[Extracted from The American Journal of the Medical Sciences ior April, 18£8.] 
ON THE ALTERATIONS INDUCED BY INTERMITTENT FEVER IN THE 
PHYSICAL AND CHEMICAL QUALITIES OF THE URINE, AND ON 
THE ACTION OF THE DISULPHATE OF QUININE. 
Bv WILLIAM A. HAMMOND, M.D., 
ASSISTANT SURGEON, U. S. A. 
(Read before the Biological Society of Philadelphia, February 15, 1858.) 
We know but little at present concerning the modifications produced by 
diseases in the function of regressive metamorphosis of tissue, and yet it is 
very obvious that here our observations, if properly directed, can hardly 
fail to lead to results of very great importance. The exhalations from 
the skin and lungs, the urine, and the feces, are so many points upon which 
to concentrate our efforts; and by carefully studying these several excretions, 
a vast amount of knowledge may be obtained relative to the pathological 
actions going on within the system. The facility and exactness with which 
such inquiries can be prosecuted is only beginning to be perceived, and a rich 
harvest is reserved for those who will devote themselves to this field of labor. 
The condition of the urine in intermittent fever has been observed by Bec- 
querel,1 and more recently by Stuart2 and others. Becquerel’s investigations 
are of the most limited character, being confined to the determination of the 
specific gravity and general characteristics of the excretion. Stuart’s re- 
searches are also very unsatisfactory, and not of such a character as to lead 
to any conclusions worthy of reliance—no means of analysis other than the 
microscope having been employed. 
The action of the disulphate of quinine upon the urine has, within a short 
period, been investigated by Ranke,3 who found that the principal effect of its 
administration was to diminish the amount of uric acid excreted. 
During a recent attack of intermittent fever of the tertian type, I had the 
1 Ssmeiotique des Urines, p. 286; and Traite de Cliimie Pathologique, p. 345. 
2 Charleston Medical Journal and Review, May, 1857, p. 323, 
3 Medical Times and Gazette, May 30, 1857, p. 537. 2 
opportunity of studying, in my own person, the effects produced by this dis- 
ease on the physical and chemical qualities of the urine, and also of noticing 
the results ensuing from the administration of the disulphate of quinine. 
There are many obvious advantages to the physiologist, and also to the 
science which he represents, in basing his conclusions, whenever practicable, 
on investigations instituted upon himself. He is assured of their correctness, 
and knows fully the conditions under which they are performed. On the 
contrary, when others (such at least as are most likely to come under his ob- 
servation) are the subjects of his researches, he can never be certain that his 
directions have been complied with, or that he has not been otherwise deceived. 
The investigations upon which this paper is based, being confined to one 
individual, are necessarily not such as to lead to general conclusions, and are 
only submitted as a slight contribution to our common stock of knowledge. 
Aside from their correctness, therefore, I have but little to claim for them. 
The quantity, specific gravity, and general appearance of the urine were 
noted, and the amount of its urea, uric acid, free acid, chlorine, and phosphoric 
and sulphuric acids separately ascertained. The methods used in these de- 
terminations were the same as those employed in previous researches, and as 
elsewhere indicated. 
The attack commenced at about 3| o’clock P. M., on the 4th of January. 
The cold stage lasted about 35 minutes; the hot until near 10 P. M., when 
profuse perspiration ensued, and I fell asleep and did not awake till morning. 
I was eating a hearty dinner when the paroxysm commenced. At 6$ P. M. 
I ate a little bread and butter and drank a cup of tea. At breakfast the fol- 
lowing morning I ate as usual. As far as possible, my food was the same 
throughout the investigations, and my general mode of life was not materially 
changed. 
At the commencement of the cold stage, the bladder was evacuated of its 
contents. At about 4j P. M., it was again emptied. The quantity passed 
at this time amounted to 93.4 cubic centimetres, and had a specific gravity of 
1016.35. It was of a pale straw colour, and deposited no sediment on stand- 
ing. The reaction was feebly acid. Before going to sleep, I passed 283.9 
cubic centimetres of urine, having a specific gravity of 1022.19. This was 
of high colour, strong acid reaction, and by morning had deposited a heavy 
lateritious sediment. On examining this with the microscope, a few crystals 
of uric acid were perceived. 
In the morning, after rising, 495.3 cubic centimetres of urine were evacu- 
ated, the specific gravity of which was 1020.43. It was of high colour and 
strong acid reaction. A copious lateritious precipitate was thrown down after 
a short time; it consisted of urates and a little free uric acid. 
For the whole period of twenty-four hours ending at 3? P. M. on the sth, 
the urine was as follows:— 3 
Quantity 1221.7 c. cm. 
Specific gravity .... 1020.06 
Urea 325.18 grains. 
Uric acid 28.39 “ 
Free acid 39.40 “ 
Chlorine 95.42 “ 
Phosphoric acid 69.18 “ 
During the subsequent twenty-four hours of intermission, the urine was of 
Sulphuric acid 32.11 “ 
the ensuing character:— 
Quantity 1650.4 c. cm 
Specific gravity .... 1022.17 
Urea 480.37 grains. 
Uric acid 16.84 “ 
Free acid 34.73 “ 
Chlorine 114.58 “ 
Phosphoric acid . . . . . 52.95 “ 
Sulphuric acid 38.14 “ 
From these records it is perceived that during the intermission there was 
an approach to the normal condition of the excretion under consideration. 
The quantity of urine, its specific gravity, and the amount of urea, chlorine, 
and sulphuric acid had increased, whilst at the same time the uric acid, free 
acid, and phosphoric acid had very considerably diminished. 
