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Showing papers in "Journal of Experimental Medicine in 1905"


Journal ArticleDOI
Oskar Klotz1
TL;DR: It is found that bone formation and pathological calcareous infiltration are wholly distinct processes, and it is shown that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction the authors associate with the presence of soap.
Abstract: IT WILL BE SEEN FROM THE ABOVE THAT WE HAVE STUDIED THE CONDITIONS ASSOCIATED WITH THE DEPOSIT OF CALCAREOUS SALTS: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them. When they are subjected to the action of the pancreatic juice with its fat-splitting ferment the cells are killed and coincidently the neutral fats are decomposed, fatty acids being deposited. The fatty acids now slowly combine with the calcium salts. In degenerating lipomata the process would seem to be similar. But in other cases the cells are not obviously fat-containing in the normal state; nevertheless prior to calcification they undergo so-called fatty degeneration, which is really a form of cell degeneration accompanied by fat infiltration. As regards the source of the cell fats in general we may safely accept: 1. That fats are transported in the blood as diffusible soaps. 2. That taken up by the cells these soaps may either- (a) Be reconverted into neutral fats and become stored in the cytoplasm as such, or (b) undergo assimilation proper, becoming part and parcel of the cell substance, in which case they are not recognizable by the ordinary microchemical tests. 3. If these two possibilities be accepted it follows that the appearance of fats and soaps in the degenerating cell may be due to either- (a) Absorption or infiltration of soaps from the surrounding medium, the degenerating cell retaining the power of splitting off the fat but being unable to utilize this in metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen combination or, more broadly, liberation of the fats from their combination with the cytoplasm. The appearances seen in the cells of atheromatous areas indicate that the first of these does occur. III. In areas undergoing calcareous infiltration we have demonstrated. the presence of soaps, and this often in such quantities that they can be isolated and estimated by gross chemical methods. By microchemical methods also we have been able to show that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction we associate with the presence of soap. And experimentally we have produced these soaps within the organism, more particularly by placing capsules containing fats and fatty acids within the tissues and after several days finding that the capsules contain calcium soaps and possess a calcium content far in excess of that of the normal blood and lymph. IV. While these are the facts, certain of the details of this reaction demand elucidation. The existence of sodium and it may be potassium soaps in the degenerated cells is comprehensible if we accept that these are present in the circulating lymph and simply undergoing absorption. But even then, as these are diffusible substances how is it to be explained that they become stored up in these particular areas? We have found that, as a matter of fact, in regions which give the reaction for soaps, but which give no reaction for calcium (which therefore presumably contain at most amounts of the insoluble calcium soap too small to need consideration, the ordinary solvents for potassium and sodium soaps do not forthwith remove the stainable material; they are relatively insoluble. The reason for this insolubility is suggested by the observations made in the test tube, that soap solutions mixed with solutions of white of egg or blood serum form a precipitate of combined soap and albumen, which likewise is insoluble in water and alcohol. The indications are therefore that in cells undergoing degeneration, with degeneration of the cytoplasm, certain albuminous molecules unite with the soaps present to form relatively insoluble soap-albuminate. V. With regard to calcium soaps, these are also present and in certain stages appear to be the dominating form in the affected tissues. Two questions suggest themselves, viz.: what is the source of calcium, and what is the process by which they become formed? As to the source, the amount present in well-marked calcification is far in excess of the normal calcium contents of the affected tissue. If in the kidneys of experimental calcification three hundred times as much calcium may be present as in the normal kidney (von Kossa), the calcium must be conveyed to the part by the blood and lymph, and that this is so is demonstrated, as we have pointed out, by the distribution of the infiltration in solid organs, that like ovarian fibroids have undergone necrosis, in which the earliest deposits are superficial. As to the process, there are three possibilities: 1. That sodium and potassium soaps and soap albuminates are first formed and that interaction occurs between them and the diffused calcium salts from the lymph, the less soluble-calcium replacing the sodium and potassium. 2. That under certain conditions the calcium salts act directly on the neutral fats present in the degenerating cells. 3. That the neutral fats are first broken down into fatty acids and that these react with the calcium salts to form the soaps. We are assured that the first process occurs and that because in the boundary zone of areas of calcification we can detect soapy particles devoid of calcium, identical in position and arrangement with the particles more deeply placed which give the calcium reactions. But this is not the only reaction. In case of fat necrosis we see clearly that the third process is in evidence. And we are far from being convinced that the second does not also obtain. We have been impressed by the large accumulation of neutral fats in the cells in cases of early atheroma and the absence at any stage of the process of recognizable fatty acid. While soaps, it is true, are compounds of fatty acids with alkalies, it is recognized in ordinary domestic life that they can be formed by the direct action of strong lye upon ordinary fats, and this even in the cold. It is quite possible therefore that there occurs a similar direct process in the organism. The point is worth noting, however, that this does not occur in healthy cells the seat of fatty infiltration. We therefore leave this an open question, only laying down that, as indicated by the hyalin albuminous matrix left when calcium salts are dissolved out of an area of calcification, there must exist a calcium soap- or fat-albuminate similar to the potassium and sodium soap-albuminates already mentioned-such an albuminate as we can form with calcium soaps in the test tube. VI. In old areas of calcification soaps are largely if not entirely wanting, although these are to be detected at the periphery, when the process is still advancing. The reactions given by these older areas are almost entirely those of calcium phosphate, though some calcium carbonate is at times to be made out. This seems surely to indicate that the final stage in calcification is an interaction between the calcium soap-albuminates and substances containing phosphoric and carbonic acids. Such substances, it is needless to say, are present in considerable amounts in the lymph and blood. We must conclude that the acid sodium phosphates of the lymph act on the calcium soap, the highly insoluble calcium phosphates being formed (plus the albuminous moiety of the original compound) and diffusible sodium soap being liberated, while similarly alkaline carbonates form calcium carbonate and liberate sodium and potassium soaps. Calcium phosphate and calcium carbonate thus become the insoluble earthy salts of old crystalline areas of calcification. VII. As already stated very little soap is to be found in these old areas. It is possibly worth suggestion that the soaps liberated in this last reaction, as they diffuse out, again react with diffusible calcium salts and form calcium soaps which once more react with the alkaline salts to produce the phosphates and carbonates; that, in short, they have a katalytic action. (ABSTRACT TRUNCATED)

121 citations


Journal ArticleDOI
TL;DR: All of the cardinal symptoms of Stokes-Adams disease may be duplicated by heart-block resulting from a lesion in or near the auriculo-ventricular bundle of His, and by this alone.
Abstract: The facts collected in the third part of this paper justify the following conclusions: (1) All of the cardinal symptoms of Stokes-Adams disease may be duplicated by heart-block resulting from a lesion in or near the auriculo-ventricular bundle of His, and by this alone. (2) No typical case of Stokes-Adams disease has been described in which heart-block might not have been the cause of the trouble. (3) It can be shown that all cases of Stokes-Adams disease which have been studied by sufficiently accurate methods were cases of heart-block. (4) It would appear that heart-block without and with syncopal attacks are two stages of the same disease process.

