Part 17

The experiments of Villemin have not only demonstrated the infectious nature of tuberculosis, but have also led to a more accurate knowledge of the relation between tuberculosis and its allied affections, scrofula and pearly distemper.

The anatomical characteristics of scrofula have obviously proved insufficient in determining the relation presented by this affection to tuberculosis. The tendency to cheesy degeneration of its inflammatory {99} products was the feature of chief importance. Villemin showed that portions of a scrofulous (cheesy) gland when inoculated were followed by tuberculosis, and that the inoculation of cheesy material from non-tuberculous or non-scrofulous sources was not followed by this result. The assumption of Buhl, that the absorption of cheesy material, as such, was the cause of tuberculosis, was thus disproved. The frequency with which the inoculation of cheesy material, from what were regarded as scrofulous sources, was followed by tuberculosis, led to more exact studies concerning the anatomical peculiarities of scrofulous inflammation. Köster called attention to the regularity of the occurrence of miliary tubercles in the fungous granulations of the inflamed joints of scrofulous and tuberculous individuals. Wagner and Schüppel discovered that scrofulous glands, in most if not in all instances, were tuberculous glands. The regularity of the presence of tubercles in scrofulous abscesses and ulcers of the skin and in scrofulous caries was shown by Friedländer. This observer likewise called attention to the presence of agglomerated tubercles as the chief constituent of the new formation of lupus. These anatomical discoveries resulted in uniting more closely the affections scrofula and tuberculosis from the histological standpoint, and the union has become more firmly cemented from the etiological investigations.

Schüller has shown that the introduction of finely divided material from a scrofulous joint--that is, from one containing tubercles--into the lungs of rabbits was followed by a tuberculosis of the tracheal wound, the lungs, and liver. Similar experiments with reference to the introduction of lupus-tissue produced results suggestive of tubercle, if not actually tuberculous.

The intimacy of relation between tuberculosis and pearly distemper is a necessary result of Villemin's experiment, in which the rabbit became tuberculous after inoculation with fragments of the pearly tumor. Gerlach, and especially Schüppel, showed that the structure of the nodules of the pearly distemper is the same as that of the tubercles of man, and that the two diseases are identical from the histological point of view.

From the anatomical identification and the etiological connection, as shown by Villemin, Gerlach, and Aufrecht, the pearly distemper became designated as a bovine tuberculosis.

The experiments of Villemin were further productive in leading to the discovery by Koch of the bacillus tuberculosis. It was early obvious that certain cheesy material and gray tubercles possessed the infectious qualities, and Villemin maintained that the immediate cause of the latter was a germ introduced from without, which propagated and perpetuated itself in man and certain animals. This view acquired prominence through the investigations of Klebs, who in 1877 claimed to have isolated the micrococci which produced tubercles when injected into animals. Three years later Schüller confirmed the statements of Klebs, and asserted that he had been enabled to obtain infective micrococci by cultivation from {100} miliary tubercles, scrofulous glands and joints, and from the tissue of lupus. Aufrecht found micrococci, single and in chains, and short glistening rods, within tubercles resulting from inoculation with material from pearly tumors. The same organisms were found in tubercles produced by the inoculation of tubercles from man, and he regarded these rod-shaped bodies as the specific element productive of miliary tuberculosis.

The isolation of the virus of tubercle was thus regarded as an open question till the announcement by Koch of the constant presence of a hitherto unknown, characteristic, well defined organism in all tuberculous affections, which, when isolated and introduced into animals, produced tuberculosis, the resulting tubercles likewise containing the organism.

The latter, the bacillus tuberculosis, was to be seen in preparations methodically treated and carefully stained with aniline colors, by all of which, excepting the browns, the bacillus was tinged. It was found in miliary tubercles of the lung, cerebral and intestinal tubercle, cheesy bronchitis and pneumonia, phthisical sputa, scrofulous glands, and fungous inflammation of the joints. It was also seen in the nodules of pearly distemper and in the cheesy masses from the lungs of cattle. It was furthermore met with in the cheesy lymphatic glands of swine, in the tubercular nodules of a fowl, and in the tubercles of guinea-pigs, rabbits, and monkeys. The bacilli were likewise found in the tubercles resulting from the inoculation of animals with tubercular virus from its various sources.

The microphytes were described as very slender rods, varying in length from one-fourth the diameter of a red blood-corpuscle to its entire diameter, and spores were occasionally seen within the rods. In shape and size they resembled the bacilli of leprosy, but the latter were narrower and pointed at the ends. They were found in greatest abundance when the tuberculous process was recent and rapidly advancing, and were present within, as well as between, cells. The younger giant-cells contained them in larger numbers than the older forms. They were present at the periphery of cheesy nodules rather than at the centre.

