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The physiological study of experimental nephritis caused by poisons of bacterial origin demonstrates that the poisons may produce types of nephritis in which either vascular or tubular changes predominate. Diphtheria toxin produces a nephritis which in its late stage is of the vascular type, but in its early stage is distinctly tubular. Tuberculin and mallein uniformly cause lesions of the tubular type, which do not pass into the vascular type. Nephrotoxic and hemolytic immune sera cause changes in the kidneys which by physiological methods of observation present no evidence of vascular injury, but which are anatomically characterized by exudative glomerular lesions of moderate severity. This discrepancy between the results of anatomical and physiological study indicates that a lesion of the membrane controlling the passage of fluids may occur without alteration in the power of the vessels to contract and dilate. This fact is shown clearly by the lesion caused by hemolytic immune serum, which is in sharp contrast to the lesion caused by diphtheria toxin, since the latter substance not only alters the permeability of the membranes but also influences markedly the power of the vessels to contract and dilate. It is necessary therefore if the term "vascular" is used in its broadest sense, to recognize three types of vascular nephritis: (1) one in which little or no anatomical evidence of vascular injury is found, but in which physiological methods show profound vascular changes, as in arsenical nephritis; (2) one in which anatomical evidence of vascular (exudative) injury is prominent, but in which the physiological tests are negative, as in nephritis caused by a hemolytic immune serum; and (3) one in which both anatomical and physiological changes are prominent, as in diphtheria toxin nephritis.

1. The liver of the dog in which necrosis has been produced by injection of haematoxic immune sera is characterized in the less marked forms by a storing up of nitrogen in the persisting living cells, while in the diffuse forms the total nitrogen content is but slightly above the normal. This last is to be explained by the great diminution in persisting liver substance which limits the power of nitrogen accumulation. 2. In all forms of necrosis there occurs an absolute increase of nitrogen precipitable by phosphotungstic acid (hexon bases) but the percentage increase, in relation to total nitrogen, diminishes in those forms (focal) in which the products of autolysis may be readily carried off by the blood stream and greatly increases in the diffuse form with large areas in which the circulation is seriously impaired. 3. Although the absolute amount of nitrogen representing arginin and histidin varies, a relative increase is evident when this fraction is compared with the total diamino-nitrogen. This increase corresponds to the degree of necrosis and attendant circulatory disturbance and indicates that in necrosis as opposed to degeneration (Wakeman) arginin is not split up by arginase. The lysin also bears a definite relation to the total hexon nitrogen. 4. The diamino-nitrogen of the normal liver after autolysis in vitro shows a slight variable increase over that of the unautolyzed, while the necrotic livers showed a decided decrease. 5. The diamino-acid nitrogen of normal horse liver is only about one half of that of the dog; the relative proportion of the bases is about the same. In necrotic livers with amyloid the diamino-nitrogen is markedly increased which is in accord with Neuberg's observations on the high hexon base content of amyloid.

Extracts of the kidneys of normal rabbits prepared one, two, three, and four days after the intravenous injection of egg-albumin and horse serum have the power to sensitize guinea pigs to a second injection of these proteins. The sensitization by first and second day extracts was constant and intense, that by the third day extracts was less marked and sometimes was not evident, and that by the fourth day extracts was only occasional, and when present was always weak. Comparative studies of the power of the blood, liver, and kidney to sensitize, indicate that this sensitization depends on the content of foreign protein in the circulating blood and not upon its accumulation or fixation in the tissues of an organ. This opinion is supported by other experiments in which the sensitizing power of the blood and of the extracts of unwashed kidneys was compared with the sensitizing power of extracts of washed kidney. The weak sensitizing power of washed kidney extract is taken as evidence that foreign proteins of the kinds used are not held in the tissues of the kidney, and if these results may be applied to nephrotoxic proteins, it follows that nephritis is not due to selective and persisting fixation of a protein by the renal cells, but is due to the action of such protein merely during the process of its elimination. In experimental acute nephritis of the type due to uranium nitrate, the power of sensitization to egg-albumin is prolonged for twenty-four hours, and in the chrornate type for forty-eight hours, thus indicating that in nephritis, of the acute type at least, the elimination of a foreign protein is delayed. Attempts to study by the same methods the elimination of vegetable and bacterial proteins have failed.

