[Chemical substances in the environment: new inadequate legislation].
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Biomedical subjects
Publications and source records attributed to M Døssing.
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A 21-year old man died of an extensive anteroseptal myocardial infarction 16 months after receiving megavoltage radiotherapy to a mantle field for Hodgkin's disease stage PS IA confined to the midcervical lymph nodes on the left side of the neck. Post mortem findings revealed severe atherosclerotic changes in the coronary arteries. This case and a review of the literature suggest that irradiation to the heart may induce or accelerate atherosclerosis of the epicardial vessels. This should be taken into consideration when starting prophylactic irradiation to the mantle field in patients with Hodgkin's disease stage IA without obvious involvement of the mediastinun. Histologic examination of the heart and coronary vessels should be performed in any fatal case after megavoltage therapy involving the heart.
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Recent research indicates that physical exercise and fitness are new host factors with impact on hepatic drug metabolism, contributing to the intra- and interindividual variation in drug response. Moderate to heavy physical exercise for a few hours reduces liver blood flow as assessed by indocyanine green clearance, leading to a decreased elimination of drugs exhibiting flow-limited metabolism (high clearance drugs) such as lignocaine (lidocaine). However, hepatic elimination of drugs exhibiting capacity-limited metabolism (low clearance drugs) such as antipyrine (phenazone), diazepam and amylobarbitone (amobarbital) is not affected by acute physical exercise. Improved physical fitness as expressed by the maximum oxygen uptake seems to increase the elimination rate of the low clearance drug antipyrine and possibly also aminopyrine, while investigations of the biotransformation of high clearance drugs are contradictory. The sum of research in this recent field is rather limited and the mechanism whereby changes in physical fitness influence hepatic drug metabolism needs to be established. It is not known if other liver functions are changed. If the findings also apply for drugs with a low therapeutic index, there may be a risk of exercise-induced changes in drug efficacy and toxicity. It is suggested that future studies on host factors influencing drug metabolism should include information on physical activity.