tion appears as a terminal or agonal event in various diseases not necessarily involving the myocardium primarily.] The transverse striations may be absent over large areas, while the nuclei also show changes. (Plate 4, Fig. I.) Here and there the nuclei are found increased in numbers, so that in a single muscle-cell several nuclei occur in rows; or they are found enlarged, ballooned, with a loose chromatin network. Through disintegration of the cells part of these nuclei become free. The most striking changes, however, are observed in the intermuscular connective tissue. The fixed connective-tissue cells proliferate and produce fibroblasts-large spindle-shaped or round, plasmatic cells with vesicular nuclei. These accumulate especially around the blood-vessels, forming numerous foci, while the surrounding muscle-tissue disintegrates more and more.

Gradually, these areas are transformed into íibrous scars, which remain after the inflammatory processes have subsided. In this manner various sized scars are developed without necessarily being preceded by infarction or necrosis of muscle-tissue, which, as it degenerates, is substituted by fibrous tissue. Myocardial scars, therefore, may develop in three ways: After infarction, after healing of an abscess, and as a termination of acute interstitial myocarditis (Plate 4, Fig. II); but their genesis is not yet exhausted, inasmuch as focal disappearance of musclesubstance, accompanied with chronic proliferative changes of the interstitial connective tissue, occurs in all cases of narrowing of the coronary arteries in endarteritis and arteriosclerosis-chronic fibrous myocarditis or arteriosclerotic myocarditis.

Infectious new growths, as syphilis and tuberculosis, are rare in the heart-muscle, but occasionally are observed. They do not present any special histologic peculiarities.

PLATE 4.

FIG. I.--Acute Interstitial Myocarditis. 300. The transverse striæ of the muscle-fibers are obliterated in places, their nuclei increased and swollen, and partly rounded in shape.

Between the muscle-fibers are seen (1) small round cells, lymphocytes and leukocytes, (2) also young connective-tissue cells (fibroblasts).

FIG. II. Chronic Fibrous Myocarditis. 80. 1, Heart musculature; 2, long connective-tissue fibers between the muscle-bundles, containing but very few nuclei and blood-vessels.

upon

Endocardium.

Inflammation of the endocardium is usually localized the valves of the heart, and especially upon those of the left side, because their exposed position and peculiarity of function render them liable to the primary and most intense action of the infectious agents. It has, therefore, become customary to apply the term endocarditis to an inflammation of the valves of the heart, while the much rarer inflammation of the mural endocardium is generally designated as mural endocarditis. According to the views now current, all forms of acute valvular endocarditis are considered as infectious diseases that is to say, as due to the action of micro-organisms-while the slow, chronic, and sclerotic forms are due to atheromatous and arteriosclerotic changes in the intima of the larger vessels that spread to the valves, especially to the aortic valve and the aortic curtain of the mitral valve.

It is customary to distinguish two varieties of acute endocarditis-the verrucose or rheumatic (sometimes designated as benign) and the ulcerative or diphtheric (also malignant) form. This classification may be retained, provided gradual and quantitative, and not essential and qualitative, differences are thereby understood. Quite frequently, wart-like vegetations and ulcerative changes

occur at the same time; they either develop simultaneously, or ulceration is established in a valve the seat of warty outgrowths. Both forms occur primarily as the result of minute lesions of the endocardium, which, in turn, are due to the action of micro-organisms. The organisms either accumulate directly on the valves from the blood, or act on the endothelial lining by their toxins, causing minute necrosis on the basis of which other inflammatory changes develop.

In all cases of endocarditis two groups of processes occur namely, inflammatory and thrombotic; at first distinct, they later cooperate in producing the so-called endocardial vegetations or efflorescences. The inflammatory process runs its course in the substance of the valve, and the thrombi are deposited from the blood upon the diseased valve.

Verrucose endocarditis is characterized by the formation upon the valves, at their lines of closure, of either single or rows of wart-like excrescences, which later in their course usually become organized—that is to say, are transformed into connective tissue. (Plate 5, Fig. II; Plate 6, Fig. I.) At first there are small defects of the endothelium, followed by proliferation and hyperplasia of the fixed cells of the underlying connective tissue of the valve. From the latter develop strings and groups of spindle-shaped, polygonal, and round cells,-so-called fibroblasts, among which lie single small round cells. Occasionally, micro-organisms accumulate upon the surface of these cellular nodules, either singly or in small masses. At the border of the proliferating zone are seen, embedded in the normal connective tissue, single, large, star-shaped, richly protoplasmic cells with oval and vesicular nuclei, evidently formed by mitosis from small, spindle-shaped, connective-tissue cells. Before long there is deposited upon the surface of these cellular nodules constituents of the blood, because of the endothe