Journal of the American Medical Association
None
5.100.000 7,130 100 0 12 2.5 81 1.5 0 0 2 0 i Mav 1, 1904. 5,700,000 8 921 100 0 10 2 X2 1 0 Uj z 2 1 Tnlw 1 1QR1 11,204 4 8< . . .. rl 0 5 0 September 4. 1904 . . .. 5,120.000 53,480 10C 2 4 5 64 2 19 0 4 2 October 2, 1904. 2.580,000 78.910 6f 7 2 1 65 . . .. 23 1 .1 6 November 14, 1904 . . .. 3,510,000 5,601 7C 1 5 4 c M 7 6 Clinical Diagnosis. — Splenomyelogenous leukemia. Treatment . — The patient was informed of his condition and advised to stop work. We gave arsenic and iron internally and tf-ray treatments to the splenic region twice a week. Course of the Disease. — After one month the patient seems improved ; he feels stronger, and his appetite is better. On examination the spleen is apparently smaller, the right edge extending only to the sternum and the lower edge on a line with the navel. The ankles are still swollen, but the blood shows a marked decrease in the number of leucocytes, with a slight increase in the red blood corpuscles and in the amount of hemoglobin. Blood smears show an apparent increase in the transitional forms with decrease of myelocytes. The nor¬ moblasts are markedly increased. The urine still contains a trace of albumin. September 1 : The patient has returned to work. His gen¬ eral condition is improved ; appetite good, with a gain in weight. The spleen has decreased in size and a notch is felt for the first time. Edema of ankles is less. Blood: Leuco- eytes decreased to 58,000, with an increase in the red blood corpuscles to over 3.000,000. 1. Medicine, July, 1904; also Til. Med. Jour., September, 1904. 2. Amer. Med., Dec. 24, 1904. March 25, 1905. LEUKEMIA— BROWN-JA CK. 957 Encouraged by the results of treatment, which had varied very little in the last two months, and by Senn’s article which appeared at this time, it was decided to discontinue the iron and arsenic and to increase the frequency and distribu¬ tion of the a;- ray exposures. These treatments were now given daily to the splenic region, the ends of the long bones and to the sternum. In place of the iron and arsenic, one- grain capsules of quinin, three times a day, were given as a placebo. October 1 : The patient has not missed a day’s work in the last month. The blood shows an increase in the number of leucocytes; the number of red blood corpuscles and the amount of hemoglobin, however, still show an increase. The spleen can be pushed to the edge of the ribs. An x-ra. y dermatitis of the splenic region has appeared once or twice, the outer layers of the skin desquamating, but by discontinuing treat¬ ment for a few days and using a dusting powder, no bad re¬ sults have followed. The skin over the exposed surfaces was rough at first, but after exfoliation has become smooth again. The hair and pigment have disappeared from the parts ex¬ posed. November 9: Blood: Leucocytes, 129,000; red blood cor¬ puscles, 4,124,000; hemoglobin, 85 per cent. Very little vari¬ ation in size and shape of the red blood corpuscles and no nu¬ cleated forms were found. Myelocytes, 25 per cent.; poly¬ morphonuclear, GO per cent.; eosinophiles, 5 per cent.; small lymphocytes, 1 per cent. ; degenerates, 3 per cent. Blood examinations were now being made weekly, and charts were made showing the results of these examinations, with dates when made (Chart 1). In February, after seven months’ treatment, the albumin had all disappeared from the urine and the patient weighed 182 pounds, which is more than he had ever weighed before. The spleen could only be felt on deep palpation. Treatments were reduced to every other day, and the patient was advised to take long walks on the intervening days. April 10: There is very slight edema of the legs. General appearance is excel¬ lent; color good; pulse full and com¬ pressible, with rate of 70. May 1 : The appearance of the patient at present is that of robust health. His complexion is florid, quite a contrast to the cachectic appearance of ten months ago. He is working daily and rides his bicycle back and forth from work. The liver is of normal size, and the spleen is not palpable even on deepest inspiration. The ankles show no edema. His weight is 1S4 pounds. The abdominal parietes are relaxed, but there is no ascites. The previous inguinal adenitis has entirely disappeared. July 1: Patient returns for blood ex¬ amination. Is working every day and feels fairly well. A leucocytosis of over 11,000 is found, 7 per cent, of which are myelocytes. September 4: Patient did not return in August, but returns to-day complain¬ ing of weakness and pains in the back. He weighs 182 pounds, which is a loss of two pounds. The spleen is apparently somewhat larger, but firm. The blood shows a leucocytosis of over 50,000. Urine clear ; specific gravity, 1,022 ; no albumin, but a few hyaline casts. X- ray treatment given. X-ray treatments were continued for seven weeks, but the patient gradually became weaker, and on October 7 he was foimd to have a temperature of 102, so he was sent home to bed. His symptoms were those of a severe intoxication not unlike typhoid. The spleen had become much larger. On October 10 a marked diazo-reaction was present in his 'urine. Widal test was negative. He had now become delirious. On October 16 his fever began to decline. The blood showed a marked decrease in both hemoglobin and the number of red cells, and still a high leucocyte count. Within one week the leucocytes dropped to normal and the spleen became much smaller. A severe diarrhea devel¬ oped; some blood and much mucus was passed in the stools. On October 28 urinalysis showed a clear urine; specific gravity, 1,018; acid; diazo-reaction present; al¬ bumin, 2.5 per cent. ; hyaline and granular casts numer¬ ous and a moderate amount of calcium oxalate crys¬ tals. The low typhoid state continued for two weeks longer, the condition being a semi-delirium, with great emaci¬ ation, no apparent suffering, no edema; death occurred on November 15, just sixteen months after first coming under our observation. Chart 1. 