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Biomedical subjects

J W Meijer

Publications and source records attributed to J W Meijer.

At least 55 records · Page 3Linked to original sources
PubMed1989

Distribution of drugs over whole blood: III. The transport function of whole blood for hydrocortisone.

Hydrocortisone (HC) distribution over the three main components of blood, i.e., plasma water, plasma proteins, and erythrocytes, was studied in vitro at various HC concentrations in plasma, in a suspension of washed erythrocytes in plasma water, and in whole blood. The distribution ratio of HC in the system of erythrocytes in plasma water was 2.1 when HC, 0.18-10.8 micrograms/ml, was added. In whole blood, however, this ratio was 2.4 for the same concentration range. In the HC range of 0.18-0.68 micrograms/ml of whole blood, the uptake percentage of HC by erythrocytes increased from about 16 to 28% of the amount of HC added. By adding blank ultrafiltrate to HC-enriched blood, it appeared that the erythrocyte fraction released HC in overproportional quantities compared with the release by plasma proteins. Similar findings have previously been reported regarding the drugs valproic acid and phenytoin. Migration of HC from HC-spiked plasma to blank erythrocytes reached an equilibrium within 5 min.

Blood Proteins↗
PubMed1987

Seven day administration of lamotrigine in epilepsy: placebo-controlled add-on trial.

A double-blind placebo-controlled trial of 7 days administration of lamotrigine as add-on therapy was performed in 10 patients with frequent therapy-resistant, chiefly partial, seizures. Dosage was adjusted on the basis of estimated half-life. Six patients showed a 50% seizure reduction on lamotrigine and two an increase. Side effects (ataxia, dizziness and apathy) occurred in 3 patients, but only at blood levels above 3 micrograms/ml, and were rapidly relieved when the dose was reduced in two. EEG spike counts were significantly reduced on lamotrigine. There was no evidence of interactions with co-medication.

Adolescent↗
PubMed1986

Extraction of nuclei from selected regions in paraffin-embedded tissue.

A method for the extraction of nuclei from selected regions in paraffin-embedded tissue is described. Fifty-micrometer sections are cut, dewaxed, and rehydrated. For the final handling, the sections are manually transferred from one tray to another. The sections are put on a slide under a dissection microscope and the region of interest is isolated by scraping off the irrelevant region with a scalpel. An optimal number of single nuclei is obtained by incubation in a protease solution with intermediate syringing. The nuclei are washed and can be used for flow cytometry. Resuspension of the nuclei in foetal calf serum and cytocentrifugation results in preparations suited for image analysis. DNA cytometric measurements of nuclei in a carcinoma in situ and an invasive carcinoma region in breast tissue present in the same tissue block and in a severe dysplasia/carcinoma in situ (CIN III) region of the cervix are presented.

Breast Neoplasms↗
PubMed1985

Assessment of effects of antiepileptic drugs.

Pharmacological studies form an important adjunct to epilepsy monitoring and conversely long-term EEG and video recording are of value for assessing antiepileptic drug (AED) effects. Clinical estimates of the incidence of brief frequent seizures as absences is often difficult but greater reliability can be achieved by long-term monitoring of the seizures themselves or of the associated EEG discharges. There are, however, very marked spontaneous short-term fluctuations in discharge rates and the amounts of ictal epileptiform activity in short conventional EEGs rarely provide any useful index of AED action. Acute investigations are of value for assessing new AEDs or experimental methods of administration and for pharmacokinetic studies. For this purpose either spontaneous EEG discharges or photosensitivity may provide quantitative measures of antiepileptic effect. Long-term AED monitoring by means of an indwelling catheter indicates the time course of blood drug levels to be more complex and variable than might be expected from simple pharmacokinetic models. Short-term fluctuations in AED concentrations have little effect on epileptiform EEG activity or seizure control but are often responsible for intermittent side-effects. Conversely diagnostic EEG and monitoring studies may be required to classify seizures as an aid to determining appropriate medication and may explain apparent resistance to therapy, due to pseudo-seizures, reflex or self-induced epilepsy. Finally a case is presented for combined pharmacological EEG and video-monitoring in the preliminary assessment of new AEDs in order to improve the design of subsequent clinical trials.

