under observation, is to give a dose of salvarsan or neosalvarsan at once, then a course of mercury lasting six weeks, then another injection of the drug followed by a six month's treatment with mercury, pushing the mercury pretty vigorously and giving potassium iodide about one week in every five, and having a serum test made about every six weeks.

It has long thought that the first six months were the most important period of treatment, even under the old regime. There was a dictum to the effect that if the patient could be well treated during the first six months, he had little to fear afterward.

One is here between the-Scylla and Charybdis. He is between the danger of insufficient treatment on the one hand, allowing the disease in its period of highest amenability to treatment to lapse into a state of refractory latency, and on the other hand to overtreat the patient with drugs, which are undisputedly harmful to the organism generally, and greatly disorder the body metabolism.

At this time I advise about three months' rest, to give the patient a chance to recover from his strenuous treatment, assisting with tonics. At the end of the three months a Wassermann may be taken, and the subsequent treatment will somewhat depend upon the result of this. If it is negative, a further respite may be allowed. If it is positive, the salvarsan and mercury treatment may be repeated, of course all the time fortifying the patient as much as possible with general tonic and hygienic treatment.

Among men who do a great deal of this sort of work, there seems yet to be a great difference of opinion as to the proper kind and duration of treatment. Campbell and Patch of Montreal, recommend a dose of salvarsan, repeated in two or three weeks in secondary cases and depend for further treatment upon the further indications. Boos, of the Massachusetts General, recommends eight injections of calomel at intervals of four or five days, from 70 to 40 mg. at a dose, the injections being given in the afternoon and the patient put to bed immediately afterward. This is to be followed by injections of salvarsan (0.5 to 0.6 gm.) at intervals of three or four days, and five or six being given in all. He reports 25 cases so treated to show absence of the serum reaction and all clinical symptoms to the date of his article. A serological test was made every two weeks. He claims that it is possible to finish the treatment in four or five weeks. Corbus of Chicago,

gives doses of salvarsan repeatedly, meanwhile giving inunctions of mercury, has a blood test made frequently, and continues the mercury by the mouth and by inunctions for eighteen months after the serum test becomes negative.

This difference of opinion seems to apply only to the secondary cases. Practically all are united in the belief that where the primary lesion can be positively diagnosed by means of finding the spirochetae in the lesion, that immediate and energetic treatment by salvarasn should be begun. We have abundant evidence of the possibility of aborting the disease in the primary stage by the use of salvarsan. Boos reports cases treated by his method as mentioned above, that show a complete absence of clinical symptoms and a permanently negative serum reaction at the end of four years. By Campbell and Patch, 21 cases of primary were followed after being given "606", in 19 all the secondary symptoms were entirely aborted, in two cases recurrences occurred at the site of the primary lesion, which were cured by a second injection. Swift and Ellis think it possible to prevent the infection from becoming general by early use of salvarsan, in those cases in which the Wassermann test is not positive at the time of appearance of the chancre. According to Bruck only 40 per cent are Wassermann positive at the time of the appearance of the lesion, in the following three weeks only about 75 per cent become positive, but at the time of the appearance of the secondaries practically all are positive. Swift claims that if the Wassermann is allowed to become positive, the time of treatment is increased threefold.

Personally I have knowledge of two cases of primary genital chancre diagnosed by the finding of the spirochetae in the lesion, which were given one intravenous dose of salvarsan and remained Wassermann negative for six months thereafter, when they were lost to observation. In the Journal A.M.A., August 10, 1912, A. A. Thibaudeau states that he found spirochetae resembling the pallida, probably the S. microdentia, in 41 per cent of normal mouths examined. This was in addition to several other varieties. The presence of the s. refringens has many times been demonstrated in non-luetic genital sores.

Considering these facts, and the impossibility of other than the most highly trained laboratory men, by cultural methods establishing the exact form of organism, one may find considerable difficulty in making exact diagnosis, especially in mouth

an

chancres. However, the benefit of an early treatment so far offsets the possibility of treating some cases that do not need it, that I think it advisable in all cases where the history as to possible contact and the time of appearance of the lesion and its general characteristics, even in the absence of the serum test, point strongly toward a primary syphilitic lesion, to treat it as such. The reports of such cases would be worth very little as scientific observations, but in my own mind I am satisfied that many cases would remain purely local lesions rather than going on to be a general systemic infection as would be shown by the serum test becoming positive.

The subsequent indications for treatment would depend upon the clinical symptoms and the Wassermann reaction.

Very difficult it is also to tell when the patient is cured. We all know that the Wassermann test disappears under treat ment, only to reappear later. Clinical symptoms remain quiescent for years. Not all patients can afford to pay for a serum test every few weeks. How, then, are we to tell when the patient has had enough treatment?

