Search

The generalized Shwartzman reaction (GSR) was induced in rabbits. Blood samples were obtained at intervals and determinations were made of fibrinogen concentration, platelet count, soluble fibrin monomer complexes (SFMC) and the fibrinolytic activity of the euglobulin fraction. In addition, the tissue plasminogen activator activity in kidney sections was measured. An increase in SFMC and decrease in tissue activator activity in the outer medullary zone of the kidney were observed 6 hours after the preparative endotoxin dose as well as 3 and 6 hours after the provocative injection. The maximal fibrin deposition within the kidney glomeruli was observed 6 hours after the provocative endotoxin injection and 18 hours later the amount of intraglomerular fibrin decreased but the secondary, necrotic changes of the kidney cortex progressed. The fibrinolytic activity in the outer medullary zone of kidney returned to the normal values at the same time. The importance of the fibrinolytic activity in kidney as a defensive mechanism in GSR is discussed.

Fourteen volunteers with far-advanced malignant tumours were treated by a method in which an attempt was made to immunise them against their own tumours. The method consisted of chemically coupling the tumour cell to a highly antigenic foreign protein (rabbit gamma-globulin) with bisdiazobenzidine and reinjecting this complex back into the tumour donor. Of the fourteen patients treated, two are alive and have been tumour-free for about 4 years. Biopsy of their tumours revealed necrotic changes. Three patients have shown stabilisation or slow progression of tumour; nine patients have died. Antibodies in high titres directed toward the tumours, were demonstrated by various means in thirteen of these patients.

Ten femoral heads (diver's disease: 1, caisson disease: 1, the idiopathic: 2, the steroid therapeutic: 2, the post-traumatic: 4) were obtained from the patients. To observe the changes of the osteocyte, the undecalcified sections were prepared.In the cases of idiopathic necrosis, the necrotic change of the osteocyte and the bone marrow was severe and it prevailed to almost all parts of the head. In the cases of steroid therapy, there could be found a wide spreading dystrophy of the osteocyte, but no remarkable changes in the bone marrow. The circumscribed osteocyte death resulting from the repairing of the pre-existing lesion were found in the case of the diver's, the caisson and the post-traumatic bone necrosis.

The morphological changes of Yoshida sarcoma cells infected with ectromelia virus were studied with the electron microscope using the thin sections and the phase contrast microscope.Phase contrast microscopic observations: The inclusion bodies were clearly found in the cytoplasm at 72 hours after inoculation. They were frequently revealed as an accumulation of elementary bodies and varied in size. The serious necrotic changes were seen in the cytoplasm at the later stage, and the diffuse distribution of elementary bodies was observed in them.Electron microscopic observations: The inclusion bodies and matrix regions were found in the infected cytoplasm as they were in the case of other tissues. The inclusion bodies were sharply outlined from the cytoplasm. The elementary bodies embedded within the inclusions showed polymorphological appearances and their density was less than that in mature particles. Though empty circles were found in matrix region, it was not proved that the relationship was present between these bodies and mature virus particles.

A degeneration of the phloem elements of the potato, which occurs in plants suffering from Leaf-roll, was first described by Quanjer (1913). Since them phloem necrosis has been recorded by many workers, some ascribing it to specific pathogenic causes while others state that it occurs in both healthy and diseased plants. Esmarch (1921) states that it is always present in the ripening plant, and v. Brehmer (1923) shows three types of necrosis, viz., Nekrobiose , Obliteration and Necrosis , of which only the last is necessarily due to virus infection. On the other hand, Artschwager (1923) found necrotic changes only in virus infected and injured plants. In this paper an attempt is made to correlate the histopathological changes occuring in virus diseased plants with the external symptoms which they exhibit. A large part of the work is devoted to the morbid anatomy of certain “Streak” diseases, for a detailed account of the external symptons of which see Salaman and Bawden (1932).

Anesthetics like ether, halothane and methoxyflurane may cause side effects on the circulation of pedicle skin flaps. In patients operated under halothane anesthesia the circulatio of pedicle skin flaps was observed to be exceptionally often disturbed. The authors demonstrated in experimental pedicle skin flaps in rats, that halothane may cause larger necrotic changes than expected, especially if the flap is of unfavourable size and “critical” and subjected to bleeding.

SUMMARY Bone changes of the fetus following toxemia of pregnant mother, is studied. This study shows: (1) Slight shortening of the proliferative cartilage zone. (2) Evident shortening of the zone of ossification and chondro-osseous trabeculae that are arranged and shaped irregularly, and the irregular dilatation of the primary marrow. (3) The primary marrow capillaries seem to have the pathologic hyperfunction to invade the cartilage. (4) The dilatation of marrow, and the narrow trabeculae. (5) The thin cortex and the dilatation of the canals of Havers. These changes occur in proportion to the extent of clinical symptoms at the time of labour. The more serious the clinical symptoms at the time of labour are, the more evident these changes become. (6) The increase of osteoblasts: some show atrophic changes, others necrotic changes. (7) The decreasing of calcification stained by hematoxylin. (8) The hemorrhage in the marrow. These changes are in proportion to the course of clinical symptoms and not specific to toxemia, but have only a difference of extent. The irregular arrangement of the capillaries invading the cartilage is specific in toxemia.

