27.005 grms. daily. The nitrogen multiplied by 6.25 represents proteid in every case. We see in the first part of the experiment that more proteid was eaten than corresponded to the amount of nitrogen found in the excreta; some proteid must therefore have been retained in the body, and since the difference between nitrogen eaten (20.549 grms.) and nitrogen excreted (19.837 grms.) represents this proteid (i. e. 0.712 grms. N), we may calculate (0.712 × 6.25) that 4.45 grms. of proteid was each day added to the body. Quite different are the relations in the second part of the experiment, where the carbohydrates are no longer given. Here the daily loss from the body above what is fed to it, reaches the equivalent of 6.456 grms. of nitrogen, which corresponds to the destruction of 40.35 grms. of the body's proteid. The same characteristic metabolism is manifest in the diabetic. Because he has lost the power to burn the carbohydrates his proteid decomposition is above the normal. To a certain extent fat will protect the decomposition of proteid, but not to the same extent as carbohydrates, and then again the intestinal tract is incapable of absorbing fat in the quantity now needed. So we find the fat of the body drawn upon, and the patient gradually loses both flesh and fat in the satisfaction of the needs of his tissue, because he cannot absorb them in quantity sufficient to protect his tissue. A diet of meat and fat may suffice for the Esquimo and other races habituated to it, but in the diabetic, as will be shown, nearly half the energy in the proteid is lost through its partial transformation into sugar. His requirements are therefore abnormally large. A second point of interest lies in the frequent occurrence of B-oxybutyric acid, acetoacetic acid, acetone, and the lower fatty acids in the urine of patients suffering from severe forms of diabetes. These substances may all be obtained from the chemical treatment of sugar, and at first thought might be attributed to its abnormal decomposition, but further investigation leads to the belief that this cannot be so. These bodies are found in the urine whenever there is decomposition of the body's own proteid. This is strikingly illustrated in cases of inanition, and experiments (by Zuntz) made on Cetti, the starvation artist, showed that acetone was present in the urine from the first day of fasting, and that acetoacetic acid appeared on the third day, the two continuing present till normal food was given on the tenth day, when they immediately disappeared. The presence of these substances is noticed in leucocythemia, fever, and whenever decomposition of organized proteid goes on. The source of 6-oxybutyric acid, acetoacetic acid and acetone seems to be a common one, for on feeding B-oxybutyric acid, the other two, acetoacetic acid and acetone, appear in the urine (Minkowski, Araki) the reactions for which may be written thus: CH-CHOH-CH,-COOH+O=CH,-CO-CH,-COOH+H,O B-oxybutyric acid. Acetoacetic acid CH,-CO-CH,COOH=CH,-CO-CH,+CO, Only in the more severe forms of diabetes does ẞ-oxybutyric acid appear in the urine, it being usually oxidized into one of the other two bodies. The increased amount of lower fatty acids present in the urine in diabetes is likewise believed to be the accompaniment of the abnormal decomposition of the organized proteid and contributes to increase the acidity of both urine and blood. The acidity is, of course, still further increased by the production of sulphuric and phospheric acids from the oxidation of the sulphur and phosphorus containing proteid. The final acid. intoxication which results in coma diabeticum has been ascribed to a large production of B-oxybutyric acid, though this is not clearly demonstrated. A case related to me by Dr. E. L. Munson instanced a diabetic fed on proteid diet who had marked cerebral symptoms, which disappeared on feeding a mixed diet. In this case the partial burning of ingested carbohydrates served to diminish the decomposition of organized proteid, thereby diminishing the production of the toxic acids. There are several methods by which sugar may be made to appear in the urine and among them may be mentioned the irritation of the "diabetic center" in the medulla, the extirpation of the pancreas and the administration of phloridzin. The first does not give a true diabetes, but is due to an irritation which affects the vasomotors of the liver causing a sudden removal by the blood of the glycogen stored there, and the resulting excess of blood sugar is removed by the kidney. If no glycogen be present in the liver the experiment is unsuccessful. The second form of artificial diabetes is called "pancreas diabetes" and has been thoroughly investigated by Minkowski. After a complete extirpation of the pancreas in dogs, there sets in a typical diabetes in its severest form. If the dog in such condition be starved, the blood will be found surcharged with sugar, and the urine will contain sugar and nitrogen in the nearly uniform proportion of two and eight-tenths is to one, (Dextrose : Nitrogen :: 2.81). The dextrose does not come from fat, and must therefore come from proteid decomposed. Likewise on feeding proteid to such dogs the same relation between sugar and nitrogen is maintained. Furthermore if dextrose be given subcutaneously to the dogs it reappears in the urine gram for gram. So the diabetes is complete, that is, the body has lost the power of burning the ordinary blood sugar, dextrose. Such dogs were, however, able to burn levulose, as had been likewise shown by Fr. Voit in a case of human diabetes. Levulose fed to the diabetic dogs increased, however, the dextrose in the urine to an extent of about fifty per cent of the levulose fed, which corresponds to the well established fact that levulose is in part changed into dextrose by the liver. Still we have the important knowledge that the diabetic organization still retains the power to burn levulose. What the pancreas manufactures and gives to the blood and tissues thereby causing oxidation of the sugars, is unknown, and speculation upon it is hardly consistent or profitable within the limits of this article. It is therefore left to the reader to imagine it as a "catalytic agent" or