and finished their courses in schools situated in large centers naturally commanding greater clinical advantages than those obtained in a small. inland town.

Was the medical department of the University of Michigan destined to serve only as a preparatory school for the clinical years in some other medical college, or was it to develop its own clinics and make up for any paucity in numbers by a thorough utilization of the material at hand?

Doctor Breakey, in 1890, joined forces with those who believed in developing a clinic at Ann Arbor. His nearly twenty years of work in the dermatological clinic has shown what can be accomplished in a specialty particularly difficult to build up outside of a large center. The last annual report of the University Hospital shows the immense number and variety of skin lesions Doctor Breakey has at his disposal for teaching purposes. Best of all, this large material is carefully studied, and the student so thoroughly drilled in diagnosis and treatment as to make him competent to apply in his future practice the principles learned in the medical school.

Perhaps the crowning glory and reward of a life of toil for the attainment of the highest ideals lies in the respect and veneration of his pupils, which are his beyond what comes to most medical teachers. Eminently fair in his dealings with individual students, sympathetic, kindly and ever helpful, no student leaves him but feels he is the better for association with such a man-and what greater reward can come to a teacher?

ANNOTATIONS.

CONCERNING TYPHOID CARRIERS.

WEBER has demonstrated the possibility of determining the infectious nature of the dejecta of typhoid fever convalescents by a bacteriologic examination of the bile. The procedure is readily adaptable to either hospital or private practice, and providing recent claims are verified, will aid materially in preventing the dissemination of this disease. While living typhoid bacilli may only be an accompaniment of the dejecta of the walking typhoid convalescent at intervals, the stools of the walking typhoid contingent demand careful attention since the bacillus typhosus is undoubtedly an invariable concomitant factor and facilitates the divining of a condition sometimes diagnosed as general malaise. The author takes cognizance of the hypothesis that the gall-bladder is the habitat of the offensive bacillus and proceeds to obtain a specimen of the bile for examination. The method employed is to introduce about six fluid ounces of olive oil into the empty stomach and withdraw the gastric contents one-half hour later. This soon separates into two strata-an upper oily layer and a lower watery layer. The secretion of pancreatic juice is incited by the oil and a certain portion of this alkaline digestant is diverted into the

According to Weber if

stomach, carrying some of the bile thereto. chemical tests show the presence of bile in the siphoned stomach material the typhoid bacillus will invariably be found in the biliary secretion of typhoid carriers.

ALARMING INCREASE OF ANIMAL TUBERCULOSIS.

EXAMINATION of animals at various slaughtering centers in this country. discloses the information that about one per cent of cattle and above two per cent of swine subjected to slaughter are afflicted with tuberculosis. Figures compiled by the Bureau of Animal Industry of the United States Department of Agriculture show that over ten billion pounds of meat were inspected during the past year, and that forty-six million pounds were condemed, nearly three-fourths of this amount being tuberculous. As an index to the condition of live stock in various states the tuberculin test has been administered with the result that reaction was obtained in from 2.79 to 19.69 per cent of the bovines, while conservative estimate of dairy herds throughout the country reveals that about ten per cent of the cattle react. However, the officials have found that in the more limited area of the District of Columbia, where the testing has been persistently conducted, the cattle have reacted in seventeen per cent of the cases. The ingestion of feces and milk from tuberculous cattle is considered the principal source of the infection in swine, a conclusion that has been reached after a carefully conducted series of feeding experiments. Disregarding for a moment the loss of life resulting from this disease and considering the effect merely in the light of lucre, ample reason obtains for enedeavoring to better conditions. For instance, Argentina requires. that a clean bill of health accompany cattle imported into that country or that the animals be subjected to the tuberculin test on landing. When the fact is known that compliance with the latter requirements entails. rejection of fifty per cent of the pure bred herds shipped by exporters in the United States, and that as a consequence sales cannot be consummated, the exigency of the situation becomes apparent. Referring now to the enormous sacrifice of human beings daily offered on the altar of tuberculosis, there would seem to be urgent reason for concerted action by laity and profession to exterminate white plague from the earth.