958 L E UREMIA — BR OWN -JACK. Jour. A. M. A. AUTOPSY. Seventeen hours postmortem. The subject is a man of average size. Skin pale and sallow; muscles smalj and emaciated ; panniculus almost absent. Both pleura free and no fluid in pleural cavities. The heart is of normal weight, its endocardium slightly thickened; muscle is firm and of a brownish-red color. The auricles contain ante¬ mortem clots and the ventricles fluid blood. The valves are normal. The lungs show marked anthraeosis and yield slight exudate on pressure. There are no airless areas, but a slight hypostasis over lower lobes. The bronchi are empty and the mucosa pale. The spleen weighs 1,133 gms. and measures 15x9x6 cm. There is one notch. The capsule is greatly thick¬ ened and cuts with resistance. The cut surface is firm and dark bluish-red in color. The stroma is greatly increased, but the malpighian corpuscles are not visible. The liver is enlarged but firm. The left lobe is atrophic. The veins of the capsule are congested, the capsule being thickened. On section the organ is fairly rich in blood. The cut surface is granular, brownish-red in color, and the outline of the lobules is distinct. The fibrous capsule of the kidneys strips off easily. The surface is slightly pale. On section the labyrinth and the cells of the endothelial type. There are few eosinopliiles, and no myeloid changes. Leucocytes are relatively few in the blood vessels. The general picture resembles that of a spleen of splenic anemia and not that of a leukemic case. Liver: There is atrophy, chronic passive congestion, and some parenchymatous degeneration. Connective tissue is rela¬ tively and in some areas absolutely increased. There is no leukemic infiltration. Glisson’s capsule is somewhat more cellular than normal, but the cells are chiefly of a connective- tissue type. Leucocytes are not increased in vessels. Pancreas: Postmortem change. There is some atrophy with slight fatty infiltration. There is no leucocyte infiltra¬ tion. Leucocytes are not increased in vessels. Small Intestine: There is slight atrophy and there are a few lymphoid elements. There is no evidence of leukemia. Large Intestine: Small chronic ulcers are present. There is no evidence of leukemia. Kidney: Sections of the kidney show remarkable lesions in the form of extensive deposits of lime salts, involving chiefly the convoluted tubules. For the greater part these tubules are replaced by masses of lime salts, either com¬ pletely filling up the tubule and replacing the epithelium or confined to the epithelium alone, either partly or wholly sur¬ rounding the lumen of the tubule. Some glomeruli show small T7 8 C L= 1 u 1 -12 ” LbkJ 15— \C 1 =nj -wrt*-s ■ - MV M ! wmmm ■ 105* 104' • loa’ x. 7 K 102 n 7 \ IS L LA / 7 ior /N i \A r i n v7 (V f jj t 7 A W.A - too' 7 V; 7^ J r - 1 d jf T 7 -E W—  lm^m M — _ — — Chart 2. medullary rays are distinctly outlined. Connective tissue is increased. The stomach is in normal position. Walls are pale. The small intestine shows no ulcers. The mucosa is pale. No enlarged glands in the mesentery. The rectal walls are much thickened and the mucosa is pale. The retroperitoneal glands are not enlarged. Pathologic Report. — The following pathologic report was kindly made for us by Dr. A. S. Warthin of Ann Arbor, Who is now doing much experimental work in this line: Lung: There is moderate chronic passive congestion; there is some atrophy, and the smaller bronchi are somewhat di¬ lated. The number of leucocytes in the blood vessels is not perceptibly increased. Lung does not show the characteristics of lung from case of leukemia. Spleen: Marked fibrosis. There is a fibroid hyperplasia of the reticulum of the pulp closely resembling that of splenic anemia. There is marked chronic passive congestion, the venous side being greatly dilated and filled with blood. Fol¬ licles are not preserved. The cells of the pulp are chiefly of a fibrous-connective-tissue type or endothelial. Lymphocytes are relatively very few. Cells of the type of large lympho¬ cytes are more numerous. There are numerous large atypical deposits, and casts of lime salts are found also in the straight tubules. The deposit is, however, for the chief part, in the convoluted tubules. Such convoluted tubules as are in part free from lime salts show more or less parenchymatous degen¬ eration. Localized areas of acute interstitial inflammation are also present and hyaline casts are found in some straight tubules. There is no leukemic infiltration and no increase of leucocytes in the blood vessels. The general picture closely resembles the parenchymatous changes with deposit of lime salts seen after poisoning with mercuric chlorid. Lymph Glands: The small lymph glands show a lymphoid hyperplasia resembling that of lymphatic leukemia or of some of the cases reported as lymphosarcoma (aleukemic leuco- blastoma ? ) . The distinction between cortical and medullary portions is lost, the sinuses are filled with or obliterated by lymphoid cells, and the gland presents an almost uniform lymphoid structure. No germinal centers are found. The capsule in many places is infiltrated, and such infiltration extends also beyond the capsule into the surrounding fat tis¬ sue. There are no myeloid changes. Numerous large lympho¬ cytes are present throughout the gland. There are a few eosinophiles. Leucocytes in surrounding vessels are not in¬ creased. March 25, 1905. 