In all these cases it is seen that the amount of urine excreted after the second operation is very large, and in all the cases where the amount of urine was also determined before the operation it is found that the latter daily quantity is far less. In only four out of the six cases was the daily output of urea investigated both before and after the operation. In Dog No. 5 the urea was apparently decreased in amount, but in reality it must have been greatly increased, as, owing to a mistake and absence from the laboratory, the urines, after the operation, were put aside for several days, and only tested when putrefaction had taken place; hence the real amount was probably far greater than 8 grams. In the other three cases, the output of urea was either slightly diminished or slightly increased; this result is of considerable interest from the fact that these dogs ate little or nothing after the operation. Thus, No. 22 passed 5 grams of urea daily with a diet of 230 grams of dog biscuit; after the operation 5-5 grams of urea were excreted, but no food was taken, the animal refusing to eat the biscuit.

In No. 28, 9 grams of urea were excreted per diem with 100 grams of meat and 100 grams of biscuit daily; after the operation 8 grams of urea, with the ingesta diminished to 40 grams of meat and 20 grams of biscuit daily. Similarly, in No. 14, a liberal allowance of meat and biscuit were given and eaten before the operation, but after only small quantities of meat were eaten, and often none at all. The comparatively small quantity of urea excreted in these cases, when compared to the instances given in Table II, is not dependent upon any inability on the part of the fragment of kidney left to excrete urea. This is well shown by the following observation on No. 22. This dog, as just mentioned, excreted only 5.5 grams of urea per diem with no ingesta; but, on a diet of 200 grams of meat, the daily output of urea rose immediately to an average of 15 grams, and on some days as much as 19 grams were excreted by a fragment of kidney found on post-mortem examination to weigh only 10 grams. Hence, even in the cases where the urea is not absolutely largely increased, it is really increased when we remember that the ingesta are greatly diminished, and that the dog may pass as much, or even more, urea during a whole week with no food as the animal previously passed on a full diet, e.g., No. 22. In all six cases described in Table II the operation was followed by death in from one to four weeks.

It is to be noted that in all the ten cases summarised in Tables II and III, the total amount of kidney substance removed amounted to some three-fourths or more of the total kidney weight, with one exception, where only two-thirds was removed. In all these ten cases there were emaciation, hydruria, and polyuria, absolute or relative.

VOL. LI.

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In the remaining four dogs described in Table IV the amount of kidney removed was slightly less, and, as the table shows, the results are different to those described in the ten rapidly fatal cases.

In none of these cases was the operation fatal, and, as previously mentioned, the animals were killed 47 days, 60 days, 14 days, and 30 days respectively after the second operation. In no case was there any great emaciation, the greatest loss of weight being in No. 11, where the body weight fell from 14 lbs. to 12 lbs. In all cases there was marked hydruria, but the polyuria was slight or absent, notwithstanding the fact that there was no failure of appetite. Thus these four experiments are in great contrast to the other ten, where a larger amount of kidney was removed with a uniformly fatal result. It is clear from these results that the increased flow of urine is not dependent simply upon any increased excretion of urea, since the former may exist without the latter. In no case, however, has an increased excretion of urea been obtained without an increase in the quantity of urine.

In no case amongst the ten fatal ones (where three-fourths of the total kidney weight was removed) has the operation been followed by a diminution in the output of urea, provided the ingesta were not diminished.

We may then form the following conclusion, that when a dog is left with only one-fourth of its total kidney weight, a condition of extreme hydruria invariably results. This hydruria is accompanied, provided the appetite does not fail, by a large increase in the output of urea. Further, that if the ingesta are diminished even to zero, the output of urea remains at the height it reached with a diet sufficient to maintain the weight of the animal when in a normal condition.

That the hydruria, although associated with an increased excretion of urea, is not dependent upon it, is shown not only by the fact mentioned above, that by removal of a smaller amount of kidney hydruria pure and simple is produced, but also by the fact that when both hydruria and polyuria are produced they do not begin simultaneously. In other words, when hydruria and polyuria are both ultimately produced by removal of three-fourths of the total kidney weight, the hydruria precedes the polyuria. To illustrate this, it will be sufficient to quote one experiment, i.e., No. 23. After the first operation, when 6.5 grams of the left kidney were removed, the dog passed 140 c.c. of urine containing 15 grams of urea per diem, with a diet of 150 grams of meat. On increasing the food to 200 grams of meat per diem, the urine rose to 212 c.c., containing 17 grams of urea. The second kidney, weighing 22 grams, was then removed. In the week following the operation the ingesta fell to 120 grams, 13 grams per diem, the urine rising to 380 c.c.