CONTEMPORARY.

THE MECHANISM OF HEMOLYSIS IN CERTAIN LESS CONSIDERED ASPECTS.

[ CLEVELAND MEDICAL JOURNAL.

IN the last decade the literature of hemolysis has grown beyond all bounds. Pathologists, physiologists, bacteriologists, surgeons, internists (this barbarous word seems nowadays too convenient to be dispensed with) have vied with each other in swelling the interminable list of agents which

have the power of causing the liberation of the blood-pigment from the colored corpuscles. Besides an almost countless host of chemical hemolytics (such as ether, alcohols, chloroform, benzole, the saponins, et cetera), the most varied biological products (spider poison, bee poison, bacterial toxins, normal sera and tissue liquids, and the so-called "immune sera" obtained by injecting the corpuscles of one species into animals of another species), have been more or less deeply investigated. For the explanation of certain of the properties of the biological group the famous side-chain theory of Ehrlich has been applied with, upon the whole, remarkable success, although it perhaps begins at last to show signs of breaking down under the strain of the immense accumulation of facts which it has been called upon to cover. But with all the restless activity of research in this domain, the detailed study of the intimate mechanism of the process of hemolysis, the unveiling in logical sequence of the actual changes which take place in the erythrocyte under the influence of any given hemolytic substance and. which lead to the liberation of the blood pigment, has been surprisingly neglected. Recently, however, there have been symptoms that this inquiry. is beginning to excite an interest more adequate to its importance. It is to certain of the more general aspects of the mechanism of hemolysis that we desire briefly to direct attention.

Take, for example, the classical instance of the laking of corpuscles by an alien serum. It has been quite clearly proved that in the action of many such sera two bodies are concerned, although their chemical nature has not been as yet satisfactorily defined. One of these, the so-called amboceptor, is relatively stable when heated; the other, the complement, is inactivated even at a temperature of 56° to 60° centigrade. The conditions under which the appropriate ambocepter is fixed by the erythrocytes erythrocytes which have already taken up amboceptor, unfolds its action have been extensively investigated. The same is true of some of the and the conditions under which the complement, in the presence of chemical laking agents, especially, perhaps, saponin and ether. But when these conditions have been determined a new series of questions immediately present themselves. What, for instance, are the changes, chemical, physical or physico-chemical, which occur in the erythrocyte under the action of amboceptor-complement on the one hand, of saponin and its congeners on the other? Why do these changes, whatever they may be, cause the corpuscle to part with its hemoglobin? Are the essential changes produced by the various hemolytic agents always fundementally the same, or are they fundamentally different for each group or even for each member of a given group? If the process is always fundamentally the same under the conditions of our test-tube experiments, are we justified in concluding without further evidence, as we are perhaps only too apt to do who live so much under the twin tyranny of the incubator and the centrifuge, that the same is true of the physiological hemolysis constantly going on in the body on which, to cite only one of its consequences, the normal production of bile

pigment depends, and true also of that pathological hemolysis associated with such conditions as paroxysmal hemoglobinuria, certain of the anemias and perhaps the so-called hematogenic forms of jaundice.