959 A CASE OF MACROCHEILIA — LINDEN BERGER, Summary. — The only pathologic finding suggestive of leu¬ kemic disease is the condition of the lymph glands. This re¬ sembles the gland picture seen in some cases of lymphosarcoma (aleukemic leueoblastoma?) or that of a lymphatic leukemia minus the increase of mononuclear elements in the blood. The spleen picture is of the same type as that of the splenic fibrosis of splenic anemia. Counts made of the leucocytes in the vessels of all the sections show an unusually high percent¬ age of mononuclears. Because of the fixation, these cells could not be satisfactorily studied. There is, however, no¬ where any increase of leucocytes in the vessels suggesting the existence of a leukemia. The calcification existing in the kidney is remarkable for its extent. It would suggest the occurrence of an intoxication causing degeneration or necrosis of the epithelium of the con¬ voluted tubules followed by deposit of lime salts, such as occurs m poisoning with mercuric chlorid, chromates, etc. Remarks. — The postmortem findings in this case are very interesting in connection with the experimental work that has been done by H. Heinecke,8 and also the work now being done by Warthin which he will soon publish. Heinecke found that a brief exposure of mice, rabbits and dogs to the rays in¬ duces a distinct destructive process in the lymph follicles. With an exposure too brief to induce changes in the skin, he could cause a distinct destruction of the nuclei of the leuco¬ cytes in the follicles of the spleen, leading to their almost com¬ plete disappearance. Analogous processes took place in other lymphoid elements. His remarks on the changes in the bone marrow are not clear except that some destruction of lymphoid elements took place. These experiments might suggest a physiologic basis for the use of the a;-ray in leukemia, so far as the excess of white cells in the circulating blood and the presence of abnormal cell elements are concerned, and they compare most favorably with the results in our case. Un¬ doubtedly the x-ray has a selective action, apparently affect¬ ing tissue undergoing pathologic hyperactivity and causing degeneration and necrosis of such tissue; however, the damage done is apparently greater than the good. Dr. Warthin, in summing up the pathologic findings, says: “If any conclusion is warranted from the study of the specimens, it would seem to be that the x-ray treatment has resolved the leukemic condition into an aleukemic state, but that the essential disease process, as evidenced by the condi¬ tion of the lymph glands, is still active. The leucocytes have been removed from the general circulation and from the areas of infiltration, the spleen presenting the characteristics of a chronic fibrosis. The part played by the latter would appear to be secondary. The remarkable condition of the kidneys offers room for some speculation as to the source of a toxin. Such might result from the destruction of enormous numbers of leucocytes.” It is much to be regretted that no specimen of bone marrow was obtained, for, as we believe this disease to be primarily in the bone marrow, we can come to no real conclusion until this part of the subject has been thoroughly studied. It is to be hoped that the stimulation this form of treat¬ ment has given workers may at least lead to some conclusion as to the cause of this most interesting disease. A CASE OF MACROCHEILIA DUE TO ENLARGEMENT OF THE MUCOUS GLANDS OF THE LIP. IRVIN LINDENBERGER, M.D. FRENCH LICK, IND. This condition may be due to one or several causes. With the exception of inflammatory affections, neoplastic growths occupy a prominent position. With inflammatory thickening there exists an enlargement not only of the glands but of the tissues of the whole lip, and affecting one or both lips; there is 3. Miinchener med. Wochenft., May 3, 1904. no increase in the number of glands affected. Congenital dila¬ tation of the lymphatic vessels, which is, more strictly speak¬ ing, an overgrowth when occurring in the tongue, produces macroglossia; when occurring in the lip, labium and other sub¬ cutaneous parts it is known as macrocheilia. Acquired lymph- angiectasis is most commonly observed in the lower extremities and in the external genitals, being due to an obstruction of some nature and characterized by hyperplasia of the skin and subcutaneous tissues, producing the condition known as ele¬ phantiasis. Fraenkel1 states that prior to a case reported by him, macrocheilia due to a neoplasm of the mucous glands of the lips was unknown. This case was more fully reported by Dr. Daniel N. Eisendrath of Chicago,2 with a case of his own. From the photograph of the present case, it will be noticed that the enlargement is only of the upper lip. This enlarge ment was especially noticeable in talking and laughing. On palpation, the lip was found to be soft and smooth, but on pressure there was a slight “shotty” feel in one or two glands on each side of the median furrow. The condition dated from a blow in the mouth, received about fifteen years previously. There has been no appreciable enlargement in the past ten years. His general health has always been good; there is no history of any specific trouble. A wedge-shaped incision dis¬ closed a number of small glands, slightly smaller than buck¬ shot, on each side. They were removed and the mucous mem¬ brane was sutured. Healing was prompt and the cosmetic effect wras good. 1. Arch, fur klinische Chirurgie, voi. xliv, 1892. 2. Annals of Surgery, September, 1904. Lowering of the Arterial Pressure Reliable Danger Sign in Chloroform Anesthesia.