1. The removal of one half, two thirds and sometimes three quarters of the kidney substance in the dog causes no change in the general nitrogenous metabolism as determined by estimations of the total nitrogen, urea and ammonia elimination by the urine. 2. The removal of larger amounts, and sometimes of three quarters of the substance, leads to the metabolism condition of starvation. This, however, is apparently the result of the gastro-intestinal disturbance constantly associated with extensive kidney reduction and not of a disturbance of general nitrogenous metabolism. 3. The determination of the amount of faecal nitrogen indicates that the gastro-intestinal disturbance is not due to diminished absorption; and except in one instance there was no evidence of its being due to an increased elimination of nitrogenous substances into the intestine. 4. These experiments do not support the theory that the kidney furnishes an internal secretion having an important influence on general nitrogenous metabolism. At least, if such a function exists, it is not disturbed by the removal of three quarters of the kidney substance. 5. The metabolism in excessive kidney reduction is that of inanition dependent on gastro-intestinal disturbances presumably due to faulty chemical correlation. In this connection further knowledge concerning the elimination into the intestine of toxic substances is desirable.

Blood destruction due to a single injury, as by sodium oleate, or acting through a short period of time, as by toluylenediamine or hemolytic immune serum, is not characterized, in the absence of hemoglobinuria, by an increased elimination of iron in the urine. This holds, not only for the evanescent injury caused by sodium oleate, but also for the severe type caused by hemolytic immune serum, in which a progressive destruction of the blood may persist for 2 weeks or more with constant evidence of the disintegration of erythrocytes as shown by bile pigment in the urine. This finding is in accord with previous investigations of anemia in both man and animals. Likewise, no striking increase is evident, under such circumstances, in the percentage of iron excreted in the feces. The total amount of iron in the feces has been notably increased in two experiments with hemolytic serum, but as the percentage was not appreciably altered, the difference depends presumably on variations in the bulk of feces rather than upon increased elimination. This evidence of the power of the body to conserve the iron rephagocytosis is negligible, is to be fragmented one by one, while still circulating, to a fine, hemoglobin-containing dust. The cell fragments are rapidly removed from the blood, but their ultimate fate remains to be determined. The facts indicate that they are removed from the blood by the spleen, and under exceptional conditions, by the bone marrow.

In the splenectornized dog the anemia caused by hemolytic poisons (hemolytic immune serum and sodium oleate) and by bleeding is of a severer grade, runs a longer course, and is accompanied by a less rapid regeneration of the blood than is the case in the normal dog. Also in the splenectomized dog, especially after the use of hemolytic serum, the leucocytosis is greater than in the normal animal. The splenectomized dog almost uniformly exhibits an increased resistance of the red cells to hypotonic salt solution, but after the administration of hemolytic poisons, and especially hemolytic serum, this increased resistance disappears and a decreased resistance persists for long periods of time. The same change occurs in the normal dog, but in the latter the return to the previous degree of resistance is more rapid than in the splenectomized animal.

The venom of Crotalus adamanteus when administered intravenously to rabbits in properly graded doses causes lesions of the glomerulus of tile kidney which may be either hemorrhagic or exudative in character. Both types of lesion are usually associated but either one or the other may predominate. The hemorrhagic lesion, which may be confined to the glomerular tuft, or, by rupture of the latter, may involve the capsular space, is a peculiar localization of the hemorrhage so common in other parts of the body in venom intoxication. On the other hand, the exquisite exudative lesion involving usually the capsular space but sometimes limited, as in the hemorrhagic type, to the tuft itself and with little or no tubular injury, constitutes a type of experimental vascular nephritis, hitherto undescribed, which differs widely in its anatomical appearance from that due to arsenic, cantharidin and other vascular poisons. As the limitation of the lesion to the glomerulus indicates a selective action of the venom, and as the histological changes in the tuft are suggestive of gradual endothelial destruction and solution, the lesion can be explained by the action of the endotheliolytic body of crotalus venom described by Flexner and Noguchi.

The anemia which develops after splenectomy is most marked in animals on a mixed table scrap diet of meat, bread, cereals, and vegetables, which is essentially a cooked diet. Control studies in which a unilateral nephrectomy precedes splenectomy demonstrate that the anemia is not due to operation, hemorrhage, or accidents of convalescence but develops only in the absence of the spleen. The results of studies of the influence of food containing a large amount of iron in presumably easily utilizable form, as in raw beef spleen, do not support the view that the anemia is due to lack of iron in the food. Observation on the influence of a diet of raw meat as contrasted with cooked meat shows a more severe anemia in animals on the cooked diet and suggests the possibility that heat alters some substance which, in the absence of the spleen, the body cannot utilize. A final conclusion in regard to this point must, however, await the results of more detailed studies now in progress.

