PRESIDENT AND PROFESSOR OF NEUROLOGY AND CLINICAL MEDI- ON our return trip from the International Congress of Medicine which met in London last August, one of us (Crowell) prepared a paper giving briefly the results of the latest work done in Prof. Ehrlich's Laboratory. This information was obtained from him while conducting our party through his laboratory and from his paper on chemotherapy, which he read at the above-named congress. Believing the members of this Society would be interested in some phases of this paper and especially that portion with reference to the use of salvarsanized serum in the treatment of certain cases of syphilis affecting the central nervous system we decided to reproduce this paper briefly and report some cases in which we have treated the spinal fluid with salvarsanized serum with apparent excellent results. In his investigations to ascertain the way in which salvarsan acted upon the Spirocheta pallida, Professor Ehrlich found it somewhat different from what was first supposed. (In this, parenthetically, we will say that we believe he has laid the foundation upon which a chemotherapy may be built that will eventually result in the discovery of specific therapeutic remedies that will apply to all infections equally as efficient as "606" in the treatment of syphilis.) It is now known that parasites are killed only by those drugs for which they have an affinity. These drugs are termed parasitatropic. At first the theory was that "606" destroyed the spirochete by direct action, but further investigation shows it to be indirect as well, in that it fixes the remedy and excites the organism to the formation of specific antisubstances. This view is based upon the fact that a solution of salvarsan may be added to a tube which contains the microorganisms without either destroying them directly or diminishing their motility. If, however, these are injected into test mice they will not infect the animal, while those not so treated will. This shows that the salvarsan is absorbed by the spirochetes and so damages them as to prevent their increase in the human body. In this way the direct effect of the remedy by fixation is proved, but it acts in a different manner from what was first supposed. Ehrlich found that when a race of trypanosomes had been rendered immune against all the allies of fuchsin it was still not immune against arsenic and other compounds. This shows that the immunity is of specific nature since it is limited to a definite class of substances and shows it to be a purely chemical process. He also discovered that in the parasites there are different specific chemoreceptors which condition. the fixation of salvarsan and other drugs at the same time. This gives an intelligent reason for the use of mercury with salvarsan in the treatment of syphilis and the only one I have ever heard. A complete knowledge of all chemoreceptors of a given parasite is the basis upon which rests the success of chemotherapy and which is gradually and surely being worked out. The larger the number of different chemoreceptors, therefore, which can be demonstrated, the greater is the possibility of a successful chemotherapy. To apply specific remedies, it is necessary to select one chemically allied to one of the chemoreceptors of the parasite; one which is not only haptophoric (fixes) but is toxophoric (destroys) as well. "The toxophoric groups of synthetic drugs poison the protoplasm of the bacterial cell when a chemical affinity exists between the toxophoric grouping and the cell constitutent." It is not a difficult matter to destroy germs in a solution, but the question of internal disinfection is a very difficult one, as the living parasites are within the infected organism. Such poisons as would destroy the germs in solution may be powerful cell poisons-organotropic as well as parasitotropic. Bichloride of mercury would be useless for this purpose, though a parasitotropic, yet so powerfully organotropic as to render it useless for such a purpose. Only such substances can be considered therapeutic agents of which a fraction of the dosis tolerata is sufficient to bring about therapeutic effects. The organotropic effect of a drug is due to the fact that there are quite different chemoreceptors in the various cells of the body, just as found in the parasites. Ehrlich domonstrated that parasites possess a whole series of chemoreceptors different from each other. If we can discover a grouping in the parasites which has no analogue in the organs of the body, the possibility of constructing an ideal remedy is accomplished. Such a remedy would be innocuous, as it is not fixed by the body cell and strikes the parasites with full