The megaloblastic degeneration of the bone-marrow is no doubt due to chemical influences, which alter the type of regeneration in a disadvantageous manner. We do not for the most part yet know the exciting causes of the toxic process; consequently we are unable to put a stop to it, and its termination is lethal. The Bothriocephalus anæmias, which in general as is well-known offer a good prognosis, by no means contradict this view. They hold their privileged position amongst the anæmias of the megaloblastic type, only for the reason that their cause is known to us, and can be removed. As in many infectious diseases, individuals react quite differently to the presence of the Bothriocephalus. Some remain well; others show the signs of simple anæmia, ultimately with normoblasts; whilst a third group presents the typical picture of pernicious anæmia. For many years, so long as its ætiology was unknown, Bothriocephalus anæmia was not separated on clinical grounds from pernicious anæmia. Severe Bothriocephalus anæmia may be described as a pernicious anæmia, with a known and removable cause. Good evidence for this point of view is afforded by a case of Askanazy, who describes a severe pernicious anæmia, with typical megaloblasts, in which after the complete expulsion of the Bothriocephalus, the megaloblastic character of the blood formation quickly vanished, was replaced by the normoblastic, and the patient rapidly recovered. This observation is so unequivocal, that it is a matter of surprise that Askanazy chooses to deduce from it, the ready transition from megaloblasts to normoblasts; whereas it is clear and definite evidence that megaloblasts are only produced under the influence of a specific intoxication. And in this way the presence of megaloblasts in the pernicious anæmias is to be explained. The megaloblastic degeneration of the bone-marrow depends on the presence of certain injurious influences, of which unfortunately we are as yet ignorant. Were it possible to remove them, it is quite certain à priori that the bone-marrow—if the disease were not too advanced—would resume its normal normoblastic type of regeneration. Clinical observation supports this contention in many cases. In megaloblastic anæmias apparent cures are by no means rare, but sooner or later a relapse occurs, and finally leads with certainty to a lethal issue. These cases, familiar to every observer, prove with certainty that the megaloblastic degeneration as such may pass away, and that in isolated cases the conventional treatment by arsenic suffices to bring about this result. A definite cure however under these conditions is not yet attained, since we do not know the ætiological agent, still less can we remove it. For this reason, the prognosis of megaloblastic anæmia, apart from the group of Bothriocephalus anæmia, is exceedingly bad.
FOOTNOTES:
[8] Dunin, on the contrary, designates the appearance of nucleated red blood corpuscles within the first 24 hours after the loss of blood as normal and regular. This view does not correspond with the facts. A single case on one occasion may exhibit a rarity of this kind.
[9] Probably the dot-like and granular enclosures in the red corpuscles, which stain with methylene blue, and which Askanzy and A. Lazarus have observed in numerous cases of pernicious anæmia are also products of a similar nuclear destruction.
[10] It does not seem superfluous in this place expressly to emphasise, that what has been said on the diagnostic importance of the megaloblasts only holds for the blood of adults. For the conditions of the blood in children, which vary in many respects from that of adults see "Die Anæmie," Ehrlich and Lazarus, Pt. II. (Anæmia pseudoleukæmica infantum).
THE WHITE BLOOD CORPUSCLES.
The physiological importance of the white blood corpuscles is so many sided that they form the most interesting chapter of the subject. That the white corpuscles play a significant part in the physiology and pathology of man has been recognised but slowly, obviously because there was at first some hesitancy in ascribing important functions to elements that are present in the blood in such relatively small numbers. A place in pathology was first assured to them by Virchow's discovery of leukæmia. The interest in the question was increased by Cohnheim's discovery that inflammation and suppuration are due to an emigration of the white blood corpuscles, and these conditions were particularly suitable for throwing light on normal processes. The fact that in diffuse inflammations, large quantities of pus are often produced in a short time, without the blood being thereby made poorer in leucocytes,—that the opposite indeed occurs,—necessitated the supposition that the source of the leucocytes must be extraordinarily productive. Hence in contradistinction to the red blood corpuscles, their small number is fully compensated by their exceptional power of regeneration.
Nevertheless, a considerable time elapsed before the powerful impulse that started from Cohnheim, bore fruit for clinical histology. As we have mentioned this was due to the circumstance that an exact differentiation of the various forms of leucocytes was very difficult with the methods in use up to that time. Although such distinguished observers as Wharton Jones and Max Schultze had been able to distinguish different types of leucocytes, Cohnheim's work remained clinically fruitless since the criteria they assigned were far too subtle for investigation at the bedside. Virchow indeed, the discoverer of leucocytosis, interpreted it as an increase of the lymphocytes; whereas it is chiefly produced by the polynuclear cells. Only after the distinction was facilitated by the dry preparation and the use of stains, did interest in the white corpuscles increase, and continue progressively to the present day. This is borne out by the exceptionally exhaustive hæmatological literature, and particularly by that of leucocytosis.