traces of movement. The lymphoid cells were most numerous in the first five or six observations, before the spleen had become markedly enlarged; after this had occurred the somewhat larger ordinary corpuscles were found to be most plentiful. No intermediate forms between coloured and colourless corpuscles were found. One point of some interest is, that coagulation took place much more rapidly in the later than in the earlier specimens, the field becoming very quickly covered with threads of fibrin which started from, or, at any rate, were connected with, the colourless corpuscles. It will be seen on reference to the table that only a very small proportion of the corpuscles exhibited even the sluggish movements which I have described, the highest number being a little over 24 per cent. (Obs. 2), and the lowest under 4 per cent. (Obs. 8). Further, that with the progress of the disease during the time the patient was under observation there was a very distinct diminution in the proportion of amoeboid corpuscles, the mean of the first six observations being about 12 per cent., while that of the last six is not more than 6 per cent. Although there is thus an unmistakable decline in the total number for the whole period, it will be seen that the numbers in successive observations often do not show a regular downward course; there is sometimes a decrease, but at others an increase in the percentage (compare Obs. 1, 2, and 3, and also 5, 6, 7, 8, and 9). I am not able to associate this fluctuation with any obvious change in the patient's condition, and suppose that it is merely an expression of the unexplained temporary improvements and deteriorations which occur so frequently in this disease. It is a question of some interest whether the loss of amoeboid movement takes place at the earliest onset of leuchæmia; on this point I cannot speak with certainty, as my first observation was made when the disease was already well marked, and had existed for at least six weeks, according to the patient's statement of the time at which he began to feel out of health; but I think we are justified in assuming a longer duration than this would give us, as hæmorrhages, which are among the later occurrences of leuchæmia, had already taken place before admission; further observations are necessary, therefore, to determine this point. It is, however, very probable, in my opinion, that loss of contractility in a large proportion of the colourless corpuscles will be found among the earliest phenomena. Whether, and how far, amoeboid movements are affected in various other diseases, is a not unimportant question which remains to be solved by future observations, and will, I think, repay investigation. I may here state that, for purposes of comparison, I examined the blood in two cases of chloro-anæmia, and one of anæmia from cancer of the stomach. The colourless corpuscles in these three cases were all amoeboid at ordinary temperatures. The earliest observations on the point I have brought before the Society were, so far as I have been able to find, made by Dr. Laking in 1873, at St. George's Hospital, with very similar results. They were not published, however, and, unfortunately, no record of them has been preserved. In 1878 the absence of amoeboid movement was communicated to the Pathological Society on April 16th, during the discussion on leuchæmia, by Dr. Pye-Smith, to whom I had mentioned it, and was again shortly described by myself in a letter to the Lancet,' dated April 27th. It was, however, stated at the same discussion by Dr. Moxon, that Mr. Golding-Bird had found the leucocytes in leuchæmic blood to have active 4 1 Since this paper was read, Dr. Bastian has pointed out that he has long been familiar with "the sluggishness of the white blood-corpuscles in this disease," and has informed me that the fact has been known to him since the latter part of 1868. Priority of observation on this point, therefore, belongs to him. (See 'Brit. Med. Journ.,' Nov. 27, 1880, p. 845, and ditto, Dec. 4, 1880, p. 881.) 2 See report in 'Lancet,' vol. i, 1878, p. 607. 3 Loc. cit., p. 662. 4 Loc. cit. p. 607. ex amoeboid movements. The next observation with which I am acquainted was published in 1878 by E. Neumann,' and is of considerable interest. He examined the blood of a leuchæmic patient, and found it to contain chiefly small lymphoid cells, with a certain proportion of ordinary colourless corpuscles. No detailed account of his observations is given, but he states that the former showed no amoeboid movement, and that the latter were tremely sluggish, even at high temperatures. examined the pus-cells obtained by blistering from the same individual, and found them all amoeboid at ordinary temperatures, and very active on the hot stage. He conIcludes that the cells found in the blister-fluid cannot have migrated from the blood, but must have had some other origin, such as proliferation of connective-tissue corpuscles. The observations I have brought forward warrant, I believe, the following conclusions: I. The great majority of the colourless corpuscles in leuchæmia are dead or dying, and hence obviously incapable of further development. II. As amoeboid movement is practically lost, emigration from the blood-vessels is rendered impossible. III. Coagulation, and hence the formation of capillary and other thrombi, is largely favoured. The characteristic accumulations of lymphoid cells and colourless corpuscles which are found after death from leuchæmia in various organs and tissues, are attributed by Mosler and Rindfleisch, partly to extravasation by hæmorrhage, but they consider that a true emigration of colourless corpuscles, in the sense of Cohnheim, has a large share in their production. Further, Mosler accepts the doctrine of lymphatic new growth as accounting for a "Farblose Blut- und Eiterzellen," Berlin. Klin. Wochenschrift,' 1878, p. 607. 