Four dogs have been subjected to metabolism studies before splenectomy and at intervals of three days to three months after splenectomy. In three of the four animals the removal of the spleen was not followed by any disturbances of nitrogen metabolism, fat utilization, or iron elimination. Two of these animals showed no anemia, and the third only a slight reduction in hemoglobin and number of red cells. A fourth animal, studied ten days and three months after splenectomy, developed eventually a definitely progressive anemia of moderate severity. This animal showed a slight loss of weight, a slight disturbance of nitrogen balance, and of creatine-creatinine partition, with a marked increase in the elimination of iron. We conclude therefore that the spleen has no important influence on metabolism, and that the disturbances occurring in one of our dogs were due to the coexisting anemia and not to the absence of the spleen.

The immediate effect of the operation on the portion of the kidney remaining is an infarcation of the tissue compressed by the sutures. This area of necrosis extends but a short distance into the adjacent kidney tissue. The infarcated tissue gradually becomes replaced by fibrous tissue and in three to four week's time the necrotic tissue entirely disappears. The amount of fibrous tissue in time becomes so slight and the healing so perfect that it is difficult to detect the site of the operation. The renal elements sometimes persist in the infarcated area and the glomeruli apparently are more resistant than the tubules. The tubules in the infarcated area sometimes become calcified and bone formation beneath the epithelium of the pelvis is of very frequent occurrence. The pelvic epithelium usually shows marked proliferation and may invade the field of operation in alveolar masses. Calculi may form in the pelvis of the kidney. Sutures penetrating the pelvis as well as the necrotic tissue resulting from the compression of the sutures probably furnish the nuclei for the calculi. Removal of approximately half of one kidney did not alter either the remaining portion of that kidney or the size of the opposite kidney in two animals of this series. These experiments were terminated on the thirty-fourth and forty-seventh days. In a similar experiment of twenty-one day's duration there was slight but definite atrophy of the remaining tissue of the kidney operated upon. Removal of approximately half of each kidney at one operation did not alter the remaining kidney tissue in two animals of the second group. The longest period of observtaion was fifty-four days. On the other hand in a similar experiment where 164 days elapsed, the remaining portions of each kidney had increased markedly in size. Removal of one kidney and approximately half of the other did not alter the remaining kidney tissue in six animals in which from five to fifty-six days elapsed before termination of the experiment. In six experiments in which one kidney was removed and approximately half of the other, three of the animals died as a result of the operation on the sixth, seventh and tenth days. The probable cause of death was renal insufficiency: the animals refused food, vomited persistently and lost strength and weight. The other three animals recovered and were killed at periods varying from five to eight weeks. The reduction of the kidney tissue to one quarter of its original amount at one operation was attained with danger but was not necessarily fatal. In every experiment there was a loss of weight varying from four to twenty-four per cent. To what extent this loss in weight is due to the reduction of kidney substance and to what extent it is due to diet and confinement it is impossible to say, as we made no control experiments to elucidate these points.

1. Changes which occur in the fat content of the liver of dogs receiving haemotoxic serum bear no relation to the degree of necrosis produced by this serum. 2. An increase in water content of the tissue seldom occurs, but where present is due to the nitrogenous autolysis rather than to the deposition of fat. 3. The appearance of fat in the cell is not associated with a decomposition of the proteid component of the compound fats, but rather to a simple splitting off of the fatty radical. This is shown by the slight variations occurring in the percentage nitrogen of the fat-free substance. 4. The iodine equivalent diminishes as the fat content increases. This would indicate that in the fatty changes which occur, fats other than those containing oleate radicals make their appearance. 5. The ratio of phosphorus to nitrogen in the alcohol-chloroform extract remains practically constant in all degrees of necrosis. Hence the substances of the protagon and jecorin type hold the same relation to the lecithins during the autolysis as they do normally. 6. In a general way it may be said that the results obtained in the microchemical staining of the fats with Scharlach R agree with those found by chemical extraction methods.

