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Biomedical subjects

M Kristensen

Publications and source records attributed to M Kristensen.

At least 73 records · Page 4Linked to original sources

Influence of rifampicin and isoniazid on the kinetics of phenytoin.

Clearance of phenytoin after i.v. injection of 100 mg was studied in six patients before and after 2 weeks daily treatment with 450 mg rifampicin, and in 14 patients with tuberculosis receiving standard treatment with 450 mg rifampicin, 300 mg isoniazid, and 1200 mg ethambutol daily. Acetylator status was measured by urinary acetylated sulphadimidine. Clearance of phenytoin in patients receiving only rifampicin increased from 46.7 ml min-1 +/- 20.6 ml min-1 to 97.8 ml min-1 +/- 33.4 ml min-1 (P less than 0.01), while clearance in patients on three drugs increased from 47.1 +/- 23.4 ml min-1 to 81.3 ml min-1 +/- 41.6 ml min-1 (P less than 0.01). No significant differences were observed between the six fast acetylators and the eight slow acetylators. Phenytoin kinetics were unchanged after further 3 months of combined treatment. Rifampicin is a strong inducer of the elimination of phenytoin. Combined treatment with isoniazid has no counter-acting effect in either fast or slow acetylators.

Acetylation↗

Mucus secretion in hypertrophic, hypersecretory, protein-losing gastropathy.

A 48-year-old man presented with giant folds of the gastric mucosa, hypoalbuminemia, and hypersecretion of acid. In vivo labeling of plasma proteins by 51CrCl3 disclosed an abnormal gastric protein clearance. Mucus secretion, evaluated by the output of dry matter, mucosubstance constituents (hexosamine and fucose), protein (by the method of Lowry), and sodium were five to eight times those in nine healthy volunteers, but were normalized by the histamine-H2-receptor antagonist cimetidine. The proportion of dry matter and protein was the same in the patient and in healthy subjects, indicating that the loss of plasma protein into the stomach probably occurred as part of an abnormally great secretion of mucus.

Cimetidine↗

Assessment of the thiamine nutritional status. An evaluation of erythrocyte transketolase activity, the stimulated erythrocyte transketolase activity, and the thiamine pyrophosphate effect.

The most widely accepted approach to estimation of thiamine nutrition has been the measurement of the erythrocyte transketolase activity (ETKA), the ETKA stimulated in vitro with thiamine pyrophosphate (TPP) (which is suggested to be designated ETKAS) and the percentage increase of ETKA after stimulation with TPP in vitro, called the thiamine pyrophosphate effect (TPPE). In spite of 30 years of experience in the determination of these variables doubtfulness still exists of how to assess them. On the basis of a study of a group of alcoholics and a group of non-alcoholics a system of evaluation of ETKA, ETKAS and TPPE is proposed.

Adult↗

The relapse-preventing effect of methyl-salazosulphapyridine compared to salazosulphapyridine during long-term treatment of ulcerative colitis. A double-blind controlled trial.

In an attempt to improve the relapse-preventing effect of salazosulphapyridine (SASP) and to encircle the part of the molecule essential for therapeutic actin, methyl-SASP was compared to SASP in a controlled double-blind trial without cross-over. The patient group comprised 33 patients with ulcerative colitis who had been symptom-free for 1--6 months on continuous treatment with SASP (on an average 2 g daily). The daily doses were SASP 1 g X 3 and methyl-SASP 125 mg x 3. Thirty patients completed the trial, 14 on SASP and 16 on methyl-SASP. Applying clinical criteria, the relapse rate after 6 months was 0.14 in the SASP group and 0.69 in the methyl-SASP group. The difference is highly significant. The blood concentrations of SASP, methyl-SASP, sulphapyridine (SP), and methyl-sulphapyridine (methyl-SP) were measured after 3 and 6 months. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-SP on an average 1/10 of SP (the differences are significant). It is concluded that whereas SASP showed a relapse-preventing effect in ulcerative colitis in this study comparable to that previously reported, the effect of methyl-SASP was only comparable to that of placebo, and the active substance in SASP does not seem to be unsplit SASP.

Adult↗

The therapeutic effect of methyl-salazosulphapyridine versus salazosulphapyridine in active ulcerative colitis. A double-blind controlled trial.

In an attempt to improve the ratio between therapeutic effect and side effects of salazosulphapyridine (SASP), methyl-salazosulphapyridine (methyl-SASP) was compared with SASP in a randomized controlled double-blind trial, without cross-over, in patients with active ulcerative colitis. The patient group comprised 53 patients. The daily doses were 1 g SASP x 3 and 125 mg methyl-SASP x 3. The methyl-SASP group comprised 26 patients, the SASP group 27 patients. The treatment period was 4 weeks. Applying clinical symptoms (bowel movements, registered by the patients on special charts), clinical condition (assessed by the patient), proctoscopic signs, and registration of side effects, it is concluded that methyl-SASP had an effect on ulcerative colitis indistinguishable from that of SASP. The rate of side effects was significantly less in the methyl-SASP group. The blood concentrations of SASP, methyl-SASP, sulphapyridine, and methyl-sulphapyridine were estimated at start during, and at the end of the trial. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-sulphapyridine on an average 1/13 of sulphapyridine, the differences being significant. It is concluded that methyl-SASP presents an improvement in the effect/side effect ratio when dealing with symptomatic ulcerative colitis. The discrepancy between the outcome of the present trial and the lack of effect in a controlled trial on the relapse-preventing effect of methyl-SASP is at present unexplained. A type II error in the present trial (or a type I error in the prophylactic one) is a possibility, or the patient-group selected for the present trial had a spontaneously benign course, cases demanding prednisone or colectomy having been excluded.

Adult↗

Choreoathetosis during phenytoin treatment.

A patient with symptomatic epilepsy receiving only phenytoin developed choreoathetosis and orofacial dyskinesias. These movement disorders disappeared when the drug was stopped and reappeared when the patient was challenged. Throughout the period of treatment, concentrations of phenytoin in serum were consistently low within the therapeutic range. Interfering symptoms from the cardiovascular system and the absence of some classic symptoms of phenytoin intoxication (nystagmus and dysarthria) contributed to delay the diagnosis. The patient died in hospital and autopsy of the brain showed rather localized encephalomalacies of corpus striatum. The pathogenic action of phenytoin and the role of preexisting brain lesions are discussed. Phenytoin must be suspected as the cause, when patients on this drug present with uncontrolllable epilepsy or neurological or mental deterioration.

Aged↗