intensity. The theoretical and experimental work is easy, but the step from the laboratory to the bedside is difficult and dangerous, on account of the idiosyncrasies of men to certain drugs. This supersensitiveness does not exist in animals. Salvarsan is so constructed that a manifestation of a supersensitiveness to it is one of the rarest occurrences, owing to the fact that the protoplasmic cell receptors do not fix the drug, but it is fixed only by the cell receptors of the spirochete. The apparent idiosyncrasies following its administration in man are due to errors in its preparation and administration. Too large an addition of alkali injures the veins used for injection, too small an amount causes blood coagulation and leads to thrombosis. Lengthy shaking of the solution and standing in the air oxidize the drug and make it much more toxic, forming an oxide of arsenic. Secondly, certain constitutional diseases, such as Addison's disease and status lymphaticus, cause a supersensitiveness to arsenic compounds. the resisting power is lowered in addition to the supersensitiveness to the drug. Here The seat and location of the disease may bring about a supersensitiveness excited by a local reaction. The rapid disintegration of a focus of parasites liberates toxins, which irritate the tissues and produce a hyperemia and swelling. This is of no significance if the reaction center is in the skin, but if it is located in the neighborhood of vital organs (brain) then this reaction may bring about changes inimical to life, or may even cause death. We believe this fact calls for a thorough investi gation of each patient coming under our care. Also the administration of iodide of potassium previous to giving salvarsan for the liberation of such central focuses is very advisable in many cases. These facts make the treatment of syphilitics not only a difficult but a responsible task. To free the body of spirochetes by means of one or two injections of "606," it is necessary that the dose be in proportion to the advance of the disease, since a definite number of parasites is destroyed by a definite dose of the remedy. The amount of the drug must be increased in proportion to the multiplicity of the parasites. These important facts call for the earliest treatment of syphilis possible, since not only is it far more possible to stamp out the disease with one or two doses of salvarsan in the early stages, but there is danger of irreparable injury to health or even the possibility of producing death in the late stages by endotoxins. Here the dark field illuminator and serological aids in our diagnostic work are of greatest importance. The causes which make it possible to rid the system of parasites are not only the drug administered but the action of the antibody produced by the cell under the influence of the drug. This is especially true of the protozoa. Spirochetes may escape the destructive action of both the drug and antibody and be changed into a new serum-proof variety known as a relapsing group. This is especially true of the trypanosomes, in particular those of syphilis. Such parasites offer very great difficulty in their treatment, since the auxiliary forces of the body fail to act. This makes it quite important to destroy the parasites all at once by means of drugs. Their great power of adaptation makes it possible for a single germ to cause a fresh outbreak of the disease. The great difficulty then of a complete sterilization of the body by means of a single dose of medicine is due to the fact that there are in the body what are known as dead spaces or corners, one of which is the hollow situated between the spinal cord and the dura. This is filled with fluid almost entirely free from cells and albumin, the cerebrospinal fluid. The cells by which this fluid is secreted are highly impervious to most of the constituents of the organism such as albumin, and permit only a limited quantity of substances with small molecules to pass through. The drug with more complex molecules are, like albumin, kept back and unable to exert their influence on the cerebrospinal fluid; this makes it well nigh impossible to destroy parasites located here. Another reason for deficient sterilization is that among the large number of parasites there may be some unaffected by salvarsan. This fact does not play an important part in the course of fresh infection, but is quite important in connection with certain cases of syphilis characterized by innumerable relapsing crops of the microorganism. Here one of two things may occur: First, it is possible for a drug-proof stock to be formed by adaptation, or, in other words, a strain may arise which is immune to the