The bacilli were cultivated through successive generations and required a temperature of between 30° C. and 41° C. (86° F.-105.8° F.) for their development, one of 37° C. or 38° C. (98.6° F. or 100.4° F.) being the most favorable. The crop first became apparent on the tenth day after sowing, and the growth extended through a period of three to four weeks, forming a compact scale. The cultivated bacilli, even propagated through several generations, when inoculated, produced the same positive results as follow the inoculation of fragments of tuberculous material, although animals might be used which are not easily infected with tuberculosis.

Koch's publication was immediately followed by a statement from Baumgarten of his discovery of rod-like bacteria in the tubercles of rabbits resulting from the inoculation with pearly masses, and in the pleural and pericardial tubercles of man. They were made evident by treating the sections for microscopic examination with very dilute solutions of soda or potash.

{101} The discoveries of Koch thus show that the production of tuberculosis is dependent upon the presence of distinctive bacilli, and that these bacilli are present not only in miliary tubercles, but in scrofulous glands and joints, in cheesy inflammation of the lungs, and in the pearly distemper of animals. The identification of tuberculosis with the pearly distemper and certain scrofulous affections is thus established from the etiological as well as the histological point of view.

As the bacilli are to be regarded as the virus of tuberculosis, so their introduction into the human body is necessary for the production of this disease in man. It is obvious, however, that other factors than the virus are necessary, for not every one exposed to the reception of tubercular bacilli becomes tuberculous. It may well be that scrofula is still to be regarded as that condition of the solids and liquids of the body which offers favorable opportunities for the retention and growth of the bacilli, and thus for the production of tuberculosis. Formad claims that he has discovered structural peculiarities of tissue as a cause for the scrofulous habit, which he regards as synonymous with a predisposition to tuberculosis. These peculiarities are manifested by a narrowness of the lymph-spaces and their partial obliteration by cellular elements. He also maintains that these features are not only of congenital origin, but may be acquired through malnutrition and confinement.

The occurrence of a local, circumscribed tuberculosis in extreme old age, without antecedent or other concurrent evidence of scrofulous disturbances, suggests that favorable opportunities for the development of the tubercular bacillus may arise in advancing years. In like manner, the frequent termination in phthisis of cases of diabetes suggests the likelihood of tuberculous inflammation arising in the absence of any evidence of previous scrofulous or tuberculous disease. The scrofulous condition or constitution, as indicated by vulnerable tissues, with a protracted course of inflammations, and a persistence of their products, with a tendency to cheesy degeneration, may still exist without a sign of tuberculosis. Those who claim that scrofula and tuberculosis are identical must, in the light of Koch's discovery, demonstrate the presence of the bacillus in all scrofulous inflammations, and deny the existence of scrofula apart from indisputable manifestations of the activity of the bacilli of tuberculosis. It may be that such evidence will be presented; until it is collected scrofula and tuberculosis are to be regarded as distinct though often coexistent. The scrofulous person is frequently tuberculous, the tuberculous person is usually scrofulous; the non-scrofulous person, however, may die of tuberculosis, while the individual may be scrofulous without containing tubercle.

The actual inheritance of tuberculosis is very unlikely, although this disease is frequently found in successive generations of a single family. The various members of the family are rather to be regarded as furnishing a suitable soil for the growth of the tubercular bacillus, and their exposure to its seed is favored by the existence of tuberculosis in one or more members of the household. The scrofulous condition is still to be regarded as hereditary as well as acquired, and the scrofulous remain as the class to be especially protected from the reception and effects of the bacilli of tuberculosis.

{102} It is obviously a matter of importance to determine in any given case of phthisis whether bacilli are present or absent. A ready means of ascertaining this fact is offered by the examination of the sputum in cases of pulmonary phthisis, the feces in intestinal phthisis, the urine in renal phthisis, and the aspirated pus in cases of supposed tuberculosis of the joints. Koch has found in examining the sputa from numerous cases of phthisis that the bacilli were present in one-half the number, and that they were absent from the sputa of individuals who were not phthisical. Balmer and Fraentzel have found bacilli in the sputum from one hundred and twenty cases of phthisis, and concluded that the progress of a case of pulmonary tuberculosis might be readily determined from the number and degree of development of the typical bacilli present in the sputum. The more numerous and well-developed bacilli, with distinct and constant spores, were found in the graver cases, which advanced more rapidly. The sputum of the protracted cases contained few, small, and thin bacilli with scanty spores. The presence of fever was associated with numerous bacilli, while its absence was noted in those cases where but few were present.

