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was apparently unchanged for about a week and then subsided. The duration of the phenomenon was ten days.

At 2 a.m., March 14, the patient complained of a pain above her left eye.

The nurse relieved this to some extent, but at 4 o'clock the pain was complained of in the eye. A severe conjunctivitis was seen when the patient was visited in the morning. The same evening the inflammation was worse.

Next day Dr. James M. Patton saw the patient and announced the presence of a virulent panophthalmitis and that the eye had already been destroyed. This proved to be true. Suppuration continued and six days later the crystaline lenze escaped from the eye and eventually little of the eye was left within the orbit.

On March 20, an area of redness, heat and pain appeared, about four inches in diameter, covering the right costal arch. The swelling was considerable and the area markedly edematous. This condition developed during one night, but in three days it was gone.

For twenty-four days from the beginning of the attack the temperature ranged from 99 to 102. Occasionally it went to 103 or 103.5. Usually it was higher in the afternoon, but not always. Later on it gradually declined and by the end of six weeks it was usually normal in the morning. It was at least three weeks after this time before there was complete absence of fever. Extreme, sudden, and erratic fluctuations of temperature did not occur. Nor was there a definite periodicity at any time. Chills of moderate severity were of frequent ocThe pulse in rate and quality, was quite remarkable. It very seldom during the course of the sickness reached 90. As a rule when the temperature was 102 or 103.5 the pulse was 80 to 84. The range

currence.

of the pulse throughout the disease was 76 to 86, and of surprisingly good quality. The respirations were generally 26 to 30, rarely as high as the latter figure. At no time during the progress of the disease was there evidence of pulmonary involvement, other than a bronchial cough with little expectoration. This cough persisted for several months during convalescence, and gave rise to apprehension lest it be due to the development of a tubercular process. Repeated examinations of the sputum failed

.

to discover bacilli and eventually the cough disappeared. It seems probable that the slow expansion of the lung, which had been for a long time compressed by the enormous liver, may have been responsible for this cough.

At

The kidneys were normal always. times there was a slight, tendency to constipation, but for the most part the bowels were normal.

Three or four days from the beginning of the delirium the mind was entirely clear and remained so, though rather sluggish. No other nervous symptoms appeared.

At times arthritic pains were severe, but no objective signs of arthritis appeared. Examination by the vagina and rectum gave negative result.

The following is the report of a blood examination made by Dr. R. W. Bliss, March 22: Red blood count not made. White cells 16,900 per cu. cm.; hemoglobin 70 per cent; differential count, polymorphonuclear neutrophiles 90 per cent; small lymphocytes 8 per cent; large lymphocytes, none; eosinoNo mast philes 2 per cent; total 100. cells, no myelocytes, no plasmodia malariae, many blood platelets.

On

Meanwhile a constant watch was kept for evidence of abscesses internally. March 11th a search was made with an exploring needle, with negative result. Dr. B. B. Davis saw the patient several times with a view to possible surgical intervention. The repeated statement of Dr. Davis was that should he undertake to operate he would have not the slightest idea at what point to make the attack. No operation was performed.

To all appearance the whole right side of the abdomen shared in the pathology but as to where it originated we remain in total ignorance.

Eventually the symptoms began to improve. Improvement was very slow and occupied not less than half a year. Quite recently I have heard from the patient that she is wearing her glass eye gracefully and enjoying the best of health.

The case is related as one of cryptogenetic septico-pyemia. It is remarkable also because it terminated favorably and as presenting ground of encouragement in the face of the most appalling degree of infection.

No shame to us that stumble if we try to do our part,
No shame to us for failing, if we made an honest start.
-Virginia Frazer Boyle.

THE EFFECT OF ORGANIC SILVER SALTS ON THE GONOCOCCUS IN THe male URETHRA.

Thomas M. Paul, M. D., St. Joseph, Mo.

S early as the day when gonorrhea and syphilis were believed to be caused by the same virus, nitrate of silver was used in the treatment of urethritis, and it has ever since played an important role in the therapeusis of that disease.

The first step in the direction of our present knowledge was made when the gonococcus was discovered. This fact caused silver nitrate to be looked upon as a germicide. Coincident with the development of bacteriology, great strides were made in chemistry. Nitrate of silver being very irritating, an attempt was now made to retain its germicidal action and overcome this, its chief fault, by substituting an organic radical for the NO3 group.