In necrosis of the liver of the dog produced by haemotoxic immune sera, the increased excretion of uric acid, purin bases and inorganic phosphorus pentoxide is the result of the hydrolysis of nuclear material occurring during the autolysis of the necrotic tissue.

1. The presence of blood serum has a decided inhibitory effect on autolysis. Thus in the normal unwashed organs the non-coagulable nitrogen increase was 100 to 300 per cent., while in the washed it amounted to 450 per cent. The washed necrotic livers showed an increase of from 600 to 850 per cent., while that of the unwashed necrotic was only slightly above the normal unwashed. 2. While the initial amount of non-coagulable nitrogen varies it is greater in those livers showing the more extensive forms of necrosis. The final amount of autolysis is also greatest in livers of this type. As regards the rate of autolysis fifty per cent. of the total occurs in the first day in the normal and in all types of lesions both washed and unwashed. The maximum is usually reached on the third day in the unwashed, while in the washed there is a continued increase to the eighth day. At this time in the necrotic livers about two to three times as much of the total nitrogen is in the form of non-coagulable nitrogen as in the normal. 3. In the necrotic tissue the initial controls show the content of monamino-acids, with one exception, to be practically doubled. In the washed necrotic the final amount is seventy per cent. of the total nitrogen against forty-six to fifty-seven per cent. in the washed normal. In all cases the monamino-acid nitrogen runs parallel to the nitrogen in non-coagulable form, but in relation to the total nitrogen it shows a greater increase in the washed than in the unwashed organs. 4. The ammonia production in the necrotic livers as shown by the partition experiments is greater than that in the normal and this increase corresponds to that of the non-coagulable nitrogen. In the experiments concerning the absolute production of ammonia in the presence of serum a greater amount was produced in the two and five hours' lesions than in the normal livers. On the other hand, the forty-eight hour diffuse necrosis equaled the normal and the focal fell below. 5. Arginase was obtained from normal but could not be isolated from necrotic livers. 6. No constant relation could be demonstrated between the anatomical lesion in the liver and the presence of leucin and tyrosin in the urine. Leucin was found occasionally in the urine, but none in the liver. On the other hand, tyrosin was constantly present in livers with diffuse but rarely in those with focal necrosis. In the instances of diffuse necrosis in which the liver and urine of the same animal were examined tyrosin was found in both. 7. The presence of large amounts of proteoses in the necrotic liver indicates that the elimination of these substances (colloidal nitrogen of Salkowski) under such circumstances may account for a part of the total nitrogen of the urine usually attributed to the monamino-acids.

In the continuous blood destruction, essentially a chronic experimental anemia, caused by injecting the dog with Trypanosoma equiperdum, no increased elimination of iron is observed in the feces. The storage of iron in the liver and spleen under these experimental conditions is somewhat greater in amount, but of the same general character as in transient experimental anemia. Splenectomy before or after infection, i.e. the development of anemia, influences neither the elimination of iron in the feces nor its storage in the liver. The retardation of the course of the trypanosome infection and thus the production of a more chronic anemia by treatment with a trypanocide, arsenobenzol, likewise does not affect iron storage. These experiments have therefore failed to reproduce the changes in iron metabolism seen in certain of the chronic hemolytic anemias of man. In the presence of a bile duct-ureter fistula the iroh content of the mixture of urine and bile is not appreciably greater than that of the urine alone. In the dog, therefore, the elimination of iron in the the bile would not appear to be an important factor. On the other hand, when bile is excluded from the intestine an unusual storage of iron occurs in the spleen. For this no explanation is offered.

1. In focal and diffuse necroses of the liver due to haemotoxic sera there occurs an increased elimination of total nitrogen with a corresponding augmented output of urea. The ammonia excretion becomes slightly diminished at first, but later rises somewhat above normal. The undetermined nitrogen is markedly increased. 2. In diffuse degeneration with no necrosis on the other hand only a slightly increased output of total nitrogen is evident. A rearrangement of the urea-ammonia proportion occurs in that the ammonia excretion is augmented while the urea elimination is correspondingly diminished. The undetermined nitrogen rises but little. 3. In control experiments with normal serum no effect is produced. 4. These results would appear to indicate that in lesions characterized by uniform degeneration of the liver parenchyma, in contradistinction to necrosis, there occurs no increased nitrogen elimination but merely a disturbance of the urea-forming function of the cell without the appearance in the urine of products of autolysis. On the other hand in necrosis, of even considerable extent, the total-nitrogen is greatly augmented, as is also the rest-nitrogen; while the production of urea, on account of the persistence of normally functioning liver cells, remains relatively unchanged. This "factor of safety"(32) possessed by the liver is, we think, one of the most important results brought out in this investigation and must be given great weight in any consideration of the chemistry of hepatic disturbances.