action of the drug. Second, the continual formation of relapsing crops can bring about a change in the chemoreceptors of the parasites and result either in an increased or a reduced power of resistance to the drug. We should expect, however, that the relapsing crops would become much less sensitive to the action of the drug than the original stock. These few facts show how difficult it is to cure syphilis in the late stages. In fact, I heard no less an authority than Professor Wassermann say at the International Congress in London that he doubted very much our ability to cure syphilis (up to the present) where it had existed for three years. Others thought it possible but only after a long series of injections-the socalled serial treatment. I believe it possible to cure almost any case at any stage of the disease by treating the dead spaces in the body and persisting in the treatment sufficiently long. Efforts have been made to render the epithelium more previous to therapeutic agents-so to change the cells as to allow more of the therapeutic agent to pass into the cerebrospinal fluid. This has proved unsuccessful. Direct injection of the remedy into the cerebrospinal fluid has been tried, but Professor Ehrlich is of the opinion-as the result of experimental work on animals-that these membranes are too sensitive for this, and advises the use of salvarsanized serum according to the plan suggested by Swift and Ellis of the Rockefeller Institute. The technique of this operation is as follows: First, give the salvarsan and draw into sterile tubes one hour thereafter about 50 c.c. of blood. Serum is obtained from this and 30 c.c. of a 40 to 50 per cent. solution of this serum is injected into the spinal fluid twentyfour hours thereafter. The saline solution for diluting this serum should be made of freshly distilled water. It is always well to withdraw as much as 30 c.c. of the cerebrospinal fluid before injecting the serum, and more if the pressure is high. This is practically always the case when the cell count is high and the globulin and Wassermann reactions are positive. It is well to bring the pressure down to 30 mm. before injecting the serum. This plan of administering the remedy obviates the ill effects of the drug on the sensitive central nervous system and at the same time makes it possible to apply the curative agent in sufficient quantities. Our investigations have not gone sufficiently far for us to say what are the positive indications for this method of treatment. At present, it appears to us the cases most likely to be benefited by this plan of treatment are those that have a spinal fluid with high pressure, a high cell count, a positive globulin and a positive Wassermann reaction. The following cases which we have treated upon this plan with results obtained are reported by Dr. Munroe: As the clinical forms of syphilis of the nervous system are largely abstractions yet for the definite application of therapeutic measures it is well to have distinctive lines drawn to indicate the recognized clinical types. It is not the purpose of this paper to discuss this classification, but it is necessary to refer briefly to the fact that a distinction is hereby made between cerebral syphilis and paresis. There are those who maintain that there are no real distinctions to be drawn. drawn. The majority perhaps say that the distinctions are justified not only by clinical symptoms but by the histological pathology, the different biological tests and the diverse results of therapy. It is only true to state that these differences are gradually melting away under the influence of more accurate clinical examinations and fuller laboratory researches. Strictly speaking, one should say paresis is one form of cerebral syphilis, the spirochetes which are being now recognized as the etiological factor having been demonstrated in the brain tissue. Yet, therapeutically, the same results have not been obtained as the condition known as cerebral syphilis ; and for this reason it may be well, for the present at least, to observe the distinction. There have been those who have contended that the therapeutic tests draw a decisive line, arguing that the paretic cases would not yield at all to treatment. It is true that paresis and tabes have been most resistant to ordinary treatment and it has been in hope of overcoming this resistance that we have been experimenting with a view to reaching more directly the diseased tissues. In the application of this treatment, however, we have not confined our work to paresis but are trying this method as described above on all cases that show disease of the central nervous system. We are not prepared yet to give the final results of this treatment because sufficient time has not elapsed. Our present purpose is to make a preliminary report of a few cases in which the results, up to the present at least, appear nopeful. The important points to be considered in connection with the diagnosis are: (1) Wassermann of the blood; (2) Wassermann of the spinal fluid; (3) pressure of the spinal fluid; (4) cell count of the spinal fluid; (5) globulin reaction of the spinal fluid; (6) condition of pupillary reflexes. Favorable therapeutic results are predicated on improvement in any or all of these features, together with improvement in the general symptoms of organic nervous diseases. CASE I.