The resulting organic silver salts were made by firms who kept the process of their manufacture a secret. These firms published literature, usually in the form of pamphlets, describing the action of their products. So sharp became the competition between manufacturers, that some of them adopted a form for their pamphlets closely resembling a scientific reprint.

Since a strong spirit of aversion to the use of proprietaries exists among the scientific members of the medical profession, the names of organic silver salts were usually avoided in articles on the treatment of gonorrhea. This prevented physicians from profiting by the experience of one another and forced them to depend largely upon the manufacturers' pamphlets for their information.

Until recently the authors of text-books devoted a great deal of space to the detailed description of the symptoms of gonorrhea and yet ignored utterly its micro-pathology. This was due, in great part, to lack of information. As our knowledge of this phase of the subject increased, we learned that, immediately after the infecting coitus, the gonococci entered the epithelial interstices and mucous follicles of the urethra. Indeed, did this not occur, the individual would rid himself of the invaders the first time he urinated. Lodged in their position of security however, the germs rapidly multiplied, and before an inflammatory reaction ensued, the submucous and periglandular tissues contained myriads of micro-organisms.

The manufacturing chemist was not slow to incorporate this information in his liter

ature. Soon each firm that made an organic silver salt claimed that its product had greater penetrating qualities than any of the others. The description of the action of silver compounds on the gonococcus in Petri dishes and test-tubes was superseded by an explanation of how a solution of the drug would penetrate an animal membrane, without injuring it, and destroy the gonococcus beneath. Since, as already stated, it was believed that the germicidal power lay in the silver, each maker vied with the others in claiming the greatest percentage of that metal in his salt.

Had Paul Ehrlich discovered 606 and expounded his theory of chemo-therapy about the time these pseudo-scientific publications first made their appearance, no doubt some of these firms would have claimed that their particular form of organic silver was parisitothropic for the gonococcus. Gonococci are minute particles of protoplasm, so also are the epithelial and glandular cells composing the urethral mucosa. Now if the former are imbedded among the latter, it is impossible to conceive of a chemical substance destroying the one without affecting the other. A silver compound would really have to be parisitothropic to attain this end. So far we have dealt with the subject as though the gonococcus invaded only that portion of the genito-urinary tract which lies between the meatus urinarius and the compressor urethrae muscle. The subject is seen in this light by most sufferers from gonorrhea, and unfortunately also by many physicians. This view gives origin to the question, "What's good for clap?" and the literature of the manufacturer of organic silver preparations seems, to the uninformed, to furnish an adequate answer.

The absurdity of this conclusion becomes apparent when we think of the fact that the submucous lymphatics of the urethra may carry gonococci back into the prostate, thence to be poured out upon the surface of the posterior urethra in the consequent inflammatory discharge. Prostatic folliculitis seldom occurs without a coincident seminal vesiculitis; and, indeed an ascending ureteritis, secondary to gonorrheal trigonitis, is not unheard of.

Organic silver salts are expensive and are therefore seldom used in the quantity necessary for irrigations. Since hand injections. reach only as far as the cut-off muscle,

what good will they do if the parts beyond be affected?

Having shown that if a solution of one of these drugs is capable of destroying a gonococcus, it will also destroy the epithelium around it, we may well ask, "Do organic silver compounds bring about the destruction of the gonococcus, and if so, how do they accomplish it?" The answer is that they do, and the purpose of this paper is to show how they do it.

We have already stated that immediately after the infecting coitus the gonococci penetrate the surface and lodge themselves between the epithelial cells and in the mucous follicles. The tissues seem to ignore their presence until they have enormously multiplied. The invading germs now meet with a warm reception, in the form of a phagocytic onslaught from the leucocytes brought to the site of infection by an inflammatory congestion. These phagocytes, by means of their ameboid movements, wander among the cellular elements of the urethral lining and devour the gonococci. The germs seem to try to multiply more rapidly than the leucocytes can ingest them. While a few of the phagocytes may recover from having incorporated the microorganisms in their substance, and thereafter re-enter the blood stream, the vast majority of them are cast out in the accompanying serous exudate.