The acute exudative glomerular lesion of the rabbit's kidney caused by crotalus venom does not lead to a subacute or chronic glomerulonephritis. The hemorrhagic lesion of the glomerular tuft may show a process of repair characterized by the ingrowth, into the hemorrhagic masses, of endothelial cells from the uninjured part of the tuft. This process is, however, more analogous to the organization of a red thrombus than it is to any form of glomerular lesion known in man, and can hardly serve as an experimental demonstration of the mode of development of a subacute or chronic glomerular nephritis. On the other hand, crotalus venom causes a persistent albuminuria and extensive tubular degeneration and cast formation, with death, preceded by great emaciation, after five to six weeks.

1. The sera of rabbits injected repeatedly with the nucleoproteins, globulins, and albumins of the liver and kidney of the dog give no evidence in vitro or in vivo experiments of organ affinity. The precipitin test offers no proof of the specificity of these sera for the proteins employed as antigens. 2. The anaphylaxis reaction applied to the same proteins indicates a slight relative organ affinity but no specificity as far as the respective protein fractions are concerned. The relative organ affinity resides, rather, in the globulin and albumin fractions than in the nucleoprotein fraction. Dog serum used both as a sensitizing and an intoxicating agent gives rise to very active cross reactions with organ proteins, thus failing to support the theory of organ or of protein specificity. 3. These results do not support the view put forward that nucleoproteins play an important part in the course of production of cytotoxic immune sera.

Vaquez and Aubertin advance three theories in explanation of the adrenal hyperplasia; first, that it may not be the cause of hypertension but "an antitoxic hyperplasia" caused by the retained products of metabolism which may be responsible also for the hypertension; second, that it may be the cause of hypertension but secondary to the renal lesion; third, that it may be the cause of hypertension but may antedate the renal lesion or be entirely independent of it. They, as well as other French writers, insist that this hyperplasia is almost constantly associated with chronic nephritis of the interstitial type and it is seldom found with the parenchymatous type of nephritis, or with other lesions. Hyperplasia of the adrenal, as far as my material enables one to judge, does not occur during the first and second decades. In the third decade it is relatively frequent in the absence of chronic arterial and renal disease but reaches the maximum in association with such disease after the fourth decade. It is an almost constant lesion in arteriosclerosis associated with chronic interstitial nephritis and left-sided heart hypertrophy, but occurs with almost equal frequency in arteriosclerosis with chronic nephritis of the parenchymatous type. It is a relatively frequent lesion of arteriosclerosis without chronic nephritis and of the latter without arteriosclerosis also. As the result of this analysis one is led to the view that while hyperplasia of the adrenal is a very frequent concomitant of chronic renal and arterial disease it is not exclusively a feature of either type of nephritis or yet of chronic vascular disease; but it probably represents the effect of some factor operating in that period of life in which chronic renal and arterial affections are most frequent. Worthy of special emphasis is the observation that the characteristic lesion of an adrenal, the seat of local arteriosclerosis, is of the type of the chronic productive inflammation seen in arteriosclerosis of the pancreas and kidney; that is, thickening of the vessels, increase of connective tissue and round cell infiltration. Associated with these changes is a hyperplasia which is very constant, and which may be, in part, of the nature of a compensatory hyperplasia similar to that seen in the liver of cirrhosis and acute yellow atrophy. A hyperplasia of this type, as has been shown, may occur in destructive lesions of the gland. This, however, does not explain hyperplasia in the absence of local vascular changes which fact is, possibly, as suggested by Landau, evidence, not of a correlation between kidney and adrenal, but of a vicarious hypertrophy depending upon lesions of some other organ of the body than the kidney, possibly some other ductless gland, affected by arteriosclerosis or other disease.