74 citations


Journal ArticleDOI
TL;DR: The disease which formerly has been described as a form of protozoon-infection is due to an infection with a pathogenic fungus that is pathogenic for dogs, rabbits and guinea-pigs probably other animals also, and in them produces lesions very similar to those which the authors encounter in the human being in this disease.
Abstract: From the preceding I derive the following conclusions: 1. The disease which formerly has been described as a form of protozoon-infection is due to an infection with a pathogenic fungus. 2. The infection may primarily be either a cutaneous or a pulmonary one. 3. The lesions produced by this fungus fall under the general head of infectious granulomata and consist partly in nodules resembling altogether those produced by the tubercle bacilli and partly in chronic abscesses. 4. The adult forms of the parasite are more apt to produce nodules, the sporulating forms abscesses. 5. The fungus is pathogenic for dogs, rabbits and guinea-pigs probably other animals also, and in them produces lesions very similar to those which we encounter in the human being in this disease. 6. Supurative periorchitis in guinea-pigs is not pathognomonic for glanders.

68 citations


Journal ArticleDOI
TL;DR: By a series of controlled experiments with inoculated frogs, it is shown that, while temperatures a little above freezing have no harmful effect upon the frogs, they completely control all manifestations of the disease in inoculated or diseased frogs, if the frogs are left in the cold for a period as long as seven days; and that even short periods in thecold chamber will bring about a delay of the fatal results in diseased or inoculatedfrogs.
Abstract: The epidemics we have observed, were due to the presence and growth in the frogs of Bacillus hydrophilus fuscus. This was proved by recovering the bacillus in pure culture from the body fluids of frogs sick or dead of the disease, and the inoculation of healthy frogs with an emulsion of the pure culture, and by obtaining the same clinical picture and pathological findings as in the original diseased frogs; and, finally, by recovering the bacillus in pure culture from frogs inoculated and sick or dying as a result of the inoculation. The disease is widely distributed throughout North America and Europe, and in this country and Canada is known as "red-leg." It has been observed by us chiefly in the warm weather of September and October. The disease is characterized by congestion of the ventral surfaces of the body, with more or less ulceration in, and haemorrhage beneath, the skin, bloating due to serous exudation into the lymph sacs, gradual failure to respond to stimuli, which symptoms are followed by coma and death, the last being occasionally preceded by tetanic seizures. After death haemorrhages into the muscles and degenerative changes in the muscles, spleen, liver, and, to a slight degree, in the intestinal tract, are found. The blood shows an advanced degree of anaemia and leucocytosis. Predisposing causes of the disease are lesions of the skin, which seem to be the usual portal of entry of the infection, and lowered resistance from heat and from anaemia. By a series of controlled experiments with inoculated frogs we have shown that, while temperatures a little above freezing have no harmful effect upon the frogs, they completely control all manifestations of the disease in inoculated or diseased frogs, if the frogs are left in the cold for a period as long as seven days; and, further, that even short periods in the cold chamber will bring about a delay of the fatal results in diseased or inoculated frogs. The anaemia so often found in apparently healthy frogs seems in many cases to be due to the presence in the lungs of the frog of a parasite, the Distomum cylindraceum, which, occurring in sufficiently large numbers in an individual frog, is capable of materially diminishing the available supply of red corpuscles. Severe laking of the blood, the presence of numerous isolated red-cell nuclei, and great diminution in the number, or almost total absence of the red cells in the diseased frogs, are in proportion to the severity of the infection and due to bacterial action. The presence of the haematozoan parasite, the Drepanidium, does not play any part as a predisposing or exciting cause of the disease. The ascarid Rhabdomena nigrovenosum, although frequently present as a parasite in the lungs of the frogs, plays no part in causing or promoting the disease.

59 citations


Journal ArticleDOI
TL;DR: Pneumonia and bronchitis are found in all animals after the injection of formalin and similar phenomena occur in the trachea, bronchi and lungs of animals subjected to formaldehyde inhalations.
Abstract: THE RESULTS OF THIS INVESTIGATION MAY BE SUMMARIZED AS FOLLOWS: 1. The inhalation of formaldehyde gas in even small quantities is followed by bronchitis and pneumonia. Pneumonia is due to the inhalation of the gas and not to secondary infection. 2. Formalin belongs to that rare group of poisons which are capable of producing death suddenly when swallowed. 3. The introduction of formalin into the stomach is followed by the production of a gastritis which varies greatly in character. The duodenum and upper jejunum may also be involved in the inflammatory process. 4. Intraperitoneal injections of formalin cause peritonitis of a fibrino-haemorrhagic character. A definite reaction is obtained when very dilute formalin (1-1000) is employed. In the peritoneal cavity formalin exercises a destructive action upon all organs (pancreas, liver, peritoneal fat, Fallopian tubes, etc.) with which it comes in contact and causes inflammation in these organs. 5. The lethal dose of formalin when injected intraperitoneally into guinea pigs is approximately 2 cc. of 1-1000 formalin for each 100 grm. of body weight. 6. The injection of formalin into the lungs is followed by pneumonia and bronchitis. 7. The inflammation which follows subcutaneous injections of formalin is characterized by intense exudation. 8. The injection of formalin into the muscles produces myositis. 9. The injection of formalin into the anterior chamber of the eye causes the accumulation of an exudate containing leucocytes and fibrin. When formalin is dropped into the conjunctival sac iritis follows and may be severe enough to destroy the eye. 10. Formalin in whatever way introduced into the body is absorbed, and is then capable of producing lesions in the parenchymatous organs. 11. Changes in the liver after absorption of formalin consist of mild or severe grade of cloudy swelling accompanied by vacuolation of the protoplasm, changes in the nuclei and leucocytic infiltration. Focal necrosis may result. Similar changes follow the inhalation of formaldehyde. 12. The injection of formalin or the inhalation of the vapors of formaldehyde produces cloudy swelling of the parenchyma of the kidney. Focal necrosis may result. 13. Pneumonia and bronchitis are found in all animals after the injection of formalin. 14. The leucocytic infiltration which follows the introduction of formalin into an organ has these general characteristics: The eosinophiles are the first leucocytes to appear; these are followed by the other polynuclear leucocytes; last appear the large and small mononuclear leucocytes. Similar phenomena occur in the trachea, bronchi and lungs of animals subjected to formaldehyde inhalations. 15. Formalin is, directly or indirectly, chemiotactic for leucocytes. The tissues which are not infiltrated with leucocytes after the injection of formalin are those which have been so injured by the chemical that an inflammatory reaction is impossible. 16. Animals subjected to chronic poisoning with formalin administered by intraperitoneal injection develop fibrinous peritonitis, associated with marked eosinophilia. The changes in the kidneys and liver consist of cloudy swelling, fatty degeneration, focal necrosis and leucocytic infiltration.

