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406 PATHOLOGY fleisch would regard as distinctively "scrofulous," the substance is opaque and yellowish-white ; there are many epithelial-likc cells, or cells with a considerable zone of protoplasm round the nucleus, and, mixed with these, giant -cells or cells with many nuclei, usually marginal. Except in the most acute cases of miliary tuberculosis, the new formation, whether in the shape of isolated nodules or continuous tracts of " infiltration," undergoes changes. Sometimes it becomes a fibrous substance, but by far the most common change is into a yellow cheesy matter. This degeneration is comparable to the gummutous change in syphilitic formations, but in tubercle the degenerate tissue is much less cohesive, more friable, drier, more apt to fall into a molecular detritus. The caseous change is the distinctive degeneration of tubercle, the more occasional fibrous and calcareous changes being either its associates or its mollifications. The reason of this change is the insufficient blood-supply of the new formation. Nothing so clearly accounts for the structural as well as the degenerative characters of tubercle as growth of tissue without adequate provision for admitting the blood into it. Dovine Bovine Tubercle. In the corresponding disease of the domesti- tubercle. cated bovines a very common disease of cows in town dairies the characters of the new formations are equally determined by the kind and degree of blood-supply. In this form of tubercle the nodules are, in the first instance, on the serous membranes of the thorax and abdomen ; they often attain a considerable size, and sometimes the size of quite large tumours ; the vascularity of their surface is very considerable, and it is around their periphery that they grow, as in the case of sarcomatous tumours ; but the- blood-vessels do not go all through the nodules, their central parts being either calcareous, or caseous, or reduced to a thick riiortar-like substance. The chief differences between this form of tubercle and the varieties ordinarily met with in man are that it is a more vascular structure, more like a sarcomatous or fibromatous tumour, with a power of growth from its surface (where the vessels are numerous), and some times attaining a great size, often suspended from the serous mem brane by a vascular stalk or pedicle, and, in the interior of organs such as the lung, surrounded by a translucent capsule of vascular tissue, or excavated into a smooth-walled cavity, the thick trans lucent capsule being all that remains of the original nodule. The origin of these peculiar multiple new formations in the domesticated bovines is a more likely subject of inquiry than the origin of human tubercle. The bovine disease is generally admitted to have its nodules referable to two distinct classes primary and secondary: the primary are the multiple nodular tumour -like growths of the serous membranes, and the secondary are the in fective descendants of these in the lymphatic glands, the lungs, the liver, spleen, kidneys, Fallopian tubes, bones, and joints. The secondary infectiveness of primary new growths is otherwise intel ligible, according to analogies, and the interest therefore centres in the conditions of origin of the primary, parent, or infecting growths on the serous membranes. They occur by far most fre quently in the cows of town dairies, that is to say, in animals closely confined for long periods, deprived of pure air and sunlight, forced in their feeding and milking, and altogether placed under such conditions of nutrition as commend themselves, not to an intelligent acquaintance with ruminant requirements, but to the -short-sighted maxims of profit and loss which govern the policy of the cowkeeper. The vicissitudes of nutrition are pretty clearly indicated as the starting-point of tubercle in the cow. In human tubercle we have no such indications of a division into primary new formations arising out of errors or vicissitudes of nutrition in some tissue, and into secondary new formations due to the infectiveness of the primary. On the other hand, the various new formations in a case of tubercle in man would appear to be co-ordinate, or all of them due to a common cause. Human tubercle is not by any means a multiple nodular eruption on the serous membranes first and in the lymphatic glands and lungs afterwards ; if the disease occur in these three localities it is necessary to assume the same infective cause for it in them all. Most usually the first indications of human tubercle are at the apex of one or both lungs, and, in a considerable proportion of cases, the disease never goes beyond the lungs. But it is not on that account a purely pul monary disease. For some reason the lungs are most apt to become the seat of the. infection ; but there are many cases in which the infection locates itself elsewhere as well, and there are some cases in which it avoids the lungs altogether. An infective virus has to be assumed, and yet we are unable, as in bovine tubercle, to dis cover any primary source of it in the physiological aberrations of the human body itself. The problem of human tubercle, therefore, may be said to be : Does the infection reach the body from with out ? and, if so, whence are its structural or morphologically mimetic characters originally derived ? While some such question as that has to be stated for human tubercle in the last resort, it has to be kept in mind that a very la.