anæmia; (5) occasional febrile disturbances; (6) the yellow tint of the skin; (7) hemorrhages, particularly retinal; (8) a progressive course and the inefficiency of treatment.

Treatment.-Iron in pernicious anæmia seems to be worthless. The main reliance must be placed on arsenic in full doses, given to the point of tolerance. Osler's plan is to give Fowler's solution in 3-minim doses after meals, increased to 5 minims at the end of the first week, to 10 minims at the end of the second week, and so on until the patient is taking 20 or 25 minims after each meal. Toxic symptoms are rare. Should they occur, the drug is to be discontinued until the poisoning symptoms cease, and is then to be resumed at the dose at which the patient left off. In some cases the addition of phosphorus seems to be beneficial. Iron may be given if arsenic disagrees, but not much is to be expected from it. Rest in bed from time to time is important in conserving the patient's strength. Prolonged residence in a warm inland climate has been recommended, but the climatic treatment is often disappointing. The diet should be light and nutritious. Massage is sometimes found to be beneficial.

Delafield describes a clinical set of cases midway between simple and pernicious anæmia, occurring in those past middle life. The etiology of these cases is obscure. The blood shows the changes only of secondary anæmia. The symptoms are those of a fairly marked anæmia, but improvement under treatment reaches only to a certain degree, and the patients relapse as soon as treatment is discontinued. Absolute recovery does not occur. In this class of cases arsenic seems to be of no use. Iron is the drug on which reliance is to be placed, but dietetic and hygienic treatment seems to be of almost equal service.

LEUCOCYTOSIS.

By the term "leucocytosis" is meant a temporary increase in the number of the white blood-corpuscles; this is a condition entirely distinct from the disease leukæmia. Normally the ratio of white to red corpuscles is 1 500, but in leucocytosis the proportion may be 1: 150 or even 1: 50.

Physiological leucocytosis occurs during pregnancy and after hearty eating.

Inflammatory leucocytosis occurs in acute infectious diseases attended with local inflammatory reaction. It appears most commonly with pneumonia, diphtheria, and suppurative processes, and it is said to be a sign of good prognostic value.

Cachectic leucocytosis occurs in the cachexias of malignant

tumors.

Relative leucocytosis occurs in anæmia, where, from diminution in the number of the red corpuscles, the white cells appear in an increased ratio, although they are not actually increased in number.

LEUKÆMIA (LEUCOCYTHÆMIA).

Etiology. The cause of the disease is obscure. There occur acute cases which suggest bacterial infection, but upon this point definite knowledge is lacking. In about one-third of the cases there is the history of malarial poisoning. Syphilis seems to possess some obscure relation to the disease. Leukæmia may occur at any age, but it is most common in middle life. Males are affected twice as frequently as females. In women the disease often appears at the time of the climacteric or after pregnancy.

Pathology. The essential lesions are found in the blood, the spleen, the lymphatic glands, and the bone-marrow. The blood-changes are constant. According to the relative

intensity of the changes in the other structures mentioned, splenic (or lienteric), lymphatic, and myelogenous forms have been described. As true myelogenous leukæmia is so very rare, the disease is usually described under two principal forms, (1) splenic-myelogenous or lieno-myelogenous, and (2) lymphatic leukæmia.

Blood-changes consist in the increased number of white cells, their proportion to the red corpuscles rising to 1: 20 or I 5, or the cells even being in equal proportions. The increased proportion is greater in the splenic-myelogenous form than in lymphatic leukæmia. The blood is pale and watery and may be whitish or brownish-red in color. The red cells are diminished, but not to an excessive degree; hæmoglobin is reduced to a somewhat greater proportion. Nucleated red cells may be seen. Charcot's octahedral crystals separate when blood-slides are kept for some time.

A more detailed account of the changes of the white cells is deemed advisable.

In the normal blood, Ehrlich describes the following varieties of white cells: 1. Lymphocytes, small, equal in size to a red corpuscle. The nucleus is large, round, stains deeply, and is surrounded by a narrow rim of non-granular protoplasm.

2. Large mononuclear leucocytes, several times larger than the red cells. The nucleus is oval or elliptical and is surrounded by a wide margin of nongranular protoplasm.

3. A transition form resembling the preceding, but the nucleus is indentated.

4. Polynuclear leucocytes, smaller than the large mononuclear forms, with long, twisted nuclei which stain deeply. The protoplasm is granular and does not stain easily. To these cells, owing to peculiarities of staining, the name "neutrophiles" is given.

5. Cells like the preceding, but the protoplasm contains coarse granules which stain deeply with eosin, hence the name "eosinophiles."

In normal blood these varieties of white cells bear a fixed proportion to each other-the lymphocytes, from 15 to 30 per cent., the polynuclear leucocytes, from 65 to 80 per cent., the mononuclear and transitional forms, 6 per cent., the eosinophiles, from 2 to 4 per cent. According to Osler, the charac

ter of the cells in splenic-myelogenous leukæmia differs materially from that in the lymphatic form.

In splenic-myelogenous leukæmia the lymphocytes are rarely, if at all, increased; the eosinophiles are present in normal or increased proportion, so that there is a great total increase. The polynuclear neutrophiles are usually relatively diminished. In this form there appears a new variety of cell, derived from the marrow of the bones, and known as the myelocyte. These cells are large and contain a single nucleus, but the protoplasm is finely granular and does not stain well with acid coloring matters, resembling in this regard the neutrophiles.

In lymphatic leukæmia the ratio of white to red corpuscles rarely exceeds I: IO. The increased number of colorless corpuscles is due to the lymphocytes, which may form 93 per cent. of the total number of white cells. Eosinophiles and red nucleated cells are rare, and myelocytes do not occur.

In mixed forms of leukæmia the blood-condition may deviate from either of these classical types.

The accurate study of stained blood-specimens is highly important for diagnostic purposes in obscure cases.

The spleen is usually much increased in size, weighing from two to eighteen and a half pounds. The enlargement is due to a true hypertrophy of all its constituents. In acute cases the spleen is soft and may even rupture. In protracted cases the organ becomes firmer and the capsule is often thickened and adherent to surrounding structures. On section hemorrhages may be found in its substance, and there may be seen grayish-white areas which consist of aggregations of lymphoid cells.

The lesions in the bone-marrow are usually associated with the splenic enlargement. A pure form of medullary or myelogenous leukæmia is exceedingly rare. The marrow, which is yellowish or even purulent in appearance, contains many lymphoid and nucleated red blood-cells.

The lymphatic glands may be involved alone (lymphatic leukæmia) or in connection with the splenic and medullary lesions. The histological change consists of hyperplasia of the glandular tissue. The glands are enlarged and soft, but are freely movable and do not mat together. In many cases

Blood stained with Ehrlich's "triple stain" of acid fuchsin, methyl-green, and orange-G; drawn with the camera lucida from normal blood (Osler, in American Text-Book of the Theory and Practice of Medicine): a, red corpuscles; b, lymphocytes; c, large mononuclear leucocytes; d, transitional forms; e, neutrophilic leucocytes with polymorphous nuclei (polynuclear neutrophiles); ƒ, eosinophilic leucocytes.