Anticonvulsants↗
PubMed1984

The circadian distribution of interictal epileptiform EEG activity.

Eighteen continuous 48 h monitoring studies are reported from 17 patients with epilepsy. The numbers of epileptiform discharges over corresponding epochs of the 2 days were significantly positively correlated in 16 studies. However, this was explicable by masking due to the sleep/wake cycle and when waking and sleep were considered separately a minority of studies showed significant correlations. The difference in total 24 h production of discharges between the 2 days ranged from 1.3 to 30.3%, mean 15.1%. The maximum discharge rate in 75% of the studies occurred during sleep; during waking the distribution of discharges was random. Even in the waking state the 0.5 h discharge rate was extremely variable and in few patients could a single 30 min epoch be regarded as a reliable sample of the mean rate over the waking day. The intervals between events showed a Poisson distribution during 9 days and 5 nights, but there was no within-patient consistency between the first and second 24 h period. The occurrence of discharges was periodic significantly more often at night than during the day, but the periodicities did not clearly correspond to the REM cycle. Discharges increased overall during sleep in 14 studies, were unchanged in 2 and decreased in 4. The time of occurrence of maximal discharge rate during sleep was consistent from night I to night II only in patients exhibiting generalized regular spike-wave activity but random in the others. A negative correlation between antiepileptic drug levels and discharge rate was rarely observed.

Adult↗
PubMed1984

Double-blind placebo-controlled trial of flunarizine as add-on therapy in epilepsy.

In a therapy-resistant epileptic population with partial complex seizures with or without secondary generalization, addition of flunarizine to existing therapy was accompanied by a significant reduction in complex partial and tonic-clonic seizures. This result did not appear to be due to serial effects or changes in the plasma levels of the co-medication. Side effects were rare. The serum flunarizine levels (13.8 ng/ml; range, 3-32.5 ng/ml) were lower than previously reported on a daily dose of 10 mg. This may reflect increased metabolism due to induction of liver enzymes by the co-medication. Given this finding, together with the low incidence of side effects, a further study is required to determine whether higher blood levels would give an improved degree and incidence of seizure reduction.

Adolescent↗
PubMed1984

Influence of Intralipid infusion on the elimination of phenytoin.

On the ground of clinical observations the hypothesis was tested that a changed disposition of phenytoin could bring about a shortened half-life. In vitro it appeared that the amount of phenytoin bound to the Intralipid fraction was more than twice the amount present in the plasma fraction. In an in vivo rat model it was shown that the half-life of phenytoin was indeed influenced by Intralipid administration, but contrary to clinical observations phenytoin half-life was prolonged. Some possible explanations for this discrepancy are discussed.

Animals↗
PubMed1983

Valproate-ethosuximide combination therapy for refractory absence seizures.

Five patients had absence seizures refractory to treatment with either ethosuximide or valproate sodium. To determine their response to combination therapy with the two drugs, four of the five had serial 24-hour intensive monitoring studies that included cable telemetric EEG recording, closed-circuit television observation, and frequent antiepileptic drug (AED) serum level determinations. The resultant data confirmed the clinical and EEG effects of serial alterations in AED programs. All five became seizure free with combination therapy. Combination therapy with ethosuximide and valproate should be considered in patients whose absence seizures do not respond to standard therapeutic measures.

Adolescent↗
PubMed1981

Systematic method of development in liquid chromatography applied to the determination of antiepileptic drugs.

The object of a liquid-chromatographic analysis is to separate, identify, and quantitate the constituents of interest in a sample mixture within an acceptable analysis time. This will be achieved by a systematic analysis development rather than by a trial-and-error approach. Such a systematic procedure requires a knowledge of the chromatographic parameters governing resolution and analysis time and their relative influences on resolution and its experimental implication. Furthermore, basic information about the mechanisms of the modes of liquid chromatography (adsorption, partition, ion exchange, and steric exclusion) and about the types of sample which can be preferentially analyzed by them is necessary. This information leads to a rational selection of the separation system that promises the best chance of success. In the subsequent experimental work, the analyst systematically measures and calculates resolution and analysis time as functions of selectivity, capacity, and efficiency of the phase system under selected chromatographic conditions. The essential chromatograms, tables, and graphs resulting from this systematic method of development are documented so that it is possible to replicate the analysis procedure in the laboratories involved. The result is a set of chromatographic conditions capable of achieving an optimum compromise between resolution and analysis time. The procedure is applied to routine therapeutic drug monitoring of antiepileptic drugs in patient serum.

