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Biomedical subjects

J W Meijer

Publications and source records attributed to J W Meijer.

67 records · Page 4Linked to original sources

The extraction of antiepileptic drugs. Model study on partition coefficients.

To compare the extraction behaviour of hexane, toluene, chloroform, 1,2-dichloroethane, diethylether, ethyl acetate and acetone towards phenobarbital, phenytoin, primidone and carbamazepine, partition coefficients of these drugs between the above solvents and water (saturated with ammonium sulphate when working with acetone) were measured at different pH-conditions. Acetone rendered the highest partition coefficients for all drugs. Ethyl acetate was second in the range, except for carbamazepine, which showed a specific affinity for the chlorinated hydrocarbons.

Anticonvulsants↗

Experiements with an inactivated hepatitis leptospirosis vaccine in vaccination programmes for dogs.

A fluid adjuvanted vaccine consisting of inactivated hepatitis virus (iH) and leptospirae antigens (L) was developed. The vaccine (Kavak iHL; Duphar) was tested in several vaccination programmes both alone and in combination with freeze dried measles (M) or distemper (D) vaccines. The results demonstrate that this new vaccine is also effective in pups with maternally derived antibodies, although a second vaccination at 14 weeks of age is recommended to boost the first vaccination. For the booster vaccination either the iHL-vaccine or the liver attenuated hepatitis vaccine (H) can be used.

Adenoviruses, Canine↗

Evaluation of a new immunoassay for determination of phenytoin and phenobarbital: results of a European collaborative control study.

The performance of a new enzyme multiplied immunoassay technique (EMIT) was compared with other current methods, namely gas-liquid chromatography and thin-layer chromatography, for the determination of phenytoin and phenobarbital in serum. Forty-three serum samples were sent as unknowns to the participating laboratories for determination. The precision of repeated determinations was very similar for EMIT and chromatography. There was good agreement among gas chromatography, thin-layer chromatography, and EMIT results. Interlaboratory variability was lower for EMIT determinations of both antiepileptic drugs. The rapid analysis of small samples, made possible by the EMIT system, could have beneficial effects on the treatment of epilepsies.

Chromatography, Gas↗

Interlaboratory variability of valproic acid determinations.

19 pooled plasma specimens were sent as unknowns to 13 participating research laboratories. The interlaboratory variability between the results was very high. Only 4 out of 13 laboratories had 6--12% of their results within the 95% confidence limit for each sample. The precision of repeated determinations was fairly good. 6 out of 10 participating laboratories had a coefficient of variation of less then 5%. The reproducibility and the agreement between the different procedures for quantitative analysis of dipropylacetate is similar to that reported for other major antiepileptic drugs.

Laboratories↗

Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy.

A double-blind, placebo-controlled trial is reported of lamotrigine as add-on treatment in therapy-resistant epilepsy. A within-patients serial design was used, with two 3-month treatment periods and an intervening 6-week washout/crossover period. An unblinded investigator adjusted lamotrigine dosage to achieve a plasma concentration within a previously predicted therapeutic range. All patients had therapy-resistant partial seizures, some in combination with other seizure types and were without serious neurological or intellectual deficit. Of 34 patients recruited only one was withdrawn because of an adverse experience (maculo-papular rash) probably related to the experimental drug and 30 completed the trial. The other 3 withdrawals were due to default during baseline, dispensing error and cholecystectomy. There was a modest statistically significant reduction in total and partial seizures on lamotrigine compared to placebo treatment. There was no difference in adverse experiences or abnormal biochemical or haematological findings between the lamotrigine and placebo periods. The plasma concentrations of concomitantly administered antiepileptic drugs were not affected by lamotrigine treatment. It is concluded that lamotrigine shows promise as an antiepileptic drug with low toxicity.

Adolescent↗

Open dose-ranging trial of flunarizine as add-on therapy in epilepsy.

A double-blind placebo-controlled crossover trial of flunarizine as add-on treatment in therapy-resistant epilepsy offered significant evidence of efficacy, but the plasma levels of flunarizine were lower than anticipated, probably due to induction of liver enzymes by comedication. An open dose-ranging trial was therefore undertaken to investigate the relationships among dose, efficacy, side effects, and blood level. With basal medication held constant, flunarizine was added at 3-month intervals in increasing doses of 0, 10, 15, 20, and 25 mg daily, or until side effects occurred or marked seizure reduction was obtained. Forty-seven patients completed the trial; all were adults with therapy-resistant epilepsy who had at least 3 seizures per month. All had complex partial seizures, with additional types in 20. Sixteen patients showed a 50% and 24 a 25% reduction of seizure incidence on flunarizine; 6 and 7, respectively, showed a corresponding increase. The greatest seizure reduction, when observed, occurred generally at a daily dose of 15-20 mg. Side effects, chiefly drowsiness and weight gain, increased markedly between 15 and 20 mg daily. Flunarizine administration produced no change in serum levels of comedication, but flunarizine levels were lower in patients taking more than one other drug. Seizure reduction was obtained most consistently in patients with secondary generalized epilepsy or neurologic deficits. The findings confirm the antiepileptic action of flunarizine in humans and justify further trials.

Adolescent↗

Acute effects of lamotrigine (BW430C) in persons with epilepsy.

Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photosensitivity after lamotrigine administration. Five subjects with frequent interictal spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half-life (t1/2) of lamotrigine in subjects taking sodium valproate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co-medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.

Adolescent↗

Relationship between dose and serum concentrations of carbamazepine, phenytoin, phenobarbital, and primidone in a Sri Lankan population compared with a European population.

Concentrations of carbamazepine, phenytoin, phenobarbital, and primidone have been measured by high pressure liquid chromatography (HPLC) in serums of 177 Sri Lankan epileptic patients. Relationships between concentrations and dose per kg body weight of these drugs have been compared with those of patients in the Netherlands, using a matching procedure. Although variabilities in dose-concentration ratios were somewhat larger in Sri Lanka than in the Netherlands, no evidence was found of a systematic difference in pharmacokinetics between both populations.

Adolescent↗

Intermediate filament proteins in spindle cell carcinoma of the larynx and tongue.

In an analysis of intermediate filament protein expression of spindle cell carcinoma, a variant of squamous cell carcinoma, occurring in larynx and tongue, vimentin positivity was found in sarcomatoid areas in 12 of 13 patients. Scattered expression of keratin was observed in sarcomatoid areas in tumours of 10 patients. However, large parts of sarcomatoid areas of such tumours were negative for keratin. Overlying dysplastic epithelium and squamous cell carcinoma components were positive for keratin. In a number of cases there was a strong indication of co-expression of keratin and vimentin in parts of cells that, on histological grounds, belong to sarcomatoid areas or to cells in the interface between carcinoma and spindle cell area. The use of keratin and vimentin type intermediate filament antibodies could be of great help for the correct classification of these tumours.

Aged↗