— J. Tissot of Paris has been studying on dogs the relations between the modifications in the arterial pressure and the toxic action of chloroform on the heart. The arterial pressure is a reliable index of the contracting power of the heart. We know that fatal accidents from chloroform are due to the toxic action of the drug on the heart or on the nerve centers controlling its action. He found that the dogs never displayed any threatening symptoms as long as the arterial pressure was above 100 mm. Hg, but respiratory ar¬ rest occurred whenever the pressure dropped to 60 mm. Cardiac syncope occurred if it fell near or below 50 mm. Hg. The chloroform ization in his experiments was always slow and gradual. Tissot believes that these data will be found to apply also to man, and that by watching the arterial pressure we will be able to detect impending danger long before it is revealed by any other sign. Tissot’s communication was pre¬ sented at the meeting of the Paris AcadGmie des Sciences, February 20, 1905. 960 EDITORIALS. Jour. A. M. A. THE  Address . . . “Medic, Chicago” _ Subscription price . Five dollars per annum in advance SATURDAY, MARCH 25, 1905. EPIDEMIC CEREBROSPINAL MENINGITIS. Just as there are numerous forms of arthritis due to different etiologic factors, but one in particular due to a specific micro-organism and characterized by a defi¬ nite symptomatology, namely, acute rheumatic polyar¬ thritis, so also among the several varieties of menin¬ gitis of diverse origin there stands out one different from all the rest and dependent on its own specific bacterial cause, namely, epidemic cerebrospinal men¬ ingitis. While no doubt cases of the latter disease had been recognized previously, its epidemic occurrence was first noted at Geneva in 1805. A year later the occur¬ rence of an epidemic at Medfield, Mass., was described independently, and a most complete report on the sub¬ ject was made to the Massachusetts Medical Society in 1809 by a committee appointed for the purpose. In 1811 a classical study of the disease was published by Elisha North of Goshen, Conn., and an admirable ac¬ count of its history and its relation to other epidemics was given by Dr. S. G. Weber in the Boylston Prize Essay for 1866. A thoroughly modern and scientific report on the subject, was made to the Massachusetts State Board of Health in 1898 by Councilman, Mallory, and Wright, bearing on the epidemic in that state dur¬ ing the winter and spring of 1896-1897. The following anatomic peculiarities were early noted in cases of epidemic cerebrospinal meningitis as com¬ pared with other varieties of meningitis, namely, the character of the exudate, the greater degree of involve¬ ment of the spinal membranes, extension of the inflam¬ matory process to the brain and spinal cord and along the nerves, together with a general absence of in¬ flammatory lesions in the intima of the blood vessels. It was not, however, until the dawn of the bacteriologic era that it became possible to establish the absolute identity and distinctiveness of epidemic cerebrospinal meningitis. Leichtenstern, in 1885, found cocci, singly and in groups, arranged like gonococci in leucocytes in the meningeal exudate. Weichselbaum, in 1886, ob¬ served a diplococcus resembling t.he gonococcus, in small numbers, in cases of acute cerebrospinal menin¬ gitis, and occurring almost solely within the cells. The organism grew best on agar-agar, but it did not thrive at room temperature. It was not, however, readily dem¬ onstrable in sections of the meninges, in which and in cultures it was decolored by Gram’s method. It proved pathogenic for lower animals, and was given the name of Diplococcus intracellularis meningitidis. These ob¬ servations were subsequently confirmed by numerous other investigators, while in 1896 Heubner discovered the organism in fluid obtained by lumbar puncture from cases of epidemic cerebrospinal meningitis. Schwabach. in 1891, described diplococci in pus cells from a case of otitis media secondary to meningitis. Kiscliensky, in 1895, found the same micro-organisms in hemorrhagic foci in the lungs, and Scherer, in the same year, found them in the nasal secretion. The specificity of the dis¬ ease has thus been established. Epidemic cerebrospinal meningitis occurs most com¬ monly in late winter and spring, and especially in young adults and children. It has often been observed earliest among troops in a community. The disease does not always occur in epidemic form and the extension is not continuous. Isolated epidemics are the rule and sporadic cases are not uncommon. Like other infectious diseases, epidemic cerebrospinal meningitis is essentially transmissible. The channel of communication has not been demonstrated, but the atmosphere is most prob¬ ably the medium of conveyance. On account of the concealed and inaccessible localization aL the morbid process the danger from this source is probably compar¬ atively slight. Nevertheless, a limited number of cases have been placed on record in which more than one member of a family or household has been attacked by the disease. Osier, in the Cavendish Lecture for 1899, stated that he knew of no case in recent American ex¬ perience in which a physician or nurse had been attacked or in which cases had developed among other patients in a hospital, but an unfortunate exception to this is afforded in the death at Philadelphia recently of Dr. A. B. Craig, who acquired the disease from attendance on a patient suffering from cerebrospinal meningitis. It has been suggested that an insect may play the part of intermediate host, but evidence in support of such an hypothesis is as yet wanting. The disease usually sets in suddenly, with severe headache