LESIONS WITH ACCELERATED PARTICLES 827 



published), investigation of human hypophyseal proton radiation was begun. 

 Today more than 100 patients have had pituitary radiation (Tobias et al., 

 1958; Born et al., 1960). Many cases of advanced metastatic mammaiy car- 

 cinoma and a few of prostate carcinoma, advanced diabetes mellitus, acro- 

 megaly, malignant exophthalmos, leukemia, and Cushing's disease were 

 treated, and it appears that the hypophyseal radiation is useful in producing 

 some regressions and in allowing studies of hormonal aspects of the abov^e 

 mentioned diseases. The radiation is so well concentrated in the pituitary 

 that only occasional mild secondary neurological effects are encountered. 



Several years ago it was also realized that accelerated particles made the 

 production of lesions in the brain possible, so that the Berkeley group has 

 initiated some studies on the hypothalamic radiation syndrome (Anderson 

 et al., 1957). It was found that for production of radiation lethality the 

 hypothalamic region is more sensitive than either the cerebral cortex or the 

 pituitaiy. The hypothalamic lethal syndrome is a symptom complex inte- 

 grated from failures of a number of homeostatic regulatory functions and 

 often results in abdominal or intestinal bleeding as a cause of death. It was 

 also shown that lesions in the region of the median eminence lead to diabetes 

 insipidus, glycosuria, thyroid abnormality, and delayed sexual development. 

 Roberts, Thorell, and associates (1957) demonstrated that a lesion in the 

 posterior hypothalamus, not identical with the "appetite center," leads to 

 decreased rate of growth and degeneration of eosinophilic cells in the 

 pituitary. An interesting use of the Bragg ionization peak of alpha particles 

 was made by von Sallmann et al. (1955) who selecti\ely irradiated the lens 

 of the rabbit eye and determined the relative effectiveness of alpha particles 

 and deuterons on lens epithelium for producing cataracts. 



In 1955 and 1956, the author and his colleague, Victor Burns, ^ had the 

 opportunity to collaborate with a team at the University of Uppsala, at a 

 time when their proton synchrocyclotron was adapted to tumor studies and 

 neurologic irradiations (Larsson et al., 1956). Larsson and his associates 

 developed a method for production of cutting "knife edge" lesions with a 

 narrow beam of 185 Me\' protons which were passed through a narrow slit 

 made of absorbing material. Knife edge lesions of the spinal cord were studied. 

 By the use of a 1.5 mm wide beam on a rabbit spinal cord, it w'as possible 

 to produce a sharply limited lesion with only minimal hemorrhages (Larsson 

 et al., 1958; 1959). Rexed et al. (1959) produced cutting lesions in the 

 upper anterior part of the rabbit brain with doses of 20,000 rad and found 

 destruction of myelin sheaths, axons, and nerve cells. The lesions in the first 

 3 months were confined to the region irradiated. Working with pigeons, 

 Fabricius and Larsson (1959) are in the process of studying the localization 



' Present address: Biophysics Department, Stanford University. 