43 citations


Journal ArticleDOI
TL;DR: The case of Wagner's case has caused a good deal of confusion among writers on this disease, for Herrick, Jacoby, and others have described it as another case of an earlier observation, while Lewy thinks it is an additional one which Unverricht has later more fully reported.
Abstract: Inflammatory changes in muscles have long been recognized as occurring independently or in connection with certain diseases. Hunter (1) is said to have described cases of myositis in 1784 and to have noted the insusceptibility of muscular tissue to inflammation and its consequences. I have been unable to find any such reference in his writings. During the past century cases have been published in many different countries and a considerable amount of literature is to be found on this affection. A multiple muscle inflammation, however, presenting also other well known symptoms, was not described as such until 1887. In that year E. Wagner (2) of Leipsic, Unverricht (3) of the Poly-clinic at Jena, and Hepp (4) of Kussmaul's clinic at Strasburg, almost simultaneously reported cases. Though Wagner's case was first published, it was in reality the last seen, for Hepp made his observation two months previously and Unvcrricht's case had been noted seven years before either of the above two. The pathological findings, with a meager history of this last case, were presented by Marehand (5) to the Schlesische Gesellschaft fiir vaterl~nd. Cultur on October 2~, 1880, and later appeared in the society's transactions and in the Breslauer ~rztliche Zeitschrift of that same year. The case has caused a good deal of confusion among writers on this disease. Herrick (6), Jacoby (7), and others have described it as another case of an earlier observation, while Lewy (8) thinks it is an additional one which Unverricht has later more fully reported. This error may be due to the fact that Unverricht in two of his articles

41 citations


Journal ArticleDOI
TL;DR: The serum of an inflammatory exudate has the power of inhibiting the action of proteolytic ferments contained in the leucocytes, and this anti-enzymotic action is favored by an alkaline reaction, but is completely lost in an acid medium.
Abstract: The serum of an inflammatory exudate has the power of inhibiting the action of proteolytic ferments contained in the leucocytes This anti-enzymotic power is possessed by the blood serum from which it doubtless passes into the exudate In the later stages of inflammation there is some diminution of this anti-enzymotic action The anti-body contained in the serum is destroyed by a temperature of 75 degrees C The proteolytic ferments of the leucocytes act both in an acid and in an alkaline medium but are most efficient in the latter The anti-enzymotic action of the serum is favored by an alkaline reaction, but is completely lost in an acid medium

28 citations


Journal ArticleDOI
TL;DR: Evidence is afforded that there are well-marked differences between the metabolic activities of pneumococci and streptococci, which may prove useful in the differentiation of these organisms.
Abstract: By morphological examination and with current cultural methods a clear differentiation cannot always be made between pneumococci and streptococci. The chief differential character usually depended upon is the capsule of the pneumococcus. Well-marked capsules, however, may occur on organisms which have with reason been classified as streptococci. On the other hand, capsules may not he demonstrable on pneumococci by the usual methods, especially when growing on artificial culture media. The usual cultural characters and reactions are at best not diagnostic, and are subject to variations which may render them useless as evidence of specific difference. The experiments recorded in this paper, however, afford some evidence that there are well-marked differences between the metabolic activities of pneumococci and streptococci, which may prove useful in the differentiation of these organisms. These differences in metabolism become apparent when the pneumococci and streptococci are cultivated in an alkaline serum medium, or in a serum medium to which the carbohydrate, inulin, has been added. Pneumococci slowly produce acid in the alkaline serum.