2 Art. "Leukämie," Ziemssen's Handbuch d. Speciellen Pathol. u. Therapie,' Bd. viii, 2te Hälfte, 1875, pp. 155–162. Handbuch d. Pathol. Gewebelehre,' ed. 4, 1875, p. 153. portion, at least, of the secondary infiltrations, but this view is considered incorrect by Rindfleisch. Now, as the power of amoeboid movement, on which emigration depends, is nearly lost, we must reject this process as capable of explaining the presence of more than an extremely minute proportion of colourless corpuscles or lymphoid cells outside the blood-vessels. The vast majority must have escaped by rupture, but it is, I think, probable that an accumulation of lymph-cells in perivascular and other lymphatic channels has also much to do with their origin. It is a warrantable supposition that many of the cells shed directly into the lymphatic system have remained there without ever penetrating as far as the blood-vessels. In support of this view I may adduce the important part played by the colourless corpuscles in coagulation, and the production of the fibrin factors.1 The researches of A. Schmidt and later observers render it extremely probable that the components of fibrin, especially the fibrin-ferment, are contained in the colourless corpuscles, from which they are discharged on their death and disintegration; if, then, the vast majority of these corpuscles in leuchæmia are dead or dying, the fibrin generators must be liberated in large quantity and thus give rise to the formation of clots, coagulation being doubtless favoured by textural changes in the vessels and tissues due to mal-nutrition. In this way thrombi will be formed, not only in blood-vessels, but also in lymphatics, and an effectual obstacle opposed to further circulation through the plugged vessels. In the case of the lymphatics it is theoretically probable that many corpuscles would thus be prevented from entering the blood. So far as the blood-vessels are concerned, the investigations of Cohnheim 2 have shown what an important part is played by embolism and thrombosis in the production of extravasations. I believe that the majority of secondary leuchæmic nodules is to be explained by these two See, On Coagulation, Foster, Text-book of Physiology,' ed. 3, pp. 1216; Landois, Lehrbuch d. Physiologie,' pp. 49-57. * 'Untersuchungen über die Embolischen Processe,' 1872. 40 AMEBOID MOVEMENTS OF BLOOD-CORPUSCLES IN LEUCHÆMIA. processes, extravasation and lymphatic accumulation, and that emigration has only a very minute share in their production. With regard to lymphatic new growth we must be sure that the so-called "stroma" to be seen in pencilled or washed sections is a true adenoid reticulum, and not simply composed of a network of threads of fibrin,1 a point which requires further histological investigation. If In conclusion, I may point out that the absence of amoeboid movement has a bearing on diagnosis as well as pathology. It is known that cases of early leuchæmia often present great difficulties, which cannot be at once settled by a simple examination of the blood. The colourless corpuscles may be found largely increased, and still it may not be by any means easy to decide whether we have to do with leuchæmia, or with simple leucocytosis, especially as cases occur in which a splenic tumour, arising from causes other than leuchæmia, is accompanied by a temporary increase in the colourless corpuscles. the absence of amoeboid movement be, as I believe, an essential character of true leuchæmia, it is plain that attention to this point may prove of great value in doubtful cases. I have already referred to a case of cancer of the stomach in which I examined the blood; there was in this instance a very large increase in the colourless corpuscles, but they were all actively amoeboid, even at ordinary temperatures. I mention this only as an illustration of the fact that leucocytosis may occur without loss of amoeboid movement; and although it is perhaps too early to draw a final conclusion, I think we may reasonably expect that its presence, or absence, will prove of primary importance when we are called upon to distinguish between leuchæmia and increase of colourless corpuscles from other causes. 3 1 Greenfield, Path. Trans.,' vol. xxix, 1878, p, 303. 2 Mosler, Pathol. u. Therapie d. Leukämie,' 1872, pp. 204, 222, 224. 3 Communicated to the Clinical Society by Dr. Whipham, on May 28th, 1880. |