A fairly definite answer, we believe, can be given to some of these questions. A very general, perhaps a universal consequence of the action of hemolytics, whatever their nature, is increased permeability of the corpuscle to water. The easily observed fact that in so many forms of laking the corpuscles swell up before the hemoglobin escapes, proves that the entrance of water is an important step in the process. It is not only an important step, but when the amount of water taken up by the erythrocyte passes a certain limit, it is of itself sufficient to complete the liberation of the blood-pigment. As to the manner in which hemolytic agents favor the entrance of water into the corpuscles, there are many reasons for thinking that they act by producing changes in the chemical and physical condition of certain constituents of the superficial layer (envelope) of the erythrocyte as well as changes in its interior. Saponin and ether, for example, are known to be solvents of cholesterin and lecithin, and cholesterin and lecithin are important constituents of the stroma and envelope of the colored corpuscle. It is easy to understand that if a portion of one or both of the substances is dissolved or altered in its physical or chemical condition without being actually dissolved by the hemolytic agent, profound changes may be produced in the permeability of the corpuscle to water and to the salts dissolved in the serum or other liquid in which the erythrocytes are suspended. Where the process is less clearly demonstrated, as in the case of the biological hemolytics, there is also evidence that changes in the permeability of the corpuscles to water, due to chemical or physicochemical actions, play a role in producing hemolysis. The most probable explanation of the action of the water, once it has been admitted in more than a certain amount into the corpuscle, in determining the exit of the blood-pigment is as follows: In the interior of the erythrocyte the pigment does not normally exist in true watery solution but in the colloid condition in the form of what the physical chemist calls "gel" and the plain cook a jelly. When more than a certain proportion of water is added to the gel the colloid substance goes into solution. There is reason to believe that this is only one of the events that follow the entrance of water into the corpuscle. Not only does the blood-pigment pass from its jelly-like condition into aqueous solution but it alters its character in doing so and now becomes capable of crystallization. The net result, then, of the water action is that the native colloid blood-pigment, which some writers term hemochrome, becomes changed to a crystalline pigment hemoglobin, and that this crystalline pigment dissolves in the water. Whether the hemochrome is chemically altered in this process, perhaps by the splitting off of a constituent which normally links the pigment to the stroma, or only physically altered is not quite settled, although there is some evidence for the former view. The important point, however, is that after the

entrance of a sufficient amount of water an aqueous soluion of hemoglobin is present for the first time in the history of the corpuscle, and the next step in the hemolytic process, the extrusion of this distinctly foreign substance seems a natural and indeed, since there is no reason to suppose that the stroma has any affinity for crystalline hemoglobin, an inevitable one. The change in the permeability of the erythrocyte which leads to the entrance of an amount of water beyond the permissible limit is not the only way in which hemolytic substances act. Although this change would of itself suffice to ensure complete liberation of the blood-pigment, there are facts which indicate quite clearly that in addition many laking agents, perhaps all, exert also a more direct influence on the normal relations of the native blood-pigment to the stroma. Substances like ether and saponin, for instance, which have the power of dissolving lipoids (like lecithin, cholesterin, et cetera) seem to act in two ways, by disorganizing the envelope through solution of its lipoids and thus increasing its permeability to water, and by helping to dissociate the hemochrome-stroma complex by exerting a pull on the lipoids of the stroma, while the water simultaneously exerts a pull on the pigment.

The interesting conclusion follows from this view of hemolysis, that the erythrocytes, normally so perfectly adapted to the plasma in which they float, may when the conditions on which their equilibrium with it depends are altered, be rapidly and inevitably destroyed by that very plasma itself. It is indeed the very fact of the exquisite adaptation of the liquid and the cell for a strictly regulated exchange of material which constitutes the danger when the regulation is upset. A liquid like mercury which is not adapted either to give anything to erythrocytes in contact with it or to take anything from them would not cause hemolysis, even if the permeability of the corpuscles for water or sodium chlorid were increased to any extent. The continued survival of the erythrocytes in an aqueous solution of salts and proteins like the blood-plasma, nay more, the protection of the corpuscles up to a certain point by the plasma against the attack of extraneous hemolytic agents, are facts we are prone to take so much for granted as to forget that they depend entirely upon a most delicate adjustment of the permeability of the corpuscles for essential constituents of the plasma. Disturb those relations to a sufficient degree and the plasma becomes a poison to the erythrocytes not much less deadly than distilled water. When we add to blood a hemolytic substance and see that presently the bloodpigment has left the corpuscles we are apt on first impulse to attribute the whole effect to the foreign material added. We are apt to say that the saponin, the ether, the alien serum has laked the blood. In a certain sense this is true. But it is not the whole truth. In reality the hemolytic agent has acted in an essential degree, although not exclusively, by overthrowing the equilibrium between the corpuscles and the aqueous solution of certain substances in which they are suspended. In the presence of another liquid, of water-free glycerin, for instance, the action of the hemolytic substance