Malignant Form.-We had several of these cases, the onset being with violent headache, delirium, rapidly passing into unconsciousness, with general muscular spasms and frequent convulsions. In the beginning there was usually a distinct chill, pulse very slow and feeble, with only a moderate elevation of temperature. Most cases showed marked purpuric eruption, and death usually occurred in twenty-four to forty-eight hours. Many of these cases were diagnosed in the early part of the epidemic as apoplexy, heart failure, etc. A few were punctured and the fluid was very purulent and under high pressure, most of these cases developed Cheyne-Stokes respiration before death.

Ordinary Acute Form.-This form is the one in which we are most interested, and I shall attempt to give the most usual symptoms and the ones most likely to lead us to a diagnosis, as well as the many variable symptoms noted in our series of 450 cases in the hospital. Probably the most constant symptom is headache, a symptom found in practically all acute infectious diseases, but the headache of meningitis is entirely different from any other headache, it is excruciating, keen and boring, the patient will say that the top and back of head feels like it will come off, it is truly pressure headache, which opiates will not relieve, being relieved only by the lumbar puncture, and sets up again as the fluid accumulates. Rigidity of the neck and muscles of the shoulder is a fairly constant symptom; one will find both antero-posterior and lateral rigidity with severe pain caused by an attempt to move the head in any direction. In this connection you will often find tenderness and pain at the angle of the jaw by manipulation. The rigidity of the neck varies from that of very slight to complete stiffness and marked opisthotonus. other sign that I consider of diagnostic value is the Macewen. It is a tympanitic note obtained by percussing the head over the ventricles, demonstrating the presence of fluid in the ventricle. Some would anticipate a dull or a flat note in percussing over fluid, but in this case it is a tympanitic one, and I am positive that I have made a diagnosis from this sign in some early cases, and in each instance large quantities of fluid was obtained by lumbar puncture. One case in particular, I recall, was that of one of my assistants, Macewen being very distinct, with slight general symptoms, on lumbar puncture fifty-eight c.c. of fluid. was obtained. The Macewen can be easily elicited in children with open fontanelles.

An

Dilated pupils unresponsive to light are found in most cases, due to the fluid pressure in the ventricles and it is interesting to note the varying change in pupils as the fluid accumulates or is withdrawn. The mental picture of the patient is certainly one of our main reliances in diagnosis. The patient's condition may vary from the slightest inattention to those around or to lack of concentration of thought to the wildest delirium or absolute

coma.

Ordinarily in the acute cases at the onset, the patient is rather dull and apathetic but can be easily aroused when spoken to. In some cases the mind seems clear, but there is double vision due of course to the pressure. We had some cases in which this was the only symptom, to attract the attention at first, late the usual symptoms developed. Quite a few cases began with active. delirium gradually going into coma and in children convulsions were quite frequent and occurred in adults in many cases. Kernig's sign occurred in practically all of the cases, and is of diagnostic value only in conjunction with other symptoms, which is also true of the tache-cerebrale, both of these signs being obtained in other diseases. The petechial eruption which is pathognomonic occurred in a large percentage of our cases, 39.5 per cent being found on all parts of the body, most marked on the chest and extremities, and I have observed it on the conjunctiva of the upper eyelid. The petechial eruption is a manifestation of general sepsis and all of these cases are very serious, many of them proving fatal. The rose-colored spots from which the disease gets the name of spotted fever, were not nearly so constant as the petechia, but were noted in some of our cases. General hyper-sensitiveness of the skin and intolerance of the eyes to the light were noted in most of the cases. Another symptom that I have never heard spoken of, that I almost invariably found charateristic is the breath. The breath has a peculiar sweetish odor, very disagreeable to the sense of smell and can hardly be mistaken when once noted; this symptom was noted immediately by our internes and nurses as being peculiar to meningitis. Herpes occurs in a large percentage of the cases, 43 per cent, and on most unusual places of the body, most common on the lips, as in other febrile conditions, but I have seen them on the limbs, between the shoulders, on buttocks, on the cheeks, on the eyelids, and inside the mouth. One patient I recall had a beautiful crop of herpes on the posterior pharyn

geal wall.

The temperature in these cases is not at all characteristic, and is very variable. I have seen typical cases with very slight elevation of temperature, and other cases in which quite a few of the cardinal symptoms were lacking and the temperature would run very high. I should say the usual temperature chart would show variations from 101 F. to 103 F., with marked remissions, especially a few hours after lumbar puncture. I have seen the temperature go to 106 and 107, and in one case to 108 just before death. Most of the high temperature patients died, but I remember distinctly of two patients recovering after the temperature had gone to 106 with convulsions. The pulse is usually slow and full, especially when there is much pressure though many of the patients had rapid. feeble pulse, especially among children. The respiration like the temperature is not characteristic, except late in fatal cases, when we often get cerebral breathing. The bowels are usually constipated, and acute retention of urine is very common, and catheterization should certainly be done at least every eight to twelve hours, as urinary retention aggravates the restlessness of the patient. Some of our cases showed hematuria, but I am sure this was due to the large doses of uroptropin as this symptom usually cleared up upon removal of the drug.

