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M Michiels

Publications and source records attributed to M Michiels.

At least 19 recordsLinked to original sources
PubMed1996

Present state of development of neo-electroencephalography.

Neo-electroencephalography (neo-EEG) is a new technique for recording and analyzing brain activity. Mathematical and computerized reconstitution yields a monopolar-like montage. Given the polymorphism of the brain's electrical activity, the computer detects the correct monopolar-like montage for each activity in steps of 0.25 Hz. Conventional EEG detects the difference in potentials between two electrodes. Through the use of monopolar-like montages neo-EEG analysis reveals the amplitude and phase that actually underlie each electrode. The report describes with precision the features of the recording extracts that have been chosen for the analysis, i.e., the number of dominant frequencies, the frequency to the nearest 0.25 Hz and the frequency spectrum for each dominant frequency, then the amplitude to the nearest 0.1 microv and phase shift to the nearest 0.001 sec at each electrode. Some examples of comparisons between neo-EEG and conventional EEG findings are shown and demonstrate the advantages of neo-EEG in detection and differentiation of organic and functional pathologies.

Alpha Rhythm↗
PubMed1988

Hypnoanalgesia with R 8110/fentanyl in the dog: pharmacodynamic and pharmacokinetic interactions.

The pharmacokinetics and clinical effects of the short-acting hypnotic R 8110 and of the narcotic analgesic fentanyl were studied in the dog. The effects of separate intravenous (i.v.) injections of R 8110 (4 mg/kg) and fentanyl (0.015 mg/kg) and of concurrent i.v. injection of the two were studied. After administration of R 8110, induction of hypnosis occurred within 1 min, maximal depth of anaesthesia and satisfactory analgesia and muscle relaxation were obtained after 5 min. The effects had decreased within 15 min and full recovery occurred within 30 min. Fentanyl alone produced neither hypnosis nor muscle relaxation. When fentanyl and R 8110 were given simultaneously, the duration of hypnosis was doubled in comparison with R 8110 alone. Moreover, markedly improved and longer lasting analgesia and muscle relaxation were observed with the combination. When the drugs were injected together, the plasma concentrations of R 8110 were initially much higher than after separate injection of R 8110, but they became similar after 30 min. Although statistically non-significant, fentanyl reduced the total plasma clearance of R 8110 (31.1 +/- 6.9 vs. 21.9 +/- 2.3 ml/kg/min) and decreased the volume of distribution (3.78 +/- 1.83 vs. 2.23 +/- 0.90 l/kg, P less than 0.05). Fentanyl did not alter the elimination half-life of R 8110. R 8110 had no apparent influence on the pharmacokinetics of fentanyl.

Animals↗
PubMed1988

Pharmacokinetics and tissue distribution of ketanserin in rat, rabbit and dog.