-Mr. W. Cerebral Syphilis.-Had been treated previously with five doses of salvarsan, intravenously. At the beginning of the present course of treatment the blood Wassermann was very positive, the spinal fluid Wassermann weakly positive, globulin weakly positive, cell count 11, pupils negative. Five treatments of salvarsan were given intravenously and in three of the treatments salvarsanized serum was injected into the spinal cavity. After this course of treatment the blood became negative. Spinal fluid negative. Cell count reduced to 3. The general symptoms had entirely disappeared. CASE II.-Mr. L. Paresis. In this case blood Wassermann strongly positive, spinal fluid Wassermann positive, globulin reaction positive, cell count 48. The pressure in this case was 160 mm., Hg. Pupils small and sluggish. Three treatments were given of salvarsan and in connection with two of them salvarsanized serum was injected into the spinal cavity. Mercury inunction was also used. As a result of these treatments the blood became negative to Wassermann, cell count 5, and globulin negative. Pressure not taken. I regret to say that this case did not remain with us long enough to complete even one course of treatment and has not been under observation since these treatments and I am quite sure that he will need further treatment and examination if any permanent results are to be expected. (Since this report was made the patient has returned and has been given more treatments of salvarsanized serum. Mental condition still good and Wassermann negative. Cell count 5.) ČASE III.-Mr. H. Cerebral Syphilis.-Blood Was sermann positive. Special Wassermann positive. Globulin weakly positive. Cell count 22. Pressure was not taken. Pupils negative. Five salvarsan treatments were given and along with three of the five, salvarsanized serum was injected into the spinal cavity. After treatment, cell count was 3, globulin slightly positive, and Wassermann on spinal fluid and blood negative. General symptoms very much improved, These are three of a number of cases now under treatment and observation and a mere outline is given showing improved conditions of spinal fluid in every case. We have not gone into details of the general symptoms, but as intimated these have shown marked improvement, some of them disappearing all together. It is our purpose at a later time to report these and other cases with tabulated statements of results. It is too early yet to predict what the ultimate results will be nor do we yet claim that this should be recognized as a firmly established mode of treatment. COMPARATIVE WASSERMANN, COBRA, AND GLOBULIN TESTS IN SYPHILIS. WITH A REPORT OF ONE HUNDRED AND FIVE REACTIONS.* BY WILLARD J. STONE, M.D., TOLEDO, OHIO. IN 1909 Weil' described the resistance of luetic red cells to cobra-venom hemolysis as a reaction of possible value in the diagnosis of syphilis. He found that while normal red cells were more or less rapidly hemolyzed with cobra-venom dilutions varying from 1 in 20,000 to 1 in 40,000, luetic red cells showed resistance to hemolysis with these dilutions. The reaction consisted in adding a portion of a 4 per cent. suspension of washed red cells to an equal portion of venom dilutions of the following strengths: 1 in 10,000, 1 in 20,000, 1 in 30,000, and 1 in 40,000. The resistance of luetic red cells to cobra-venom hemolysis has been considered to be due to (1) a decreased lecithin cell content as a reactive phenomenon to the luetic toxin; (2) that the cells had become lecithin-fast, with the result that less lecithin was available in a free state for hemolysis; (3) that the cholesterin of luetic red cells was increased which inhibited hemolysis in certain dilutions; or (4) that neither the lecithin nor cholesterin content was altered, but that a dissociation had occurred with inhibition of hemolysis by the latter substance. According to Pascucci2 the stromata of red blood. cells consist of one-third lecithin and cholesterin and two-thirds protein substances; while Wells states