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The autopsy was made twelve hours after death, in the presence of Drs. Bowditch, Buckingham, Ellis, Webb, and McCollom.

Rigor mortis was well marked; the body not greatly emaciated. The color was normal; there had not been any cachectic appearance during life.

About three quarts of fluid were found in left pleural cavity. It was at first light-colored, but became dark at the bottom of the chest. The left lung was contracted and crowded upwards, so that its lower edge came opposite the nipple. It was very firmly adherent at the top, and part way down the back and sides. The lower portion was crowded against the thoracic walls by the fluid, thereby explaining the failure to obtain fluid at the last tapping. The lung was hard, contracted, slightly compressible, and, with the whole pleural surface, closely infiltrated with encephaloid cancer. A section of the lung looked not unlike miliary tubercle, and this form of disease has been called. miliary

cancer.

The following is Dr. Fitz's report of the appearances of the organs: "The left lung more particularly, the right one to some extent also, contained numerous nodules and granules varying in size from that of the head of a small pin to that of apricots. With the exception of the smallest ones their borders were not circumscribed, but they assumed rather the appearance of a diffuse infiltration of a grayish color, and were of a soft-solid consistency. On pressure there exuded drops of opaque, gray fluid, which readily became confluent. These drops consisted almost wholly of large, flat, finely granular cells, of exceedingly irregular shapes. Their nuclei were large, and presented the indentations and septa indicative of proliferation.

"From the smallest bronchial tubes yellow drops could be squeezed, which were mainly composed of similar cells in a state of fatty degen

eration.

"The left pleura more particularly was thickened, reddened, and dotted with slightly elevated patches and granules varying in color from gray through white to yellow. In the subpleural fat-tissue, similar granules were observed, often as beaded lines; and the subpleural lymphatics of the lung were injected with a yellow material. The bronchial glands were enlarged, soft and gray, exuding white drops on press

ure.

"The nodules in the kidney were firmer, but possessed a similar structure to that of the pleural nodules, and, so far as the cells were concerned, to those of the diseased portions of the lungs. The cells were arranged in an alveolar manner.

"When portions of the infiltrated lung-tissue were shaken in a bottle containing water, the elastic fibres of the affected portion of the lung presented a normal arrangement, and the cells referred to were occasionally found as clumps representing casts of the alveoli.

"The tumor thus presented the characteristics of a medullary cancer." The right pleural cavity contained between one and two pints of clear serum. The lung was somewhat adherent at the apex, but not as much shrunken and contracted as was the left. The pericardium contained three or four ounces of thin, deep red fluid; but there were no patches of lymph, nor adhesions, nor redness on its inner surface. The heart was slightly enlarged. Its valves and walls were normal. In each kidney was found a small nodule of whitish substance, the size of a pea, of the same nature as the growth in the lungs, but secondary to it. The liver was somewhat enlarged. Its substance was apparently healthy, as was its capsule. The gall-bladder was filled with a very dark fluid, but did not contain calculi. The stomach and spleen were normal. A few glands behind the duodenum were enlarged, and infiltrated with what appeared to be the cancerous material.

Remarks. Primary cancer of the lungs is so very rare, and the symptoms so obscure, that the above case is of peculiar interest. At the first examination the diagnosis was thought to be plain. Dullness, and subcrepitant and finer râles at the base, with a gradual loss of flesh and strength, naturally led to the diagnosis of chronic catarrhal pneumonia. But at the second examination, six weeks later, although the dullness had greatly increased, the râles were gone, and the respiration at the base was nearly so. Moreover, vocal fremitus was absent. There was evidently effusion. But effusion supervening upon catarrhal pneumonia is very uncommon. This peculiarity in the symptoms, coupled with the fact that the patient experienced much less relief from emptying the pleural cavity than is usually obtained in ordinary cases of effusion, led us to think that we had to deal with some unusual affection of the lungs. That this affection was probably malignant was the unanimous opinion of all the physicians who saw or attended the patient. Another peculiar feature of the case was the pain. For thirty years and more, Dr. C. had invariably suffered pain after eating, at a point just below the ribs, on the right side, about two inches from the median line. This region was frequently tender and distended. During his last illness all of the pain and discomfort, except the stitch-pains felt after tapping, were situated in this spot or radiated from it. He had no pain whatever, with the above exception, in his left chest, the principal seat of the cancerous affection. As the autopsy revealed nothing to account for the abdominal pain which troubled him so many years, it would probably be called neuralgia.