The plasma kinetics and tissue distribution of ketanserin [+)-3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)- quinazolinedione, R 41 468) were studied in the rat, rabbit and dog. The studies were performed utilizing 3H- and 14C-labelled ketanserin and appropriate techniques to measure levels of radioactivity, unchanged drug and a major metabolite ketanserin-ol in plasma and tissues. Following intravenous administration to male rats and dogs (10 mg/kg), plasma levels could be described by a two-compartment model. The plasma clearance (C1) averaged 3.8 and 19.2 ml/min/kg and the volume of distribution (Vdss) 0.67 and 4.7 l/kg in male rats and in dogs, respectively. Following oral administration (10-40 mg/kg), ketanserin was rapidly and completely absorbed in all species studied. The absolute bioavailability of oral ketanserin was more than 80% in both rats and dogs. Due to the high clearance of the metabolites in rats, ketanserin was the main component of the plasma radioactivity. In dogs, the fraction of the metabolite ketanserin-ol was more pronounced than that of ketanserin. The apparent elimination half-life of ketanserin was 1.5 h in rabbits, 2-5 h in rats and 3-15 in dogs. The pharmacokinetics of ketanserin were dose-related after single and chronic intravenous and oral dosing. Distribution studies in rats after intravenous and oral administration (10 mg/kg) demonstrated an almost immediate equilibrium between plasma and tissues, resulting in slightly higher tissue than plasma concentrations in the well perfused tissues, and similar or slightly lower levels in the remaining tissues. Ketanserin was the main component of tissue radioactivity. The drug crossed the blood-brain barrier only to a slight extent, brain levels of the unchanged drug being similar to the free fraction in plasma. Ketanserin disappeared from tissues with a similar half-life to that in plasma. On repeated dosing, a small fraction of metabolites was more slowly eliminated. The excretion of the urinary and faecal metabolites after repeated dosing was very similar to that after a single dose. Placental transfer of ketanserin in the rat was limited. On average 0.3% of the maternal radioactive dose, preferentially metabolites, was recovered from the combined foetuses. In dogs orally treated with doses of up to 40 mg/kg/d for 12 months, no undue accumulation or retention of ketanserin or ketanserin-ol was found in any tissue. In lactating dogs orally dosed at 10 mg/kg, preferentially metabolites were excreted in the milk. Concentrations of ketanserin and ketanserin-ol in the milk were respectively 2 and 4 times higher than plasma levels.

Animals↗
PubMed1988

Pharmacokinetic evaluation of the in vitro and in vivo pharmacological profile of the major metabolites of ketanserin in the rat.

In order to explain the differences between the in vitro and in vivo pharmacological activity of two major metabolites of ketanserin [+)-3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]-2,4(1H,3H)-quinazolinedione , R 41 468), viz. 6-hydroxyketanserin and ketanserin-ol, the pharmacokinetics of ketanserin and both metabolites were studied after oral and subcutaneous administration to male Wistar rats. The intrinsic potency of 6-hydroxyketanserin as a serotonin S2-antagonist is similar to that of ketanserin, as assessed by receptor-binding and pharmacological studies in vitro. In vivo, both substances are equipotent after s.c. administration, but 6-hydroxyketanserin is shorter acting and has a weak oral activity. In vitro studies indicated that ketanserin-ol is 2-3 orders of magnitude less potent than ketanserin and 6-hydroxyketanserin, but its in vivo activity is higher than could be expected from the in vitro studies. When ketanserin was administered to rats, only ketanserin and none of the metabolites was detected in plasma, indicating that the parent drug is the pharmacologically active substance. After s.c. administration of 6-hydroxyketanserin, its plasma levels decreased rapidly, explaining its short duration of action. The oral bioavailability of 6-hydroxyketanserin was very low, accounting for its low in vivo activity after oral administration. The rapid elimination and the low bioavailability of 6-hydroxyketanserin are explained by hepatic conjugation and subsequent biliary excretion. After administration of ketanserin-ol to rats, the metabolite was converted in vivo to ketanserin giving much higher plasma levels for ketanserin than for ketanserin-ol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Modal completion: critical variables in apparent transparency.

Conditions for perceptual modal completion are investigated using a stimulation pattern consisting of a figure moving behind a black opaque strip. This configuration leads, depending on conditions, either to the amodal Michotte tunnel effect, or to modal completion, ie the apparent transparency phenomenon. Four experiments are reported in which an attempt was made to define the critical variables of this latter effect. The results show that modal completion is not typically related to luminance interactions, ie to assimilation, but depends on the figural dominance of the filled-in object, this being determined by structural factors such as figure-ground relationship and stimulation change. The effect also depends strongly on the complexity of the spatiotemporal integration needed to maintain phenomenal identity of the object. No significant effect was found for the two other variables investigated, ie formal complexity of the figure and depth between the figure and the strip. The data are discussed in relation to those on moving visual phantoms.

Attention↗
PubMed1987

The metabolism and fate of closantel (Flukiver) in sheep and cattle.