The method then by which nature attempts to rid the infected tissue of the diplococcus of Neisser is by phagocytosis. The leucocytes need no training; they instinctively seek after the offenders in the most minute inter-epithelial spaces and most remote gland tubules. During their incessant wanderings, they kill all the gonococci they find, and leave the cells of the organism to which they themselves belong, unharmed. This being true, it is obvious that anything which helps the attack of the phagocytes is a valuable aid in the cure of the disease. The severity of the symptoms in a typical acute urethritis is an evidence of the natural defensive efforts just described. To add further irritation to such an already over-irritated mucosa, by any form of silver salt, is the height of folly. To put the patient on oil of sandalwood internally, and bicarbonate of soda if his urine be acid, is sufficient. After a time, varying in different cases, the ardor urinae, the chordee, and the profuse discharge diminish. This amelioration of symptoms is an evidence of lessened fierceness in the attack of the phagocytes. Whether this is due to the germs multiplying less rapidly, or to the development of an antitoxin or antibody,

or to an increase in the opsonic index, can, at present, only be conjectured. Suffice it to say that it does occur.

Since phagocytosis ceases before all of the gonococci have been eliminated, it behooves the physician to induce an artificial attack of acute urethritis to force the leucocytes to finish their uncompleted task.

With this end in view alone, should silver salts be used. The physician should select a preparation with whose action he is familiar, beginning with a weak solution and gradually increasing its strength. The patient's sensations are the best guide as to the rate of increase. When slight burning, at the time of injection, and perhaps during the next urination, are no longer produced, the percentage of the drug in solution should be raised.

Under this course of treatment, at first a diminution in the discharge occurs, followed later by an increase. When the higher strengths are reached, the discharge may be as profuse as before the treatment began. After this, when the treatment is discontinued, the discharge will immediately disappear.

Following the discharge with the microscope, we will note first a diminution and then a disappearance of the gonococci. The leucocytes becomes less numerous and lose their sharp outlines, having a smeared appearance. Epithelial cells, with perhaps a few attached gonococci, may now be found. By the time the profuse discharge, due to the final strong injections, is reached, all cellular elements have disappeared.

In cases of anterior urethritis, this plan of treatment, is, from a clinical standpoint, a success. No doubt the injections have a germicidal effect on the gonococci they reach, but it is inconceivable that the deep seated germs can be killed by the silver salts without, at the same time, destroying the epithelium in which they are imbedded. Solutions sufficiently strong to reach submucous bacteria, would burn off the superimposed tissues and act as escharotics. This clearly demonstrates the absurdity of attempting to abort this disease, for the germs which are not killed by the severe injections, wreak great havoc on the chemically devitalized tissues.

We have stated that we begin the injections as soon as nature's phagocytic defense commences to wane. This stimulates the urethral surface and causes a renewed activity on the part of the leucocytes. As the mucosa becomes accustomed to this degree of stimulation, the stimulation has to be increased by raising the strength of the solution. Finally a solution is reached

that is so strong that it produces a discharge physically resembling that of active acute urethritis. Such a solution may even cause pain on urination, chordee and slight hemorrhage. The urethral lining is, as it were, so purged that not even a leucocyte nor an epithelial cell can be found in the discharge. In other words, we have created an artificial acute urethritis. By pursuing this plan, phagocytes may be called up through the mucosa from the subjacent capillaries. En route, these leucocytes will find, and destroy, gonococci in positions to which no silver salt can penetrate.

In the later stages of gonorrhea, the diplococci try to make a final stand on the superficial epithelial cells. It would seem that this is caused by the leucocytes having "made it too hot" for the germs beneath. Nature dislodges the bacteria from this position by epithelial desquamation. If the final strong solutions, above described, do not kill these gonococci, the profuse reactionary discharge will aid in the epithelia exfoliation.

The principles governing the treatment of anterior urethritis should be carried out in posterior urethritis. If acute trigonitis, evidenced by tenesmus and frequent and persistent desire to urinate, marks the onset of infection back of the cut-off muscle, opiates, internally, or in suppository, and hot sitz baths, should be used for some time prior to beginning the silver salts. While irrigations may be expensive, they are preferable to instillations, as they distend the mucous folds and reach every portion of the The transient attack of artificial surface. acute trigonitis following an irrigation of proper strength, is as necessary, and serves the same purpose, in posterior urethritis as

does the induced inflammatory reaction in front of the cut-off muscle. As already stated, posterior urethritis is usually secondary to prostatic folliculitis. The fact that gonococci may be carried by the submucous lymphatics to the prostatic follicles, and thence thrown out upon the surface, is contrary to the popular impression that extension by continuity takes place through the cut-off muscle. If the former idea be correct, it is obviously necessary to resort to massage per rectum, to empty the prostate of its secretion, containing gonococcus-laden leucocytes. Massage not only accomplishes this, but it also empties the prostatic veins, causing them to refill with blood drawn through the capillaries. Thus new and active phagocytes are brought to further rid the infected tissues of bacteria.