that dried red blood cells contain, according to Hoppe-Seyler, lecithin 0.3 to 0.7 per cent. and cholesterin 0.2 to 0.3 per cent. In the process of hemolysis cobra venom unites with lecithin to form what has been designated by Keyes as cobra-lecithin, or by von Dungern and Coca5 as desoleolecithin. It has been stated by Abderhalden that if red cells were washed absolutely free from serum, hemolysis did not occur with cobra venom. He does not mention the species of cells or dilutions of venom employed. He found that if a very small amount of serum or lecithin was added hemolysis took place. Lecithin was apparently necessary for hemolysis. Human red cells contain, at least under normal conditions, sufficient lecithin for the union with cobra venom. With human normal red cells hemolysis occurs after washing three to five times with sodium chloride solution in the centrifuge to remove the serum, and without the addition of lecithin. It is possible, however, that enough serum remains, even though inappreciable, to influence hemolysis. Whatever may ultimately prove to be the correct biochemical explanation, it is apparently true that luetic red cells behave differently than normal cells with the dilutions of cobra venom concerned in Weil's test. It should be mentioned in this connection that the resistance of red cells to hemolysis is *Read before the American Association of Immunologists, Atlantic City, June 21, 1914. not, in the strict sense, specific for syphilis, any more than the Wassermann reaction is specific for syphilis experimentally or clinically. Instances are common in which positive Wassermann reactions have been obtained by competent observers in a variety of conditions, such as scleroderma, scarlatina, leprosy, polycythemia, erythema multiforme, and non-luetic granulomata, such as pseudoleucemia. In addition, jaundice and chronic alcoholism interfere with complement fixation by the Wassermann method. According to Stafford the inoculation of tubercle vaccine may produce, in tuberculous patients, a positive Wassermann reaction. Nor is the reaction positive in more than 55 per cent. of latent tertiary syphilis. An analysis of 4,200 cases from the published reports of Corson-White', Schwartz, Wassermann, Fleischmann,10 Swift11 and Cummer and Dexter12 shows average positive Wassermann reactions in latent syphilis in 52 per cent. On the other hand, Schwartz obtained positive cobra reactions in one patient with scleroderma, in another with Raynaud's disease, and in three patients with advanced carcinoma, all of whom gave negative Wassermann reactions. 8 The Wassermann reaction is, however, a very important, if not the most important, confirmatory adjunct to a clinical diagnosis, and when repeatedly positive means syphilis in by far the larger percentage of cases. A negative reaction has less value in suspected latent tertiary conditions. While the cobra reaction does not fulfill all desired requirements in the diagnosis of syphilis, it nevertheless has an important field in clinical diagnosis when repeatedly positive, and is of value as an index for continued treatment of the disease. In an article on this subject by Schottstaedt and myself13 the technique of the reaction was described, together with the results obtained, to March 27, 1912, in an examination of 43 normals and controls and 87 patients with syphilis. Since then the test has been used in the examination of 105 individuals, making a total of 235 to May 1, 1914. Except in one instance mentioned below, the reaction has never been found positive in any individual in whom it was felt that syphilis could probably be excluded from a survey of the family and personal history and the physical examination. In the first test made, which was upon the blood of a patient with morbilliform erythema, the reaction was positive. It has never been possible to check this reaction with a Wassermann test, as the patient did not return. On the other hand, the cobra reaction has been negative in a number of instances of well defined luetic affections and in some others, in which from the clinical examination a luetic basis was suspected. The discrepancies were not great, barring the instances of early secondaries five and six weeks after infection. In these instances the clinical diagnosis was not in doubt. Field1 has reported the results obtained in a comparative study of the Wassermann and cobra-venom reactions in syphilis as follows: been used by me during the past year as follows: 2 c.c. of blood are drawn from one of the veins at the bend of the elbow into a 5 c.c. glass syringe containing 2 c.c. of 2 per cent. sodium citrate solution to prevent clotting. The blood-sodium citrate