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fifteenth day stood at 1005, while the urea had risen to 385 grains. Here, unluckily, the patient became mutinous; for although he had diarrhea, and slight delirium every night, he felt so well and hungry in the day-time that he was greatly disgusted with his rigid diet. I had kept him strictly upon milk alone-80 ounces daily; and except a very little lemonade, and the usual dilute hydrochloric acid mixture, nothing else was allowed to pass his lips. At this point he became so clamorous that he would probably have left the house had we not gratified him but to do so with safety we had to make the diet so complex that it would have been impossible to estimate its value by means of analysis. Accordingly, we did not estimate the urea during the next three days; but so far as the volume (judged by the eye merely) of urine and its colour1 could afford a hint, it did not seem likely that any very material change in the urea elimination had taken place during this time. After this three days' interval we resumed the diet of 80 ounces of milk only, and our first twenty-four hours' estimation gave only 316 grains urea. Next day (same diet) the urea fell to 284 grains the mean temperature was now 99°6. On the day following (twenty-first)) there was a sudden increase in the volume of the urine (from 550 c.c. to 2,000 c.c.), and the ureareading was 717 grains: but herewith a remark is necessary. No corrections had been made, at any point in the case, for chloride of sodium; for on the one hand it was impossible for me to give the time for exact estimations of the chlorides (having a large number of urines of acute diseases to examine every day), and, on the other hand, the rough formula given by Liebig for chlorides becomes worse than useless where there may be great critical variations. Throughout the decidedly febrile period of Jefferson's illness there could be little doubt, from the very moderate level of the figures representing the total effect of the nitrate of mercury test, that the chlorides were in great part either retained or eliminated in the stools, as is well known to be usually the case. But on the cessation of fever there is usually a sudden and rather considerable appearance of chlorides in the urine; and part of the 717 grains that read as urea in
1 Marked changes in urea-discharge are generally accompanied by distinct changes in discharge of colouring matters in acute pyrexia.
my table in all probability really represented Na Cl, especially as the diarrhoea was declining. Respecting the diarrhoea and its possible influence on the urea-discharge, it may be remarked, first, that during the early period (three days) of lowest urea elimination there was no diarrhoea, indeed no action of the bowels at all: and secondly, it has been long ago shown by Parkes that the diarrhoea of typhoid fever, though it does favour the escape of chlorides, is not to any considerable extent a channel for nitrogen-escape.
The volume of water steadily fell again (though no accurate measurements were taken) during the next two days. On the twenty-fourth day the volume was ascertained to be 1110 c.c. (39.6 ozs.), and the urea was (again without correction for chlorides) 383 grains. On the day following it was only 223 grains (also without correction for chlorides). At present he is on a mixed diet, approaching as fast as he safely can to the food of a healthy man. As soon as he shall have become fairly established on that, I will report on the amount of his normal urea-discharge. He is a hearty eater when in health.
The broad features of the above case are: (1) That the water elimination and the urea-discharge closely coincided in amount, but that they ran a precisely opposite course to that of the mean temperature during the whole period between the ninth and the fourteenth day. [It will be seen, hereafter, that even the water and the urea by no means always correspond in amount.] (2) That the average urea-level was exceedingly low, for it might well have been expected (according to former estimates) that such a patient would have excreted a daily average of 500 grains during the second week of typhoid, whereas he actually passed only 300 on the average. (3) I may now add that the nitrogenous matters introduced as food (in 80 ozs. milk) proved on analysis1 to yield 113.5 grains nitrogen, or the equivalent of 227 grains urea : so that it will be seen that but a small portion of the urea-discharge needs to be accounted for by destruction of proteinous tissues. (4) In correspondence with the slight degree of muscular destruction which took place in this case was the remarkably small degree in which muscular
1 The milk supplied to our hospital is good in quality. It is intermediate, qud nitrogen, between that of St. George's and that of the Middlesex
strength was affected. This was repeatedly pointed out by me to the students; and the same fact has been noted in several other cases.