Again, there was neither hæmoptysis nor expectoration during the whole sickness. All the authorities which I have been able to consult mention both of these as being very common symptoms in this affection. Neither did the patient have the general appearance or many of the symptoms of tubercular disease. There was no hectic, or great emacia

tion, or disturbance of the stomach and bowels, or sleep-sweats. Primary cancer of the lung, which, according to Niemeyer and other authorities, is an exceedingly rare affection, usually assumes the form of medullary disease; it is hardly ever scirrhus. It occurs in the form either of isolated masses or of infiltration. It seldom breaks down and forms cavities, but is more liable to extend to the pleura, and even through the walls of the chest.

The most prominent symptom in all the cases we have been able to find was dyspnoea. Cough with expectoration and blood-spitting were also present in the majority of cases. These symptoms coming on in a person suffering from a cancer in some external organ would point strongly to malignant disease in the lungs or thoracic cavity; for it is very rare to find tubercular disease in a cancerous patient. But in the case of a patient not known to be affected with cancer the symptoms might be, and often are, very obscure. Cases of primary cancer of the lungs are not unfrequently mistaken for pleurisy, or phthisis, or capillary bronchitis.

The following case is reported in The Lancet of April 3, 1869: A girl eleven years of age had severe dyspnoea. There was dullness throughout the left chest. The respiration was inaudible except under the clavicle and close to the spine. Vocal fremitus was present in these two places, but nowhere else. The heart was displaced to the right side, and there was bulging of the intercostal spaces. The diagnosis was effusion into the left chest. She was tapped twice between the eighth and the ninth rib, but only a few drops of blood and pus came from the trocar. At the autopsy a large mass of medullary cancer was found in the left chest. The lung was pushed back and spread out over the tumor. This case shows the great difficulty or even impossibility of making a diagnosis in some of the malignant affections of the thoracic cavity.

Pleuritic effusion is not as common in these cases as one would at first suppose. Dr. Risdon Bennett1 says it was present in only six cases out of thirty-nine. I found it reported as being present in three out of seven cases. Occasionally the question of effusion in these cases can be easily decided by finding the dullness at the upper part of the chest, and by the fact that it does not change its place with the different positions of the body. But the surest method to determine the presence of fluid is by aspiration. There is seldom anything in the expectoration to aid in the diagnosis of thoracic cancers. The so-called characteristic "black currant expectoration" is exceedingly rare.

Aside from pleurisy, the disease most liable to be mistaken for cancer of the lung is probably tuberculosis. In the former we should not expect to find the high pulse and temperature, pallor and emaciation, and profuse sweats, so characteristic of the latter affection.

The Lancet, 1870.

I desire to say in conclusion that the patient in this case received the kindest attentions from Drs. Bowditch, Ellis, Buckingham, Cotting, Storer, and McCollom.

RECENT PROGRESS IN MEDICAL CHEMISTRY.

BY EDWARD 8. WOOD, M. D.

URINARY CHEMISTRY.

Alkapton in the Urine. - The second case of the finding of this substance in the urine is reported by P. Fürbringer. The first case was reported by Boedeker,2 alkapton having been found together with grape sugar in the urine of a patient forty-four years old. In this case, it was found in the urine of a gold worker, twenty-nine years old, who was suffering with disease of both the lungs and of the liver.

Alkapton is a substance which has a powerful attraction for oxygen, and reacts chemically in many respects like grape sugar, and therefore may in rare instances be mistaken for it, unless the proper means be employed to distinguish between them.