-ge part of the sum-total of human tuberculous disease is an affair of strong hereditary predisposition, and even of direct inheritance. In bovine tubercle itself, which is often acquired de now by cows subjected to grossly artificial con ditions of life, inheritance is credibly estimated to be answerablo for more than one-half of its present very considerable total. The pathology of tubercle (bovine and other) has had much light thrown on it by experiments to jjroducc it artificially in animals by inoculation of minute quantities of tuberculous matter under the skin, or by mixing considerable quantities of tuberculous matter with the food for a length of time, or by feeding with the milk of tuberculous cows. A very suggestive proportion of all such experiments have succeeded. It has been boldly alleged by Koch that the active agent in the inoculative production of tubercle is not the tuberculous matter from a previous case, but a minute rod -like living parasite belonging to the order of schizo- mycetes (see SCHIZOMYCETE.S). According to this view tubercle is from first to last an affair of a parasite, equally the human tubercle and the bovine, although these two forms of tubercular disease are widely different in their anatomy. The weak point in the experimental evidence of Koch is that we are not sufficiently assured of the absolute separation of the tuberculous matter from the parasites. There is not reason enough to suppose, from the pub lished details of these experiments, that the original tuberculous matter had all been got rid of ; and there is therefore not reason enough to suppose that the induced tuberculous infection is due to anything but that matter itself, whose infective power, although not initiated by the organisms present, would probably be multi plied by their cultivation. In the same class with syphilis and tubercle should be taken Othe glanders, primarily a disease of the horse, but now and then com- eliroi nmnicated to man. There are various tropical and sub-tropical infec granulomatous infections of great scientific interest which can only tions be mentioned, such as yaics, vcrmga Pcruviana, Ahppo boil, Delhi boil. There is also the button- scurvy of Ireland, now probably extinct. Lupus holds a peculiar place in this class of diseases. The position of leprosy also is an intermediate one, and its patho logy the most difficult of all the constitutional endemic infective diseases. It was with reference to leprosy, and with particular reference to its enormous mediaeval prevalence and subsequent extinction in most parts of Europe, that Sir James Y. Simpson Sim] wrote as follows in 1841 ("Antiquarian Notices of Leprosy and on tl. Leper Hospitals in Scotland and England," Edin. Med. and Sury. origi Journ., vol. Ivi.) : " The gencratio do novo of a really new species of ilise; disease, says Dr Mason Good (Study of Med., i. pref. p. xxiii. ), is sped perhaps as much a phenomenon as a really new species of plant or of animal. Dr Good s remark is probably too sweeping in its princi ple ; for, if necessary, it might be easy to show that, if the particular diseases of particular animal species are liable to alteration at all, they must necessarily alter more frequently than those animal species themselves. In pursuing such an inquiry the pathologist labours under comparative disadvantages. The physiologist can, by the aid of geological research, prove that the individual species of plants and animals inhabiting this and other regions of the earth have again and again been changed. The pathologist has no such demonstra tive data to show that, in the course of time, the forms and species of morbid action have undergone great mutations, like the forms and species of normal life. But still we have strong grounds for believing that, in regard to our own individual species alone, the diseases to which mankind are subject have already undergone, in some respects, marked changes within the historic era of medicine." 1 17. Toxic DISEASES. In various parts of the world and at various periods there have been widespread outbreaks of sickness due to 1 See Hirsch, Handbuch der historisch-geographischen Pathologic, vols. i. and ii., 2d ed., Berlin, 1881-83 (Engl. transl., vol. i., New Sycl. Soc., Lond., 1883) ; Haser, Lehrbuch der Geschichte der Medici n und der epidcmischen Krankheiten, vol. iii. , 3d ed. , Jena, 1882; Robert Williams, On Morbid Poisons, 2 vols., Lond., 1836-41 ; Mur- chison, The Continued Fevers of Great Britain, 2d ed. , Lond., 1873 ; G. Gregory, Lectures mi the Eruptive Fevers, Lond., 1843 ; Christison on "Fevers" and "Continued Fever," in Tweedie s Library of Medi cine, vol. i., Lond., 1840; La Roche, Yellow Fever, 2 vols., Phila delphia, 1855 ; Audouard, Recueilde Mtmoires sur le Typhus nautique, ou Fievre jaune, Paris, 1825; John Simon, "On Filth Diseases," Report of the Med. Officer of the Privy Council for 1874 ; J. Hutchin- son, Clinical Memoirs . . . on inherited Sy2>hilis, &c., Lond., 1S6-5, and "Constitutional Syphilis," in Reynolds s System of Medicine, vol. i. , 1866; Virchow, Ueber die Natur der constitutioncU-syphilitisclioi A/ectionen, Berlin, 1859, and in his Krankhaftcn Geschwiilste, vol. ii. , chapter on "Gramiloma" ; Klebs, " Ueber die Entstehung der Tuber- culose und ihre Verbreitung ini Klirper," Virchovis Archiv, vol. xliv., 1868; Cohnheim, Die Tuberculosevom Standpunkte der Infectionslehre, Leipsic, 1880 ; Walley, Tlie Four Bovine Scourges, chapter on " Bovine Tuberculosis," Edin., 1879 ; Lydtin, "Die Perlsucht," in Archiv f Ar wissensch. und pract. TJuerheilkunde for 1884 (Engl. ed. by Fleming); R. Koch, " Die Aetiologie der Tuberculose," Berl. Klin. Vochenschrift, April 1882.