an "oxygen carrier" as he wills. Dogs with pancreas diabetes ultimately die in coma diabeticum, with the same characteristics in blood and urine of acid intoxication as in diabetes mellitus. The third cited example of artificial diabetes was first produced by v. Mering after administration of phloridzin to man and to animals. Contrary to other forms of diabetes the amount of sugar in the blood is reduced by the phloridzin. Thus Minkowski in his fasting dogs with the established ratio before mentioned, DN: 2.8 1, was able after administration of phloridzin to suddenly obtain the ratio D: N: 10: 1, with accompanying sinking of the per cent of blood sugar. Phloridzin acts therefore to sweep the sugar from the blood. Cremer, experimenting on starving rabbits, found that the sugar in the urine was proportioned to the nitrogen, that is to the proteid decomposed. He injected phloridzin every twenty-four hours. The subject of phloridzin diabetes has been one which has been of considerable interest to me, and in my work I have been greatly aided at different times by the valuable assistance of Dr. E. L. Munson, Dr. E. A. Lawbaugh and Mr. I. M. Heller. It is possible here only to touch upon the salient points of our investigations.' The administration of phloridzin to starving rabbits in small doses at frequent intervals (every six to twelve hours) at first sweeps the blood sugar into the urine (example; 1 The full details will appear in the Zeit scheift für Biologie. DN51) but on the second day, gives a ratio between sugar and nitrogen in the urine approximating that of Minkowski, i. e., DN: 2.8 : I. The explanation of this is simple. Long ago Voit stated that proteid fell in its first decomposition into two radicals which he termed the nitrogenous and the non-nitrogenous. The first was rapidly decomposed, appearing in its greater part as urea in the urine fourteen hours after feeding (Feder). The non-nitrogenous portion of decomposed proteid took twentyfour hours for its carbon to be completely eliminated through the lungs. Now this non-nitrogenous portion consists, in part at least, of sugar, and we have here the explanation of the presence of sugar in the blood and organization even during starvation. Phloridzin suddenly removes this, and thereafter removes all sugar as soon as produced, giving the ratio mentioned as above and strongly confirming the experiments of Minkowski. A clearer interpretation of the metabolism of proteid we may obtain from the following table made by Weintraud and Laves: 100 gr. Proteid · 34.5 gr. Urea 54.1 gr. C; 7.3 gr. H; 16.1 gr. N; 21.5 gr. O2 9.2 gr. O2 The constituents of urea belonging to one hundred grms. of proteid were first subtracted. The amount of dextrose formed when two and eight-tenths grams are produced to every one gram of nitrogen, amounts to 45.08 grms. for every 100 grms. of proteid, and furthermore we notice from the table that this process must be one of oxidation with consequent evolution of heat, though the quantity of the heat produced we are unable to calculate. But the heat value of 45.08 grms. of dextrose we may very readily calculate, since one gram of dextrose burning in the body yields 3,740 Colories (Stohmann), that is to say an amount of heat able to raise 3,740 grms. of distilled water from O°C to I°C. The heat value of the 45.08 grms. of dextrose derived from 100 grms. of proteid is, therefore, 3,740 × 45.08=168,599 Calories. The total heat value of 100 grms. of organized proteid burning in the starving body is 380,000 Cal., calculated according to Rübner. This shows us clearly that 44.4 per cent of the total energy contained in proteid is furnished by the sugar, which is split from it. This process in the animal is the antithisis to that in the plant, where proteid is probably built up synthetically from sugar and amido bodies. Dextrose fed to a rabbit with phloridzin diabetes may somewhat increase the sugar in the urine but, may in large part be burned. The body does not therefore lose the power to burn sugar, but the phloridzin itself, perhaps through chemical union with the sugar, seems to be able to protect it from decomposition. The only remaining point upon which I will speak here is the theory of the action of phloridzin, and of this I can make no certain statement. The drug is a glucoside, yielding phloretin and sugar on boiling with acids. It is said to appear quantitatively in the urine (Cremer). Phloretin when administered likewise produces glycosuria. Minkowski's theory is that phloridzin is decomposed in the kidney into sugar which passes into the urine and into phloretin which unites with more sugar in the organization and thus brings it to the kidney. Gradually the phloridzin may be given to the urine, and when all has passed the action. ceases. A synthesis within the body of phloretin and sugar, would not be dissimilar to the synthesis, after feeding chloral hydrate, between the trichlorethyl alcohol formed from it and dextrose, though here the dextrose is subsequently oxidized to the glucuronic acid radical, the whole compound being urochloralic acid, or trichlorethyl glucuronic acid. If the synthesis between the phloretin and sugar took place in the body, then after establishing with phloridzin ratio (D: N 2.8: 1) we might on venous injection of phloretin make the sugar in the urine disappear or decrease in quantity. But in repeated and careful experiments neither Dr. Lawbaugh nor Mr. Heller have been able to attain such results. The subject is full of interest and suggestive of future lines of research. THE DIAGNOSIS AND TREATMENT OF APHASIA. BY FREDERICK T. SIMPSON, M.D., HARTFORD, Conn. Few things in medical science are more interesting in historical retrospect than the gradual discovery of the nature of the disorders of the cerebral speech mechanism, furnishing as it did a key for unlocking the mysteries of brain architecture and brain. function. Passing by the fortunate speculations of Gall and others, we find three Frenchmen who on the basis of ante- and post-mortem study made three definite steps forward in the localization of the lesions of aphasia. The first was Bouillard, who in 1825, from the results of sixty-four autopsies, asserted that speech |