THE INFLUENCE UPON THE SPLEEN AND THE THYROID OF THE COMPLETE REMOVAL OF THE EXTERNAL FUNCTION OF THE PANCREAS

The complete removal of the function of the pancreas concerned in digestion is followed by marked changes in the spleen and in the thyroid apparatus. Second, the spleen shows an extreme simple atrophy. Third, the thyroid apparatus exhibits a constant change shown by the macroscopic transparency of the gland, by the microscopic increase in the amount of colloid, by the chemical increase of the iodine content of the gland, and by the functional test of the delayed appearance of tetany after the complete removal of the thyroid apparatus.     

THE INDUCED SUSCEPTIBILITY OF THE GUINEA-PIG TO THE TOXIC ACTION OF THE BLOOD SERUM OF THE HORSE

Following the divisions before used, the results presented in the preceding pages may be briefly stated. I. The particular method of sensitization and the place where the test injection is made have an important bearing on the results obtained by various workers. Comparing the results obtained by the various methods, we may conclude that the incubation period of the hypersensitive reaction is not sharply limited, but that there is a progressive increase in sensitiveness from the sixth day, and presumably before that, extending over a period of several weeks. It seems very probable that the degree of hypersensitiveness attained where the sensitizing dose consists of a mixture of diphtheria toxin and serum is greater than when a single dose of the same small quantity of serum is given alone. II. Our early experiments, the first in this field, are in thorough agreement with those first reported by Otto, and shortly after him by Rosenau and Anderson. III. This hypersensitive reaction is transmissible from mother to offspring. The transmission is probably not equally effective in all cases, and individual young guinea-pigs probably vary greatly in the rate with which they lose their ability to react. As a result not all of the young of a hypersensitive mother react to a subcutaneous dose of five cubic centimeters of serum given when they are four or five weeks old. The reaction in the young animals differs quite markedly from that in those actively sensitized. These differences are such as to indicate that in the mother there is a considerable localization of the reaction in tissues and organs whose destruction does not cause sudden death. This local reaction is a protective factor and is not transmitted to the same degree as the factors involved in the fatal acute reaction. IV. The hypersensitive reaction to horse serum depends on the development of a special anti-body during the incubation period, which anti-body may be passively transferred to a fresh animal. If the dose of hypersensitive serum be sufficient, and the intoxicating injection be given directly into the circulation, this passive hypersensitiveness may be enough so that the animal will die when tested. There is also in the serum of hypersensitive guinea-pigs an uneliminated horse serum element or "rest," which is distinct from this antibody, and probably without influence on the course of the acute reaction. V. The anti-body on which the hypersensitive reaction depends may be entirely neutralized by horse serum without causing symptoms. The gradual introduction of increasing doses over a total period of twenty-four hours suffices for this. The animal is then, properly speaking, neither immune nor refractory, but is essentially in the condition of a normal animal which has recently had a large dose of horse serum. This rapid neutralization is made possible by the great binding power which the subcutaneous and other relatively unimportant tissues have for the toxic element of the serum. The so-called "Phenomenon of Arthus" is probably the same reaction for the rabbit that we have here dealt with in the guinea-pig. The fact that the manifestation is more prominently a local one depends on racial differences. I have encountered cases in the guinea-pig in which the conditions in the rabbit are closely simulated.     

ON THE PHYSICOCHEMICAL REGULATION OF THE GROWTH OF TISSUES : THE EFFECTS OF THE DILUTION OF THE MEDIUM ON THE GROWTH OF THE SPLEEN.