and pains in the neck and the back, to which muscular rigidity is soon added. In children there may be convulsions. At times there is a brief prodromal period attended with general malaise and terminated by a chill. ■ The temperature rises, although the pulse does not increase proportionately in frequency ; both are characterized by irregularity. Other symptoms are vom¬ iting, delirium, derangement of consciousness, varying from drowsiness and stupor to coma, paralysis of vary¬ ing degree and distribution, and various cutaneous eruptions — 'erythematous, miliary, herpetic, morbilloid, petechial. The course of the disease is rapid in fatal cases, the duration varying from a few hours to several days. In less acute cases recovery may be retarded for a prolonged period. After death the pia-arachnoid of both brain and spinal cord is found early in acute cases to be the seat of hyperemia and purulent infiltration, and later it is found to be covered with a fibrinopuru- lent exudation, while in chronic cases there is fibrous March 25, 1905. EDITORIALS. 961 thickening, with or without exudation. The tissues of the brain and cord themselves are also involved, and frequently, likewise, the cranial nerves, especially the second, fifth, seventh and eighth, and the roots of the spinal nerves. Pneumonia is a frequent complication. The nose and throat may be the seat of inflammation, and the sense of smell and taste may be lost. Deafness may result from purulent inflammation of the labyrinth of the ear or from involvement of the auditory nerve. The eyes often are suffused and ophthalmia has been observed. The ocular muscles, internal as well as ex¬ ternal, may be irritated or paralyzed, so that the pupils may be contracted or dilated, and strabismus and nystagmus be present. The optic papilla may be con¬ gested or inflamed, and atrophy and blindness may re¬ sult. The joints are frequently the seat of inflamma¬ tion. Leucoeytosis is invariably present, the polymor¬ phonuclear leucocytes especially being increased. The number of red blood corpuscles undergoes little change. Mental impairment of varying degree is not a rare sequel. The diagnosis of epidemic cerebrospinal meningitis is ordinarily easy, but it should always be confirmed by the demonstration of the Diplococcus intracellularis meningitidis in the fluid removed by lumbar puncture. The prognosis is unfavorable, death occurring in from 20 to 70 per cent, of the cases. Even when recov¬ ery takes place serious sequels may persist. Little is to be hoped directly from treatment. There is no specific. The future may develop an antitoxin, but even under the most favorable circumstances this is more likely to have a prophylactic than a curative value. The antitoxin of diphtheria has been employed as a remedial measure, but its use has been unattended with success. Inasmuch as the disease is transmissible, dan¬ ger from this source should be minimized by isolating the patient and by disinfecting the discharges, espe¬ cially from the nose, the ear and the lungs. He should be placed under the most favorable hygienic surround¬ ings, in a large, well-ventilated qiriet apartment. The intestinal tract should be cleansed by a purgative dose of calomel, followed by a saline, and the functions of the emunctories generally should be sustained. The diet should be simple, digestible and nutritious. A robust patient should be bled from a vein. Leeches ap¬ plied behind t.he ear may relieve the headache and may exert a beneficial influence on the inflammatory process in the skull. A similarly good effect may be brought about by the application to the head and spine of cold in the form of ice in bags, or of water passed in a con¬ tinuous stream through tubes. Restlessness should be allayed by narcotics, of which the best is morphin, pref¬ erably administered hypodermically. If there be a tendency to stupor, stimulants, such as camphor, musk, valerian, ether, wine, champagne or coffee, will be in¬ dicated. Lumbar puncture has been proposed and has been employed as a therapeutic procedure. While it has afforded a certain measure of symptomatic relief in some cases, permanently effective results have not yet been obtained from this measure. The same statement is applicable to trephining the skull and the spinal col¬ umn, with irrigation and drainage. From the foregoing considerations it will accordingly be seen that here, as elsewhere, the most effective as well as the most feasible treatment consists in a rational application of the essential principles of modern pro¬ phylaxis, namely, separation of the sick from the well, and disinfection of all infected matters. THE NATIONAL INVESTIGATION OF LEPROSY. A bill recently passed by Congress provides that when the Territory of Hawaii shall have ceded to the United States in perpetuity a tract of land one mile square within the leper settlement on the Island of Molokai, a hospital station and laboratory of the U. S. Public Health and Marine-Hospital Service shall be established thereon for the study of the methods of transmission, cause and treatment of leprosy. It fur¬ ther authorizes the Secretary of the Treasury to cause the erection on the site selected of suitable and neces¬ sary buildings, and that the surgeon general of the Pub¬ lic Health and Marine-Hospital Service, through his accredited agent, may receive patients afflicted with lep¬ rosy and committed to his care under the legal authori¬ zation of the Territory of Hawaii. These patients are not to exceed forty in number to be under treatment at any one time, and they shall remain under the jurisdic¬ tion of the surgeon general until returned to the proper health authorities of Hawaii. The surgeon