Just before this case occurred, another patient, Mary Hughes (aged 32, single), had also been in Westminster Hospital, suffering from typhoid fever.1 The past history of the case was very confused. It was impossible to say whether, at her admission, she was already in the fourth week of typhoid fever, whether she had had a "relapse," or whether she had passed into typhoid after suffering from some other febrile affection. At any rate she was in a condition of very high pyrexia, the temperature fluctuating between 104° and 105°, or even more for the first two days, and crops of well-marked rose spots appeared daily for five or six days after her entrance to the hospital. She had no diarrhoea at any time; but this is a feature which has been exceedingly common for some months past, even in some of the best-marked cases of typhoid at Westminster Hospital, and, I believe, elsewhere. She had no delirium, no appearance of anxiety, and although she lay in bed her muscular strength seemed scarcely at all affected. It was curious to see this in a patient the dry burning heat of whose skin would have led one to expect a very profound degree of prostration. From January 24th to February 2nd inclusive (nine days), the total nitrogen of the urine was daily most carefully estimated by my friend Mr. Frederick Hicks (formerly assistant to Professor Sir Benjamin Brodie), by the soda-lime combustion process as modified by Parkes. On several of these days I myself examined, for urea only, by Liebig's method; and the difference between our figures was only so large as corresponded well enough with the probable amount of nitrogen contained in the excreted lithates, uric acid, creatine, creatinine, &c. The diet was rigidly confined to 60 oz. milk (containing a little over 85 grains nitrogen) during the first two days, for the other seven it consisted of 40 oz. milk, and 20 oz. best beef-tea (containing nearly 120 grains nitrogen). The nitrogen discharge1 was as follows:
1 Under the care of my colleague, Dr. Sturges.
2 Decimals are omitted. If the nitrogen be, for convenience, reckoned all as urea, these figures will have to be doubled, to express the whole as an urea
105 gr., 115 gr., 149 gr., 103 gr., 87 gr., 116 gr., 77 gr., 44 gr., 170 gr. As it has been suggested to me by one or two friends that cases with a low urea-discharge may perhaps void a large amount of nitrogen through the skin, I may remark that at any rate this patient did not perspire fluid at all considerably, nor did the man Jefferson.
The daily volume of water eliminated by the woman Hughes corresponded somewhat, but not closely, with the fluctuations of the urea. The figures (in cubic centimetres) are: 512-5, 570, 590, 500, 710, 635, 700, 700, 980. From this it can only be said in general terms that both urea and water were low; but it will be seen that, e.g., while on the seventh and eighth days of observation the volume of water was exactly the same, the nitrogen was 77 grains on the former and 44 on the latter day; and many other discrepancies could be pointed out. The above nine days were the only ones on which the total nitrogen was estimated; but for three or four days longer (I should mention that temperature became normal two days after the last combustion-research) I watched the urine, by Liebig's process, on the chance of a great rush of urea and water elimination, but nothing of the sort occurred. The urea slowly rose up to what appeared (on mixed diet) to be about the woman's normal discharge, viz. 350 grains. This being probably her standard in health, it is very remarkable to observe the low ratio of elimination during the nine days first mentioned, and especially during the first four of them, when the temperature was never below 103° at any part of the twenty-four hours. During these four days the urea-discharge did not average more than 238 grains; while the ingoing nitrogen averaged 102.5 grains, equivalent to 205 grains of urea. And it is interesting to observe that this evidence of a but slight destruction of the azotised tissues is fully in agreement with the woman's remarkable conservation of muscular power.
It will immediately occur to some, as a criticism on the above case, that the urea-discharge might well be low, seeing that the patient had been continuously or nearly continuously febrile for a month when our observations began, and the available albumen of the blood and tissues might have been used up by a copious urea-discharge in earlier stages of the disease. But
it seems difficult to suppose that anything of the kind had taken place; for in such case there must have been extreme muscular weakness, whereas the very reverse was the fact. And indeed, supposing that we regard the above as a case of typhoid really at the end of the fourth week at the time of admission, the best evidence hitherto obtained (including Parkes's) goes to show that when the fever keeps up at this late stage the urea-discharge keeps up also. The remark may also be made, in anticipation of a similar criticism on Jefferson's case (in which the observations were not commenced till the ninth day), that his entire freedom from muscular prostration was inconsistent with the idea that there had been any such enormous combustion during the first week as might have temporarily used up the nitrogenous matters available for elimination. Since writing the above I have analysed Jefferson's urine, first day of full diet:-Chlorides normal; urea, 503-88 grains.
Before carrying further this enumeration of cases with high temperature and low urea-discharge (which will be resumed in the next number of this journal), I wish to point out the present critical state of the questions upon which must depend the principles, which may ultimately be agreed upon, for the treatment of the pyrexial state, in order that the readers of this journal may perceive that the present investigation— though apparently concerned only with the clinical history of febrile diseases—has a practical bearing on the treatment of a number of acute diseases. But my remarks on this subject will find their most natural and relevant expression in the shape of a review (deferred, for want of space, to the April number) of Senator's work on the Febrile Process, which I would beg my readers to peruse before studying the continuation of the present paper in our next issue.
(To be continued.)
[REVIEWS, CORRESPONDENCE, and BIBLIOGRAPHY are postponed by the pressure on our space.-ED. Pract.]