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A Method for the Roentgenological Visualization of the Gall-bladder'

BY EVARTS A. GRAHAM, St. Louis, Missouri

INCE last summer Dr. Cole

and I have been carrying out experimental work along the line of the diagnosis of lesions of the gall-bladder. It has long been hoped that the gall-bladder could be made visible so that pictures could be taken by means of the X-ray which would be as clear-cut and decisive as those of the stomach when a barium meal is given. It occurred to us that since about 90 per cent of tetrachlorphenolphthalein is excreted through the bile, we might get something which would be excreted into the gall-bladder and at the same time be opaque. We have found that the sodium salt of tetrabromphenolphthalein, when injected intravenously, makes the gall-bladder show as plainly as a bone, sometimes as clear-cut as the stomach after the barium meal.

'Read at the Congress of Internal Medicine, St. Louis, Mo., February, 1924.

Since the report of this preliminary work before the Congress of Internal Medicine in February, 1924, we have made several modifications of our method and we have made many more observations. A more complete and a later report of this work will be found in the Journal of the American Medical Association for May 31, 1924.

We have injected about 28 cases and the only bad symptoms have been nausea and vomiting in some of the cases. There has been no change in the urine or bile and no abnormality in the liver itself, although we have removed small pieces of the liver frequently and searched for any possible change in the liver tissue.

In a picture of a normal gall-bladder taken two hours after the injection no gall-bladder is apparent. In a picture taken seven and a half hours after the injection there can be seen a faint shadow of the gall-bladder appearing. Twenty-four hours after the injection the gall-bladder can be seen very plainly, as plainly as the ribs. By twenty-nine hours after the injection the gall-bladder has become smaller in the attempt to force this material out. Finally, in fifty-four hours the shadow has all disappeared again because of the excretion of the substance. Pictures of a gall-bladder distorted by adhesions twenty and twenty-four hours after the injection show the lesion very clearly. We have found that this method has proved very successful in demonstrating gallbladder lesions.

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Editorial

ITH Volume III, Number

One, the ANNALS OF CLINICAL MEDICINE enters upon its third year. It has established itself so securely that the Board of Regents of the American College of Physicians and the American Congress on Internal Medicine has decided to change it from a bi-monthly to a monthly publication and to increase the size of each volume from a page-content of about six hundred to one of about a thousand pages. An effort will be made to make the ANNALS pre-eminently a journal representing the field of internal medicine from all possible points of view that concern the internist. Not only will the etiology, bacteriology, pathology, pathological physiology, biochemistry, symptomatology and therapy of the affections that fall into the category of internal diseases be represented fully; but the points of contact between internal medicine and the other branches of practical medicine, as surgery, neurology and psychiatry, obstetrics and gynecology, ophthalmology, dermatology and syphilology, radiology and the other more restricted specialities, will also be presented in timely and appropriate articles. It is not the intention of the editor to make of the ANNALS an ultra-scientific journal directed chiefly to the publication of new experimental investigations, but rather to make of it a practical scientific medium giving to practicing physicians in a

concise and usable form the information they should possess as to the new advances and discoveries in the field of internal medicine. It should serve the general practitioner as an index of the progress of the internist's science. The cultural side of this branch of medicine will, likewise, not be neglected. Articles on medical history will be published from time to time, and a special feature will be made of reprintings of the classics of internal medicine in their original form with short biographies and commentaries. It is hoped that in every number the articles printed may present such a variety of subject matter as to intrigue the interest of the reader, besides giving him new and valuable information that will be of service to him in the practice of his profession. It is not intended that contributions to the ANNALS shall come exclusively from members of the College or Congress. Articles of interest and value bearing upon internal medicine will be welcomed from any source. sides the papers presented before the annual meeting of the College and Congress it is hoped that many valuable individual observations experiences noted by practitioners may find a place of record in the pages of this journal. To every active and observant practical man of medicine there come opportunities of unique or valuable observations that may be of service in advancing the sum total of medical knowledge. The

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and

editor will, of course, assume no responsibility for the accuracy of the opinions presented in the articles accepted. The criteria of acceptance will depend upon the apparent interest and usefulness of the articles submitted. In addition to the publication of such papers there will be gradually developed a department of abstracts of important articles bearing upon internal medicine appearing in both English and foreign jour

nals and selected because of their especial interest. The department of reviews will make a special feature of the review of new books bearing upon the science or practice of internal medicine. The purpose of such reviews will be to give to the internist a definite idea of the scope and character of the material contained within such books so that he may be able to decide for himself their usefulness to him.

Abstracts

1. A Skin Test for Susceptibility to Scarlet Fever, GEORGE F. DICK and GLADYS H. DICK, Jour. Amer. Med. Assoc., January 26, 1924, p. 265.

2. The Etiology of Scarlet Fever, GEORGE F. DICK and GLADYS H. DICK, Ibid., p. 301.

3. Scarlet Fever Toxin in Preventive Immunization, GEORGE F. DICK and GLADYS H. DICK, Jour. Amer. Med. Assoc., February 16, 1924, p. 544.

