remain stationary. They may break down, forming ulcerations which do not readily heal, or they may be gradually converted into fibrous cicatricial tissue, causing unsightly deformities of the skin. The appearance of the patient's face is highly characteristic, and is known as leontiasis leprosa (Fig. 95). The mucous mem

branes and some of the internal organs may be involved. The anesthetic form is usually marked by less conspicuous lesions, but subjective symptoms, such as hyperesthesia and neuralgic pains, and later ulcerations partly tr phic in nature, may make it a more serious variety. In the skin there are found whitish or brownish spots, slightly if at all elevated or altered in consistency. Later, ulcerations may appear. Very commonly the anesthetic and tubercular varieties are coexistent.

The nodules occurring in the liver, spleen, and testes in this disease are admitted to be similar to the nodules of the skin; those found in the lungs, kidneys, and intestines, as well as those of the serous surfaces, are believed by many to be tuberculous and

the result of secondary infection. These two diseases are certainly frequently associated; probably 40 per cent. of the cases of lepra become tuberculous.

Other forms of secondary infection occur, thus injuries of superficial lesions may allow pyogenic infection, and extensive ulcerations and gangrenous necrosis may ensue. The terms lepra mutilans and lepra gangrænosa are applied to such; and various micrococci and saprophytic organisms have been discovered in such cases.

Structure of the Leprous Lesions.-The nodule or leproma is a somewhat indurated growth resembling the tubercle, but differing from it in its greater vascularity and in the absence of the tendency to cheesy necrosis. Microscopically it is composed very largely of proliferated connective-tissue cells of different forms, and leukocytes. New blood-vessels are discovered in more or less abundance, and a tendency to complete organization with the formation of fibrous tissue may be seen in the character of the cells and the presence of fibrous intercellular material. The bacilli occur within the cells and possibly also between them. They are always found in groups and usually in large numbers. They multiply within the cells, the protoplasm of the latter at the same time undergoing a process of swelling and degeneration. This at first spares the nucleus, but finally the nucleus itself is broken down and the cell is thus converted into a sac containing degenerated protoplasm and abundant bacilli (Fig. 96). The

term lepra-cell has been given to these. Giant-cells may be formed, though they are not frequent and are rarely typical. Secondary infections or injuries may lead to suppurative or other forms of softening, and the final termination either with. or without previous softening may be cicatrization. The lesions of the internal organs met with in some leprous cases, notably those of the lungs, intestine, kidney, and serous surfaces, are avascular, show more tendency to necrosis, and contain more giant-cells; in some cases inoeulation has showed that the lesions contained tubercle-bacilli. Whether they are strictly tubercles, or whether they are lepromata with secondary infection with tubercle-bacilli, cannot be decided. They are certainly not pure leprosy, and more probably are purely tuberculous.

The anesthetic areas and pigmented or light-colored spots of the anesthetic form present somewhat the same histologic features as the leprous nodule, though in a diffuse form. Formerly these lesions were considered entirely the result of trophic changes.

In these cases the more conspicuous lesion is that of the nerves. These may show nodular thickening of the perineurium with inflammatory and degenerative changes of the nerve itself. The bacilli are present in these lesions. Changes in the spinal cord have occasionally been discovered.

Pathologic Physiology.-Infection with the lepra-bacillus leads to local rather than general disturbances. The toxins of the disease, if such there be, are not of great virulence, and constitutional symptoms are therefore wanting as a rule. In the later stages fever and other systemic disorders may be occasioned by secondary infections. A supposed antitoxic substance has been prepared and has been largely used. It is impossible to claim or disclaim the antitoxic nature of this, as no toxins have as yet been isolated or obtained in any form, and the supposed antitoxic substances cannot therefore be tested.

In the anesthetic form it was formerly customary to regard the pigment or light-colored spots as a result of trophic disturbance, and more destructive lesions, such as ulceration and gangrene, received a similar explanation. Recent investigations, however, seem to show that in these cases there is usually from the first a leprous change in the tissues, and that secondary infections frequently play a part, though trophic disturbances must still be admitted to a certain extent.

GLANDERS.

Definition.-Glanders is an infectious and contagious disease of horses and asses, sometimes communicated to other animals and to man, and caused by a specific bacillus.

Etiology.-The Bacillus mallei was discovered by Löffler and Schütz. It is an organism resembling the tubercle-bacillus, though somewhat shorter and thicker. It occurs in the lesions of the disease singly or in clumps, and has been found in the blood. The bacillus is non-motile and does not possess flagella. Stained specimens show parts that do not receive the stain. These have been regarded as spores, but are more generally thought to be areas of degeneration. Ordinary solutions of anilin dyes, and especially alkaline solutions, stain the organism very well. The demonstration of the bacillus in the tissues requires prolonged staining and rapid decolorization.