It may be concluded that the degree of dilution of the culture medium has a marked influence on the rate of growth of splenic tissue. The maximum acceleration was obtained in a medium composed of three volumes of normal plasma and two volumes of distilled water. The growth in this hypotonic plasma was very much larger than in normal plasma. On the contrary, the growth of the spleen in hypertonic plasma was always less than in normal plasma. In other experiments, we found that in diluted plasma there was also an acceleration of the growth of the skin, the heart, and the liver of chickens. The skin of adult frogs also grew more actively in this plasma. The optimum degree of dilution varied according to the nature of the tissues and to the species of the animals. While the plasma containing two fifths distilled water produced the largest growth of splenic tissue, a slightly less diluted medium was more favorable for the liver and the heart, and generally for the skin also. The action of hypertonic plasma varied also in a large measure. While the spleen did not grow at all in the medium containing 0.0124 and 0.0144 sodium chlorid, the skin, on the other hand, could stand a high concentration of the sodium chlorid. Even its growth was activated in media containing 0.0094 and 0.0124 sodium chlorid and was greater than with normal plasma. The spleen of kittens was very easily affected by the changes of the dilution of the plasma, while the skin of the frog presented its best growth in plasma containing one half distilled water. Marked variations in the sensitiveness of tissues to hypertonic and hypotonic media will probably be observed in animals of different species. From these experiments, three conclusions can be drawn: namely, that certain laws of growth, discovered by Loeb, in lower organisms are true also for higher organisms; that normal plasma is not the optimum medium for the growth of tissue; and that each tissue has probably its optimum medium. The growth of the spleen is, without doubt, considerably modified by the variations of the dilution and perhaps of the osmotic tension of the plasma. It is possible then that the influence of osmotic tension, discovered by Loeb, in the growth of certain organisms, is a general law applicable as well to higher forms of life— frogs, cats, and chickens—as to lower organisms—tubularia and sea-urchins. In placing tubularia in different dilutions of sea-water and distilled water, Loeb found that the greatest rate of regeneration was observed when two volumes of distilled water were added to three volumes of sea-water. But fertilized eggs of sea-urchins were more sensitive to the action of hypertonic plasma, and they all died in a dilution of sea-water with two fifths distilled water. If only one fifth distilled water was added to the sea-water they developed normally. We found that the cells of certain tissues of the chicken follow a similar rule, since the maximal growth of the spleen is obtained in plasma containing two fifths distilled water, while other tissues grow better in a less hypotonic medium. Normal plasma is certainly not the ideal medium for the growth of tissues, since slight modifications of the tension, the alkalinity, or the addition of certain inorganic salts to normal plasma, increase the rate of the growth of tissues.     

THE EFFECT OF PULMONARY CONGESTION ON THE ON THE VENTILATION OF THE LUNGS

1. A method is described for producing pulmonary congestion, together with what may be termed a differential spirometer method for studying lung ventilation. 2. The method utilized permits an approximately accurate prediction of degrees of pulmonary edema in the living animal, and suggests avenues of approach for the very difficult problems of pulmonary capillary pressure. 3. It is shown that intravascular blood can encroach markedly upon the pulmonary air space. Although the methods used in these animal experiments do not resemble vital capacity measurements in man, their result is so definite that their applicability to clinical conditions may be considered. 4. The similarity between the experiments described and certain conditions of cardiac decompensation, of which mitral stenosis is the best example, is pointed out.     

THE PATHOGENESIS OF THE HEMORRHAGIC DISEASES OF THE NEW-BORN

Those conditions of the new-born characterized by a hemorrhagic tendency, icterus, and fatty changes, are probably all syndromes which may occur as the result of a number of toxic agents. All of them, however, have been produced, in these experiments, by the action of a single experimental agent. Thus, a picture indistinguishable from that called Buhl''s disease has been obtained by the use of chloroform, as have also the pictures known as Winckel''s disease, melæna neonatorum, etc. Chloroform is not held to be the only substance that has this power. It stands rather as one member of a group of agents, the effects of which in general and in individual organs are similar to those caused by lack of oxygen. The essential features of these conditions have also been produced by direct asphyxiation of the fetus. The suggestion is therefore made that underlying all these symptoms and pathological complexes, there is a deficiency of oxidation, general, local, or selective, thus bringing this group of diseases into the general category of acute yellow atrophy of the liver, eclampsia, pernicious vomiting, cyclic vomiting, phosphorus poisoning, etc. In human beings, chloroform and asphyxia must, in many instances, be the determining causes. There remain, however, other cases in which different factors are to be sought.     

THE EXTENT OF THE CAPILLARY BED OF THE HEART

By means of injections made into the coronary arteries of beating hearts it has been possible to determine the number of capillaries in the normal heart muscle. This study has shown a very rich blood supply with an average of approximately one capillary for each muscle fibre in the ventricular walls and papillary muscles, and a less abundant supply in the auricular muscle and Purkinje system. The number of capillaries per sq. mm. of ventricular wall or papillary muscle is about twice that found by Krogh in skeletal muscle. Capillaries were not found constantly in the valves of hearts in which there was apparently a complete injection of the capillary bed. The method described for injecting the capillaries of the heart also provides a means of studying the blood supply to the muscle, valves and aortic wall in pathological hearts.     