Chronic Form. In the chronic form we simply have a continuation of the symptoms of the acute only in a milder way. The headache persists, the patient rapidly loses in flesh and strength, the fever both remits and intermits, the pulse usually becomes weak patient is listless, often imbecilic, and usually there is a condition of chronic hydrocephalus which must be relieved by lumbar puncture. Some of these cases develop a posterior basis meningitis, there is a closure of the foramen of Magehdie, and the ventricles must be punctured to give relief. These basic cases show a typical picture, the patient lies flat on the back, the pupils are widely dilated and the eyes have a glassy, fixed stare. The patient appears to be conscious and can be fed, but takes no notice of things around. There is usually incontinence of urine and feces. Respiration slow and labored. Pulse slow and full. We had seven of these cases in our series, and the condition is one that can hardly be mistaken.

Complications.-The most usual complications are pneumonia, pericarditis, pleurisy, arthritis. The common sequela are strabismus, facial paralysis, otitis. con

junctivitis, keratitis, optic neuritis and parotitis. The headache is often persistent for weeks, some of our patients often complaining of headache weeks after leaving the hospital. Muscular pains of especially of the lower limbs, were also rather frequent.

Treatment.-As in most diseases, the treatment in meningitis is both prophylactic and curative. I believe there is quite a little to be accomplished by prophylactic treatment. We have proved beyond dispute that healthy people carry the germs

in the buccal and nasal mucous membranes. It has also been demonstrated to my satisfaction that the disease is mildly contagious, for in our series of 450 cases we were able to trace 100 of them to direct contact with an infected person, 14 of those in the hospital contracted the disease, including 11 nurses. I believe that the patient with meningitis should be isolated, and that those shown to be healthy carriers, should be quarantined until rid of the germs, instances by sprays. which I think can be accomplished in most During the recent epidemic those of us in the hospital that had repeated nasal examinations made, would show negative when using the spray, and positive when the spray was neglected. I am not prepared to say that I believe vaccination is a sure preventive, but I shall certainly give it a fair trial should another epidemic threaten, and I am sure that if the required number of doses of the vaccine are taken, there will be quite a little immunity established. Some of our nurses who contracted the disease, took the vaccine, but only one took the required dosage. I took two doses of the vaccine and 20 c.s. of the serum subcutaneously, and believe it prevented me from contracting the disease. One's general condition no doubt predisposes to meningitis, and those who have been exposed should certainly see that the nasal and buccal mucous membranes are free from inflammation, and that the eliminative organs are in good condition.

Curative Treatment.-I think all are agreed that the Flexner serum is the only treatment, though I am convinced that lumbar puncture alone does quite a little good, by means of relieving the pressure, for certainly 'tis the pressure that causes Lumbar quite a few of the symptoms.

puncture and the administration of serum have caused no little comment, pro and con, in the past few months, and has been done no doubt, by numbers of physicians present, . and some are inclined to think that the procedure is a simple and easy matter. I

haven't the exact figures at my command, but think I am conservative in saying that I have done about 2,000 lumbar punctures, and wish to state that if the procedure is properly done, it is not such a simple or unimportant matter, and life has been forfeited as a result of puncture by inexperi. enced men, due to too rapid removal of fluid, and to injection of fluid under too much pressure. The patient should be placed on the left side, with the knees flexed on the abdomen and the head bent slightly forward. An anesthetic is rarely necessary. The field for the puncture should be scrubbed with alcohol, then painted with iodine. The needle should be introduced between the 4th and 5th lumbar vertebra usually, but may be introduced as high as the first or second. The thumb of the left hand is used as a guide, being pushed firmly between the spinous processes of the vertebra, and the needle held in the right hand, is introduced directly into the canal, not at acute angle and slightly inward and upward as some recommend. This method of introducing the needle directly into the canal I learned from Dr. Sophian, and I think it has a distinct advantage over the other methods, in the fact that the left thumb is a guide and one knows just exactly what one is doing, no guess-work at all, the idea that you are more likely to pierce the plexus of veins by this method being more myth than reality. One should use a needle larger than is usually recommended, one that is not easily broken and that will allow a free flow of the fluid. The amount of fluid withdrawn depends entirely upon the general symptoms, and more especially the blood pressure. If the blood pressure drop too suddenly, stop withdrawing fluid for a few minutes then begin again, follow this procedure, withdrawing fluid very slowly until the flow is drop by drop, or until the blood pressure indicates that enough fluid has been withdrawn. I rarely allow a drop of more than 12 or 15 and usually not more than 10. The serum should be administered by gravity, allowing it to flow very slowly and stopping the flow if the blood pressure shows a too rapid drop. I cannot say definitely how much serum to introduce,