The claim made by some manufacturers that their organic silver preparations are unirritating, except in very concentrated solution, is correct. It is also true that the silver compounds belonging to this class. are very expensive and very dirty for patients to handle. Moreover, such silver salts do not exercise a stimulating effect on the urethral mucosa and therefore do not increase leucocytosis therein.

Actual clinical experience bears out the idea that in order for a silver preparation to be effective in gonorrhea, it must stimulate the urethral lining. Indeed, if silver nitrate is more effective than any other salt of the metal in very obstinate cases of the severe reactions it produces are the chronic gonorrhea, it must be assumed that sources of benefit.

King Hill Building.

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EPIDEMIC CEREBROSPINAL MENINGITIS.*
A. W. Nash, M. D., Dallas, Texas.

EFINITION.-An acute infectious, contagious disease occurring sporadically and in epidemics, caused by the meningococcus or diplococcus intracellularis, and characterized by an inflammation of the cerebrospinal meninges, with various other clinical manifestations.

History. I shall not attempt to go into any extended history of the various epidemics of meningitis which can be read in all the standard text-books. The disease was described by Vieusseux, of Geneva, as early as 1805, and several outbreaks have occurred in this country in the last century, notable among them being in 1898 and 1899, throughout the United States, especially in the Eastern and Atlantic states; and probably the most notable epidemic occurred in 1904 and 1905 in New York City in which there were 6,755 cases, with 3,455 deaths, a rate of 51 per cent mortality. paper will deal chiefly with the last outbreak in this country, that of 1911 and 1912 in the Southwestern states of which we are a part, and more especially with the epidemic in Dallas.

This

Etiology.-The disease is caused by the diplococcus intracellularis meningitidis, described first by Weiselbaum in 1877, and has distinct cultural characteristics which I shall leave to the bacteriologist to describe. The disease occurs both sporadically and in epidemics, often in isolated country districts, but more frequently in the cities in the crowded districts, in jails, barracks, etc. In the cities many cases develop in the same neighborhood, but it is also scattered over the whole locality. Some believe that squalor and filth predispose to the disease, and this is probably true, but in the recent epidemic in Dallas quite a relatively large percentage of the cases occurred

*The following papers were read before the Medical Association of the Southwest at Hot Springs, Ark., October 8, 1912.

among people in comfortable circumstances. The disease is no doubt spread quite freely by healthy carriers, and during an epidemic precautions should be taken to eradicate carriers as far as possible. During the Dallas epidemic about 60 per cent of those examined, proved to be healthy carriers.

Pathology or Morbid Anatomy.-In some cases the only change in the brain and cord is extreme congestion. There is intense injection of the pia-arachnoid. The exudate is usually fibrino-purulent, most marked at the base of the brain, where the meninges may be thickened. Sometimes the entire cortex is covered with a thick purulent exudate. The cord is always involved with the brain, the exudate is more abundant on the posterior surface, and usually involves the dorsal and lumbar regions more than the cervical. The ventricles are dilated and contain a turbid fluid, sometimes pure pus in the more chronic cases. The brain substance is softer than normal and has a pinkish tinge. The cranial nerves are of. ten involved, as shown by the various paralyses. Microscopically, the exudate consists largely of polynuclear leucocytes closely packed in a fibrinous material. In some instances there are foci of purulent infiltration and hemorrhage, diplococci being found in variable numbers in the exudate. The neuroglia cells are swollen with large clear and vesicular nuclei, while the ganglion cells show less mared changes. The general pathology is that of the complications, though in some cases we find the liver and spleen enlarged and inflammatory changes in the intestines.

Symptoms. We will describe an acute and chronic form of meningitis, though the acute form occurs with a great variety of manifestations, principally that of a malignant onset and what may be termed the usual or ordinary form.

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