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PATHOLOGY: BROWN AND PEARCE 
ON THE PATHOLOGICAL ACTION OF ARSENICALS UPON 
THE ADRENALS 
By Wade H. Brown and Louise Pearce 
ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH. NEW YORK 
Presented to the Academy, July 3, 1 9 1 5 
The fact that arsenicals of diverse chemical constitution exert a 
pronounced pathological action upon the adrenals has not been gener- 
ally recognized. The importance of this adrenotropic action was first 
impressed upon us while carrying out the routine biological tests of com- 
pounds of arsenic in our chemo therapeutic studies. Observations on 
more than sixty compounds including such substances as arsenious acid, 
arsenic acid, sodium cacodylate, atoxyl, arsacetin, arsenophenylglycine, 
salvarsan, and neosalvarsan have shown that, without exception, toxic 
doses of all of these arsenicals produce definite lesions of the adrenals. 
The adrenotropic action of all compounds of arsenic is not equally 
great or identical in character but the lesions produced by a given 
compound in a given animal species are quite constant and in some 
instances are the dominant pathological manifestations of the toxic 
action of the compounds. The essential features of this action concern 
vascular changes in the adrenal, alterations in the lipoid content, cellular 
degeneration, and the effect upon the chromaffin. 
In general, arsenical intoxication in the guinea pig produces an acute 
enlargement of the adrenals with some congestion and hemorrhage. 
The lipoid granules, normally demonstrable in the outer half of the cor- 
tex with Herxheimer's Scharlach R., first appear as larger droplets. 
Later, the demonstrable lipoids increase in amount and are spread over 
the entire adrenal cortex. This stage of lipoid increase is succeeded by 
one of diminution which with some compounds progresses almost to 
exhaustion. 
The cells of both the cortex and the medulla show a variety of de- 
generative changes and even necrosis; colloid degeneration of the medulla 
is particularly striking. While the cortex is sHghtly infiltrated with 
leucocytes the accumulation of both leucocytes and polyblasts in the 
medulla is especially marked with such substances as arsenophenyl- 
glycine. 
Regeneration of cortical cells by mitosis is very active after forty- 
eight hours and mitotic figures are occasionally seen in the cells of the 
medulla. 
The effect of arsenicals upon the chromaffin is of especial interest. 
Some compounds seem to exercise but slight influences upon the chro- 