K

but will state that the amount of serum introduced should have no distinct relation to the quantity of fluid withdrawn. I have often withdrawn 50 to 75 c.c. of fluid and only introduced 20 c.c. of serum. I should say in our series that the average amount of fluid withdrawn in the acute cases was 40 to 45 c.c., and the average of serum introduced was 25 c.c. I am not a believer in very large quantities of serum except in desperate cases, showing marked sepsis. As to how often the serum should be administered each case is a law unto itself; however one can safely say that the average case should have the second puncture sixteen to twenty-four hours after the first, and then at twenty-four-hour intervals for two or three more punctures. We had several cases to recover after two or three punctures, but the average was nearer five and six, and several had as many as ten to twelve punctures, these of course being especially obstinate cases and many of the cases being for the relief of pressure only.

General Treatment.-We gave most of the patients urotropin, chloral and bromides to quiet, and morphine when absolutely necessary. As stimulants, whiskey, camphor in oil, infusion of digitalis, atropine, caffeine citrate and strychnine. Castor oil was the principal laxative. The diet was general with plenty of water. To prevent pneumonia, which was the most common complication, the patient was repeatedly turned in bed. In the convalescent stage most of the patients were given the iodides with intent to help absorb the fluid. Several of our chronic cases, along with repeated punctures to relieve pressure, were given doses of the vaccine, at four or fiveday intervals, and I am convinced that good was accomplished, two patients in particular, I am sure were materially benefited by the vaccine.

Those cases developing the posteriorbasic meningitis, where the fontanelle was not open, were trephined and the ventricles tapped to withdraw the fluid, and in some cases serum was introduced directly into the ventricle. Two of these cases showed marked improvement for a few days, but all of them eventually died.

one.

In many respects the liver is more like the kidney, or excretory gland, than are the other digestive glands. It resembles the kidney in that as far as the present research has gone no secretory nerves have been demonstrated. Its secretion is a continuous one, made necessary by its function of removing from the body excretory products, as well as supplying a digestive juice. It resembles the kidney in another and more striking manner, inasmuch according to the work of Adami (1), and Cushing (2), it seems that it is one of the functions of the liver to receive and destroy bacteria brought to it by both the portal and systemic circulation. That this passage of bacteria through the liver occurs, just as certain bacteria passed through the kidney, has been demonstrated. Adami (1) has pointed out that the pigmented areas in the liver are derived from the pigments of destroyed bacteria, and in his contribution to the physiology and pathology of the liver gives many interesting facts in this connection. It is the infections that result from these bacteria that we wish to deal with. The results of these infections vary with the virulence of the infecting micro-oganisms and the resistance of the patient.

The frank acute attacks of cholangitis are the results of infections with virulent bacteria. When, however, the infections are more insidious in their onset the infecting organism is usually of a lower virulence and gives rise to but slight symptoms, in fact the symptoms may be entirely misinterpreted and referred to organs other than those which are the real source of trouble.

The inflammatory disorders of the biliary tract, cholangitis, cholecystitis, and cholelithiasis, thus represent varying manifestations of infection; etiologically, anatomically, and clinically they have much in common; and they occur in varying relationships the one to the others-singly or combined. It is well to bear in mind that one infectious agent-the typhoid bacillus, for instance, may give rise to cholangitis, cholecystitis, and cholelithiasis concurrently or sequentially.

First as to the organism found. The

most common ones are those belonging to the typhoid coli group. Others that are found include staphylococci, streptococic and many other pus forming organisms. In a series of cases reported from Dr. Deaver's clinic at the German Hospital in Philadelphia there were cultures made from 240 gall bladders. Of these bacillus coli communis was found in 68 cases, 28 per cent; bacillus typhosus 27 cases, 11 per cent; staphylococcus pyogenes aurens 7 cases, 2 per cent; streptococcus pyogenes 1 case, .4 per cent; staphylococcus pyogenes albus 2 cases, .8 per cent; bacillus coli and staphylococcus aureus, 2 cases, .8 per cent; unidentified bacilli 6 cases, 2.5 per cent. culture remained sterile in 127 cases, 52 per

cent.

The

The pathways whereby the biliary tract may become infected are: (1) The diverticulum of Vater and the common bile duct; (2) the portal circulation; (3) the systemic circulation; (4) the lymphatic circulation; and (5) directly through the wall of the gall bladder or the biliary ducts from the peritoneum.