general, with the approval of the Sec¬ retary of the Treasury, is authorized also to detail, or to appoint, for the purposes of these investigations, any medical officers, acting assistant surgeons and others who may be necessary for the purpose. The sum of $100,000 is appropriated for the erection of the build¬ ings, and $50,000 for the maintenance and pay of offi¬ cers and employes for the fiscal year ending June 30, 1906. The treatment of the disease in the past, with few exceptions, has been rudimentary, empirical and lacking in concerted effort to establish a cure. There can be no doubt that leprosy is spreading, and that more sys¬ tematic work should be done to prevent the further in¬ crease of the disease as well as to care for the sufferers. In spite of the discovery of the cause of leprosy, the Bacillus leprce by Hansen and its investigation by others, there is but little more known of the methods of transmission and rational treatment of the disease than was known in Mosaic times. The act above re¬ ferred to is in no sense an act to relieve the health au¬ thorities of the Territory of Hawaii of the care of the lepers of that country. It simply contemplates that the rich store of material offered by the thousand or 962 EDITORIALS. Joue. A. M. A. more lepers confined within the limits of the leper col¬ ony on the Island of Molokai should be made use of with a view to determine the methods of transmission, the cause of the spread and the treatment of leprosy. There can be little doubt that the treatment of leprosy affords a field of work full at once of promise and of arduous effort. Lepers are cured from time to time; indeed, the reports of United States consular officers in China would seem to indicate that a line of treatment instituted in that country by Raszlag promises to be of great value. It has been reported that a line of treatment, which is successful in its results, has recently been put in op¬ eration by Dr. Isadore Dyer, and it has been announced that Dr. Rost1 of the Indian Medical Service has suc¬ ceeded by special technic in cultivating the Bacillus leprce, and in preparing from his cultures a material which he designates “leprolin,” and which he claims is applicable to the treatment of the disease. Treat¬ ment, however, is of comparatively little avail unless at the same time we can arrive at definite and scientific information as to the methods of the transmission of the disease, looking to its prophylaxis as well as to its cure. How the causative organism gains entrance to the economy we do not know. Why it is that the infection of the disease is not much more widely spread among the Caucasian races than it is, we can not decide. What line affords the greatest promise of success, we can not tell. All of these questions, it is hoped, will be solved by the investigations about to be made in Hawaii. ' The condition of the leper of Hawaii, even under the enlightened management of the leper station at Molokai, is deplorable in the extreme. The search for lepers in the islands is active and unceasing. When a case of leprosy is discovered the person is brought be¬ fore a board of leprosy experts, and it being decided that the disease is leprosy, the unfortunate is sent to the Island of Molokai, there to remain for the remain¬ der of his natural life, virtually a prisoner, and not be¬ cause a crime against society has been committed, but because he has been stricken with a disease recognized as communicable and apparently incurable. It is sincerely to be hoped that succeeding congresses will make the necessary small appropriations for the maintenance of the experimental station, and that the far-reaching results will inspire those having the mat¬ ter in charge with a degree of enthusiasm which will be the best guarantee of success. Though there are not wanting instances of the establishment of settlements and leprosaria for the segregation and care of lepers, it seems to be left for the Government of the United States to have instituted systematic, well-directed ef¬ forts looking to the cure of the disease. The undertak¬ ing is worthy of every success, and it would seem that for the first time in the history of the world there is hope for the leper. 1. Indian Med. Gaz., June, 1904, abstracted in The Journal, July 23, 1904, p. 286. EXPERIMENTAL MEASLES. As early as 1758, Francis Home of Edinburgh at¬ tempted the inoculation of measles. His method con¬ sisted in saturating cotton with the blood taken from the skin of a patient suffering from the disease and applying it to an abrasion in the individual to be in¬ oculated. He reported 15 cases of inoculation, but an analysis of these cases in the light of our present knowledge makes it seem certain that he was not suc¬ cessful in reproducing the disease in any instance. Since Home’s work, many physicians have tried to produce measles experimentally, and among them Wachsel, Speranza, Katona, McGirr and Bufalini as¬ serted that they were successful. Some used blood, others tears, and others nasal mucus as a source of the virus. A critical study of their methods and results show them to be of but little value, for, in the first place, the possibility of natural infection was scarcely ever excluded, and, in the second place, the evidence that the eruptive diseases which followed the inocula¬ tion were in reality measles is not at all convincing. The only experiments in the literature reported as suc¬ cessful which can lay any claim to credence are those of Mayer of Vienna, made during the epidemics of measles in 1845-51. His results have not been reported in great detail, but they impress us as being reliable. He states that he “vaccinated” successfully six