It is in this connection that the luetin test of Noguchi comes in. He claims for it that it is possible to tell by means of the clinical symptoms, the serological test or the luetin test if a case is in the latent stage, or if a cure is had. That any two of the triad may be absent, but never the three.

To quote Noguchi, "The luetin test has its own sphere. The reaction does not appear until an allergic state of the skin developes from the presence of the infection, but seems to persist until the probable eradication of the disease from the system, and it remains uninfluenced by ineffective treatment. During the late stage, when the visceral organs are affected, the luetin test assumes an important position in determining the nature of the infection. In other words, the earlier stages can best be diagnosed by the demonstration of the pallidum, by the clinical manifestations and by the sereological tests. The late stages by resorting to the luetin test."

However, Noguchi mentions having met with a number of cases of hereditary syphilis, where, in spite of a strong serum reaction and extensive clinical manifestations, no luetin test was obtained.

He considers these cases of bad prognostic character, as indicating that the disease is too severe to enable the patients to respond by the development of allergy. Thus the luetin test indicates either that

the infection is well borne by the patient, or that it is under better control, due to treatment. It is natural to find cases with a negative Wassermann and a positive luetin, although both are many times co-existent.

In my personal experience with the luetin test, I have been limited to the observation of some ten or twelve cases inoculated by Dr. VanAtta at the old City Hospital. I made a detailed report to Dr. VanAtta at that time as to the subsequent appearances at the site of inoculation, together with the case histories and the result of the Wassermann tests as made in his laboratory. The reaction at the site of the control was in practically each instance as strong as at the site of vaccination. With a very limited knowledge of the test, I could not interpret the results of the injections which were very carefully given. The only result that I could see the rationale of was one given to a patient in the hospital for stricture, who was not suspected of syphilis. He gave absolutely no reaction. There was another case with gumma of the sternum and probably visceral syphilis who was on treatment and gave a very much delayed reaction, practically none for the first five days and then only a slight one. This may have been due, as Noguchi states, to the lack of allergic response at first, which augmented under the treatment he was in the meantime subjected to.

Fin

The occurrence of neuro-recurrences; which is taken to mean the occurrence of a nervous lesion, generally in certain cranial nerves (particularly those of the eye and ear) usually in secondary cases, from four to six weeks after the injection of salvarsan, has awakened a good deal of discussion. ger of Vienna and his followers allege that these are more frequent under salvarsan than under the mercury treatment. This latter assertion has been denied by equally competent authority. Ehrlich asserts that these lesions are caused by isolated nests of spirochetae, and by anatomical disadvantages of the parts, e.g., nerves passing through long bony canals offering a place of low resistance. These recurrences disappear under further treatment.

Practically all of the observers unite in recommending the use of salvarsan or neosalvarsan, differing only in the number of injections, the time of injection and the method of administering.

So we come to the question of the best method of administering the salvarsan. This will be sure to give rise to a good deal of discussion, as each of us who has had experience with the drug will be convinced

that his is the only way to properly use it. We have given about twenty of the intramuscular injections, after several different technics. The method of Alt we found very painful, even with the use of morphine. We also tried the method of making up a small alkaline solution, about 50 c.c. in all, and injecting it in about six different locations along the back muscles and in the buttocks. This was very painful. We also tried the iodipin suspension in a few cases, but there was a good deal of waste to this method in our hands, as some of the suspension would stick to the mortar, some to the syringe.

The iodipin suspension was less painful than any other intramuscular method tried.

In the use of neosalvarsan we tried the method of Wolbarst, using as a menstruum about 5 c.c. of glycerin and 1 c.c. of a 1 per cent solution of beta-eucaine, mixing in the neosalvarsan with a good deal of triturition and getting practically a clear solution. We also used plain sterile water as a solvent, about 15 c. c., and preceded the injection with about 1 c.c. of 1 per cent novocaine-dividing up the dose so that only about 5 c.c. was injected in any one place. In any case, in almost every instance the site of injection begins to give a good deal of pain after a few hours, when the effect of the anesthetic is gone, and may swell in a most alarming way. Some of our patients were kept in bed for the greater part of a week, but we fortunately have had no sloughs. I can find no reason for the severe reactions that some cases show. I have inserted a needle in a corresponding location in either buttock, put half the dose in one side and half in the other, at an equal depth, and have had one side to swell and gave severe pain - look almost like a phlegmon-while the other side would give almost no pain and no swelling. At any rate these unpleasant happenings were altogether beyond our control The studies of Swift on rabbits have shown that there is always necrosis at the site of injection whether salvarsan or neosalvarsan be used. the former the more severe. He also analyzed the tissue at the site of injection quantitatively for the amount of arsenic remaining unabsorbed, at the end of different periods of time. There seems to be, after the injection of salvarsan, a slow steady absorption for about three weeks. After