26 citations


Journal ArticleDOI
TL;DR: It follows logically, from the results obtained in this experiment, that the cultural findings after death are no guide to the bacterial contents of the lungs during life, and that any deductions made from such findings are unreliable and deceptive.
Abstract: The following conclusions may be drawn, based upon the result of our researches: 1. Organisms of the pneumococcus or streptococcus group are present in the lungs of practically all cases, whether normal or showing a variety of lesions; strictly speaking, they were found by us in forty out of forty-two cases, or in 95% of our series. 2. The pneumococci and the streptococci were obtained in practically similar percentages—that is, in 50 % of the cases. 3. Pneumococci were not obtained more frequently in the small series of patients exposed for some time to hospital atmosphere; our tables show the contrary to obtain. The number of cases examined were, however, insufficient, and the findings may thus be accidental, and hence of no value. 4. Test micro-organisms, namely, small portions—half a drachm or less—of B. prodigiosus, introduced into the human mouth after death, were conveyed to and recovered from the lungs by culture in a little over half of the cases in which this experiment was tried. The test micro-organisms are, we believe, conveyed to the lungs with the fluid which collects in mouths of persons after death, and which in many cases collects just before death. The numerous manipulations entailed in the removal of the body from the wards to the morgue greatly facilitate the entrance of any fluid from the pharynx and buccal cavity into the lungs. It follows logically, from the results obtained in this experiment, that the cultural findings after death are no guide to the bacterial contents of the lungs during life, and that any deductions made from such findings are unreliable and deceptive. Granted that our explanation be correct, there is every reason to believe that any of the micro-organisms present in the mouths and pharynx and in many cases in the stomach contents may enter the lungs and, if the conditions be suitable, increase in numbers, during the time between death and the examination of the lungs. There exists, perhaps, more frequently than has hitherto been suspected, a series of diplococci, intermediate between the typical pneumococci and streptococci. The diplococci of this type have been found in forty (40) per cent. of our cases. The differential diagnosis of these atypical diplococci from the pneumococci and streptococci is a difficult one, depending, as it does, upon general cultural characteristics. No single character, such as the presence of capsules or the fermentation of inulin, virulence, etc., has been found to be a certain criterion. The few agglutinative reactions we have made seem to show that these intermediate diplococci, those of Groups II, III, and IV, have no or only slight agglutinative affinities to the typical pneumococcus. Further tests must, however, be made with the various methods at our disposal before this statement can be accepted as final. These diplococci are of interest from the fact that they have been found in the blood during life, and in the pial exudate of cases of meningitis, endocarditis, etc. 6. Our studies have thrown no light whatever upon the conditions which determine the onset of lobar pneumonia in apparently healthy persons. Moreover, we have been unable to draw conclusions as to the presence of pneumococci in the lungs during life, or as to the channels by which they gain access thereto.

20 citations





Journal ArticleDOI
TL;DR: The histological changes observed in every case are secondary to the hæmolytic factor present in all cytotoxic sera, which is greater than that of other cytot toxic sera.
Abstract: (1) The cytotoxins are not specific. (2) The changes occurring after the injection of different cytotoxins are similar and do not vary in kind. (3) The changes do, however, vary in degree in the following order, the one having the most marked effect being placed first, etc.: (a) Haemolymphotoxin, (b) Splenotoxin, (c) Lymphotoxin, (d) Endotheliotoxin, (e) Nephrotoxin, (f) Hepatotoxin. (4) Nephrotoxin causes the most specific change. (5) The haemolymph glands play some important part in the production of eosinophiles. The haemolytic action of haemolymphotoxic serum is greater than that of other cytotoxic sera. (6) The histological changes which are observed in every case are secondary to the haemolytic factor present in all cytotoxic sera.

Journal ArticleDOI
TL;DR: It is shown that cells carefully separated from the serum of an inflammatory exudate obtained by injecting aleuronat into the pleural cavity of a dog cause much more active digestion of coagulated serum in a two-tenths per cent solution of sodium carbonate than in acetic acid diluted to the same strength.
Abstract: The leucocytes of an inflammatory exudate contain an enzyme which even after death of the cell is capable of digesting fibrin, coagulated serum, and other proteid substances. This digestion, as Ft. Mflller 1 has shown, occurs more rapidly in a weakly alkaline medium. It is doubtless such enzymes t h a t cause intra-cellular digestion of proteid material engulfed by phagocytic leucocytes. In a preceding article 2 I have shown that cells carefully separated from the serum of an inflammatory exudate obtained by injecting aleuronat into the pleural cavity of a dog cause much more active digestion of coagulated serum in a two-tenths per cent. solution of sodium carbonate than in acetic acid diluted to the same strength. The cells of an exudate removed twenty-four hours after the injection of aleuronat are almost wholly polynuclear leucocytes with fine granulation. Since the serum of the exudate and of the blood exerts an anti-enzymotic action which in an alkaline medium inhibits the digestion of proteid, it is necessary to free the cells from serum in order to study the behavior of the ferments which they contain. To determine the source of the ferments contained in the poly-nuclear leucocytes, attention has been directed to the bone-marrow. A suspension of cells obtained by finely dividing the bone-marrow of the dog and repeatedly washing by centrifugaliza-tion with normal salt solution (o.8 5 per cent.) has been allowed to act upon serum diluted with salt solution and heated in order to destroy its anti-enzymotic action. The amount of coagulable proteid transformed by digestion into non-coagulable form has 1 Zeit. far. klin. Med., i888, xiii, I49.

Journal ArticleDOI
TL;DR: Cases of pneumonia should be considered to a certain degree as contagious and, since the virulence of the pneumococcus may be quickly increased and since the organism is very prevalent in normal sputum, all possible measures should be taken to restrict public expectoration.
Abstract: 1. Typical pneumococci were present dunng the winter months in the throat secretions of a large percentage of healthy individuals in city and country. 2. A higher percentage of atypical strains of pneumococci have been obtained from healthy persons than from those suffering from pneumonia. In the latter cases the atypical strains may have been overlooked, because of the larger number of typical pneumococci present. Many of the atypical strains seem to be closely related to the streptococci. 3. The so-called Streptococcus mucosus Schottmuller, which has hitherto been classed with the distinct streptococci, is placed as a definite variety among the pneumococci, and it is recommended that the name be changed to Streptococcus lanceolatus, var. mucosus. 4. A lower percentage of strains of pneumococci virulent for rabbits in the doses used has been obtained from normal cases by rabbit inoculations of mass cultures than from cases of pneumonia by the same method. 5. Since the virulence of pneumococci may be rapidly increased for a susceptible species of experimental animal by successive passage, and since pneumococci obtained from most pneumonias are more virulent for experimental animals than are those obtained from healthy individuals, therefore the virulence of pneumococci from cases of human infection is probably increased for human beings; hence cases of pneumonia should be considered to a certain degree as contagious and, since the virulence of the pneumococcus may be quickly increased and since the organism is very prevalent in normal sputum, all possible measures should be taken to restrict public expectoration. 6. By repeated inoculations into sheep of a pneumococcus strain, a specific protective power of this serum for mice is developed against the homologous strain and against certain other strains, one morphological variety (Streptococcus lanceolatus, var.mucosus) being thus clearly differentiated from other strains. 7. Coincident with this production of protective power, a slight specific increase of the sheep serum in phagocytic power in vitro has been observed with some strains of pneumococci, all strains of Streptococcus lanceolatus, var. mucosus, acting similarly with the serum produced by the inoculation of one strain; the strains of some other varieties, however, have shown no definite relationship between the phagocytic power and the protective power of the serum.

