ON THE RELATION OF THE CATALYTIC ACTIVITY OF THE BLOOD TO THE NUMBER OF RED BLOOD CELLS IN HEALTH,AND TO THE NUMBER OF WHITE BLOOD CELLS AND THE BODY TEMPERATURE IN PERITONITIS

The catalytic activity of the blood of normal rabbits varies almost directly with the volume and number of red blood cells. This explains to a certain extent at least why animals of the same general degree of nutrition, and of the same litter, should have about the same activity since they are likely to have the same number of red blood cells, and why healthy large animals should read high while small poorly nourished ones should read low. Accompanying the hyperpyrexia resulting from puncture of the corpus striatum of a rabbit''s brain, there is no change in either the catalytic activity of the blood or the white blood count. In experimentally produced peritonitis, the catalytic activity of the blood always rises, and is, therefore, absolutely independent of body temperature and white blood cells since one or both of these may rise, fall or remain stationary while the catalytic action increases.     

CHEMICAL CHANGES IN THE BLOOD OF THE DOG IN EXPERIMENTAL PERITONITIS

1. A study of the blood chlorides, urea and non-protein nitrogen and the carbon dioxide-combining power in experimental general peritonitis is here reported. 2. The similarity between the chemical changes in high intestinal obstruction and general peritonitis is noted. These chemical changes suggest that the cause of death may be, at least in part, the same in the two diseases.     

CONCERNING THE RELATION OF THE COAGULATION TIME OF THE BLOOD TO THROMBOSIS IN PHLEBITIS

Positive results have been obtained in but a single set of experiments, namely those in which turpentine was employed. In so far as the results of this preliminary study go, one is led to the conclusion that thrombosis is most readily induced when active inflammatory lesions exist in the blood vessels, associated, probably in most instances, with secondary degenerative changes. Purely mechanical lesions are much less apt to be productive of conditions favorable to thrombosis as a sequence of phlebitis. Marked artificial increase or decrease in the coagulation time of the blood by the use of calcium lactate or citric acid, does not render animals abnormally prone to thrombosis incited by changes other than inflammatory. When true phlebitis exists, thrombosis is apt to be more extensive and less readily resolved, when the coagulation point of the blood has been shortened by the use of calcium lactate, and it is less extensive and more quickly absorbed when the coagulation time has been increased by the administration of citric acid. Experiments as yet incomplete appear to suggest that the increasing in rapidity or slowing of the general circulatory stream has but little bearing on the production of thrombosis in phlebitis, much less, indeed, than clinical and anatomical observations have generally led us to think. We have also been led to suspect that the presence or absence of anastomoses of abundant degree is largely concerned as a factor in determining the location and extent of thrombosis in phlebitis.     

CHEMICAL CHANGES IN THE BLOOD OF THE DOG IN EXPERIMENTAL BILE PERITONITIS

1. Changes in the chemistry of the blood of dogs with experimental bile peritonitis are here reported. 2. In all animals that died, a bile ascites was found. 3. Dogs dying of bile peritonitis showed a constant increase in the blood non-protein and urea nitrogen, and a fall in the chlorides.     

THE QUESTION OF EPINEPHRIN IN THE CIRCULATION AND ITS RELATION TO BLOOD PRESSURE

1. The modified Meyer method here proposed, of parallel tests upon segments of surviving carotid and coronary arteries from the ox, is a satisfactory means for detecting epinephrin in complex body fluids like blood. 2. At the present time there is no evidence that epinephrin, in amounts sufficient to produce its physiological effects upon any hitherto used test objects, exists in the circulating blood, with the exception of blood from the suprarenal vein. 3. The examination of uncoagulated blood from six persons with high blood pressure has failed to show the presence of epinephrin or other constricting substances. 4. The constrictor substance in defibrinated blood and serum is not an epinephrin-like substance. In its point of action and its effects it is similar to barium chlorid. It is a direct stimulant to smooth muscle and seems to have no relation to the sympathetic innervation of muscle.     