suspension is then placed in a 15 c.c. graduated centrifuge tube in the ice-box for a few hours, since less autohemolysis subsequently occurs, in the process of washing the cells, if the cells remain in contact with the serum and sodium citrate solution. The citrate and serum are then removed with a pipette and the tube filled with 0.9 per cent. sodium chloride solution, which is then placed in the centrifuge and the cells washed for about ten minutes at a speed of about 1000 revolutions per minute. This washing process is repeated three times, the supernatant solution being removed with a pipette and fresh sodium chloride solution added. After the last washing the cells are found to be packed in the bottom of the tube. It has been found convenient to remove with the pipette any cells in excess of 0.5 c.c. and then add enough 0.9 per cent. sodium chloride solution to bring the suspension to 12.5 c.c., which makes a 4 per cent. suspension of cells. The thumb is then placed over the end of the tube, which is inverted three or four times to secure an even suspension. One cubic centimeter of the 4 per cent. suspension is now added to each of four small test tubes. This is done with an accurate pipette. One cubic centimeter of cobra venom dilution, 1 in 15,000, is added to the first tube; 1 c.c. of dilution, 1 in 20,000, to the second tube; 1 c.c. of dilution, 1 in 30,000, to the third tube, and 1 c.c. of dilution, 1 in 40,000, to the fourth tube. The tubes are then covered with tin-foil and placed in the incubator for one hour at 37° C. At the end of one hour the tubes are gently shaken and placed in the ice-box for about 24 hours. At the end of this period if the blood is negative all tubes will show complete hemolysis. If hemolysis has occurred in the first tube, to which the 1 in 15,000 dilution of venom was added, but has not occurred in the others, the tubes are gently shaken, to bring into suspension any cells at the bottom, and are placed in the ice-box for one hour longer. At the end of this period, if hemolysis has not occurred in the tubes to which the 20,000th, 30,000th and 40,000th dilutions of venom have been added, the reaction is positive. Hemolysis practically always occurs in the tube to which the 1 in 15,000 dilution of venom has been added. This tube consequently serves as a check upon the reagent. In normal bloods hemolysis occurs in a 4 per cent. suspension of cells to which an equal volume of cobra-venom dilutions as high as 1 in 40,000 to 1 in 60,000 has been added. In a 4 per cent. cell suspension from patients with an active tuberculosis, hemolysis occurs six or seven times more rapidly with the dilutions concerned in this test than occurs with normal cells, a fact noticed by Schottstaedt, which was mentioned in our earlier article.13 Noguchi15 had, however, mentioned that in tuberculosis the red corpuscles are subnormal in point of resistance to hemolytic agents. The test as here applied serves to differentiate latent tuberculosis from syphilis in many cases, since in the former the red cells seem to be hypersusceptible, while in the latter the cells are hyposusceptible to cobra-venom hemolysis. In luetic bloods, about two months after the primary lesion, hemolysis is retarded or does not occur in a large majority of the cases, in the tubes to which dilutions of venom 1 in 20,000 or above have been added. The only apparent exceptions occur when the patient has had enough treatment to be considered clinically cured, or unless such a patient falls into the latent tertiary class, 25 per cent. of which may not give a positive reaction by this test, while the Wassermann fails also in approximately 50 per cent. Remarks Upon the Technique.-Too rapid centrifugation in the electric centrifuge while washing the cells will render them so fragile that hemolysis of luetic cells may occur and the reaction be considered negative. A centrifugal speed of about 1000 revolutions per minute does not entail this risk. Failure to recognize this possibility has probably militated against the results in the hands of some workers. It is important to make the 4 per cent. suspension of cells accurately, since an excess may be sufficient to inhibit hemolysis in some of the tubes and produce the effect of a positive reaction in normal blood. It is also important to have the venom dilutions accurately and freshly made. With this end in view it has been found best to powder the crystalline venom to permit more accurate weighing. This is done by rubbing it in a mortar with a few drops of commercial benzine, which is allowed to evaporate, leaving an amorphous powder. The venom powder is then weighed into 0.5 mg. portions, and each portion placed in a small dry corked test tube until ready for use. If 1 c.c. of 0.9 per cent. sodium chloride solution is added to a tube containing 0.5 mg. venom, a stock 1 in 2000, dilution is secured from which the subdilutions are readily made as follows: It will thus be seen that 0.5 mg. venom made into the 1 in 2000 stock dilution is sufficient for two tests. The subdilutions hold their potency for at least four or five days if kept in the ice-box.