Journal ArticleDOI
TL;DR: Few results of importance have been secured in this investigation beyond the technical preparation of a saltfree medium; and these are herewith reported in the hope that they may prove of service to others engaged in research along similar lines.
Abstract: Some time ago I entered upon a study of the relations of different salts and nutrients to the metabolism of bacteria. The first step in the investigation lay in the preparation of a salt-free culture medium. A perusal of the literature indicated that the preparation of such a medium had never been really at tempted with natural nutrients; and all the work upon the influence of particular salts upon bacteria is rendered of doubtful value by reason of the fact that the salt in the culture medium was not controlled or removed. For this failure technical reasons have been directly responsible. A culture medium containing natural nutrient materials cannot be controlled in its content of salt. Culture media composed of some amido body, as asparagin, plus a sugar, may be prepared in such a manner as to permit of a control of the salts. But by chemical procedures it is not possible to determine the saline content of a culture medium containing natural nitrogenous substances, nor is it possible to eliminate the salts. Thus far few results of importance have been secured in this investigation beyond the technical preparation of a saltfree medium; and these are herewith reported in the hope that they may prove of service to others engaged in research along similar lines.

Journal ArticleDOI
TL;DR: The present communication deals with the cardio-vascular effects of intravenous infusion of solutions containing sodium bicarbonate after severe hmmorrhage.
Abstract: One of several conclusions reached by Howell in his study of the phenomena of shock * is the following: \"Inject ions of alkaline solutions of sodium carbonate, intravenously or into the rectum during shock, increase markedly the amplitude of the heart-beat and bring about a rise of arterial pressure. When the shock is moderate (aortic tension of 6o-7o ram. Hg.), the injections may restore arterial pressure to an approximately normal level. When the shock is severe (aortic tension of 20-40 ram. Hg.), the injections may increase the arterial pressure by about zoo per cent for long intervals, and the effect when it wears off may be restored by repeating the injections. The effect of the injections is due chiefly or entirely to a direct action on the heart.\" Having in mind the possible clinical value of injections of alkaline solutions as a means of combating the condition of shock, Professor Howell then suggested to the author to pursue this line of investigation still farther, a suggestion which resulted in the series of experiments which will now be described. The present communication deals with the cardio-vascular effects of intravenous infusion of solutions containing sodium bicarbonate after severe hmmorrhage. The animals used were dogs, and the phenomena observed were the pulse rate and the blood \"pressures,\" viz., systolic, mean, diastolic, and pulse

Journal ArticleDOI
TL;DR: It is probable that the isotoxins will play a great role in diagnosis and pathology, and Metschnikoff found that, when he produced a chromic acid nephrit is in dogs, an isonephrotoxin developed in their blood serum, as was found in humans.
Abstract: The comparative study of the body cells of man and of those animals that are zoologically near ly related is not only of great theoretical interest, but also depends upon impor tant practical considerations. Attent ion has already been called to this point by Ehrl ich, ' who said in his address at Hamburg : \" I think it probable that the isotoxins will play a great r51e in diagnosis and pathology. Metschnikoff found that, when he produced a chromic acid nephrit is in dogs, an isonephrotoxin developed in their blood serum, as was

Journal ArticleDOI
TL;DR: A number of new color reactions are described, selecting especially those which are characterized by sensitive-ness, or by some quality which lends the reactions a degree of biological significance.
Abstract: The extraordinary capacity of naphthaquinone-sulphonic acid to enter into reactions with the production of color was first recognized by Witt and Kaufmann, ~ who first prepared the substance by oxidation of amido-naphtha-sulphonic acid. The observations of Witt were recently considerably extended by Ehrlich and Her-ter, 2 who not only described a number of new color reactions, but also indicated various biological applications which promise to increase our physiological knowledge. Since the publication of these papers I have added a considerable number of new color \" reactions to those previously observed, and it is m y purpose at present to describe some of these. I shall not undertake to discuss fully the chemistry of these reactions, which in many cases is still obscure. I shall, however, describe a number of reactions, selecting especially those which are characterized by sensitive-ness, or by some quality which lends the reactions a degree of biological significance. The 1.2 naphthaquinone 4 sodium sulphonate is an orange-colored powder, which dissolves readily in water. In 95 % alcohol it is slowly and slightly soluble, solution being aided by heat; the solubility in absolute alcohol is still less. In acetone also it is moderately soluble. In ether, chloroform, carbon disul-phide, benzene, and petroleum ether the substance is insoluble or very nearly so. The test of solubility in these cases was the failure to obtain any reaction with anilin. The substance is Berichte d.

Journal ArticleDOI
TL;DR: It is shown that when sputum containing pneumococci is sprayed the organisms rarely survive for more than an hour, and often die in less time, and the substance upon which the particles fall makes but little difference in the life of the organism.
Abstract: I. In moist sputum kept in the dark at room temperatures the average life of the pneumococcus is eleven days, though considerable variations may be noted in different specimens of sputum. In the same sputum kept at o° C. the average life of the organism is thirty-five days. In sputum kept at room temperature and in a strong light the pneumococcus lives less than five days. II. In dried sputum ( a ) in the dark the pneumococcus lives on an average thirty-five days; ( b ) in diffuse light, thirty days; ( c ) in sunlight, less than four hours. III. In powdered sputum even when kept in the dark the death of the pneumococcus takes place in from one to four hours. When exposed to sunlight death occurs within an hour. IV. No important differences were noted in the life of the pneumococcus when dried on glass, tin, or wood. On cloth the life was usually slightly longer than on non-absorbing surfaces. V. Sprayed sputum particles remain in suspension for twenty-four hours, but all masses of a size sufficient to contain bacteria settle at a rate of about 40 cm. per hour. VI. When sputum containing pneumococci is sprayed the organisms rarely survive for more than an hour, and often die in less time. The substance upon which the particles fall makes but little difference in the life of the organism. On cloth a slight prolongation is occasionally noted, due perhaps to the slow drying. VII. The mucus of the sputum exerts a destructive action on the pneumococcus. VIII. Exposure of bacterial spray to sunlight while in suspension results in the destruction of the pneumococcus within half an hour.

