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A STUDY OF THE METABOLISM OF TWO ATYPICAL CASES RELATED TO THE DEMENTIA

PRECOX GROUP.

BY FRANCIS M. BARNES, Jr.,

Assistant Physician and Director of the Clinical Laboratory, The Sheppard and Enoch Pratt Hospital, Towson, Md.

In the preceding paper the clinical condition of these two patients and the results of the examination of the blood have been reported. The details of the case histories and of the blood findings will not, therefore, be repeated here. To sum up briefly: in two individuals during their late twenties a psychosis develops, the onset and subsequent course of which in both cases are similar. The most striking features are the recurring attacks, during which varied grades of excitement and depression alternate. In the woman the excitement is still a most evident symptom, whereas in the man this element has almost entirely disappeared and its place taken by the marked depression (stupor) which in the woman now occurs only towards the end of the excited phase. Deterioration is evident in both patients. In the former paper and here they are considered as " atypical psychoses related to the dementia precox group and particularly to the katatonic variety, in which recurrent attacks, consisting of alternations between phases of varying length of excitement of a maniacal-depressive character, and stupor, persisting throughout a number of years have left the present condition of moderate deterioration noticeable principally in the affective sphere."

The blood examinations which were made on these two patients showed some interesting results but did not bring forth any proof of facts of importance from an etiologic standpoint. The coincidence of the changes in the number of leucocytes and in the temperature and pulse curves during a given phase as shown in the charts of the preceding paper suggested that a study of the metabolic processes during the different stages might afford additional knowledge of value to our understanding of these two cases. The rapidly alternating phases seemed to offer an excellent opportunity

for determining whether or not some variation from the normal of the metabolic processes might be present and bear some relation to the changes in the mental condition. Such variations have been noted to occur. Folin and Shaffer' have reported the results of a rather prolonged study of a case in which the phosphate excretion showed fluctuations in amount which paralleled the alternations in the mental state. It is to be regretted, perhaps, that the blood studies already reported could not have been carried out concomitantly with those of metabolism. Even if it had not been that the chemical work was suggested by the blood findings it is doubtful if there would have been sufficient time to carry out the two examinations over the same period. Although considerable time has elapsed between the two series of observations the condition of the patients has not changed materially and it seems that it may be assumed safely that the value of the work has not been vitiated in any way by this time interval and that the findings of several months ago are directly comparable with those made more recently during similar phases."

PLAN OF THE WORK AND THE METHODS USED.

The original object of this work was to study under suitable known conditions the metabolism of these two patients. The analytical scheme used by Folin in his studies' seemed to be quite satisfactory for the purpose and has been followed with but little change. As the urine work itself in the scheme is quite exacting the feces have not been analyzed. The diet proposed has several features to recommend it but principally because using this diet Folin has gathered together an amount of data concerning metabolism under both abnormal (mental diseases) and normal' con

'Folin and Shaffer: The American Journal of Physiology, 1902, VII, p. 135.

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During this interval between the blood and chemical work the present clinical laboratory was constructed and equipped and all methods to be used in this study were subjected to repeated controlled and checked experiments. These experiments have occupied the entire time for several months and were concluded only after the writer was satisfied that personal errors had been brought within permissible limits.

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Folin: The American Journal of Insanity, 1904, LX, p. 699.

Folin: The American Journal of Physiology, 1905, XIII, p. 45.

ditions, which is available for comparison. The diets used in this work are as follows:

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These diets were made in the laboratory. All was given the patient before six o'clock each evening. To ensure as far as possible against all preventable losses and errors reliable special nurses were with these patients constantly during the entire time of the experiment.

The methods which have been used are all well-known and need no detailed description here. The amount of urine was measured in the customary cylinder; the specific gravity determined with an accurate hydrometer at 15 degrees centigrade; the reaction taken with ordinary litmus. Total nitrogen determined by the Kjeldahl method; phosphates by titration with uranium acetate with cochineal as indicator and chlorine estimated according to Volhard. Neutral sulphur, inorganic and ethereal sulphates, urea, ammonia, kreatinin, uric acid, acidity and indican determinations were all made according to the methods which have been devised by Folin." For several months prior to beginning the work on these two patients many experiments were carried out with all methods in

Folin has published a number of papers regarding these methods, of which only those describing the methods as finally adopted will be given here. Those described in the following articles are the ones used in this work. No variations have been introduced.

Sulphur and Sulphates. The Journal of Biological Chemistry, 1906, I, p. 131.

Urea. Zeitschrift für physiologische Chemie, 1902, XXXVI, p. 333.
Ammonia. Ibid. 1902, XXXVII, p. 161.

Kreatinin. Ibid. 1904, XLI, p. 223.

Uric acid. Ibid. 1901, XXXII, p. 552.

Acidity. American Journal of Physiology, 1903, IX, p. 265.
Indican. Ibid. 1905, XIII, p. 53.

order to determine their accuracy and uniformity. Experiments were made with both known standard solutions and with specimens of urine. In some instances as many as a hundred or more estimations have been made with one method. Sometimes a dozen duplicates have been carried through and seldom less than six. Exceedingly uniform results were obtained with each procedure and the accuracy comes well within the limits of technical error. The indican is not determined quantitatively. The urea method will not yield satisfactory results unless very closely watched while boiling with the magnesium chloride.

In the preparation of all solutions the greatest care has been exercised. This is true for those used in all titrations as well as for those used in testing the methods themselves. As in many of the determinations small quantities of urine are used inaccuracy in measurement may occur. To minimize such errors small amounts have been measured from pipettes graduated in 0.05 ccm. and larger ones from burettes graduated in 0.1 ccm. In view of the uniform results obtained by these methods duplicate analyses have been made only when some error seems to have occurred or when the results have differed widely from the similar determination of the preceding day. Such occasions have, of course, occurred and are not indicated in the tables. Where differences have been detected on a second determination either a third estimation is made for verification or the one which is considered the correct one is recorded. In several instances where the undetermined nitrogen has constituted an unusually large percentage of the total, the error is undoubtedly with the urea determination and has been detected too late for repetition. Aside from these errors I think that the figures represent as accurate results as may be expected.

ANALYTICAL RESULTS.

In Table I (Case I, No. 541) are given the figures for a period of thirty-four days (only thirty-three are shown here, as on December 27 part of the day's voiding was lost and the remainder not analyzed) divided into four sections according to the diet used. During the first no nourishment or water was taken, during the third the starch diet was employed, while during the second and fourth the milk and egg diet was given. The dietary change to

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