Infection from the duodenum by way of the diverticuum of Vater and the common bile duct has long been looked upon as at once the most likely and the most common source of biliary infections, but whether with good reason remains to be decided. Although the frequency of bacillus coli communis and of bacillus typhosus in infections of the biliary tract suggests an intestinal source, these bacteria find a direct pathway from the intestine to the liver by way of portal circulation. Furthermore, whereas the jejunum and the ileum always contain many bacteria, the duodenum when free from the food is often bacteria free; certainly, in health its bacterial content is small and it does not contain the bacteria often found in cholangitis, cholecystitis, etc. It is quite conceivable, however, indeed it is quite likely, that in conditions of disease of the upper intestine, when bacteria are present in the duodenum, the biliary tract may become infected by way of the diverticulum of Vater; doubtless many cases of so-called catarrhal jaundice following gastro-duodenitis arise in this fashion. But there are at least two important factors opposing a ready ascending infection of the biliary tract. The one, the action of the sphincter of the diverticulum, which has been estimated by Oggi (3) as exerting a force equal to a pressure within the common bile duct of 700 mm. of water; the second,

the influence of the free flow of bile. Indeed, it is doubtful whether infection of the biliary tract ever takes place by way of the diverticulum of Vater in the absence of the stasis of the bile. One of the most important factors in preventing such infection is the free flow, that is, the regular periodic expulsion of the bile-the free flow of the bile rather than the bile itself, since we now know, contrary to former opinions, that the bile is a quite favorable medium for the growth of the bacteria.

Infection by way of the portal circulation is a common source of biliary infection. Definite experimental proof that the bile may become infected from the circulation was furnished years ago by Blachstein and Welch (4), and their results have been since amply confirmed and amplified, so that there is no doubt that bacteria transported to the liver by the portal circulation may be found in the bile. Under normal conditions bacteria carried to the liver by the portal circulation are there destroyed by the bactericidal properties of the liver cells; but there is a limit to these bactericidal properties, which when overcome permit the entrance of bacteria into the biliary passages. Adami (5) having shown that under normal conditions bacteria may be found in the deeper layers of the intestine, in the portal circulation, and in the liver, suggests that they invade the portal circulation through the aid of the leucocytes, which are especially active during digestion, carrying foodstuffs, foreign matters, bacteria, etc., between the epithelial cells to the lymphatic radicles and the portal venules. Ördinarily most of the bacteria are destroyed, probably in large part through the bactericidal property of the normal living intestinal mucosa, in part also by the leucocytes, the lymph nodes, and the endothelium of the liver; sometimes, however, they pass through the liver and gain the bile; in other cases, by way of the thoracic duct, they invade the general circulation, and may be found in the liver, kidneys, etc., of apparently normal animals. This is a latent infection of Adami and certain French and German writers.

Infection by way of the systemic circulation is probably not an exceedingly common source of the infection of the biliary tract. Its importance has been enhanced since we have ascertained the frequency of bacteriemia in the great majority of infectious processes-typhoid fever, pneumococci and pyococci infections, etc.; and experimental proof that the biliary passages may become thus infected was furnished, as al

ready mentioned, by Blachstein and Welch years ago, and more recently by Doerr. Doerr found that micro-organisms injected into the general circulation of the rabbits appear in the gall-bladder within a few hours, and that typhoid bacilli and colon bacilli multiple in the gall-bladder and may be recovered therefrom in pure culture even after the lapse of months. The occurrence of cholecystitis and cholangitis as a complication of general diseases; but one must concede the possibility of the local biliary infection being due to organisms other than those occasioning the primary infection, and that the complicating infection may occur by way of the portal circulation. Infection by way of the hepatic artery is a descending infection and operates as does infection carried by the portal circulation, since both circulations commingle at the periphery of the liver lobules; but infected blood carried by the cystic artery may, although probably rarely, lead directly to infection of the gall-bladder without the intermediation of the infected bile.

Infection by way of the lymphatic circulation, as suggested by C. P. Muller, is probably a most infrequent source of infection.

Direct infection through the wall of the gall-bladder or of the ducts from the peritoneum has been suggested as a possibility; but excluding cases of general peritonitis in which the gall-bladder may participate secondarily and in which the mechanism of the local infection may be quite obvious, it is doubtful if infection of the biliary tract directly from the peritoneum can ever occur in the absence of adhesions, in which event it is probably an infection by way of the lymphatic circulation. In this connection, however, we must also bear in mind that the adhesions themselves are an evidence of past infections, and that an obvious infection in the presence of old adhesions is much more likely the relighting of an old, latent infection, rather than a new infection transmitted directly through the walls of the gall-bladder or the gall ducts.

In concluding this discussion of the pathway of infections, we would urge the following points in favor of the portal vein as the principle entry of the infection. (1) Adami and Ford have proven that there is at all times a passage of bacteria through the healthy intestinal wall. (2) It has been proven by Doerr that bacteria introduced into the blood may be demonstrated within a few hours not only in the urine but also in the bile. (3) The organisms which most commonly infect the gall-bladder are but rarely found in the duodenum.