The second paroxysm came on at about 4 o’clock P. M. on the 6th, and 
was of similar character to the first. At the termination of the chill, 104.5 
cubic centimetres of urine were passed, the specific gravity of which was 
1017.41. It was of a pale yellow colour, of feeble acid reaction, and remained 
clear. During the hot stage I evacuated 325.01 cubic centimetres of urine, 
of 1021.32 specific gravity, high colour, and strong acid reaction. After 
standing long enough to reduce its temperature sufficiently, a heavy precipi- 
tate of urates was thrown down, in which, with the microscope, a few crystals 
of uric acid were perceived. The urine passed after rising in the morning 
amounted to 518 cubic centimetres, was of 1022.04 specific gravity, and pos- 
sessed the characteristics of that last described. 
The following table shows the amount and character of the urine for the 
whole period of twenty-four hours ending at 3J P, M. on the 7th:— 
Quantity 1387.2 c. cm 
Specific gravity .... 1019.45 
Urea 300.16 grains. 
Uric acid 31.54 “ 
Free acid ....... 35.72 “ 
Chlorine 108.11 “ 
Phosphoric acid 72.95 
Sulphuric acid 41.76 4 
At 4 o’clock P. M. on this day, I took ten grains of the disulpbate of quinia, 
ten grains at 11 P. M., and the same quantity at 10 A. M. the following day. 
The paroxysm which would have ensued at about 4 P. M. was thqs prevented. 
The urine passed during this period of twenty-four hours was of the ordi- 
nary normal colour, and of tolerably strong acid reaction. No sediment was 
deposited on standing. 
The following table exhibits its characters more in detail:— 
Quantity 1750.3 c. cm 
Specific gravity .... 1024.07 
Urea 589.43 grains. 
Uric acid ....... 13.79 * 
Free acid 27.54 ‘ 
Chlorine ....... 129.83 * 
Phosphoric acid 55.27 1 
Sulphuric acid 46.18 * 
The presence of quinia was demonstrated by means of Herapath’s test and 
viewing the crystals formed, with the microscope and by polarized light. 
The effects resulting from the administration of the quinine are thus shown 
to have been well marked. The quantity of urine, its specific gravity, and 
the amount of urea, chlorine, and sulphuric acid were increased, whilst the 
uric acid, free acid, and phosphoric acid were, on the contrary, diminished. 
From 3£ P. M. on this day to the same hour on the following day, I col- 
lected the urine evacuated, and submitted it to analysis. No quinine was 
taken during this period, and no paroxysm of the fever occurred. 
Quantity 1806.3 c. cm 
Specific gravity .... 1024.81 
Urea ........ 638.20 grains. 
Uric acid ....... 12.71 “ 
Free acid 25.80 “ 
Chlorine ....... 138.27 “ 
Phosphoric acid 56.22 “ 
Sulphuric acid ...... 40.10 “ 
The above table exhibits pretty nearly the average condition of my urine 
in its normal state. It is seen that, notwithstanding no quinine was taken, 
the excretion maintained its general character of the previous day. 
No more paroxysms ensued, and circumstances prevented me making at 
that time any further analysis of the urine. 
The accompanying table, in which the several results obtained are collected 
together, will tend to facilitate reference:— 5 
1st day. 
Paroxysm. 
2d day. 
Intermission. 
3d day. 
Paroxysm. 
4th day. 
Administra- 
tion of quinine. 
5th day. 
Quantity of urine 
Specific gravity 
Urea 
Uric acid 
Free acid 
Chlorine 
Phosphoric acid 
Sulphuric acid 
1221.7 c.cm. 
1020.06 
825.18 grs. 
28.39 “ 
89.40 “ 
95.42 “ 
69.18 “ 
32.11 “ 
1650.4 c. cm. 
1022.17 
480 37 grs. 
16.84 “ 
34.73 “ 
114.58 “ 
52.95 “ 
38.14 “ 
1387.2 c. cm. 
1019.45 
300.16 grs. 
31.54 “ 
35.72 “ 
108.11 “ 
72.95 “ 
41.76 “ 
1750.3 c. cm. 
1024.67 
589.43 grs. 
13.79 “ 
27.54 “ 
129.83 “ 
55.27 “ 
46.18 “ 
1806.3 c. cm. 
1024,81 
638.20 grs. 
12.71 “ 
25.80 “ 
138.27 “ 
66.22 “ 
40.10 “ 
From these data it is perceived that, during an attack of intermittent fever, 
the uric acid and phosphoric acid are very much increased in amount, and the 
urea and chlorine greatly diminished. During the intermission, there is a 
close approach to the normal proportions of these constituents, but a subse- 
quent paroxysm restores the former condition. The disulphate of quinia, 
however, produces a permanent impression on the character of the urine, and, 
with the return to the natural relations existing between the several substances 
entering into the composition of this excretion, the disease disappears. 
There are several facts indicated by the foregoing researches, to which 
attention may be directed. Thus the increase in the amount of phosphoric 
acid eliminated during a paroxysm points strongly to the nervous origin of 
the disease. The excess in the amount of uric acid excreted, whilst at the 
same time the quantity of urea was so strikingly diminished, are facts of the 
highest importance, and, in connection with the circumstance that during the 
intermission, and after the administration of the quinine, the urea was increased 
and the uric acid diminished in quantity, show the close relation existing be- 
tween these substances, and render more probable the theory that the former 
body is a product of the continued metamorphosis of the latter. 
From so limited an array of facts as the preceding, no hypothesis in regard 
to the pathology of intermittent fever can be considered as tenable. If, how- 
ever, the results of these investigations should be confirmed by subsequent 
observers, a great step will have been made towards a satisfactory theory of 
this disease, and a rational idea of the therapeutical action of the disulphate 
of quinine may be formed. The subject is, therefore, left for the present, 
with the hope that others will turn their attention to the furnishing of mate- 
rial for its elucidation.