THE RELATION OF THE AURICULAR ACTIVITY FOLLOWING FARADIZATION OF THE DOG'S AURICLE TO ABNORMAL AURICULAR ACTIVITY IN MAN

The tumultuous auricular activity which follows faradization of the auricles of mammals and which has been variously described, could be distinctly seen to consist almost constantly in our experiments on dogs of true fibrillatory movements of the separate muscle fibers coëxisting with a rapid auricular tachycardia. During peripheral stimulation of the right vagus nerve the true fibrillation alone existed, the tachycardia being inhibited. A comparison of the electrocardiograms from dogs with this abnormal auricular activity with those from patients with the type of cardiac arhythmia which has been attributed to auricular fibrillation, and from patients with so called auricular flutter, indicates that the auricular activity in patients with either of these conditions differs somewhat from that usually seen in the faradized auricles of the dog in our experiments. The auricular activity of the cases of cardiac arhythmia is apparently true fibrillation, similar to that seen in the faradized auricles of the dog during right vagus stimulation. The electrocardiograms from cases of so called auricular flutter usually give no evidence of auricular fibrillation, and the auricular activity seems to consist of tachycardia alone. Fibrillation may apparently coëxist with the tachycardia in some cases, when the auricular activity seems to resemble closely that usually seen in the dog after auricular faradization. During peripheral stimulation of the left vagus nerve, the electrocardiograms obtained after auricular faradization show changes which render them more nearly similar to those obtained from patients with auricular flutter. The facts that the auricular activity of the faradized auricles of the dog may apparently pass spontaneously into that closely resembling auricular flutter in man, that it may be changed into true fibrillation by right vagus stimulation, and that the abnormal auricular activity in man passes from a state of flutter to that of fibrillation in a similar manner, may be taken as evidence for the belief that auricular fibrillation and auricular flutter in man are closely allied cardiac disorders.     

THE RELATION TO THE BLOOD OF THE VIRUS OF EPIDEMIC POLIOMYELITIS

Specimens of human blood taken during the paralytic stage of poliomyelitis and post mortem have proved not to be capable of infecting Macacus monkeys. Specimens of monkey blood taken at various stages of experimental poliomyelitis have not proved as a rule to be capable of infecting monkeys. In a single instance, among ten tests, infection was secured with a specimen of blood removed at the beginning of the paralysis on the seventh day following an intracerebral inoculation. When suspensions of the spinal cord from a paralyzed monkey have been injected into the brain or simultaneously into the brain and spinal canal, the blood removed from one to forty-eight hours later failed to cause paralysis after intracerebral injection. When large volumes of active filtrate are injected into the circulation the blood remains infective for seventy-two hours at least, but may be no longer infective after ten days when the paralytic symptoms first appear. When, however, the filtrate is injected in smaller amount or when a filtrate of a less active virus is employed in large quantity, the blood either fails to convey infection or conveys it irregularly. It is only when overwhelming quantities of an active virus are injected into the blood that paralysis results. The injection of moderate doses is not followed by paralysis, although the virus may still be detected in a blood sample twenty-four hours after the injection. The existence of a mechanism capable of excluding the virus within the blood from the central nervous organs is therefore inferred. Infection is accomplished far less readily through the circulation than by means of the more direct lymphatic and nervous channels of communication with the central nervous system. Several series of feeding experiments conducted with the biting stable fly (Stomoxys calcitrans) resulted negatively.     

THE RELATION OF VEGETATIVE ACTIVITY OF BACTERIA TO PATHOGENICITY

The experiments which have been reported show that distinct differences exist between relatively young cultures of bacteria and the same strains during the period of decline as regards invasive power and pathogenicity, and that these differences must be distinguished clearly from specific alterations in virulence such as those produced by animal passage. The exact interpretation of these observations is not, however, perfectly clear. We were inclined to believe that simple alterations in vegetative activity might account for the differences which have been described, but to what extent the results have been due to injury to the bacteria by products of culture growth it is impossible to say, and further work will be necessary to settle this point. At any rate the experiments seem to bear definitely on the problem of infection in as far as they show that purely temporary modifications See PDF for structure of growth activity whether or not brought about by specific injury lead to changes in invasiveness which are quite analogous to the test-tube phenomenon of lag. It has previously been shown that there exists in the upper air passages a mechanism by means of which foreign particles and bacteria can be eliminated within a few hours. It seems highly likely on the basis of the present work that bacteria entering in an inactive growth phase—for example dried in dust or perhaps from a chronic carrier—may be disposed of before activity can be resumed, whereas organisms introduced in the stage of active growth—as from a case of acute disease—may be able to take advantage of a portal of entry. It is further possible that these experiments may have some bearing on the genesis of epidemics, especially as regards the preepidemic phase, and these matters will be discussed at another time.     

THE RELATION OF BLOOD PRESSURE TO THE AMOUNT OF RENAL TISSUE

The removal or destruction of about 70 per cent of the kidney tissue in rabbits does not produce hypertension even when prolonged renal insufficiency results.     