Closantel was reasonably well absorbed in sheep and cattle. After oral (10 mg/kg) or parenteral (5 mg/kg) administration, similar peak times (8-48 h) and peak plasma levels (45-55 micrograms/mL) are observed. Plasma level-time curves are superimposable for either route and increase linearly with the dose. The elimination half-life of closantel is 2 to 3 weeks. The relative bioavailability of 50% of oral closantel can partly be explained by incomplete absorption. Experiments in sheep with 14C-closantel revealed that the plasma radioactivity is almost exclusively due to the unmetabolized drug, metabolites accounting for less than 2%. At least 80% of the dose was excreted with the feces over the investigational period of 8 weeks, and less than 0.5% with the urine. Closantel was only poorly metabolized. Over 90% of the fecal radioactivity was due to the parent compound. Two monoiodoclosantel isomers were the only fecal metabolites detected with radio-HPLC. The distribution of closantel to tissues was limited by its high protein binding. Closantel bound strongly (greater than 99.9%) and almost exclusively to plasma albumin. Accordingly, tissue concentrations were many times lower than the corresponding plasma levels. Residual radioactivity in sheep in all tissues but liver was entirely due to closantel. About 30% to 40% of the liver radioactivity could be attributed to monoiodoclosantel. In both sheep and cattle, residual tissue concentrations decline parallel to the plasma concentrations. Consequently, the plasma kinetics of closantel reliably reflect its depletion from tissues. Independently of the dosing scheme and route of administration, the maximum daily intake by the consumer was always below the acceptable daily intake within 4 weeks after the last dose.

Animals↗
PubMed1987

Pharmacokinetics and tissue distribution of the new gastrokinetic agent cisapride in rat, rabbit and dog.

The plasma kinetics and tissue distribution of the gastrokinetic (+/-)-cis-4-amino-5-chloro-N-[1-(3-(4-fluorophenoxy)propyl]-3-methoxy-4- piperidinyl]-2-methoxybenzamide monohydrate (cisapride, R 51 619) have been studied in the rat, rabbit and dog. After intravenous administration to rats (5 mg/kg) and dogs (0.63 mg/kg) plasma level-time curves were adequately fitted to a two-compartmental model. The plasma clearance (ClT) and volume of distribution (Vdss) averaged 91 ml/min.kg and 4.7 l/kg in the rat and 4.2 ml/min.kg and 0.82 l/kg in the dog, respectively. Following oral administration, cisapride was rapidly and almost completely absorbed from the gastrointestinal tract in rats and rabbits. The absorption was somewhat slower in the dog. In male rats the plasma radioactivity was mainly due to metabolites, unaltered cisapride representing on average 10% of the total radioactivity. A markedly larger proportion of the parent drug was seen in female rats. Linear plasma kinetics were observed for cisapride in the dose range of 10 to 160 mg/kg. Similarly in the dog, linearity was observed after oral administration in the range of 0.31 to 10 mg/kg. The plasma kinetics remained unaltered on repeated oral doses of 10 mg/kg to rats and subchronic intravenous administration at 0.63 mg/kg to dogs. Compared with intravenous administration, the absolute bioavailability of oral cisapride was 23% in rats and 53% in the dog for the drug given in solution. The terminal plasma half-life of cisapride was about 1-2 h in the rat and about 4-10 h in the rabbit and dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Epidural and intravenous sufentanil in the rat: analgesia, opiate receptor binding, and drug concentrations in plasma and brain.