4. A Scarlet Fever Antitoxin, George F. DICK and GLADYS H. DICK, Jour. Amer. Med. Assoc., April 19, 1924, p. 1246.

5. Results Obtained with the Dick Test in Normal Individuals and in Acute and Convalescent Cases of Scarlet Fever, ABRAHAM ZINGHER, Proc. Soc. Exper. Biol. Med., March 19, 1924, p. 293. No experimental work on scarlet fever has so stirred the hopes of the medical profession that the problem of scarlet fever has finally been solved by medical science as the four papers by Dr. and Mrs. Dick given above, and the confirmatory practical work of Dr. Zingher in the last one. As is well known the Dicks have been working upon scarlet fever in an intensive manner since 1916. In 1923 they succeeded in producing experimental scarlet fever with an apparently pure culture of a hemolytic streptococcus isolated from a case of scarlet fever. The Berkefeld V filtrate of this culture did not produce scarlet fever in a person who later developed the disease on inoculation with the unfiltered culture. In a series of ten inoculation experiments two of the volunteers acquired scarlet fever. All of the ten volunteers were young adults who had never had scarlet fever, and they were all inoculated with the same culture. The failure of some of the inoculated to develop the disease while others developed typical scarlet fever is explainable on the grounds of a difference in susceptibility

and is in full accord with our old experience with this disease clinically.

Their further work showed that the filtrate of the culture that produced experimental scarlet fever, when used in the proper dilution, gave positive or strongly positive skin tests in 41.6 per cent of persons having no history of scarlet fever. All of the convalescent scarlet fever patients tested showed negative or only slightly positive reactions. The action of the filtrate on the skin was inhibited by convalescent scarlet fever serum mixed with the filtrate before it was injected, or given intramuscularly before the test was made. In two instances in which it was possible to observe the test before and after an attack of scarlet fever, it was positive during the attack and negative during convalescence. The investigators concluded, therefore, that the skin test described bears a specific relation to immunity to scarlet fever. In an editorial in the same number of the Journal of the American Medical Association the prophetic hope was expressed that the "Dick test" may assume the same importance in scarlet fever as does the Schick test in diphtheria.

In their third paper their experimental work showed that when persons having positive skin tests for susceptibility to scarlet fever are injected with suitable quantities of the toxic filtrate they may develop a scarlatinal rash with nausea, vomiting, rise in temperature and general malaise. These symptoms appear within a few hours after the injection and disappear within forty-eight hours. Following this reaction the skin test is negative or only slightly positive. The short interval between the injection and the beginning of the reaction compares with the incubation period of about forty-eight hours in experimental scarlet fever, and the more rapid disappearance of the symptoms in

dicates that the effect is produced by a soluble toxic substance rather than by a filtrable virus. The resistance to heat at temperatures ordinarily employed to kill bacteria is further evidence that we are dealing with a toxin. The similarity of the symptoms produced by the filtrate to those of scarlet fever and the resulting modification of the skin test indicate the production of some degree of active immunity to scarlet fever. The neutralization of the toxic substance in the filtrate by the blood serum of a person who had received injections of the filtrate indicates that the toxic substance is a true toxin capable of forming an antitoxin.

In their fourth paper the Dicks announce that they have succeeded in obtaining a scarlet fever antitoxin by immunizing a horse with scarlet fever toxin. This antitoxin may be concentrated by the methods employed for concentrating the antitoxic serums. The therapeutic value of the antitoxin can be determined only when the results of its use in a large series of carefully controlled cases are available.

Zingher gives the result of a study of the use of the Dick test in normal individuals similar to studies that have been made along similar lines with the Schick test, and found it very valuable for diagnostic purposes, as positive reactions obtained during the first day or two of a suspicious scarlet-fever-like rash and again two weeks or more after the fading of the rash will indicate that the patient did not have scarlet fever. He considers the test of great value and predicts that like the Schick test, it will have an increasing field of application in the selection of susceptible individuals for passive and active immunization. With the discovery of the toxin-producing power of the hemolytic streptococcus an immense field of productive research is thrown open to the investigator in regard to the character of the toxins produced by various strains of hemolytic streptococci.

The work of the Dicks may be summed up as follows:

1. From cultures of a certain strain of hemolytic streptococcus, long suspected as the cause of scarlet fever, they have succeeded in producing experimental scarlet fever in the human individual.

2. From such cultures they have obtained a soluble toxic substance that produces a well-defined local reaction when injected subcutaneously. This effect may be neutralized by mixing the culture filtrate with the serum of recovered patients. The reaction is positive in persons who have not had scarlet fever, and during the early stage of scarlet fever, but becomes less pronounced as the disease progresses, and is absent after recovery, and for a long time afterwards. A positive reaction would indicate susceptibility, a negative, an immunity to scarlet fever.

3. In persons shown to be susceptible to scarlet fever by means of the Dick test, injections of the soluble toxin produce a definite abortive scarlatinal reaction with production of immunity. Their work shows that the toxic substance is a true toxin capable of producing an antitoxin.

4. Such an antitoxin has been produced in the horse, and is capable of concentration in the same way as the antitoxic

serums.

Zingher has already shown the value of the Dick test in public health work and prophesies for it as useful an application as that of the Schick test.

Much yet remains to be done in the control of the above work, especially in so far as the therapeutic use of the antitoxin is concerned. The results of these investigators are announced, however, in so modest and scientific a manner, that they carry conviction as to their thorough sincerity. When the final controls have been carried through and full confirmation obtained, this work will be welcomed as one of the epoch-making achievements of scientific medicine.

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