The bacilli are readily detected by means of the staining method devised by Koch. Various modifications have been presented from time to time, of which that of Ehrlich has proved the most satisfactory. The essential features are to obtain a dry, thin layer of a selected portion of the suspected sputum, which is then to be deeply stained with fuchsin or methyl-violet; the excess of color is to be removed with nitric acid, and the preparation is then ready for examination with the microscope. A power of four or five hundred diameters is sufficient for the recognition, and the object should be illuminated with a flood of light through a large diaphragm or an achromatic condenser. The bacillus retains the color notwithstanding its exposure to the acid, and the violet colors are more strongly presented if the preparation is tinted yellow after the action of the acid. If the bacilli are stained red with fuchsin, the background should be made blue. It is important that the reagents should be freshly prepared and filtered, that other bacteria may not obscure the picture, and that all the apparatus employed should be thoroughly clean.

A fragment of thick, opaque sputum is to be taken in forceps, placed on a cover-glass, and spread into a thin layer by means of a second cover-glass. The prepared slide is then to be passed slowly through an alcoholic flame, or that of a Bunsen burner, till the layer of sputum is dried. A saturated alcoholic solution of methyl-violet or fuchsin is made and filtered, and added, drop by drop, to a filtered, saturated solution of aniline oil shaken in water. The color is to be added with stirring till an opalescent film forms on the surface of the mixture. The slide containing the dried sputum is to be placed in or on this staining fluid, and allowed to remain for half an hour or less, the application of warmth hastening the process, when it is removed, and the specimen is decolorized in a solution of one part of nitric acid and two parts of water. The preparation is then washed in water, and may be examined directly in water, glycerin, or, after dehydration in alcohol, in oil of cloves. The tinted bacilli are made more prominent by a secondary staining, for a minute or two, of the red (fuchsin) preparation {103} in a concentrated solution of methyl-blue, the violet preparation being secondarily stained in a like solution of aniline-brown. If the preparation is to be permanently preserved, it should be dehydrated in strong alcohol after washing with water, and it may then be treated with oil of cloves and mounted in Canada balsam.

After the observer has become thoroughly familiar with the tubercle bacilli by means of the method of Ehrlich, much time may be saved by following that of Baumgarten. The cover-glass bearing the dried sputum is placed in a very dilute solution of caustic potash (two drops of a 33 per cent. solution in a watch-glass of distilled water) till the layer of sputum becomes transparent. The cover is then placed on a slide moistened with a drop of water, tapped slightly, and examined with the microscope. The bacilli are readily seen, and may be differentiated from other varieties of bacteria, if necessary, by again drying the object and examining it in a drop of a dilute watery solution of aniline-violet or of other preparations of aniline used for staining nuclei. The tubercle bacilli remain unstained, while putrefactive bacteria are tinted.

The tubercular products of the invasion of the body by the bacillus tuberculosis are regarded as primary or secondary, according as they are present at that part of the body which directly receives the organisms or as they are dependent upon the transfer of the latter to parts remote from the region of their admission and immediate effects. This differing relation is also expressed by the terms local and general tuberculosis. In the former the bacilli excite the growth of tubercle only at a given part of the body. Their apparent effects may be wholly limited to this region, and it not rarely happens that the same is quite distant from the channels through which the bacilli are admitted. A general tuberculosis occurs when the latter are disseminated over the body, and their effects, especially the production of numerous tubercles, are found at various parts. The dissemination may take place at the time of entrance, or, as is more commonly the case, apparently occurs at some subsequent period, the immediate disturbances being localized at a given portion of the body. The necessary conditions being here offered for the propagation of the bacilli, their sudden distribution in great numbers is afterward permitted when favorable opportunities arise for their absorption. Such conditions are present when the local tubercular growths extend into lymphatics or blood-vessels. The frequency with which scrofulous glands are tuberculous--that is, contain miliary tubercles--is already fully recognized, and a tuberculosis of the lymphatic glands is essentially regional. These glands become affected in consequence of disturbances, the local effects of which may have wholly disappeared, in the region from which they receive their lymph. The cervical glands become permanently enlarged, perhaps tuberculous, in connection with persistent or recurrent inflammatory processes in the tonsils and pharynx, the bronchial glands from similar bronchial or pulmonary affections, and the mesenteric glands from like intestinal disturbances. In such instances, the direct reception of the bacilli into the lymph-current is assumed rather than demonstrated from a knowledge of the possibilities of absorption and an appreciation of the conditions in the glands.

That an actual growth of tubercles from the wall of the intestinal {104} lymphatics may take place has long been known, and Ponfick has recently discovered that tubercles may be found growing from the wall of the thoracic duct. The possibility of the direct admission into the lymph-current of the infective element in tuberculosis is thus apparent, and its indirect entrance into the blood-current is equally obvious. That the bacillus of tubercle may be directly received into the blood-current is likewise evident from the observations of Weigert, who found tubercles growing from the walls of the pulmonary blood-vessels, venous as well as arterial. This discovery of a tuberculosis of the blood-vessels was confirmed by Klebs, who had found a tuberculosis of the azygos veins. The occurrence of multiple miliary tubercles of the pulmonary veins, especially near the place of entrance of smaller branches, has been asserted by Mügge, although appearances similar to those described by him may be met with, due simply to the agglomeration of white blood-corpuscles and their necrosis. Such a condition simulates very closely the miliary tubercle, but is usually analogous to the appearances figured by Virchow, and described by him as one of the phenomena of coagulation. In his observation the white bodies were adherent to the red clots, and were with them drawn from the pulmonary artery.

