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N Gerber

Publications and source records attributed to N Gerber.

153 records · Page 9Linked to original sources

Characterization of mephenytoin metabolites in human urine by gas chromatography and mass spectrometry.

Metabolites of mephenytoin (5-ethyl-3-methyl-5-phenylhydantoin) were characterized in human urine following chromatography on XAD-2 resin, permethylation, and combined gas chromatography and mass spectrometry. Four glucuronide metabolites previously unidentified in man were characterized as their permethylated derivatives by chemical-ionization and electron-impact mass spectrometry. These metabolites included 5-ethyl-5-(hydroxyphenyl)-3-methylhydantoin O-glucuronide; 5-hydroxyethyl-3-methyl-5-phenyl-hydantoin O-glucuronide; 5-ethyl-5-(hydroxymethoxyphenyl)-3-methylhydantoin O-glucuronide; and a metabolite tentatively identified as 5-ethyl-5-phenylhydantoin N3-glucuronide in which both N-demethylation and glucuronide conjugation of the hydantoin ring have occurred. Mephenytoin, N-demethylmephenytoin, 5-ethyl-5-(hydroxyphenyl)-3-methylhydantoin, and 5-ethyl-5-(hydroxymethoxyphenyl)-3-methylhydantoin were characterized in extracts of enzymatically hydrolyzed urine.

Adult↗

Metabolism and choleretic effect of naltrexone in the isolated perfused rat liver.

A specific high-pressure liquid chromatographic assay was developed for the measurement of the narcotic antagonist drug, naltrexone. When 10 mg of naltrexone . HCl was added to the perfusate of the isolated perfused rat liver, the concentration of the drug in the perfusate declined rapidly with an apparent half-life of about 9 min. At 30 min 90% of the unchanged drug had been removed from the perfusate; the liver at this time retained 47% of the total radioactivity, of which only 75 represented unchanged drug. The bile at 30 min contained 28% of the total radioactivity and by 120 min this had risen to 70%. Initially naltrexone glucuronide was the principal metabolite in the bile. After 60 min N-dealkylated naltrexone glucuronide was the principal metabolite in bile. A marked increase in bile flow was noted immediately after the addition of the drug to the perfusate. The choleretic effect was attributed to the osmotic effect of the metabolites of naltrexone in the bile.

Animals↗

5,5-Bis(3-hydroxyphenyl)hydantoin, a minor metabolite of diphenylhydantoin (dilantin) in the rat and human.

5,5-Bis(4-hydroxyphenyl) hydantoin has been identified as a minor metabolite of diphenylhydantoin (DPH) in the rat and human. This metabolite was synthesized in the laboratory from 4,4'-dihydroxybenzophenone. Gas chromatographic and mass spectrometric comparison of the permethylated synthetic compound with the permethylated derivative of the metabolite obtained from biological sources showed that they were identical. The metabolite was excreted as a glucuronide and accounted for about 1% of the total hydroxylated metabolites of DPH in human urine and rat bile. When the synthetic standard was added to the recirculating perfusate of the isolated perfused rat liver, a monoglucuronide, a trihydroxy-DPH glucuronide, and a dihydroxymethoxy-DPH glucuronide were identified in the bile.

Animals↗

[Ankylosing spondylitis (Bechterew) and tissue antigen HLA-B 27. II. HLA-B 27 negativity in classical clinical ankylosing spondylitis: no independent nosological entity].

The question, whether HLA-B27-negative patients with classical ankylosing spondylitis (AS) belong to a separate nosological entity, was studied by a standardized analysis of 12 clinical, 8 radiological and 6 laboratory criteria in 95 cases, including 7 with HLA-B27-negativity, who reinforced international criteria for classical AS. The results showed neither definite clinical nor radiological, or laboratory differences between the HLA-B27 negative and positive group. We conclude, that existence or absence of the tissue antigen HLA-B27 has no influence on inflammatory activity of skeletal or soft tissue manifestations of the disease. The group of HLA-B27-negative patients who fulfill the criteria of classical AS does therefore not seem to form a separate nosological entity.

HLA Antigens↗

[Ankylosing spondylitis (Bechterew) and tissue antigen HLA-B 27. I. Diagnostic value of HLA-typing].

In 95 Swiss patients with classical ankylosing spondylitis (AS) the tissue antigen HLA-B27 was present in 92.6%, compared with 7.7% in healthy Swiss blood donors. Assuming the prevalence of ankylosing spondylitis in Switzerland to be 1.9 promille, the chance of a Swiss carrier of HLA-B27 to develop a classical form of AS would be only some 2.2%. For diagnostic purposes, HLA typing thus seems to be of very little value, as among the 462 000 Swiss carriers of HLA-B27 there seem to exist no more than 10 800 classical cases with clinically manifest AS. Absence of HLA-B 27 does not exclude ankylosing spondylitis, as 7.4% of the classical cases are HLA-B27-negative. However, the crudely calculated risk to develop AS is 160 times smaller compared to a carrier HLA-B27. Corner stone of the diagnosis therefore remains careful case history and radiological features of a bilateral sacroileitis of at least grade II.

Adolescent↗

[Ankylosing spondylitis (Bechterew) and tissue antigen HLA-B27. III, Heredity of ankylosing spondylitis (Bechterew)].

A family with known accumulation of ankylosing spondylitis (AS) was examined clinically, radiologically and by HLA tissue typing. Among 17 individuals of three generations there were four carriers of classical AS, all HLA-B27-positive. Five carriers of HLA-B27 were clinically and radiologically healthy, but three of them were below the age of 30, thus still being at risk of developing AS. The numerical relation between first degree relatives with and without HLA-B27 was 10:7. Genotype reconstruction of the great grandparents lead to the conclusion, that they were carriers of two different haplotype combinations, HLA-1/HLA-B27 and HLA-2/HLA-B27. Both haplotype combinations proved to be associated with AS. Among the offsprings of these great grandparents the combination of HLA-2 with HLA-B27 occurred in 3 of the 4 ankylosing spondylitics and in four of the six healthy HLA-B27-carriers. The question whether a haplotype combination of HLA-2 and HLA-B27 leads to an increased risk for AS cannot be decided without further systematic genotype determinations.

HLA Antigens↗

[Polymyalgia rheumatica. Clinical histological study of 46 cases].

The nosological relationship between Polymyalgia rheumatica (PMR) and Cranial Arteritis has been studied by comparing 46 cases of PMR with 21 cases of cranial arteritis. Symptoms consistent with cranial arteritis were present in 83% of the PMR patients, but only 32% showed giant cell arteritis in the biopsy of temporal arteries. The difference is explained by the segmental involvement of the arteritis. The patients with cranial arteritis had symptoms of PMR in 48%. It is concluded, that PMR and cranial arteritis are both manifestations of the same disease. Temporary signs of generalized arteritis seem to occur often in PMR and may lead to fatal complications. PMR may last up to ten years. Because of the potential fatality of this disease, a temporal artery biopsy is indicated in every suspicious case in order to provide a sound basis for the required long term therapy with corticosteroids.

Adult↗