STUDIES ON THE RELATION OF TETANUS BACILLI IN THE DIGESTIVE TRACT TO TETANUS ANTITOXIN IN THE BLOOD

1. The sera of twenty-six individuals who carried tetanus bacilli in their digestive tracts all contained appreciable amounts of antitoxin. 2. The sera of thirty individuals in whose stools no tetanus-like organisms were found were, with two exceptions, free from tetanus antitoxin. 3. Although we have been unable to measure accurately the antitoxin content of these human carriers of tetanus bacilli, 0.1 cc. of serum neutralizes 10 or more M.L.D. of toxin and it is evident that they have acquired an active immunity due to the bacilli in the intestinal tract. 4. These results definitely prove that tetanus bacilli grow in the intestinal tract of man. 5. Many of the individuals who have no tetanus bacilli in their intestinal tracts and whose serum is free from antitoxin show agglutinins to tetanus bacilli. It is probable that they have been carriers of the bacilli in the past and that the agglutinins have persisted longer than the antitoxins. It seems likely, therefore, that these individuals are potentially immune to tetanus. 6. If tetanus bacilli can be established in the digestive tract of man we have a means of immunization which might be useful in armies or in regions where tetanus infections are common, though we do not recommend this method of immunization at present.     

THE RELATION OF THE RETICULO-ENDOTHELIAL SYSTEM TO THE BLOOD PLATELET COUNT

1. So called blockade of the reticulo-endothelial system results in a marked increase in the platelet count. 2. The count rapidly becomes very high, shows a sharp partial recoil and then a gradual diminution even though the blockade be continued. 3. The mechanism regulating the number of platelets is a complicated one. 4. Apparently phagocytosis by cells of the reticulo-endothelial system is not the only means by which blood platelets are destroyed.     

THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE : III. THE CHANGES IN THE BLOOD FOLLOWING SPLENECTOMY AND THEIR RELATION TO THE PRODUCTION OF HEMOLYTIC JAUNDICE.

The results of this study of the changes in the blood after splenectomy and of the effect of the administration of hemolytic serum allow the following tentative conclusions: 1. The failure of a hemolytic serum to cause jaundice is due in some way to the anemia which frequently follows splenectomy. Animals, whether splenectomized or not, which have a low blood count and low hemoglobin content do not readily develop jaundice after administration of a hemolytic serum. On the other hand, in animals with a normal blood picture such a serum readily causes, during early periods after splenectomy, a well marked jaundice. 2. The difficulty of producing hemoglobinemia and jaundice in animals splenectomized one month or more, is due, as shown by blood count, the use of hypotonic salt solution test, and by the search for the presence of hemoglobin in the serum and urine, to an increase in the resistance of the red cells. The results of detailed serologic tests upon this point will be presented later. 3. It is possible that spontaneous jaundice occurring at long periods after splenectomy is an accompaniment of the complete regeneration of the blood. The study of the blood in animals splenectomized for long periods, seven to ten months, indicates that spontaneous jaundice occurs only when the animal has recovered from the initial period of anemia and has a high red cell count and high hemoglobin content. 4. As to the mechanism responsible for the anemia following splenectomy and for the increased resistance of the red cells, we can at present offer no explanation.     