By combining physiological and anatomical methods in the study of experimental nephritis it is possible to distinguish types of nephritis in which either tubular or vascular changes predominate, and are essentially characteristic of the lesion produced, but it is not possible to say that a given poison produces exclusively tubular or exclusively vascular lesions. The so-called epithelial poisons (potassium chromate, uranium nitrate and corrosive sublimate) present anatomical evidence of extensive tubular injury, and in the early stages show, on physiological study, no evidence of vascular injury other than exaggerated contraction and dilatation of the vessels and increased diuresis. On the other hand, the vascular poisons, arsenic and cantharidin, which produce but little injury to the tubules, tend to cause anuria and are characterized by minimal contraction and dilatation of the vessels and little or no flow of urine. From the physiological point of view these two types may be, for practical purposes, considered as examples of tubular and vascular nephritis. They are not, however, pure types; for the increased diuresis of the early tubular type is in itself evidence of vessel irritability and similar to the increased irritability caused by small doses of vascular poisons, and on the other hand, this essentially vascular lesion is accompanied by slight morphological changes in the tubular epithelium. Furthermore, the tubular lesions of chromium and uranium and corrosive sublimate pass into a stage closely resembling the vascular type, if not identical with it. Two forms of late tubular nephritis may be recognized. One of these, the anuric form, is accompanied by severe gastro-intestinal disturbance and evidence of approaching anuria; physiological tests show diminished power of dilatation of the vessels and corresponding inhibition of diuresis. The second form, the polyuric, is characterized by a condition of polyuria up to the moment of anesthesia; physiological tests show that the power of dilatation is retained, but little or no diuresis occurs. Whether the vascular incompetency of the anuric form of late tubular lesions is a natural consequence of the vessel irritability seen in the early stages or is the result of the elimination of secondary poisons through the glomeruli cannot be absolutely determined. The peculiar impermeability of the glomerulus following anesthetization in the polyuric form, which is essentially a stage of recovery, we hope to explain by investigations now in progress. Studies of the elimination of nitrogen show that in tubular nephritis, as represented by uranium nephritis, the output of nitrogen is considerably diminished. This apparently occurs also in chromate nephritis but is not clearly demonstrated. In both forms the onset of gastro-intestinal disturbances appears to bear a definite relation to the retention of nitrogen. On the other hand, as the nitrogen of the feces is not appreciably altered, these disturbances cannot be explained by the elimination through the intestine of toxic bodies of nitrogenous nature. The nitrogen elimination in the urine in vascular nephritis as represented by arsenic nephritis is not only not diminished but is greatly increased as the result of the increased metabolism caused by arsenic. If at the height of this increased elimination, uranium nitrate is administered, the nitrogen output is markedly diminished. These observations demonstrate that not only are the tubular lesions in arsenic nephritis of little moment, but also that serious injury of the epithelium, as that due to uranium, may cause a temporary nitrogen retention. A consideration of all the facts here presented allows us to conclude that although it is not possible to demonstrate that an experimental nephritis may be purely tubular or purely vascular, which is in accord with our clinical and pathological studies of human material, it is possible, if we combine the results of anatomical, physiological and chemical study, to recognize lesions which are predominantly tubular or vascular, or which change rather sharply from one to the other type, and are, therefore, of great value in the study of the problems of nephritis.

Splenectomy in the dog causes, as a rule, a transformation of the fatty marrow of the long bones to a richly cellular red marrow. During the early periods, one to three months, the change in the marrow is slight and either focal or peripheral; after six to twenty months the replacement of fat by marrow cells is complete or nearly so. Exceptions were, however, seen in four animals representing the 8th, 9th, 10th, and 22d months, respectively. The evidence at hand does not support the theory that this hyperplasia is compensatory either to the anemia caused by splenectomy or to an increased hemolysis in the lymph nodes. It is possible that it may be a concomitant of the activity of the bone marrow in taking over, in the absence of the spleen, the function of storing and elaborating the iron of old blood pigment for future utilization by new red cells, but our studies do not fully support this view.

Our studies give evidence of increase in the iron elimination in three of five dogs during a period of two weeks following splenectomy, but not in two other dogs. The occasional increased output of iron may have some relation to the anemia which occurs in the early weeks after splenectomy and which varies in degree in different animals. No evidence was secured of an increase in the iron output at 1, 9, and 20 months after splenectomy. From our own studies and from examination of the literature of the subject, we conclude that the spleen does not exercise a constant and important influence upon the iron metabolism of the body.

The increased resistance of the red blood corpuscles characteristic of the splenectomized animal is as evident one year after removal of the spleen as it is at earlier periods. So also is the decreased tendency to jaundice after the administration of hemolytic serum. The increase in resistance of the red cells cannot be explained on the basis of an increase in reticulated cells in the circulating blood.