times by using as his inoculation material scrapings from the center of a rubeolous spot. These scrapings must have included blood, epithelial debris and tissue juices, and the experiments, though undoubtedly successful as far as the production of the disease in at least two cases is concerned, do not permit any decision as to the exact localization of the virus in the infected individual, i. e., to say whether it exists in the blood alone, the skin alone, or in the tissue-juices. The conditions of successful experimentation with measles are difficult to realize. The possibility of natu¬ ral infection must be excluded. Candidates susceptible to the disease must be found and their consent to in¬ oculation must be obtained. They must be kept iso¬ lated. The virus must be derived from a reliable source. There must be nothing equivocal about the experi¬ menter, or in any way connected with the conditions of the experiment. The proper investigation and ideal conditions appear to have been met recently. Hek- toen,1 at the Memorial Institute for Infectious Diseases in Chicago, has brought the indisputable proof not only first of the inoculabilitv of measles by subcutaneous in¬ jection, but, second, of the existence of the virus in the blood of patients during the early eruption ; and, third, of the retention of virulence by blood introduced into ascites-broth and kept at a temperature of 37° C. for twenty-four hours. He has demonstrated that, though the exact nature of the infective agent is as yet un- 1. Hektoen, L. : Experimental Measles, Jour. Infectious Dis., Chicago, 1905, vol. 11, pp. 238-255. Abstracted in The Journal, March 18, p. 909. March 25, 1905. URIC ACID. 963 known, it is possible to obtain the virus of measles in a relatively pure state, at least unmixed with other mi¬ crobes; this gives opportunity for the fruitful applica¬ tion to the infective agent of a whole series of methods of investigation hitherto not feasible. For the details of Hcktoen’s experiments and an ac¬ count of the careful controls made, the original article should be consulted. TRUTH AND POETRY CONCERNING URIC ACID. SI. Up to the present our review has dealt chiefly with the researches bearing on the normal physiologic rela¬ tions of uric acid, and we have, we believe, presented to our readers, though in very brief form, all of the im¬ portant facts which may be considered as established in connection therewith. We desire now to turn to a con¬ sideration of the studies made on uric acid in disease, in other words, to the pathologic physiology of the sub¬ stance. Though the discussion of this side of our topic will doubtless- be even more interesting to our readers than that of the normal physiology, it is necessary to confess in the beginning that only a small number of definite facts on the pathologic side have thus far been accumulated, and that our knowledge of the signifi¬ cance of uric acid in pathologic processes is extremely fragmentary. In the researches on the pathology of uric acid we find investigators indulging in assumptions and theories, as a rule, rather than reporting facts — the articles on the topic teem with “poetry,” and are sin¬ gularly deficient in content of recognizable “truth.” Of the various conditions in which deviations from the normal uric-acid relations have been observed, two stand out prominently from the rest, inasmuch as in them it has become matter of common belief that the clinical manifestations are directly due to these devia¬ tions; we refer to gout and to the so-called uric-acid diathesis. In diseases like pneumonia and leukemia, in which, as we have seen, uric-acid formation and excre¬ tion may be increased, no one attributes the cause of the diseases or the symptoms of the patients to the al¬ tered uric-acid metabolism ; it is assumed that the change in the uric-acid relations is, in them, a secondary phenomenon, a modification resulting from the primary pathologic process. Even in the uric-acid diathesis there is a good deal of evidence to indicate that we are concerned merely with altered conditions of solubility of uric acid and urates rather than with real disturb¬ ances in uric-acid formation and destruction; so that it is practically in gout alone that disturbances of actual uric-acid metabolism are held primarily respon¬ sible for abnormal clinical manifestations. In gout, as everybody knows, two characteristic clin¬ ical phenomena are met with — the so-called gouty at¬ tacks of inflammation and the gouty deposits or tophi. The attacks of gouty inflammation are especially prone to affect the small, distal joints of the extremities, the metacarpophalangeal joint of the great toe being most frequently involved. The arthritis of gout is distin¬ guished further from the other arthritides (1) by its frequent relation to excessive eating or drinking, (2) by its tendency to come on suddenly in the night, and (3) by the marked participation in the inflammatory process of the soft, parts surrounding the joint. The gouty deposits or tophi, on the other hand, occur usually without any accompanying acute inflammatory reaction in their neighborhood. No matter, then, to what the6ry of gout we incline, we must see to it that our theory accounts for the origin of the acute gouty attacks of inflammation, that it explains how the tophi arise, and that it gives us some clue to the sites of predilection, both of the inflammations and of the gouty deposits. Even before the end of the eighteenth century, shortly after the discovery of uric acid itself, Wollaston demon¬ strated the uratic nature of gouty deposits, and gave expression to the view that uric acid, in some way or another, stands in definite relation to