Anticonvulsants↗
PubMed1981

Quantitative simultaneous determination of eight common antiepileptic drugs and metabolites by liquid chromatography.

Specific antiepileptic drug (AED) concentrations in serum are believed to cause therapeutic effects in individual patients. Communication between the clinician and the laboratory performing the drug level determinations is therefore essential for safe and effective medication. The now common practice of multiple drug therapy preferably requires simultaneous separation and quantitation of the various drugs and their metabolites. The advantages and disadvantages of current AED analysis methods are discussed. Liquid chromatography (LC) was found to be the most versatile technique for routine and research analysis and can be applied to the determination of common, less common and new AED and metabolites. Carbamazepine and its metabolite, carbamazepine-10,11-epoxide, were determined with high accuracy. The sample preparation procedures, the internal standards, and mode of LC separation used for the analysis are given. The chromatographic parameters for optimized resolution and analysis are given. The chromatographic parameters for optimized resolution and analysis time of eight AEDs and metabolites were devised with special consideration for the influence of the oven temperature on resolution. About 300 patient serum samples were analyzed by automatic unattended operation. By this method some 50 samples per day can be extracted and analysed. Quantitative results achieved by LC and gas liquid chromatography (GLC) on the same patient samples are reported and chromatograms discussed. Peak scanning was used to demonstrate the presence of compounds which could eventually interfere with the detection of phenylethylmalonamide. The overall accuracy of the employed LC method, the repeatability of retention times on three different columns, and the measured ranges of AED concentrations are reported.

Anticonvulsants↗
PubMed1980

Gas chromatographic methods for the determination of antiepileptic drugs: a systematic review.

Despite the availability of a variety of methods for determining the concentrations of antiepileptic drugs in body fluids--including thin-layer chromatography, high pressure liquid chromatography, radioimmunoassay, etc.--gas chromatography remains perhaps the routinely used tool for therapeutic drug monitoring in this area. As a result of the need to improve precision and reproducibility, as well as to reduce costs, among other factors, there has been a continuous technical improvement in the technique. And in the last 10 years, more than 100 papers have described gas chromatography for the determination of antiepileptic drugs. Needless to say, only a small percentage of these publications described methods of a significantly new character. In order to facilitate the task, of comparing methods for the purpose of choosing a technique suitable to a specific need, we have reviewed the analytic parameters described in the 114 publications of the last decade. These parameters include the following: (1) drugs determined, (2) internal standard, (3) amount of sample, (4) extraction procedure, (5) preparation of derivatives, (6) sample injection, (7) detection, (8) column support and temperature, and (9) stationary phase. We present these data in a comprehensive tabular form together with a number of comments concerning specific techniques.

Anticonvulsants↗
PubMed1979

The delayed effect of sodium valproate on the photoconvulsive response in man.

The acute effect of a single oral dose of sodium valproate on the photoconvulsive response has been studied. In 7 of 9 patients naive to this drug photosensitivity was abolished or reduced. A similar effect was seen in only 2 of 7 already receiving chronic sodium valproate therapy. The effect appeared 1 to 5 hr (mean, 3 hr) after attainment of peak sodium valproate concentration and lasted up to 5 days.

Adolescent↗
PubMed1979

Sodium valproate: serial monitoring of EEG and serum levels.

The clinical and electroencephalographic (EEG) effects of sodium valproate were studied in four patients by means of serial 24-hour EEG recordings and simultaneous hourly determinations of serum drug concentrations. The patients all had frequent clinical seizures and generalized spike-wave discharges. Valproate appeared to reduce diurnal paroxysmal discharges (PD) and clinical seizures, but the effect on nocturnal PD was less marked. The extent and duration of the depression of PD and seizures varied. Altering the distribution of the total daily dose may change the pattern of clinical seizures and PD. Valproate concentrations fluctuated widely over 24 hours, and the significance of single estimations often cited in the literature appears dubious. Peak serum concentrations above 100 micrograms per milliliter may be necessary in some patients to achieve clinical and EEG improvement.

Adolescent↗