggested, therefore, when anticonvulsive therapy is needed by alcoholics in treatment with DI.

Adult↗