Journal ArticleDOI
TL;DR: In the recent extensive studies of infections and immunity, in which inoculation of animals with virulent, toxic, or antitoxic material is one of the most extensively employed methods of investigation, this is usually accomplished by subcutaneous or intraperitoneal injections, t o which injections into the spinal canal, the brain, or the nerve were recently added.
Abstract: The rate of absorption from muscles has never yet been a subject of scientific investigation. In fact, nowhere in physiological li terature do we meet the suggestion tha t absorption from the muscles might differ from tha t of any other parenchymatous or subcutaneous tissue. Only from the serous cavities, especially the peritoneal, is it generally assumed tha t absorption takes place more rapidly than from the subcutaneous tissues. In the recent extensive studies of infections and immunity, in which inoculation of animals with virulent, toxic, or antitoxic material is one of the most extensively employed methods of investigation, this is usually accomplished by subcutaneous or intraperitoneal injections, t o which injections into the spinal canal, the brain, or the nerve t runks were recently added. In the lat ter cases, the injections are carried out rather to demonstrate their localized effect than to cause a general systemic infection or intoxication. Intramuscular injection, however, as far as we know, was never yet employed, at least not consciously, as a method of introducing infectious or toxic products into the circulation. In therapeutics, however, we now and then come across the pract.ice of intramuscular administrat ion of drugs. I t originated in the t rea tment of syphilis with mercury. When at the beginning of the '8o's of the last century it was found tha t hypodermic injections of any compound of mercury gave considerable pain and favored the development of abscesses at the site of injection, the method developed of giving deep-seated injections,

Journal ArticleDOI
TL;DR: The fact that dysentery bacilli have not been isolated frequently from the normal intestine might be explained by their habitat being possibly within the mucus tubules and their number few under normal condition, for it is well known that they are most frequently found in association with mucus.
Abstract: The group of dysentery organisms is a large and. varied one. It may be divided, as is well known, into two main sub-groups, the "Shiga-Kruse" and the "mannit-fermenters," which are of equal importance and entirely distinct. If we take decided differences in agglutination, as determined by absorptions, as a criterion of specificity, the latter group includes at least four distinct species with a number of sub-varieties and transition forms. Two of the above species are found among organisms which split either dextrose, mannit, and saccharose or in addition maltose. The other two species are represented by the bacillus "Y" of Hiss and Russell and the "Flexner-Manila" bacillus. If we adopt Ford's proposal, that a new species should be made for each culture showing a constant cultural or agglutinative difference, the number would increase considerably. At the best, however, classification of bacteria is at present very artificial. Although so many types appear among the " mannit-fermenters," there is no reason why they should not all be included in the dysentery group of bacilli, provided the reaction in litmus milk be typical. This cultural test, as Duval has emphasized, is the most constant one which we have at present, but it should extend over several weeks in order to exclude lactose fermenters. In contradistinction to the heterogeneity of the "mannit-fermenters," the homogeneity of the "Shiga-Kruse" type stands in marked contrast. Every culture of the latter which. was tested (about twenty in all) reacted in all media and agglutinated with all the various sera exactly alike. One is tempted to explain this diversity of the "mannit-fermenters" by accepting the suggestion of Flexner, that they may be occasional, if not constant, inhabitants of the normal intestine. Certainly Duval has isolated the "mannit-fermenters" from the mildest cases of diarrhœa, to say nothing of the two apparently normal infants from which he also obtained them. Furthermore, the agglutinins for the mannit group in normal blood might be accounted for on this hypothesis, as well as the many differences in fermentation and agglutination. For, as has been well said by Smith and Reagh, one " should keep in mind the various adaptations in the intestine—it may be to the food remains in the large intestine, to the mucus on the surface of the epithelium, to the contents of the tubules and the larger flask-shaped glands, and further, with this progressive adaptation are associated modifications of biological characters which most likely involve agglutinative capacities as well." The fact that dysentery bacilli have not been isolated frequently from the normal intestine might be explained by their habitat being possibly within the mucus tubules and their number few under normal condition, for it is well known that they are most frequently found in association with mucus. When abnormal conditions, however, arise and the production of mucus increases, these organisms would possibly multiply in number pari passu and find themselves in a favorable position to attack any slight injury which might occur in the wall of the intestine. The "Shiga-Kruse," or Group I, type, on the other hand, seems to present the characters of a true parasite. Only an insignificant amount of agglutinin is present for it in normal human blood and that of laboratory animals, according to most authorities; it agglutinates alike in various immune sera; it has a very marked toxicity for laboratory animals; it has never been isolated from the normal human intestine, although an organism in some respects like it has been described by Ford as being an inhabitant of the normal intestine; it produces no indol; it splits only the monosaccharids, through which it falls in line with the conclusion of Smith and Reagh, that the less a bacillus acts on sugars the more pronounced is its parasitic character. Whether or not it ever invades the blood in numbers is a question yet to be decided.

Journal ArticleDOI
TL;DR: The bodies present in blister fluid resemble very closely those granular bodies found in blood under certain conditions, and seen in vaccine lymph and in emulsions of tissues and in exudates, and it is thought that they are for the most part products of degenerating tissue cells and of leucocytes, and within certain limits specific to scarlet-fever and measles.
Abstract: In sections of control and normal skin, the nuclei of the epithelial cells were often indented by the cell protoplasm, giving them an appearance similar to those indented by Mallory's bodies. It would seem that if these bodies of Mallory's were protozoa they would have been found in the sections from both the living and the dead skin of scarlet-fever and measles, as they were present in the blister fluid. Their absence is certainly more suggestive of a degeneration than of a protozoon. This view is also borne out by the fact that they were not found immediately after death, but were present in another specimen from the same case removed twenty-four hours later. It would seem probable also that the bodies found in the blister fluid were the products of degeneration and cytolytic activity, because they were found in the antitoxin rashes as well as in the cases of scarlet-fever and measles. The histological changes in the skin of these two diseases leads us to expect the presence of cytolytic products both in the blister fluid and in the sections. It certainly cannot be stated that none of these bodies is a protozoon, but it can be positively stated that a great majority of them arise from degenerating cells; and in many cases, I think, it is not possible to differentiate a degeneration from a protozoon by the study of its morphology and staining reactions. The bodies present in blister fluid resemble very closely those granular bodies found in blood under certain conditions, and seen in vaccine lymph and in emulsions of tissues and in exudates. I think, therefore, that they are for the most part, if not wholly, products of degenerating tissue cells and of leucocytes, and within certain limits specific to scarlet-fever and measles.

