Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Application of an optimized system for the well-defined exposure of human lung cells to trichloramine and indoor pool air.

In this study an in vitro exposure test to investigate toxicological effects of the volatile disinfection by-product trichloramine and of real indoor pool air was established. For this purpose a set-up to generate a well-defined, clean gas stream of trichloramine was combined with biotests. Human alveolar epithelial lung cells of the cell line A-549 were exposed in a CULTEX(®) device with trichloramine concentrations between 0.1 and 40 mg/m(3) for 1 h. As toxicological endpoints the cell viability and the inflammatory response by the cytokines IL-6 and IL-8 were investigated. A decreasing cell viability could be observed with increasing trichloramine concentration. An increase of IL-8 release could be determined at trichloramine concentrations higher than 10 mg/m(3) and an increase of IL-6 release at concentrations of 20 mg/m(3). Investigations of indoor swimming pool air showed similar inflammatory effects to the lung cells although the air concentrations of trichloramine of 0.17 and 0.19 mg/m(3) were much lower compared with the laboratory experiments with trichloramine as the only contaminant. Therefore it is assumed that a mixture of trichloramine and other disinfection by-products in the air of indoor pool settings contribute to that effect.

Chronic toxicity of zatosetron, a 5-HT3 receptor antagonist, in rhesus monkeys.

A 1-year chronic toxicity study was conducted in which rhesus monkeys (4/sex/dose) were given daily doses of 0, 3, 10, or 25 mg zatosetron/kg by nasogastric intubation. Clinical signs of toxicity characterized by salivation, diarrhea or soft stools, and/or emesis occurred in animals that received 10 or 25 mg/kg of zatosetron. One monkey in the high-dose group and one in the middle-dose group died as a result of intratracheal administration of the compound. The death of another monkey in the high-dose group was associated with an unexpectedly high (3-fold the mean plasma Cmax value in surviving females in this group) plasma level of zatosetron as indicated by postmortem analysis of heart blood. Animals of both sexes in all treatment groups gained weight at a slightly reduced rate when compared to control monkeys. Depressed appetite occurred in some monkeys in all treatment groups but was most evident in those receiving 25 mg/kg. Evaluation of ECG's indicated that treatment with zatosetron did not produce any rhythm or conduction disturbances. However, there was a mild increase in the Q-Tc interval throughout the treatment period at 4 hours postdosing in monkeys in the middle- and high-dose groups and a slight increase prior to dosing in animals in the high-dose group. Mean plasma Cmax and AUC(0-24 hr) values on Day 360 were dose proportional for zatosetron and for the N-demethylated metabolite in both sexes over the dose range tested. The mean t1/2 (elimination phase) for the plasma disappearance of zatosetron ranged from 3.4 to 7.2 hr in males and from 2.3 to 6.8 hr in females. Hematology, urinalysis, and clinical chemistry parameters were unaffected by treatment. There were no treatment-related gross or microscopic alterations or changes in organ weights. With the exception of mild effects on body weight gain, there was no evidence of chronic toxicity in monkeys given 3 mg/kg zatosetron daily for 1 year.

Chronic toxicity, metabolism, and pharmacokinetics of the 5-HT3 receptor antagonist zatosetron (LY277359) in Fischer 344 rats.

Studies were done to characterize the chronic toxicity, metabolism, and pharmacokinetics of a 5-HT3 receptor antagonist in Fischer 344 rats. Animal were given daily gavage doses of 10, 30, or 90 (females only were increased from 90 to 120 mg/kg for months 7-12) mg/kg of zatosetron for 1 year. Treatment-related histologic changes occurred primarily in the liver and kidney of rats given 30 or 90/120 mg/kg and consisted of hepatocellular fatty change (males only), hepatic granuloma formation, and histiocytosis (females only), and renal pigment deposition (both sexes), lesions not previously described in animals treated with 5-HT3 receptor antagonists. Decreased erythrocyte parameters, increased total leukocyte, lymphocyte, and neutrophil counts, and increased serum alkaline phosphatase, gamma glutamyltransferase, alanine transaminase, and liver weights in females were most likely related to the chronic inflammatory process in the liver. Increased alanine transaminase and transiently increased alkaline phosphatase with increased liver weights in males were likely related to the hepatocellular fatty change. Increased renal tubular epithelial pigment deposition (lipofuscin and hemosiderin) was observed in males and females in the high-dose group and in females in the middle-dose group. Both had increased kidney weights and increased serum inorganic phosphorus. Females in the high-dose group had increased urine volume, decreased pH, and increased total excretion of sodium, potassium, chloride, and creatinine. These changes may have been a reflection of tubular dysfunction associated with excessive pigment deposition. No toxicologically significant effects occurred in rats treated with 10 mg/kg/day for 1 year. Plasma concentrations of zatosetron and its 3-hydroxy metabolite increased with increasing dose and duration of dosing in both males and females during the first 6 months of dosing. Subsequent values measured at 12 months showed no substantive increases except in males given the highest dose. At comparable doses, consistent sex differences (F > M) in mean 1-hr plasma content of parent compound were evident across dose and time. Zatosetron-induced hepato- and nephrotoxicity seems to be peculiar to the rat and is observed only at very high doses relative to the proposed human clinical dose.

Toxicity tests on dental filling materials.

The rabbit muscle implantation test as described by Lawrence et al. (1972) was applied evaluate the acute non-specific toxicity of 3 amalgams and 2 composite materials, in order to test both the materials' toxicity and the suitability of the method used. The materials were implanted after different ageing times: 5 min, 1 h, 24 h and 7 days. Macroscopical as well as microscopical evaluation was performed. Biological reactions of the amalgams proved to be dependent upon the ageing time. All amalgams were strongly toxic at the 5-min and 1-h periods. By the 7-day period the high-copper two component amalgam showed a moderate reaction, the other two amalgams no or uncertain reactions. The composite materials did not show a dependency of the toxicity upon the ageing time as did the amalgams. They evoked a slight to moderate tissue reaction. The results obtained in this study are in accordance with clinical experience. We regard the rabbit muscle implantation test as a suitable method for screening the chemically initiated toxicity of solid materials.