Far more important for the elucidation of the function of the
bone-marrow are =clinical observations= on cases in which considerable
portions of the bone-marrow are replaced by tissue of another kind. We
may best divide the observations on this point into two groups: 1.
malignant tumours of the bone-marrow, 2. the so-called acute leukaemia.

There are unfortunately very few available observations as yet upon the
first group. Still rarer are the cases in which as is necessary the
whole bone-marrow has been subjected to an exhaustive examination, which
alone affords adequate evidence of the extent of the defect.

Amongst the changes of the bone-marrow arising from tumours one may
distinguish two groups, according to the nature of the condition of the
blood. The first type is exemplified by a case of Nothnagel published in
his work on lymphadenia ossium. Here during life the blood shewed, in
the main, the features of a simple severe anaemia; but in addition
isolated normoblasts, small marrow cells, and moderate leucocytosis. The
autopsy, at which the whole skeletal system was subjected systematically
to an exact examination, shewed a complete atrophy of the bone-marrow,
and replacement of the same by the tumour masses. In this case then the
condition of the blood _in vivo_ is satisfactorily explained by the
absence of function of bone-marrow. Nothnagel conjectured that the
formation of the scanty nucleated red blood corpuscles occurred
vicariously in the spleen, that of the leucocytes in the lymph glands.

In the second series to which the cases of Israel and Leyden, as well as
the recently published one of J. Epstein from Neusser's wards, belong,
the blood shews, besides the usual anaemic changes, other anomalies which
are peculiar partly to pernicious anaemia, partly to myelogenic
leukaemia. In Epstein's case of metastatic carcinoma of the bone-marrow,
there was found a considerable anaemia, with numerous nucleated red blood
corpuscles both of the normo- and megaloblastic type; their nuclei
presented the strangest shapes, due not merely to typical nuclear
division, but also to nuclear degeneration. The white blood corpuscles
were much increased, their proportion to the red was 1/25 to 1/40; the
increase concerned in the main the large mononuclear forms, which bore
for the most part neutrophil granulation, and were therefore to be
called myelocytes. In all the specimens, only two eosinophil cells were
found[18].

Th