In

and the urea to the second week

the appetite was regained, the ingesta returned to 200 grams, the urea rose to 16 grams, and the urine to 480 c.c. In the third week the ingesta were 140 grams, the urea rose to 21 grams per diem, and the urine to 550 c.c.; the animal was then killed, being weak, the body weight having fallen from 11 lbs. to 7 lbs. This experiment illustrates the two stages the animals pass through, the first one where the normal output of urea is maintained, but the method of its excretion is altered, so that the quantity of urinary water is greatly increased. The second stage is one where the quantity of urine is still further increased, with a more or less sudden increase in the urea, accompanied by emaciation, &c. By the removal of very large quantities of kidney substance these two results are obtained almost together, but even then, for a day or two after the second operation, hydruria only is present. When, however, a smaller quantity of kidney is removed the condition called here the first stage is the only one produced, and this condition of simple hydruria is very permanent, as the experiments quoted in Table IV demonstrate. My observations do not show whether this stage of hydruria can be prolonged indefinitely, but they show that the second stage, polyuria, emaciation, is comparatively sudden in its onset, and rapid in its course. Character of the Urine.-The urine passed after the second operation contrasts greatly with the normal urine of the dog, inasmuch as it is very pale, abundant, and of low specific gravity, i.e., from 1007 to 1020; whereas the normal urine is dark in colour, and its specific gravity is often as high as 1050 or even 1060, and it is scanty in amount. The urine after the second operation contains neither albumen nor sugar. The percentage of solid matter is of course less than normal, but the total solids are not diminished in amount. The ash also is not diminished; but more detailed observations on these points are at present in progress.

With regard to other symptoms of the disorder produced by the operation, it is to be noted that convulsions are absent. Vomiting is rare; it has only been observed once or twice. Diarrhoea is frequently present towards the end, and small ulcers and sores occur about the lips and feet, possibly of traumatic origin. During the last twentyfour or forty-eight hours of life the flow of urine diminishes greatly, so that usually the animals have been killed whilst the polyuria, &c., was at its height, so as not to vitiate the analysis of the tissues. Thus the final symptoms are great prostration of strength and some drowsiness, together with the great fall in the temperature; the last, however, begins as soon as the polyuria is marked, and hence is present for many days before death.

The aortic blood pressure, measured by connecting the carotid artery to a mercurial manometer, is very high when the marasmic condition of the animal is considered. In three cases observed it

has varied between 95 and 100 mm. Hg, the animal being under the influence of chloroform, that is to say, the blood pressure was as high as it frequently is in normal and healthy chloroformed dogs. This height of the blood pressure is in great contrast to the blood pressure iu dogs after double nephrectomy, where even on the third day the blood pressure has sunk to a few millimetres of mercury.

Hence the arterial tension is raised when the animal has but rd to 4th of its total kidney weight.

Post-mortem Examination.-The animals are greatly emaciated, but usually some fat remains, especially the omental fat. No marked naked-eye changes have been detected, except a marked excess of cerebro-spinal fluid in the cranial cavity. No obvious change was found in the heart or vessels. The abdominal viscera have been found rather soft and sticky, but no other evidence of septic poisoning or of auto-infection has been found.

The kidney fragment has never been found hypertrophied; more frequently distinctly atrophied, the weight of the fragment found. post mortem plus the weight of the piece removed being generally less than the weight of the opposite kidney. This is in opposition to the results of a French observer.* He, however, removed at the first operation the entire kidney, and then subsequently removed pieces of the second kidney, which had, as is well known, undergone a so-called compensatory hypertrophy. Under these circumstances Tuffier states that the fragment hypertrophies considerably.

Whether the atrophy observed by me is dependent upon the part of the kidney removed, I trust to elucidate by further observations now in progress.

Nitrogenous Extractives of the Blood and Tissues.-The animals, after being anesthetised with chloroform, were bled to death. 50 c.c. of blood were placed in an excess of rectified alcohol and 50 grams of muscle, liver, brain were similarly treated after being finely divided. After prolonged extraction, the filtrate is then evaporated to dryness over a water-bath, and the dry residue repeatedly extracted with cold absolute alcohol, usually for some hours. The absolute extract is evaporated to dryness on the water-bath and the residue dissolved in water. The material insoluble in absolute is also dissolved in water, and thus two watery extracts are obtained which may, for simplicity, be called the absolute and rectified extract; these are treated as follows:-half of each is introduced separately into a Dupré urea apparatus, and the amount of nitrogen evolved by decomposition with sodium hypobromite determined. In the remaining half of each extract the total nitrogen present was determined by Kjeldahl's method. In this manner a control is kept on the hypobromite method, since, if such a body as urea is present, the Dupré and * Tuffier, 'Études expérimentales sur la Chirurgie du Rein,' Paris, 1889.