Doses of sufentanil (i.e., 0.01, 0.04, 0.16, 0.63, 2.5, 10, and 40 micrograms/rat) were injected either into the lumbar epidural space or intravenously in rats weighing +/- 250 g, and in vivo pharmacologic activities (i.e., prolongation of latency to tail withdrawal in response to noxious heat, blockade of cornea and pinna reflexes, increase of skeletal muscle tone), ex vivo mu-opiate receptor binding (i.e., displacement of specific 3H-sufentanil binding in thalamus, striatum, hippocampus, cortex, mamillary body-medulla oblongata segment, medulla oblongata, and in cervical, thoracic, and lumbar spinal cord), and drug concentrations in plasma, brain, cortex, and cerebellum, were determined. An ED50 dose of intravenous sufentanil of 0.075 micrograms/rat produced analgesia. CNS-mediated in vivo side effects (i.e., blockade of pinna and cornea reflexes, muscle rigidity) were apparent at 6-28 times higher doses. Epidural sufentanil also produced analgesia at an ED50 dose of 0.08 micrograms/rat, but CNS-mediated side effects occurred only at 35 to 76 times higher doses. This greater in vivo selectivity of epidural sufentanil in producing analgesia was consistent with ex vivo binding data that showed that in most areas of brain, but not in spinal cord, more mu-opiate binding occurs with intravenous than with epidural sufentanil. The two routes nonetheless differed by no more than a factor of approximately two in producing detectable levels of sufentanil both in plasma and in brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1985

Preparation and characterization of antisera and monoclonal antibodies to haloperidol.

For the first time a library, of monoclonal antibodies (MoAbs) to the butyrophenone haloperidol (D-2 antagonist) has been prepared. Synthesis of a haloperidol derivative suitable for chemical coupling to a protein carrier via oxobutyric acid produced an immunogen which was used to develop two polyclonal antisera and twelve MoAbs specific for the hapten. Our library of MoAbs can be grouped into three classes; 1) high affinity and specificity for free 3H-haloperidol, 2) moderate affinity with significant cross-reactivity to other butyrophenone ligands, and 3) a group which binds poorly to free 3H-haloperidol but instead recognizes the ligand only when it is coupled to carrier protein. Clone (189(2)-6) was found to have the highest equilibrium binding affinity (Kd = 4 nM) and is far more specific than the currently available antisera to haloperidol. This MoAb has significantly lower affinity for all of the common metabolites of haloperidol. This capability makes 189(2)-6 a candidate for further development with regard to use in clinical radioimmuno-assays of therapeutic drug levels. In addition, one of the anti-haloperidol Moabs (190(2)-6) binds more tightly to spiperone than to haloperidol and displays a qualitative correlation in the rank order of neuroleptic binding affinity for a limited series of analogs when compared to membrane bound D-2 receptor binding.

Animals↗
PubMed1984

The sylvian fissure: a commonly mislabeled cranial landmark.

The bright echo in which the middle cerebral artery pulsates has been termed by many authors the "sylvian fissure." The authors present anatomic, embryologic, and sonographic evidence that this terminology is inappropriate, and that the correct term should be "insula."

Cerebral Cortex↗
PubMed1983

Radioimmunoassay of the new opiate analgesics alfentanil and sufentanil. Preliminary pharmacokinetic profile in man.

The development of two analogous radioimmunoassay (RIA) procedures based on dextran-charcoal separation is described for the quantification of two fentanyl-like analgesics, alfentanil and sufentanil. Immunization of rabbits with conjugates of bovine serum albumin and carboxy-derivatives of the respective drugs resulted in the production of antisera capable of detecting less than 0.05 ng ml-1 of the parent analgesics with high specificity and almost no cross-reactivity with major metabolites. Excellent agreement was obtained between RIA--without prior extraction--and gas chromatography for alfentanil concentrations in human plasma. Because of sufentanil's low therapeutic plasma levels, no comparison could be made between its RIA and an alternative assay, however, there was strong evidence for the specificity of the assay when applied directly to plasma. With these RIA methods preliminary information was obtained on plasma concentrations and elimination of alfentanil or sufentanil in patients given an intravenous bolus injection of 50 micrograms kg-1 of alfentanil, or 5 micrograms kg-1 of sufentanil. For both analgesics, the pharmacokinetic profile in man could be described by a three-compartment model. The terminal elimination half-life was 88 min for alfentanil and 140 min for sufentanil. Six hours after a therapeutic dose, plasma levels were in the order of 3 and 0.3 ng ml-1 for alfentanil and sufentanil respectively.

Alfentanil↗