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The urine, the specific gravity of which varied from 1010 to 1025, was remarkable for its dark color (between numbers seven and eight of Vogel's color table), and for the small amount eliminated during the twenty-four hours, the average amount being about six hundred cubic centimetres (minimum three hundred cubic centimetres; maximum eight hundred cubic centimetres). This condition had lasted but a few weeks previous to his admission to the hospital, and did not seem to be at all dependent directly upon the lung or the liver disease. The urine had a pretty strong acid reaction, no special odor, and no abnormal sediment, except occasionally one consisting of amorphous urates. At times a trace of albumen could be detected, but usually none was present. The excess of color was due to a very large proportion of urophæin, and to no abnormal pigment.

The urine was tested for sugar by Trommer's test (liquor potassii and sulphate of copper), and an abundant precipitate of the suboxide of copper was obtained, a result which was entirely unexpected. It was also noticed that immediately upon the addition of the liquor potassii a very dark brown color was produced, which is not one of the reactions of sugar, but is of alkapton. When alkapton is treated with an alkali, the solution absorbs oxygen very rapidly, in varying proportions according to the amount of alkapton present. When this urine was rendered alkaline and shaken with air, it absorbed about four fifths of its volume of oxygen. In Boedeker's case the urine similarly treated

1 Fresenius' Zeitschrift, 1875, page 408; from Berliner klinische Wochenschrift, 1875, No. 24.

2 Annalen der Chemie und Pharmacie, cxvii. 98.

absorbed somewhat more than an equal volume of oxygen. It is, of course, upon this property of alkapton that its reaction with Trommer's test depends. It is impossible to detect sugar by this test, unless the urine be first freed from alkapton by precipitating it with the basic acetate of lead (which throws down the alkapton and leaves the grape sugar in solution) and filtering.

Moore's or Heller's test (heating the urine with liquor potassii alone), which is, perhaps, the most frequently employed test for sugar in the urine, will not serve to detect sugar in the presence of alkapton, on account of the dark brown color produced by the latter. There are, however, two common tests for grape sugar which are not interfered with by the presence of alkapton, namely, Boettger's and the fermentation test, since the latter substance does not reduce the subnitrate of bismuth to the form of metallic bismuth, nor does it give rise to the production of carbonic acid and alcohol when mixed with yeast, as does grape sugar.

Mulder's test for sugar reacts only partially with alkapton. When a dilute solution of indigo carmin is mixed with an equal volume of liquor potassii, then a little of the urine is added, and the whole heated, the play of colors, through a blue, green, violet, and red to a reddish brown, is produced both with alkapton and with sugar; but upon shaking again with air, the reverse takes place only when sugar alone is present, alkapton preventing the reoxidation.

The importance of being able to detect this substance in the urine depends upon the liability of diagnosticating diabetes mellitus when no sugar exists in the urine, since nothing as yet is known concerning the method of the formation of alkapton in the body. In the case reported no alkapton could be detected after death in the fluids of the body.

Determination of Uric Acid in the Urine. The method usually employed for estimating uric acid in the urine, namely, precipitation by hydrochloric acid, has many disadvantages, the principal one of which is that there are certain substances present in many specimens of urine which apparently hold the uric acid in solution. A new method is given by A. P. Fokker, which depends upon the insolubility of the acid urate of ammonium in alkaline solutions, and which gives excellent results.

The method is as follows. One hundred cubic centimetres of urine are treated with a solution of the carbonate of sodium until the reaction is strongly alkaline, and filtered from the precipitated earthy phosphates. To the filtrate is added ten cubic centimetres of a solution of chloride of ammonium, and the whole is allowed to stand for several hours, when all of the uric acid will be precipitated in the form of urate of ammonium, which for the most part collects at the bottom of the vessel,

1 Fresenius' Zeitschrift, 1875, page 206; from Pflüger's Archiv, x. 153.

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