[Gynecomastia caused by digitalis?].
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Biomedical subjects
Publications and source records attributed to U Peters.
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Hydrolysis of 3H(G)-digitoxin by hydrochloric acid and human gastric juice is described. Incubation temperatures of 37 degrees C and 22 degrees C were chosen for electrolyte solutions, and 37 degrees C for the experiments with gastric juice. After dichloromethane extraction, the radioactive metabolites were separated by thin-layer chromatography, localized and quantified by a radiochromatogram scanner. The degradation products separated by TLC were digitoxigeninbis-digitoxoside, digitoxigenin-mono-digitoxoside, and digitoxigenin. After 10 min of incubation at pH 1, digitoxin amounted to 38.6% of the total radioactivity in electrolyte solution and 37.6% in gastric juice. After 60 min, the percentage of digitoxin decreased to 5.9% and 0%, respectively. After 120 min at 22 degrees C, amounts of unhydrolyzed digitoxin were: at pH 1 55%; and at pH 2 84%. After 10 min at pH 1, and 60 min at pH 2, digitoxin was hydrolyzed to such an extent that bioavailability should have been significantly reduced. Absorption of digitoxin (liquid) from the stomach was studied during gastroscopy in five patients. Among them, significant differences in absorption kinetics and bioavailability existed, as revealed by radioimmunological measurements of the digitoxin blood levels.
Several methods for the determination of dihydrometabolites of digoxin are described. Dihydrometabolites of digoxin are essentially inactive. They are the most important group of metabolites of digoxin. Seven (7) percent of a group of in-patients excreted more than 35% of these metabolites. The average was 13%, with respect to total extractable digoxin and metabolites in urine. In blood up to 40%, and in urine up to 52% dihydrogenated metabolites were found. The main metabolite was dihydrodigoxin, but the hydrolytic metabolites of digoxin exist also in reduced form. Neither the dose of digoxin, impaired renal function, nor an increased body content of digoxin seems to affect the rate of formation of these dihydrometabolites.
In 100 patients receiving digoxin to control heart disease, metabolic reduction of the lactone ring of digoxin was investigated. An average of 12.4% +/- 11% (range 2.2% to 52%) of the lipid-extractable cardenolides in a 24-hour urine sample contained the reduced lactone ring. Fifty-three excreted more than 10% while seven excreted more than 35% of these metabolic products. Reduction was not influenced by age, sex, dose, or blood level of digoxin. One patient who excreted 52% reduced products in the urine had 40% reduced digoxin-metabolites in the blood; the main metabolite was dihydrodigoxin. We found no influence of other drug therapy or concurrent disease on reduction of digoxin in this group.
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Digitoxin concentration, measured by radio-immunoassay, was significantly lower in 51 patients in chronic renal failure (23.2 +/- 7.8 mug/l) than in 29 patients in heart failure (26.5 +/- 7.3 mug/l), although both groups were on the same maintenance dose of 0.1 mg daily. Despite a normal serum albumin concentration, digitoxin protein binding was less in uraemic patients than in those with normal renal function. Renal failure did not affect intestinal digitoxin absorption. In patients in chronic renal failure elimination half-time was significantly shorter (5.7 +/- 0.9 days) than in healthy controls (7.6 +/- 1.6 days). There was no significant difference in the excretion of water-soluble ("cardioinactive") digitoxin metabolites in urine between patients in chronic renal and those in heart failure. In patients with normal renal function, of dichloromethane-soluble (cardioactive) metabolites only digitoxin could be demonstrated by thin-layer chromatography. The results indicate that patients in chronic renal failure can safely be given the same dose as those with normal renal function, without danger of over- or underdosage.
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A radomized study was done in 2 groups of male patients operated upon 3-17 years ago either by partial gastrectomy (Billroth II type) or hermiotomy. The inquiries covered eating, drinking and smoking habits, occupation, body weight, subjective complaints, and use of drugs. Body weight and professional activity after operation were not different in both groups. Gastrectomized patients avoided milk or foods with milk, sweets and legumes more often. Feeling of fullness, vomiting and diarrhea occurred more frequently in gastrectomized subjects, as well as statements about good or even ravenous appetite and thirst. Gastrectomized men, besides, had a higher consumption of alcoholic drinks, preferably of beer.
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By 8-11 enzymes, using polyacrylamide gel electrophoresis, 378 isolates from R. opimus, 3 isolates from M. libycus, 4 isolates from P. andrejevi, 1 isolate from P. papatasi, 1 isolate from S. murgabiensis and 25 isolates from human patients with skin leishmaniasis have been identified. Using starch gel electrophoresis, 17 strains from R. opimus and 3 strains from patients have been additionally identified by 12 enzymes. All the isolates were tested for ability to cause leishmaniasis disturbances in golden hamsters intracutaneously injected into the ear. It is established that L. major is a polytypic group which on the territory of the USSR consists of 3 independent species: L. major (in a narrower sense), L. gerbilli and L. sp. nov, a new earlier unknown species. All three types of Leishmania are specific parasites of R. opimus and only L. major may affect man and M. libycus. 3 types of Leishmania may coexist in the body of one animal. In R. opimus and golden hamsters, all of them caused only skin damages, visceralization was never registered. In golden hamsters, L. major always caused progressing ulcers, while L. sp. nov. and L. gerbilli caused only infiltrative damages. Only 9 (3%) of 268 L. sp. nov. isolates caused ulcers developing similar to those caused by L. major in the experimental animals. The data obtained account for the local nature and seasonal regularities of the epidemic process in the natural foci of skin leishmaniasis by the changing proportion of L. major in the complex of Leishmania encountered in R. opimus.
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A yeast artificial chromosome (YAC) contig was constructed encompassing the entire region on chromosome 17p13 where the autosomal recessive disorder infantile nephropathic cystinosis (MIM 21980, CTNS-LSB) has been genetically mapped. It comprises seven clones ordered by their content of a series of six sequence-tagged sites (STSs). Fluorescence in situ hybridisation (FISH) revealed two chimaeric clones. The order of four polymorphic STSs mapped with the contig was consistent with that of the known genetic map with the exception of markers D17S1583 (AFMb307zg5) and D17S1798 (AFMa202xf5) where a telomeric location of D17S1583 was inferred from the contig; two non-polymorphic STSs were localised within the marker frame-work. From the analysis of recombination events in an unaffected individual as defined by leucocyte cystine levels we support the high-resolution mapping of this region to a small genetic interval and show that it is entirely represented on a single, non-chimaeric YAC clone in the contig.