THE FUNCTIONS OF THE THYMUS SYSTEM AND THE BURSA SYSTEM IN THE CHICKEN

The bursa of Fabricius and the thymus are "central lymphoid organs" in the chicken, essential to the ontogenetic development of adaptive immunity in that species. Surgical removal of one or both of these organs in the newly hatched chicken, followed by sublethal X-irradiation the next day, has permitted recognition of two morphologically distinct cell systems in the "peripheral lymphoid tissues" of the spleen, gut, and other organs, and clear definition of the separate functions of each cell system. The thymus-dependent development is represented morphologically by the small lymphocytes of the circulation and the white pulp type of development in the tissues. As in mammals, the thymus-dependent tissues of the chicken are basic to the ontogenesis of cellular immunity: graft versus host reactions, responses of delayed hypersensitivity and homograft rejection; and play a less clearly defined role in the antibody response to at least some antigens. Thymectomized-irradiated chickens are deficient in all these responses, and grow more slowly than any of the other experimental groups. In these animals germinal centers, plasma cells, and capacity for immunoglobulin synthesis remain intact. The bursa-dependent development is represented morphologically by the larger lymphocytes of the germinal centers and the plasma cells, and functionally by the immunoglobulins. Bursectomized-irradiated chickens are agammaglobulinemic and unable to produce detectable antibody despite intense, repeated stimulation with bovine serum albumin and Brucella abortus organisms. The thymus-dependent development in these animals seems to be normal; they have adequate numbers of lymphocytes in the circulation and tissues, are able to reject skin homografts, though more slowly than usual, and to exercise graft versus host reactions. The short life span of these chickens has precluded adequate study of responses of delayed hypersensitivity. There was no evidence of significant impairment of reticuloendothelial function in either the bursectomized-irradiated or the thymectomized-irradiated group, as judged by the clearance of colloidal gold and I¹³¹-tagged keyhole limpet hemocyanin.     

THE ROLE OF THE SCAPULA

Previously, the scapular musculature was often neglected in designing a rehabilitation protocol for the shoulder. In the past two decades a significant amount of research has been performed in order to help identify the role of the scapula in upper extremity function. Weakness of the scapular stabilizers and resultant altered biomechanics could result in: 1) abnormal stresses to the anterior capsular structures of the shoulder, 2) increased possibility of rotator cuff compression, and 3) decreased shoulder complex neuromuscular performance. This clinical commentary presents facts about the anatomy and biomechanics of the scapula and surrounding musculature, and describes the pathomechanics of scapular dysfunction. The focus is upon the assessment of dysfunction and retraining of the scapular musculature.

Level of Evidence:

5     

THE INFLUENCE OF THE VAGUS NERVES ON THE FARADIZED AURICLES IN THE DOG'S HEART

An abnormal auricular activity is produced by faradization of the right auricle of the dog, which frequently becomes established and continues for varying periods of time after faradization is discontinued. This auricular activity consists of a rapid auricular tachycardia coexisting with true auricular fibrillation. In some dogs the auricles are thrown into this abnormal activity more readily by faradization after the vagi have been cut than before. Cutting the nerves has little or no effect on the abnormal auricular activity, but the ventricular rate may be much increased if the vagi are cut after the abnormal auricular activity has been established, apparently because of an improvement in the auriculoventricular conductivity. Stimulation of the right vagus nerve changes the character of the activity of the faradized auricles by inhibiting the auricular tachycardia while the fibrillation is uninfluenced. Stimulation of the left vagus nerve has little or no apparent inhibitory effect on the auricular tachycardia, but has possibly an inhibitory effect on the auricular fibrillation. Vagus stimulation increases the susceptibility of the auricles to faradization. The abnormal activity set up by faradization may be established in hearts otherwise refractory by vagus stimulation of short duration following the faradization. Vagus stimulation usually holds the auricles in the abnormal activity set up by faradization as long as it is continued in hearts in which, without vagus stimulation, the sequential beat always returns as soon as faradization is stopped. The right vagus is more effectual in this respect than the left. In some hearts vagus stimulation alone is capable of initiating the same abnormal auricular activity which is caused by auricular faradization. The normal sequential beat is often restored by vagus stimulation. It replaces the abnormal auricular activity not during, but a few seconds after, the termination of vagus stimulation. Left vagus stimulation is somewhat more effectual in producing this result than right vagus stimulation.     

ON THE TRANSPLANTATION OF THE GUINEA PIG SUPRARENAL AND THE FUNCTIONING OF THE GRAFTS

1. The suprarenal cortex of the guinea pig can be transplanted autoplastically into the abdominal wall and may remain for months, growing to fairly large size. 2. The suprarenal cortex of the guinea pig can be transplanted homoplastically but these transplants usually degenerate after a few months. 3. Small autoplastic transplants are capable of maintaining the life of a completely suprarenalectomized guinea pig for weeks and large transplants maintain the animal indefinitely in good condition. 4. Irritation phenomena follow the grafting of suprarenal cortex due to the entrance of epinephrine into this tissue during the manipulation involved in removal of the gland.     

THE ACTION OF THE SYMPATHETIC UPON THE EXCITATORY PROCESS IN THE MAMMALIAN HEART

Stimulation of the sympathetic nerve endings, after paralysis of the vagus, accelerates the transmission of the excitatory process in the dog''s auricle. Following the functional exclusion of the vagus ergotamine slows the rate of the sinus rhythm, depresses A-V conduction, and delays the transmission of the excitatory process in the auricle. The relation of the sympathetic and parasympathetic nerves in the control of the cardiac rhythm is discussed.