Cultivation.-Cultures are best obtained from softened nodules of guinea-pigs inoculated with infected pus, or from the testicles after injection of infective matter into the peritoneal cavity. The organism grows quite readily upon ordinary media, but the most characteristic culture is seen upon boiled potato. The colony first appears as a honey-like layer, which becomes brownish in

color. The potato itself becomes greenish-brown beneath and around the colony. The cultivation is most successful between 30° and 40° C. (86° and 104° F.).

Drying and elevated temperatures rapidly destroy the organism, and antiseptics kill it quite readily. The bacillus is a pure parasite, multiplying only in the body of infected animals or

man.

Pathogenicity. The specific character of the bacillus is unquestionable. Inoculation of guinea-pigs, rabbits, field-mice, or other animals with infected pus or with pure cultures leads to nodular lesions at the point of introduction, with subsequent softening and ulceration. After death nodules are found in the liver, spleen, kidneys, or other organs, and these contain the bacilli. In horses and asses characteristic lesions of the mucous membranes have been produced experimentally; while in man accidental infection of hostlers or others coming in contact with diseased animals, and of bacteriologists working with cultures, has been repeatedly observed. In one case in my own knowledge a man was infected in a stable in which a glandered horse was kept, and the bacteriologist who isolated the organisms from the patient accidentally infected himself with the cultures.

Pathologic Anatomy.-In horses glanders presents characteristic lesions of the mucosa of the nose. At first there are found slightly elevated nodules, which have a marked tendency to soften, forming irregular ulcerations that become confluent. The floor and edges of the ulcers are yellowish and necrotic in appearance, and discharge more or less purulent matter. The lymphatic glands of the neck and elsewhere enlarge and may suppurate. In the skin the lesions are much the same, but more sluggish. Nodules are not rarely met with in the lungs. These are grayish or pinkish in color, and tend to rapid necrosis. More rarely nodules or ulcers are found in the mucosa of the gastro-intestinal tract.

In man similar nodules and ulcerations may be found in the nose, larynx, or trachea; and external lesions resembling small or large carbuncles are found.

Histologically the lesions of glanders consist of aggregations of round cells of lymphoid or polymorphonuclear type. There is a marked tendency to suppurative or necrotic softening, and sometimes hemorrhagic infiltration may be pronounced.

Pathologic Physiology.-A toxic substance called mallein (a bacterial protein) has been obtained from cultures of the bacilli. Injected into infected animals this acts somewhat as does tuberculin in tuberculosis. A special toxin is probably active in the production of the general symptoms of the disease. By repeated dosage with mallein it is claimed that immunity may be conferred.

MALIGNANT EDEMA.

Definition.-Malignant edema is a form of intense infective inflammation and necrosis observed in certain animals and in man, and is due to a specific micro-organism. The condition has frequently been described by clinicians as gaseous gangrene, traumatic gangrene, gangrene foudroyante, etc. Infectious emphysema (q. v.) has doubtless often been mistaken for this disease.

Etiology. The micro-organism of malignant edema was described by Pasteur and named the Vibrion septique. Koch showed that it does not flourish in the blood, and that the name given by Pasteur is therefore not appropriate. He therefore named it Bacillus ædematis maligni. This organism is widely distributed. It is very commonly present in the soil, particularly in garden-earth, and is often found in dust and in the intestinal contents of animals. Introduced into the subcutaneous tissue of animals it multiplies greatly and sets up a violent local process. The bacilli are readily obtained from the diseased area, and may be stained with the ordinary anilin dyes, but not by Gram's method. The bacillus resembles the anthrax-bacillus very closely, but is somewhat more slender. It is prone to occur in long chains, the organisins being apparently in contact end to end. Movement of the organisms is frequently observed, and lateral flagella are found by appropriate stains. In the spore-formation the center of the organism swells and the spore is developed within.

Cultivation. The cultivation of this organism is generally easy. White mice or other susceptible animals are first infected by introducing powdered garden-earth into a subcutaneous sac. Direct infection of the open wound will not succeed, as the organism is strictly anaerobic.

From the pus in the subcutaneous tissues growths may be obtained upon the surface of gelatin in an atmosphere of hydrogen, or in puncture-cultures in gelatin from which oxygen has been excluded. On the surface of the gelatin are formed small grayish-white bodies, which increase in size with advancing age. Portions removed from these and stained show masses of bacilli in the form of long filaments. In the gelatin (Fränkel and gelatin-tube there are formed whitish spherical

Pfeiffer).

colonies of a somewhat cloudy appearance. These consist of a turbid liquid, the gelatin undergoing liquefaction. There is also some gas-production, the gas formed having a peculiar and unpleasant odor. This is marked when the medium contains glucose (Fig. 97).