With the admission into the body, and the colonization of the tubercular bacilli, their effects may either be progressive until the death of the individual is occasioned, or, with the cessation of the growth of the bacilli or a possible modification of their noxious properties, recovery may ensue. The history of scrofulous glands, as well as that of circumscribed pulmonary inflammation in scrofulous persons, both presumably of a tuberculous nature, show that the effects of an invasion of the parasites may be overcome.

The regions of the body which are usually the seat of a primary tuberculosis are unquestionably the respiratory and intestinal tracts. With regard to the first of these regions, the one most frequently affected, there can be no doubt that in most instances the inhaled air carries the bacilli or their spores, or both. Their constant presence in the sputum of the frequent cases of tuberculous phthisis suggests a ready means for their escape into the atmosphere. The well recognized infective qualities of the sputum, as demonstrated by the various experiments before the bacillus was discovered, demand the thorough disinfection of phthisical sputa, since these are in all probability the chief source of the dissemination of the disease.

The tuberculosis of the intestine in like manner is to be regarded in the main as the result of an absorption from its surface of the specific agent. An obvious direct means of the approach of the bacilli is offered in the sputum, which, when swallowed, is likely to retain its virulent properties. The frequent coexistence of chronic pulmonary and intestinal tuberculosis is thus most readily explained. To what extent the presence of the bacilli in the pearly distemper of cattle and in the tuberculosis of other edible domesticated animals, as fowls and swine, may lead to an infection of the intestinal wall, still remains an unsolved problem. It is not yet determined at what temperatures the bacilli are destroyed, although their growth takes place only between 30° C. (86° F.) and {105} 41° C. (105.8° F.). The inoculation of pearly masses produces tuberculosis in certain animals, yet the effect of cooking in destroying the bacilli and their spores is likely to prove of great importance. Aufrecht's attempts at inoculating rabbits with cooked pearly masses proved unsuccessful. Schottelius publishes an interesting series of observations relating to the prolonged use of meat from cattle affected with the pearly distemper, and shows that after a period of years no disease of the nature of tuberculosis occurred among the one hundred and thirty individuals included in the families concerned. Whatever may be the value of this negative testimony, there is, as yet, no evidence on the other side which satisfactorily determines the point in question--viz. that the flesh of animals affected with pearly distemper produces tuberculosis in the human consumer.

The milk from cows thus diseased has likewise been regarded with suspicion, and the frequency of intestinal tuberculosis among children has been attributed to this source. Although the theoretical possibility of the escape of the bacilli into the milk of cows affected with pearly distemper is obvious, their presence in such milk is first to be demonstrated under conditions which necessitate their origin from the animal. If boiling the infective material for three minutes destroys its virulence, as claimed by Aufrecht, a ready means is offered of destroying the tubercle bacilli which may be present, not only in the milk from animals affected with pearly distemper, but in all milk which has been exposed for a certain time to an atmosphere which may contain the bacilli of tuberculosis. In the light of our present knowledge extreme hygienic precautions are only demanded in those cases where such a congenital or acquired basis (constitution) is present as facilitates the development of tuberculosis.

Morbid Growths.

In a system of practical medicine it is obviously important to include under the head of Morbid Growths not only what is spoken of by the surgeon as a tumor, but also those new formations of tissue which, in virtue of their nature, seat, manner of growth, and retrograde changes, produce an important series of disturbances in the physiological processes of the individual. The surgeon deals essentially with the swelling, which, producing irregularities in the outline of the accessible surfaces of the body, is regarded as an excrescence or outgrowth. It is important for him to realize the nature of this swelling, that he may follow a different treatment for the abscess, the wen, the watery accumulation, or the fleshy mass. The last is the tumor in the limited sense; it is the growth which, though called morbid, becomes so only in consequence of its presence being associated with symptoms whose existence and persistence interfere with the well-being of the possessor.

The physician, on the contrary, is more concerned with the tumor as a growth than as a swelling. The latter element in deeply-seated portions of the body may not be brought to his attention. The growth takes place in such a manner as to be productive of certain symptoms more or less serious, among which swelling is least obvious. The morbid {106} growth to him becomes prominent as it displaces or replaces normal tissues by those newly formed, which may or may not be normal to the part in which the growth is situated. His tumor is therefore a morbid growth, a new formation, a neoplasm or pseudoplasm, rather than a swelling, a bunch, or an excrescence.