No abstract

Tumor necrosis factor, or cachectin (TNF-alpha), a protein with a wide range of biological activities, is produced mainly by macrophages and may be important in inflammatory processes. The role of TNF-alpha in the pathogenesis of cerebral malaria was investigated in a murine model. Most CBA mice infected with Plasmodium berghei anka die between days 6 and 14 with acute neurological manifestations unrelated to the level of parasitemia, whereas mice of some other strains have malaria of the same severity that ends in death after 3 to 4 weeks without neurological manifestations. The activity of serum TNF-alpha was considerably increased in CBA/Ca mice with cerebral malaria but not in Plasmodium berghei-infected mice that did not develop this complication. One injection of rabbit antibody to TNF-alpha on day 4 or 7 fully protected infected mice from cerebral malaria without modifying the parasitemia, whereas immunoglobulins from normal rabbit had no effect. In mice with cerebral malaria, the cerebral vessels showed focal accumulations of packed macrophages often containing infected erythrocytes; this lesion was not seen in mice treated with antibody to TNF-alpha or in untreated mice without cerebral malaria. These findings indicate that TNF-alpha has an important role in the pathogenesis of cerebral malaria in this murine model and suggest that local accumulation and activation of macrophages may lead to the predominance of lesions in the central nervous system.

The heart has traditionally been considered a radio-resistant organ that would be unaffected by cardiac doses below about 30 Gray. During the last few years, however, evidence that radiation-related heart disease can occur following lower doses has emerged from several sources. These include studies of breast cancer patients, who received mean cardiac doses of 3–17 Gray when given radiotherapy following surgery, and studies of survivors of the atomic bombings of Japan who received doses of up to 4 Gray. At doses above 30 Gray, radiation-related heart disease may occur within a year or two of exposure and risk increases with higher radiotherapy dose, younger age at irradiation, and the presence of conventional risk factors. At lower doses the typical latent period is much longer and is often more than a decade. However, the nature and magnitude of the risk following lower doses is not well characterized, and it is not yet clear whether there is a threshold dose below which there is no risk. The evidence regarding radiation-related heart disease comes from several different disciplines. The present review brings together information from pathology, radiobiology, cardiology, radiation oncology and epidemiology. It summarises current knowledge, identifies gaps in that knowledge, and outlines some potential strategies for filling them. Further knowledge about the nature and magnitude of radiation-related heart disease would have immediate application in radiation oncology. It would also provide a basis for radiation protection policies for use in diagnostic radiology and occupational exposure.

This article presents a brief description of the effects of ionizing radiation in human tissues, as seen by the Pathologist. The lesions that occur in multiple organ/tissues will be discussed, dividing them into those that affect (a) the parenchyma or epithelia, (b) the stromal elements, and (c) the blood vessels. Since not all lesions fit into these patterns, the exceptions will be described as characteristic organ lesions. Unless specified otherwise the alterations presented are those that result from electromagnetic radiation (x-rays and gamma rays) as used for clinical radiation therapy. Most of the material presented will be delayed injury (i.e. months-to-years after exposure). The epithelial/parenchymal lesions include atrophy, necrosis, metaplasia, cellular atypia, dysplasia, and neoplasia. The common stromal lesions--the best recognized by pathologists--include fibrosis, fibrinous exudates, necrosis (with a paucity of cellular inflammatory exudates), and atypical fibroblasts. The vascular lesions are quite consistent: most often they affect the microvessels (capillaries, sinusoids) producing lethal and sublethal damage to the endothelial cells, with capillary rupture or thrombosis. Medium-size vessels show neointimal proliferation, fibrinoid necrosis, thrombosis, or acute arteritis. Damage in large vessels is less common; it occurs more in arteries than in veins and includes neointimal proliferation, atheromatosis, thrombosis and rupture (a dramatic complication). Some of the characteristic organ lesions are veno-occlusive liver disease, acute radiation pneumonitis, permanent bone marrow hypoplasia or aplasia, and colitis cystica profunda. Neoplasms are a well-recognized delayed complication of radiation and will not be described in detail. It is important to remember that there are no pathognomonic features of injuries produced by ionizing radiation. Nonetheless, although not specific individually, the combined features are characteristic enough to be recognized.