this period the absorption was much slower, so that after ten weeks from 5 to 20 per cent of the arsenic could still be recovered from the tissues. The reaction seemed to be dependent to some extent on the degree of injury, due to the irritative reaction of

the particular substance injected. Neutral inflicted less injury than either acid or alkaline solutions. However, in the intramuscular use of neosalvarsan, the absorption is much more rapid and complete. After one week as much absorption has taken place as after six weeks following the salvarsan injection. After one week only about 15 per cent remains unabsorbed -this being slowly taken up until at the end of six weeks only about 5 per cent remains.

From the foregoing it would seem that as an intramuscular injection, the neosalvarsan would be preferable. However, as there is no especial advantage in giving the remedy in the muscles other than the ease of administration, and there is the disadvantage of considerable pain and disability, I think the intravenous method preferable.

The reasons for preferring the intravenous method are: The lack of pain or discomfort on the part of the patient.

The almost immediate efficacy of the dose.

The freedom from troublesome nodules or possibly abscesses at the site of injection.

The fact that the full dose is utilized, and not from 5 to 20 per cent remaining unabsorbed at the end of ten weeks.

The possibility of repeating the dose as often as may be necessary, the patient not being deterred by dread of the pain.

Although there is nothing difficult about the intravenous injection of salvarsan or neosalvarsan, it is a surgical procedure, and should be approached with a healthy respect for the possibility of the result of poor technic. In the fairly large number of injections we have made in this way, we have used water that has been distilled not more than six hours before the injection. This is boiled again in a sterile flask just before using it.

For the injection we use a 50 c.c. serum syringe with an asbestos plunger, that will stand boiling.

The reason for taking this seemingly extraordinary care in the matter of the water is due to the studies of Wechselmann (who has given several thousand injections) in the matter of the solvent used. He holds that many if not all the reactions following the intravenous use of salvarsan were due to dead saphrophytic bacteria or the products of their metabolism, which may be present in distilled water after it has been allowed to stand. The contamination is a chemical rather than a bacteriological

one.

After preparing the arm with soap and water, alcohol and iodine, a tourniquet is tightened about it above the elbow and the vein dilated, the syringe is filled with the sterile freshly distilled water, the air forced out of it, and the needle (No. 26 Burroughs and Wellcome platinum needle) plunged into the vein. The water is then slowly injected to make sure that the needle is in the vein, the tourniquet very carefully removed, the receiving tube of the syringe put into the bottle of salvarsan solution, which has been made with the freshly distilled water and properly alkalinized, the syringe is drawn full of the solution, the stop-cock turned to direct the current into the vein and slowly injected. The filling and emptying process is continued slowly without removing the needle from the vein, until the whole amount is injected.

In about one case in ten, especially in women with fat arms, it is necessary to cut down upon the vein. In this case a canula is inserted and the vein afterwards ligated. It is always better, when possible, to use the needle, as no scar is left and it is possible to make a subsequent injection in the same vein. If the vein be cut down upon, it is a good practice to end the operation by putting in a half syringeful of the water, to wash out any of the solution which may have a tendency to stop in the "dead end" formed by ligating the vein, and possibly might set up a phlebitis.

As for the relative use of salvarsan and neosalvarsan, the only difference, when used intravenously, seems to be that the latter must be used in somewhat heavier dosage; that it does not have to be alkalinized, and that the whole amount of solution is smaller (about 150 instead of 240 c.c.). As far as the therapeutic value goes, I do not know of any difference.

We never have any reaction of any moment to follow the injection. Rarely is there more than one degree of fever. A few complain of nausea, and about one in twenty vomits. Only two in the entire series have had a chill. If given during the fading period of a secondary eruption, it sometimes seems to bring out the erup

tion more definitely for a few hours. In old cases, there is seldom anything to remark. In repeated examinations of the urine in the evening following the injection albumin is almost always absent.

From the foregoing we contend that salvarsan or neosalvarsan is of use in all the stages of syphilis, that it should be fortified by the use of mercury, and possibly iodine, and that the intravenous method is the method of choice in administering it.

A Merger of Medical Colleges.-The Atlanta College of Physicians and Surgeons and the Atlanta School of Medicine have been consolidated under the name of the Atlanta Medical College. Dr. W. S. Elkin will be dean of the new institution, and Dr. W. F. Westmoreland, president.

