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of Cytoryctes variole are found in the cells of the rete during these early 
stages of the lesion. 
From the third day of the disease onward the picture becomes more 
complicated. The degeneration of the epithelial cells is quite extensive 
and is evident for some distance from the line of inoculation. This 
degeneration is preceded by more or less swelling of the individual cells 
and some, though not wide spread, proliferation. The thickening of the 
epidermis about the inoculation is in the main due to the former process. 
Concomitant with the appearance of these phenomena we find fluid 
collected between the epithelial cells which finally leads to the formation 
of definite cavities, the vesicular space being partly contributed to by 
the solution of the swollen and degenerated epithelial cells. The poly- 
morphonuclear leucocytes pass into the fluid of this vesicle, and their 
increasing numbers finally give to the lesion the macroscopic character 
which we designate as a pustule. While this vesiculation has been in 
progress, the crust which originated in the inspissated exudate in the 
inoculation scratch increases in extent and in thickness. ‘The degenera- 
tion of the epithelial cells about the lesion is most marked where they 
form the floor of the vesicle, and becomes less and less as we pass to the 
peripheral portions of the lesion. Similar cell changes are found in 
the sheaths of the hair follicles close to the lesion. 
While the vesicle has been forming in the epidermis, a reaction in the 
corium has become manifest. The first change, besides the collection of 
-polymorphonuclear leucocytes in the vessels and their migration toward 
the vesicle, is enlargement and proliferation of the endothelial cells of 
the lymphatics and blood vessels. The connective-tissue cells in the 
corium undergo similar changes. Later in the disease a definite oedema 
of the corium and of the adjacent subcutaneous tissue is present, and an 
area of necrosis can be made out beneath the center of the lesion  As- 
sociated with this cedema and necrosis there is a large increase in the 
number of endothelial cells. These cells appear not only in and around 
the lymph vessels and capillaries but are found in the surrounding tissue ; 
they contain cytoplasmic phases of Cytoryctes variole both when in situ 
on the walls of capillaries and when free in the tissue. Mitoses in these 
cells are frequent and some are met with containing two nuclei. The 
phagocytic properties of these cells are shown by their including leucocytes 
and other cells. Lymphoid and plasma cells, together with a certain 
number of eosinophile leucocytes are found in the corium at this time. 
During the later stages of the lesion the process of repair dominates 
the picture. The epithelium grows in from the sides and up from the 
hair sheaths and finally closés the defect caused by the variolous process. 
In the corium the solution of the necrotic tissue and the new formation of 
blood vessels and connective tissue shows repair to be active. 
(b) The exanthem.—In the development of the exanthem, the process 
seen in the epithelium agrees with that found in the primary lesion. 