Although the study of experimental nephritis by physiological methods shows that the most striking effect of cantharidin is injury of the blood vessels, the great abundance of mitotic figures in the tubular epithelium in the stage of repair points to an equally widespread and severe epithelial injury. Caution must therefore be observed in ascribing the physiological disturbances of kidney function caused by cantharidin as due exclusively to a vascular injury, and in regarding cantharidin nephritis as a pure type of vascular nephritis.

1. Extracts of the rabbit's kidney injected into the rabbit cause a slight, increase in blood pressure which is barely more than that due to the mechanical effect of the injection. 2. Extracts of the dog's kidney injected into the dog cause a decided fall in pressure; an equal fall may be caused by the dog's urine. A series of control experiments indicates that the fall caused by the kidney extract may be due to the urinary salts which it contains. 3. Extracts of cat's kidney cause a rise in pressure. As the cat's urine causes a fall, this rise in pressure indicates the possibility of a kidney extract containing a pressor substance which cannot be influenced by the depressor substance of the urine. 4. Rabbit's kidney, which in the rabbit produces a slight rise, when injected into the dog causes a drop comparable to that caused by the dog's kidney itself. Similarly, the dog's kidney, which injected into the dog causes a drop, produces in the rabbit a rise analogous to that produced by rabbit's kidney. It is evident therefore that these pressor and depressor substances of the kidneys in question do not have a constant effect on all animals as do the extracts of the adrenal gland. 5. Extracts of kidneys which are the seat of various forms of nephritis cause the same effect as extracts of normal kidneys. 6. The serum of dogs with considerable reduction of kidney substance causes a slight fall in pressure; the serum of dogs with spontaneous nephritis gives divergent results, as does also the serum of rabbits with various forms of acute nephritis. The serum of dogs with chromate nephritis causes a slight rise, while that of dogs with uranium nephritis produces a sharp and decided fall in pressure. Although there is no uniformity in these results, their general character, and especially the experience with uranium and chromate sera of the dog, suggests that pressure-disturbing substances are present in the serum as the result of the kidney lesion. The very slight evidence of the constant presence of a pressor substance, however, offers little support to the theory that such a substance is furnished by the diseased kidney or is due to disturbances of metabolism caused by disease of the kidney.

1. The erythrocytes of splenectomized dogs show increased resistance to the action of hypotonic salt solutions and to specific hemolytic immune serum. The degree of resistance appears to increase with the length of time that has elapsed after splenectomy. 2. This increased resistance of the erythrocytes is not due to an increased antihemolytic power of the animal's serum or to a diminished complementary value of the serum, but is a property depending upon the erythrocytes themselves. 3. Non-splenectomized animals receiving a single injection of specific hemolytic immune serum and developing a temporary anemia show likewise on recovery an increased resistance of the corpuscles without the presence of antihemolysin in demonstrable amount. 4. As anemia of varying grade is a characteristic result of splenectomy, it would appear that the increased resistance of the corpuscles is a concomitant of the regeneration of the red cells following such anemia and is thus analogous to the increased resistance of such cells not infrequently observed in various forms of experimental anemia. 5. There is no evidence to indicate that the anemia after splenectomy is due to the presence of hemolytic bodies, or that the increased resistance of the cells is due to antihemolytic bodies, accumulating in the serum as the result of the ablation of the spleen. It is evident therefore that the spleen in some way controls or regulates blood destruction (and regeneration ?), and in the hope of throwing light on the subject, an investigation of the bone marrow and lymph nodes of splenectomized dogs is now under way.

The reparative process which follows the wide spread necrosis of the dog's liver caused by the injection of haemagglutinative serum constitutes a chronic interstitial hepatitis of definite and constant character. This is not only a new type of experimental hepatic lesion, but is more definitely a cirrhosis than is any other experimental lesion hitherto described. It is of importance in explaining the histogenesis of cirrhosis, and incidentally various repair processes in the liver; but it does not aid in the elucidation of the etiology of cirrhosis in man, nor does it explain the peculiar arrangement of the new connective tissue in any form of human cirrhosis except possibly that associated with chronic passive congestion. It definitely demonstrates, however, that cirrhosis may follow extensive primary destructive lesions, a view not yet fully accepted, and supports the contention of Kretz that cirrhosis is essentially a reparative process.