County Hospitals.-No state could devote its funds to better purposes than to see that every county in the State were provided with the proper hospital facilities. These county hospitals would not only provide to the sick and injured of the community proper facilities for the relief of disease and the results of accidents, but they would also furnish education to the community in the matter of right living and as to the nature of disease, and an incentive to the medical men to do better work. not in competition with, but in emulation of, their professional brethren. Any one who has had any hospital experience knows how residence in a well-appointed and well-conducted hospital raises the respect that the average patient has for the profession, and knows that the patient leaves the hospital better prepared to care for himself in the future. If the object of government is the welfare of man, surely the health and life of man should be the first care of statesmen. There are many counties in the United States where medical missionaries are needed worse than they are in Asia, Africa, or the islands of the sea.-LancetClinic.

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THE TREATMENT

OF PRE-TUBERCULOUS STAGE OF CONSUMPTION. ALFRED S. GUBB, M. D., L. R. C. P. Lond., M. R. C. S. Eng., D.H.P., etc., Aix-le-Bains, Savoie, France.

Except for the discovery of the bacillus of tuberculosis, the most interesting outcome of recent research has been to show that the germs of tuberculosis will only grow on suitable soil, that is to say, soil which has been prepared for infection by inherited or acquired debility. It is this stage of liability to infection that constitutes the so-called pre-tuberculous period, the investigation of which has revealed several interesting facts.

Thanks in a great measure to Professor Albert Robin of Paris, who made a special study of the physiological features of this pre-tuberculous period, we know that it is characterized by a curious but striking instability of the mineral constituents of the tissues, notably the chlorides and phosphates. This tendency to phosphaturia of course is by no means peculiar to tuberculosis for in a more or less fugitive form it is met with in many morbid states, from simple dyspepsia to albuminuria. The distinguishing character of the leakage of phosphates occurring in connection with tuberculosis is its constancy. It is this constancy that constitutes it gravity, because, in the long run, it determines pronounced impoverishment of the tissues in respect of their mineral constituents.

It would be rash to assume forthwith that the amenability of the tissues to tuberculous infection is the direct, inevitable consequence of this loss of phosphates, because the inability to hold and to retain the mineral elements may, after all, be merely an outward and visible effect of the same vital weakness that creates the proneness to infection, just as the loss of appetite determines a state of debility that predisposes to infection from lack of nourishment.

However produced, and whether due to an inherited inability of the tissues to maintain their nutrition or to the disturbing influence of chronic intoxications and other causes of organic debility, the persistent phosphatic waste engenders a state of malnutrition that places the organism in a manifest condition of inferiority.

The recognition of this predisposing process affords a clear indication for treatment, and the measures that have for their object the remedying of this source of debility and the cutting short of the pre-tuberculous

stage constitute the prophylactic treatment of consumption. Just as drainage and the application of lime to an impoverished land wards off mildew and blight that attack imperfectly nourished vegetables, so hygienic measures and the administration of lime salts to persons who are threatened with consumption tend to enable the tissues to resist their natural enemies.

That this is no more theoretical conception is shown by the comparative case with which threatened consumption, and even the incipient stage of the actual disease, can be averted or cured by appropriate treatment. Remove the cause, said Hippocrates, an the effect will disappear, and in most instances it is possible to remove the cause of the predisposition to phthisis.

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But before we discuss the treatment there is another physiological factor that calls for notice, namely, the persistently low arterial tension. So constant is this low blood pressure that it is now regarded, in the absence of any other explanation, as diagnostic of impending consumption. young man apparently in the enjoyment of a fair standard of health, whose blood pressure is persistently below 110 millimeters should be looked upon with suspicion, although for the time being there may be no signs of pulmonary mischief accessible to the stethoscope.

The two principal features of the pre-tuberculous stage of pulmonary tuberculosis are, therefore, increased elimination of phosphates and a persistently low blood pressure.

Other disturbances of the vital processes have been noted-changes in the respiratory quotient, for instance-which likewise possess grave significance, but we need not dwell upon these, seeing that they have no direct bearing on treatment.

Inasmuch as the phosphatic waste may conceivably be due to tissue debility, it behooves us to place the organism under conditions favorable to its recuperation, and these may be summed up in the therapeutical trinity: fresh air, good food, and rest. These alone, however, may not suffice to restore the nutrition of the tissues. There is lost ground and arrears of nutrition to be made up, and it is asking too much of the jaded organism to expect it to "pay in advance," that is to say, not only to secure the adequate nutrition of the tissues which it has so far been unable to obtain, but also to restore the debit balance created by past depredations.

Medicinally the plan of campaign is al