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Biomedical subjects

U Franke

Publications and source records attributed to U Franke.

50 records · Page 3Linked to original sources

Drug monitoring of quinine by HPLC in cerebral malaria with acute renal failure treated by haemofiltration.

The monitoring of quinine by HPLC in 3 patients suffering from cerebral malaria with acute renal failure and treated by haemofiltration is reported. The recommended dose of quinine in this situation is reduced to 10 to 15 mg.kg-1.day-1. However, in the first patient, when given quinine 10 mg kg-1.day-1 the plasma concentration was mainly below the recommended therapeutic range of 5 to 15 mg/l. In consequence, the dose of quinine in the second patient was elevated to quinine dihydrochloride 15.1 mg.kg-1.day-1 which produced plasma concentrations in the low therapeutic range. In the third patient, an unreduced dose of quinine dihydrochloride 25.7 mg.kg-1.day-1 was employed, resulting in plasma concentrations above 15 mg/l, which is generally assumed to be toxic, although, no sign of acute quinine toxicity was seen. The antimalarial effect in all three patients was satisfactory. Quinine was estimated in the haemofiltrate in two patients and was found to be below the limit of sensitivity (0.25 mg/l). Plasma quinine did not change during or shortly after haemofiltration. It is concluded that in case of acute renal failure in cerebral malaria the dose of quinine should be reduced, but that the common recommendation of 10 to 15 mg.kg-1.day-1 may be too low, and that haemofiltration has no marked influence on the total body clearance of quinine.

Acute Kidney Injury↗

High susceptibility for diploidy in ovulated oocytes from XO mice.

Adult female mice of the "sensitive" NMRI/Han strain ovulate diploid oocytes after gonadotropin treatment. Other mouse strains are "non-sensitive" with respect to the ovulation of such diploid oocytes. In this study we combined the impaired ovarian situation in the XO karyotype with the trait "diploidy", which is determined genetically, by mating Ta/O (Ta = Tabby) females of C3H X 101 background to males of the NMRI/Han strain. The adult female F1 hybrids were stimulated to ovulation by gonadotropins and identified by their karyotype (XX or XO). The cytogenetic analysis of ovulated oocytes revealed a low level of diploidy in the XX littermates (1.0%), but a very high level in females with the XO karyotype (24.6%). All of the XO females ovulated at least one diploid oocyte. We suggest that it is the XO status which drastically impairs meiosis I in our "gonadotropin-sensitive" F1 females due to (1) alterations of the developmental program within the oocyte, (2) a disturbed communication between oocyte and follicle, (3) a preferential maturation and ovulation of "follicles at risk", or (4) an exceptional recruitment of many such follicles, by, e.g., a premature responsiveness to gonadotropins in our XO females. An interdependence of several such mechanisms is possible.

Animals↗

Mechanisms of nondisjunction: facts and perspectives.

An ordered segregation requires distinct processes of differentiation within the germ cell for recognition and segregation of homologous chromosomes/chromatids. These include synchronous maturation of the nucleus and cytoplasm, chromosome pairing and assembly at the metaphase plate, and movement within the spindle; all of them may be under direct/indirect regulatory control by the surrounding somatic compartments. Interference, e.g., by hormonal alterations at any of these steps, may alter the normal program of differentiation, thus increasing the risk of chromosomal malsegregation. Hence, many different causative mechanisms may exist which basically, nevertheless, act via (a) nonsegregation, (b) chance segregation, both during meiosis 1 and 2, or (c) presegregation during meiosis 1. In our animal models of the Djungarian hamster and the NMRI/Han mouse strain, we are analyzing the mechanisms of nondisjunction and presegregation during meiosis 1 in oocytes, as well as during aging of the females, by the application of hormones (gonadotrophins and steroids) and specific microtubular inhibitors (colchicine and methylbenzimidazolcarbamate). We suggest that chromosomes play a relatively passive role, although chromosomal properties, e.g., length, chiasma number, NORs, and position within the spindle, may provide an individual risk for each bivalent to be affected by nondisjunction. Failures in the endocrine control of follicular and germ cell maturation are considered to be primary causes for nondisjunction in young and aging oocytes. The understanding of the differentiation processes resulting in the maturation of follicles "at risk" may provide us with the tool to prevent the generation of aneuploidy in man.

Abortion, Spontaneous↗