Journal ArticleDOI
TL;DR: The methods which have been used in the operation for directing the blood of the portal vein into the vena cava are discussed, and a new instrument for cut t ing the opening between the veins is described.
Abstract: I t is the purpose of the following paper to discuss briefly the methods which have been used in the operation for directing the blood of the portal vein into the vena cava, and to describe a new instrument for cut t ing the opening between the veins. The operation is named after N. V. Eck (i), who conceived the idea of establishing an artificial anastomosis between the portal vein and the vena cava, in order to relieve the congestion of the portal system in cirrhosis of the liver. Never a t tempted upon the human being, the operation performed on dogs has yielded a great par t of the experimental facts concerning the normal physiology of the liver, and still offers an invaluable method for approaching many problems of metabolism. I shall leave aside for the present the question of the changes in the animal economy which follow the diversion of the portal blood current, simply appending a list of the literature bearing upon the subject. The necessity of a stringent asepsis during a surgical procedure requiring between one and two hours for its completion is self-evident. The unusual difficulties encountered are peculiar to this operation and are purely of a mechanical nature: one is referable to the inaccessibility of the site of the opera t iontha t portion of the portal vein extending about five to eight centimeters below the opening of the vena pancreatico-duodenalis, and the somewhat longer section of the vena cava between the


Journal ArticleDOI
TL;DR: Washed blood corpuscles of certain species of animals in a concentration of about 5 per cent suspended in salt solution containing above 4 per cent of cobra venom undergo changes in their resistance to certain physical and chemical agents.
Abstract: Washed blood corpuscles of certain species of animals in a concentration of about 5 per cent suspended in salt solution containing above 4 per cent of cobra venom undergo changes in their resistance to certain physical and chemical agents. They become non-haemolyzable by water, ether, saponin, and quite strong solutions of lecithin, provided always that the excess of venom has not been entirely removed. On the other hand, certain acids and alkalis, excepting ammonia, lake the venomized corpuscles more easily than they lake normal corpuscles. Venom solutions of 2 per cent and less exert no protective property upon blood corpuscles, but they induce changes in the corpuscles whereby they are rendered more easily laked by the same physical and chemical agents.

Journal ArticleDOI
TL;DR: Repeated attempts to prepare a permanent staining fluid by Nocht's method succeeded in so far that in the later preparations the same method of procedure was followed, but the polychrome tint for the nuclear material and the chromatin staining in the malarial parasite was unable to be obtained.
Abstract: The possibility of preparing a permanent staining solution from the formulas for Nocht's (I) stain was suggested by the constant use of Jenner's (2) stain for routine blood examinations and malarial staining during the summer and fall months of ~9ox. In malarial blood the pigmented bodies of tertian fever and the crescent bodies of mstivo-autumnal fever are readily demonstrated with Jenner's stain, and the use of poly-chrome stains was resorted to only in doubtful cases showing no full-grown forms of parasites. Goldhorn's (3) method of staining with the polychrome blue prepared from methylene blue and lithium carbonate proved valuable, but we were never able to obtain the constantly per-feet results obtained by employing the methods of Noeht as described by Lazier (4) and Ewing (5). No other method gives results comparable to these. The only objection to them is the time required (from two to twelve hours) for good staining. During the fall of ~9oI, repeated attempts to prepare a permanent staining fluid by Nocht's method succeeded in so far that in the later preparations the same method of procedure was followed, but we were unable to obtain the polychrome tint for the nuclear material and the chromatin staining in the malarial parasite until the publication of Leishman (6) suggested the final simple step in staining, that of diluting the staining fluid with distilled water after staining one minute in full strength and allowing this diluted stain to remain in contact with the specimen from three to five minutes.