THE OXYGEN OF THE ARTERIAL AND VENOUS BLOOD IN PNEUMONIA AND ITS RELATION TO CYANOSIS

1. A simple method for arterial puncture is given which does no permanent injury to the artery. Arterial and venous punctures have been done on 33 cases of pneumonia and five normal subjects, and the blood thus obtained has been studied with reference to the oxygen capacity and arterial and venous unsaturation. 2. In five normal subjects the mean arterial unsaturation was 5 per cent of the total oxygen capacity; the mean venous unsaturation was 26.8 per cent. 3. In the pneumonia cases the arterial oxygen unsaturation varied over a wide range. The arterial unsaturation varied from 0.0 to 68.2 per cent, the venous from 14.4 to 85.5 per cent. In the fatal cases as opposed to the non-fatal cases of pneumonia, the mean arterial oxygen unsaturation was 32 per cent as against 13.9 per cent. As a rule, an arterial unsaturation of over 20 per cent was associated with a fatal outcome. Similarly, the mean venous oxygen unsaturation was 57 per cent in the fatal cases and 36.3 per cent in the non-fatal cases. 4. In five cases in which no cyanosis was observed at any time the mean arterial oxygen unsaturation was 5.4 per cent, the mean venous oxygen unsaturation 31.5 per cent. In cases which showed cyanosis of varying degree during the course of the illness, the mean arterial unsaturation was 24.7 per cent, and the mean venous unsaturation 44.5 per cent. Cases without cyanosis have an arterial unsaturation close to the normal. 5. There is a definite relation between the degree of cyanosis and the per cent of arterial unsaturation. With increasing cyanosis the arterial unsaturation becomes greater. The venous unsaturation varies similarly. 6. In individual cases with marked cyanosis associated with high arterial unsaturation, the clinical improvement of the patient and the diminution of the cyanosis are accompanied by a similar diminution in the arterial and venous unsaturation. Conversely, an increase of cyanosis is accompanied by an increase in arterial unsaturation. It is evident that the cyanosis of pneumonia patients is due to the incomplete saturation of venous blood with oxygen in the lungs, and that the various shades of blue observed in the distal parts are caused by an admixture of reduced hemoglobin and oxyhemoglobin in the superficial capillaries. 7. No unusually low total oxygen capacities were observed, even in fatal cases with intense cyanosis. On the contrary, in these cases the total oxygen capacity was unusually high, pointing toward a concentration of the blood. Again in only one case was there any marked fall in the oxygen capacity during the illness. Therefore, methemoglobin formation, in these cases, can hardly have occurred to such an extent as to be an important factor in the production of cyanosis. Of the 33 cases studied, however, only seven were lobar pneumonia, the rest being of types ordinarily unusual, which have accompanied the recent influenza epidemic; and of the seven, not all were in all respects typically lobar. The possibility still remains, therefore, that in typical lobar pneumonia caused by the pneumococcus methemoglobin may play a part in the cyanosis. 8. The oxygen consumption, i.e. difference between arterial and venous contents, was within normal limits, indicating that the cardiac output was not diminished in the cases (chiefly post influenza) of pneumonia studied.     

THE DIASTATIC ACTIVITY OF THE BLOOD IN EXPERIMENTAL HYPERGLYCEMIA

1. The diastatic activity of the blood is not materially changed by the subcutaneous injection of phlorhizin, uranyl nitrate, or adrenalin. 2. The diastatic activity of the blood is not affected by puncture of the floor of the fourth ventricle. 3. The diastatic activity of the blood is definitely increased by subcutaneous injections of morphia when a marked hyperglycemia is produced. The same phenomenon appears in asphyxia. 4. Complete pancreatectomy in dogs produces an increase in the diastatic activity of the blood. 5. The diastatic activity of the blood is not altered by the diet. 6. Ether anesthesia, alone, produces a very slight tendency to increase in the diastatic activity of the blood. 7. Repeated periodic small hemorrhages (4.5 cc.) produce no change in the diastatic activity of the blood until a definite color anemia results, when a slight tendency toward increase occurs simultaneously with the rise in blood sugar. 8. The diastatic activity of the blood is not proportional to the concentration of the sugar in the blood.     

BLOOD CELL FORMATION AND DISTRIBUTION IN RELATION TO THE MECHANISM OF THYROID-ACCELERATED METAMORPHOSIS IN THE LARVAL FROG

1. Thyroid-accelerated metamorphosis in the larval frog is accompanied by changes in the hemopoietic centers and in the blood cell distribution in the various regions of the body. These changes are interpreted as results of the fundamental change in basal metabolic rate induced by the thyroid treatment. 2. There is initiation of the shift of hemopoietic locus from the kidney, the larval hemopoietic organ, to the spleen, the adult hemopoietic organ. The spleen, being chiefly an erythrocyte producer, becomes of greater importance with the transition from the lower metabolic rate to the higher, since greater erythropoiesis becomes necessary to supply the physical basis for the maintenance of the higher metabolic rate. 3. It is suggested that the appearance of red bone marrow in the later history of the frog is correlated with a still higher metabolic rate. Phylogenetically, in the vertebrate series, red bone marrow is also associated with higher metabolic rate. 4. The new metabolic rate initiated in tadpoles by thyroid administration sets up a demand for (a) erythrocytes, (b) granulocytes and lymphoid phagocytes for distribution to regions of regressive change, (c) lymphocytes, (1) as progenitors of erythrocytes, granulocytes and phagocytes, (2) for promoting growth of cells in regions of progressive change. 5. Upon the hemopoietic reserve, which in the last analysis is the lymphocyte (and its mesenchymal precursor), depends the extent to which metamorphosis will proceed. Inability on the part of the hemopoietic centers, chiefly the spleen, to keep pace with the demand for blood cells during metamorphosis results in metamorphic stasis, a condition of anemia which is usually followed by death. 6. The growth-promoting function of leucocytes, as demonstrated by Carrel, is probably to be ascribed to the lymphocyte component of leucocytes. 7. The granulocytes have probably also a glandular function, and may exert a lytic effect upon adjacent tissues in regions of regressive change.