the pathologic physiology of gout. Though Wollaston’s idea received support from Forbes and later from Cruveilhier, it was strongly opposed by Scudamore, an authority whose opinion had great weight with his contemporaries. Ac¬ cordingly, we find in the early part of the nineteenth cen¬ tury a whole series of hypotheses developed to explain the essential nature of gout, independently of the rela¬ tion of uric acid to it. Some attributed the disease to alterations in the vascular system, others to intestinal disturbances, still others regarded it as of neural origin, and finally, there were those who believed it to be due to a toxemia, to the existence of some materia morbi cir¬ culating in the blood. Scudamore himself asserted that gout is due to weak¬ ness of the blood vessels in the portal system, and that as a result there is abnormal secretion of the bile, and, indeed, a .general disturbance of secretion throughout the intestinal canal. Gairdner held that the goutj^ pains are due to the rupture or extreme dilatation of capil¬ laries around the fine nerve fibers as. a result of venous congestion. Parry maintained that the essential path¬ ology of gout consists in an uneven distribution of the blood, and that the gouty paroxysm is to be viewed simply as an effort to restore the normal equilibrium. Of those who favored an intestinal origin, Sutton and Todd, both English physicians, may be mentioned. Todd’s idea was that in gout, through some pathologic activity of the duodenum, there is increased formation of lactic acid, and further, that, owing to hepatic dis¬ turbances, biliary constituents are retained in the blood. Cullen was the especial champion of the theory of a nervous origin of gout; the affection of the nervous sys¬ tem leads, he thought, to a depression of tonus. That gout is due to some sort of toxemia was the view ad¬ vanced by Henry Holland, though he did not speculate as to the exact nature of the noxa concerned. Note how gratuitous were most of the assumptions 964 MINOR COMMENTS. Jour. A. M. A. in these older theories of gout! For the most part, they were mere creations of the imagination, unsub¬ stantial fumes of fancy, effects of the indulgence of rev- ery. Such stretches of the imagination, uncontrolled by actual observation and scientific experiment, have never brought us far in medicine, and never can bring us far. Instead, nature must be interrogated and she must be compelled to answer the questions herself. If we are to get accurate ideas regarding what goes on inside a gouty patient, we must draw the information in some way out of the patient himself, and take it into our minds through the medium of our organs of sense ; we may not hope to attain to any significant truth in the matter simply by the use of our so-called “mind's eye.” To some of the objective studies of gout in contrast with these subjective inventions it is our intention to advert in the next installment of this review. MORBID ALTERATIONS IN BONE MARROW. A satisfactory explanation is yet wanting for the dif¬ ference in the changes that take place in the number of leucocytes in cases of typhoid fever on the one hand and of other infectious diseases, notably pneumonia, on the other hand. In the former, when uncomplicated, the number, as is well known, is invariably diminished, while in the latter it is generally increased. It has been demonstrated that a close relationship exists be¬ tween certain cells of the hemopoietic organs and the cells of the circulating blood. A^arious alterations in the bone marrow that appear to be absent in cases of other infectious diseases have been observed in cases of typhoid fever, and in this fact may reside, in part at least, the explanation for the phenomena under con¬ sideration. These interesting observations have been confirmed by the results of a comparative study recently made by Dr. Warfield T. Longcope.1 Examination of the material from 26 cases of typhoid fever disclosed the existence of certain definite and histologic lesions closely resem¬ bling the changes in the mesenteric lymph nodes, in the lymphatic follicles of the intestine and in the spleen. These alterations consisted in the presence of many lvmphoid cells, large phagocytes and foci of necrosis, with more or less hyperplasia of the blood-forming cells. In the marrow from many eases in which death was due to perforation and general peritonitis there were in addition diffuse degenerative changes in the blood- forming cells, together with marked edema and con¬ gestion of the tissues. Differential counts of the bone- marrow cells from 10 cases disclosed a marked relative increase in the lymphoid cells over the granular myelo¬ cytes. The bone marrow from 15 cases of acute lobar pneumonia, 4 cases of peritonitis, 1 of acute cerebro¬ spinal meningitis, 1 of retroperitoneal abscess and 1 of puerperal septicemia exhibited similar alterations, 1. Bulletin of the Ayer Clinical Laboratory of the Pennsylvania Hospital, No. 2, January, 1905. though differing in many important particulars from those observed in the cases of typhoid fever. There was more or less extensive hyperplasia of the blood-forming cells, with a marked relative increase in the granular myelocytes over the lymphoid cells. In the cases of peritonitis due to other causes than typhoid perfora¬ tion, diffuse degenerative changes were absent. In none of the cases of this group were foci of necrosis found. Large phagocytic cells were exceedingly rare or entirely absent. The bone marrow from 4 cases of nephritis and from 1 of carcinoma of the gall bladder exhibited no distinctive pathologic alterations, and seemed to resemble closely the marrow from two nor¬ mal individuals. 