Journal ArticleDOI
TL;DR: It is shown in the evidence set forth in this paper that the arginin base is lost to the proteid molecule more rapidly than the lysin base, and the correspondence between the findings in the liver and in the urine is thus a close one.
Abstract: The results above reported lead to the conclusion that while in the degenerating cells chemical changes are taking place tending toward a diminution of the hexon bases as a whole, they affect the arginin especially. One may picture the process either as a partial or as a complete breaking down of certain proteid. material more or less rich in hexon bases, leaving behind. proteid matter poorer in bases. The meaning of these changes is, however, obscure, and with the limited number of known facts bearing upon the subject, it would seem idle even to attempt to formulate an hypothesis to explain them. Certain work of other investigators is, however, suggestive in this connection. Kossel and Dakin, for instance, as illustrated by their work upon the simple proteid body clupein, found that a partial destruction of the proteid molecule, involving the arginin group, is brought about by a ferment furnished by the animal organism. When subjected to the hydrolytic action of a mineral acid, clupein yields arginin in considerable abundance. But if the clupein is first acted upon by the ferment arginase found in the liver, and then subjected to acid hydrolysis, the yield of arginin is appreciably diminished. Among the cleavage products in the latter instance are the components of arginin, namely, omithin and urea. It would seem, therefore, as if the ferment had loosened the union between the omithin and urea in the arginin group, so that upon subsequent hydrolysis a diminution of arginin resulted. In the cases studied by me, it may be that the conditions were favorable for some such ferment action as that above described, and hence the relatively low yield of arginin. No attempt, however, was made to ascertain if omithin were present in the urine. Its presence there would seem not wholly unlikely when one considers the diminished power of oxidation of the phosphorus-poisoned cell, although Thompson has shown that arginin or omithin when administered to a healthy dog as food or by hypodermic injection is eliminated for the most part as urea, no ornithin being found. There might seem to be a conflict between this view and the results recently published by Wohlgemuth, but it must be borne in mind that the influences at work causing the breaking down of the proteid molecule are probably quite diverse in character. Wohlgemuth has recently shown for the first time that a diamino acid may actually find its way into the urine in phosphorus poisoning. He found arginin in the urine not only in rabbits poisoned with phosphorus but also in a patient suffering from phosphorus poisoning. On the other hand, he was unable to find lysin in the urine. This fact is of especial interest in view of the evidence set forth in this paper that the arginin base is lost to the proteid molecule more rapidly than the lysin base. The correspondence between the findings in the liver and in the urine is thus a close one. How much of the arginin liberated from the proteid molecule may find its way into the urine is of course uncertain. It seems reasonable to suppose that a portion of the base is acted upon by the arginase ferment in the manner already described. Of the seventeen to eighteen cleavage products of the proteid molecule thus far isolated, the hexon bases are among the most stable. One or more of these bases have been found in practically all proteid matter thus far investigated; in fact arginin is so uniformly present that Kossel has made the suggestion that it is the kernel of the proteid molecule. At all events, the question may be asked, whether, if the influences at work in the altered liver tissue were of a general character causing a diminution of the hexon bases, the monoamino acid groups would not suffer even a greater diminution; and since the pathological condition is undoubtedly associated with impaired oxidation, their presence should not be expected in the urine. As a matter of fact, Ignatowski found considerable quantities of monoamino acids in the urine of patients suffering from gout, pneumonia, and leukaemia, though under normal conditions no monoamino acids were found in the urine, indeed, not even after the subcutaneous injection of glycokoll. Furthermore, the loosening of the amino acids from the proteid molecule is suggested by the fact that Taylor found such acids in the liver of a patient who died from a hepatic disease of obscure etiology, but which he was inclined to attribute to chloroform poisoning. Taylor found not only leucin and tyrosin in the liver, but also arginin, a fact not without interest in view of the diminished arginin content found in the livers of the chloroformed dogs after acid hydrolysis. Moreover, the falling off of the hexon bases under the conditions studied seems quite in accordance with some results recently reported by Levene. He has shown that certain cleavage products obtained by the action of mineral acids upon self-digested pancreas, spleen, and liver, are much diminished when compared with the products obtained from the fresh glands. The lysin and arginin of the digested liver, for example, showed a diminution of over 50 per cent. It is now well established that in course of the process of aseptic autolysis, the proteids of the liver cell undergo decomposition into simpler substances, and Jacoby showed that during life autolysis may go on in portions of the liver in which the circulation has been hindered. But of greater significance still in this connection, is the observation made by Jacoby on the autolytic changes in the liver during phosphorus poisoning. He found that when the normal liver substance is permitted to autolyse the solution of the liver substance is a slow one. On the other hand, under similar conditions the liver of a phosphorus-poisoned animal undergoes rapid and almost complete solution. The difference in the behavior of the normal and damaged liver points to an increase of normal ferment action in the case of the poisoned organ. It thus seems reasonable to suppose that in phosphorus poisoning we have during life an exaggerated breaking down of the proteid molecule associated with an over-action of certain ferments, and among them probably arginase. The pathological process in the liver during life may, therefore, be thought of as proceeding in the same general direction as the process of post-morten autolytic decomposition. By means of further studies along lines indicated in this paper, it should be possible to gain a deeper insight into numerous pathological processes. The changes in amyloid degeneration are among those which promise to be better understood through the application of the new methods of chemical analysis. Moreover, it cannot be doubted that pharmacology as well as toxicology has much to gain from a study of what happens to the proteid molecule under the influence of poisons.

Journal ArticleDOI
TL;DR: With the living organisms, while the bactericidal immunity obtained from the inoculation of animals with the virulent organism is greater than that produced with the avirulent, such immunity is not in direct proportion to the virulence of the bacteria introduced.
Abstract: The virulent cholera spirillum possesses a greater number of bacteriolytic and agglutinable haptophore groups, or these groups are endowed with a greater avidity for uni- and amboceptors than the avirulent. The number or the avidity of the bacteriolytic receptors possessed by a bacterium is directly proportional to its virulence. However, the agglutinable receptors do not follow this law, i.e., the agglutinable haptophore groups are not necessarily present in the same proportion as the bactericidal ones. While the energy of growth is a very important factor in relation to virulence, other phenomena must also be considered. The virulent organism possesses a greater number of toxic haptophore groups than the avirulent. The binding power of the free receptors of the organisms for bacteriolytic amboceptors in vitro is proportional to the bactericidal immunity produced in animals by each, which latter is in turn proportional to the virulence of the organisms from which the receptors were extracted. The binding power in vitro of the dead micro-organisms of different virulence for bacteriolytic amboceptors is not in proportion to their toxicity. The bactericidal immunity obtained by means of the inoculation with the dead organisms of different virulence, or their extracts obtained by autolytic digestion, is proportional to the virulence of the living strains of the bacteria employed. With the living organisms, while the bactericidal immunity obtained from the inoculation of animals with the virulent organism is greater than that produced with the avirulent, such immunity is not in direct proportion to the virulence of the bacteria introduced. These conclusions apply to the two strains of cholera spirilk employed in the foregoing experiments. Whether they will also hold good with other strains of this spirillum or for micro organisms in general, must be decided by further experimenta work.

Journal ArticleDOI
TL;DR: During the investigations described in another paper defibrinated blood and blood serum were frequently used, either alone or mixed with agar, as media upon which to grow pneumoeocci and streptococci, and certain changes besides the actual agglutination were noted in the bacteria and serum.
Abstract: During the investigations described in another paper defibrinated blood and blood serum were frequently used, either alone or mixed with agar, as media upon which to grow pneumoeocci and streptococci. It was immediately noted that the organisms grew very differently in serum obtained from different individuals. The variations were so marked and the results obtained so striking that it was decided to study the matter more carefully. To this end the growth of pneumococci and streptococci was studied in the blood serum of thirty-two individuals. Besides the human sera, horse's serum, calf's serum, and rabbit's serum were used. In the researches conducted by Besangon and Griffon, 1 Huber, 2 Neufeld, 3 and Wadsworth 4 upon the agglutination of pneumococci by the serum of pneumonia patients and of immunized animals, certain changes besides the actual agglutination were noted in the bacteria and serum. Huber in particular calls attention to the heavy precipitate formed by growing pneumococci in pneumonic serum, a phenomenon which did not occur in the serum from normal individuals, when used as a culture medium for pneumococci. Neufeld describes swelling of the capsules of the pneumococci when treated with the serum from cases of pneumonia or from immunized animals. Wadsworth has confirmed these observations. Recently Rosenow s has called attention to another very interesting result of the