* Fresh specimens of venom should be tested and the hemolytic activity determined on normal and luetic red cells. In performing the Noguchi butyric acid test for increased globulin the following procedure has been followed: To 1 c.c. of a 10 per cent. solution of pure butyric acid in physiological salt solution, in a test tube, 0.2 c.c. of blood serum or cerebrospinal fluid is added. The mixture is heated to boiling, 0.2 c.c. of normal sodium hydrate solution is added, and the mixture again boiled. In the presence of increased globulin a definite flocculent precipitate occurs either immediately or within an hour or two. In performing the test on cerebrospinal fluid only clear fluid, free from blood, should be used. The same procedure is applicable to clear blood serum, from *Those who may desire to secure cobra venom should address inquiries to the Loomis Laboratory, 414 E. 26th St., New York, where it may be possible to secure a limited amount by importation. One gram is sufficient for 4,000 tests. which all blood cells have been removed by centrifugation. Hemoglobulin stained serum should be discarded. Part of the Wassermann tests were performed with the anti-sheep method; in the balance the anti-human method was followed. Summary.-The conclusions here given comprise comparative cobra, Wassermann, and globulin tests in one hundred and five individuals. All "suspicious" reactions have been excluded. 1-In 30 normals and controls the Wassermann and cobra tests were negative. In 6 of these the globulin test was negative in spinal fluid. In 90 other normals and controls the cobra test was negative. 2-In 22 patients with secondary syphilis the Wassermann and cobra tests were positive. In 5 of these the globulin test was also positive in the spinal fluid, while in 7 the globulin test was positive in the blood serum. 3-In 7 patients with active and latent tertiary syphilis the cobra blood test was positive, and the globulin tests in blood serum and spinal fluid were positive. 4-In 24 late tertiary and clinically cured cases both Wassermann and cobra tests were negative. 5 In 1 patient with cerebral lues the Wassermann and cobra tests were negative, while the globulin test was positive in blood serum and spinal fluid. 6-In 7 patients with syphilis the cobra test was positive and the Wassermann was negative, while in 14 instances the Wassermann was positive and the cobra negative. Two of the latter were instances of early secondaries five and six weeks after infection, in which the diagnosis was not in doubt. I am indebted to Dr. Richard Schottstaedt for his assistance in the tests and the tabulation of results. REFERENCES. 1. Weil, R.: Proc. Soc. Exper. Biol. and Med., 1909, VI, 49; 1909, VII, 2, and Journal Infect. Dis., 1909, VI, 688. 2. Pascucci: Hofmeister's "Beiträge," 1905, 6, 543, quoted by Hober; Physik. Chem. d. Želle u. d. Gewebe, 1906, p. 176. 3. Wells: Chem. Pathol., 1907, p. 239. 4. Kyes: Berl. klin. Wochenschr., 1902, XXXIX, 886; 1903, XLII, 21; 1903, XLII, 956; Biochem. Ztschr., 1907, IV, 109; Jour. Infect. Dis., 1910, VII, 181. 5. von Dungern and Coca: München. med. Wochnschr., 1907, IV, 2,317; 1908, LV, 105; Biochem. Ztschr., 1908, XII, 407; Jour. Infect. Dis., 1912, X, 57, 6. Abderhalden: Physiol. Chem., 1908, pp. 115, 117. 7. Corson-White: Personal communication. Corson-White and Ludlum: Jour. Nerv. and Mental Dis., 1910, XXXVII 721. 8. Schwartz: N. Y. Med. Jour., 1912, XCV, 23. 9. Wassermann: Quoted by Bolduan, "Immune Sera," 1911, p. 198. 10. Fleischmann: Quoted by Bolduan, “Immune Sera," 1911, p. 197. 11. Swift: Archives Int. Med., 1909, IV, 376. 12. Cummer and Dexter: Ohio State Med. Jour., December 15, 1911. 13. Stone and 1912, X, 8. Schottstaedt: Archives Int. Med., 14. Field, C. W.: Proc. New York Path. Soc., 1912, new series, VI. 15. Noguchi: "Serum Diagnosis of Syphilis," edition 1910, p. 78. Old Injury to Elbow.-C. Woodward reports the case of a child aged 7 years who fell on a stone and was treated with a splint for "fracture of a small bone and a bone out of place." All movements were remarkably free but the arm was very weak. The skiagram showed an anterior dislocation of the radius and the site of fracture of the ulna.-Proceedings of the Royal So ciety of Medicine. |