1. The injection of a single dose of aqueous beef spleen extract containing 50 mg.-150 mg./ml. of solid materials directly into the peritoneal cavity of mice bearing ascites sarcoma 37 resulted in inhibition of mitosis for a period of at least 48 hours, and in some cases in complete cessation of mitosis that persisted for even longer periods. Mitotic inhibition was accompanied by a marked inflammatory reaction. Cell counts per cc. of ascites fluid were lowered and the percentage of viable tumor cells decreased, partly as the result of cessation of mitosis and necrotic change, and partly through dilution with white blood cells.2. The reduction of tumor cell population was accompanied by the aggregation of tumor cells into islands which presumably served as centers for the formation of solid tumors. When the tumor masses thus formed were large, no regression was observed, though survival time was considerably lengthened; however, small masses were completely resorbed under continued spleen extract therapy i...

Aseptic necrosis involving 6 joints (shoulders, hips, one knee and one ankle) is described in a young woman with systemic lupus erythematosus (SLE) treated with systemic corticosteroids. This is the largest number of joints involved by this process in a single case yet reported. Vasculitis, with ischemia of bone, is thought to be the pathogenesis of the necrotic changes observed. Es describite necrosis aseptic afficiente sex articulationes (spald coxas, un genu, un cavilia) in un juvene femina con disseminate lupus erythematose sub therapia a corticosteroides in administration constitutional. Isto es le plus grande numero de articulationes unquam reportate como afficite per iste processo in un caso particular. Vasculitis, con ischemia del ossos, es reguardate como como le mechanismo del pathogenese del alterationes necrotic observate.

Histopathological studies were made on mouse lung infected with the PR 8 virus intraperitoneally in an effort to differentiate the mode of infection from that of natural or intranasal infection.First of all, the fact was noticed that the necrotic change or desquamation of the bronchial epithel, usually described as a characteristic feature of influenzal infections were not obvious when the virus was given intraperitoneally. However, the virus titers found with both lung tissue and bronchial washings were quite high and just comparable to the value obtained at the time of intranasal infection.In order to explain the inconformities between the virus growth and development of consolidations described above, detailed study was carried out. Firstly, growth of virus, development of lung lesions and their correlations were carefully pursued against time. Secondaly, methylgreen and pyronine staining was used to examine lung tissues in addition to hematoxylin-eosin staining. As a result, it was found that the virus growth at the time of intraperitoneal infection was immediately accompanied by increased pyronine staining of bronchial epithel cell. This was concordant to the detected virus growth. In spite of this result, the necrosis or desquamation of these epithelial cell did not follow. Rather the development of consolidation, i.e. increase of histiocytes in alveorar septa was an event to be considered as a primary response.The observation here made will point out the neccessity of plausible explanation for the desquamation of bronchial epithel which is usually found at the time of intranasal infections, but it was left for further studies. As a whole, the development of consolidation was understood as an immediate inflammatory response to the process of viral synthesis in bronchial epithel.

I. With the object of producing standard low-temperature burns in animals, and of studying the area of tissue only partly damaged in a burn, a burning iron has been made capable of applying temperatures from 45°-80°C. to the skin; with this the amount of heat and temperature causing skin damage has been studied, and the macroscopic and microscopic damage due to graded temperatures have been delineated. II. Macroscopic Changes. 1. Graded temperatures of 45°-80°C. have been applied to the skin of shaved, anaesthetised guinea-pigs, and in some cases rats, for times varying from 10 sec. to 6 and 10 min. Observations have been made of the development of erythema, flare, blanching, blueing, heat fixation, incipient blister formation, œdema, and edge wheal, as also upon the later scab formation and rate of epithelium regeneration. 2. Applications of 47°C. up to 6 minutes produce no visible change. 3. At 50°-55°C. applied for 1 minute and over, there is a critical temperature for the development of permanent and irreversible damage; in animals good scab formation occurs after burning at this temperature. 4. After temperatures of 60°-65°C. the epidermis can be peeled off from the exposed area, leaving a punched-out exposed surface area somewhat like the exposed human blister. 5. A temperature of 70°-80°C. for 10-20 seconds produces severe scabbing. 6. Observations of œdema formation have been checked by wet and dry weights of specimens of skin taken 2 hours after heating. At 55°C. there is some change, but this is more definite at 60°C. 7. The observations recorded here are readily reproducible and provide a standard method of burning for experimental work. III. Microscopic Changes. 1. The histological effects of mild burns of varying intensity and duration have been described in detail. They follow the general picture previously recorded in necrotic changes. 2. Two different types of reaction are described; with milder burns there is cellular disintegration; with more intense burns, heat coagulation. 3. In more intense burns there is a peripheral shell of changes characteristic of burns of lower temperature. 4. Two substances are lost by the epithelium of skin which has been subjected to a burn: (a) Basophil granules from the cytoplasm. (b) Nucleoprotein from the nuclei. These two substances can be identified in the intercellular blister spaces. 5. Collagen fibres change in structure and staining affinity in the more intense burns. Our thanks are due to the Carnegie Trustees for a personal grant to one of us (R. J. Rossiter); to the Nuffield Committee and Trustees and to the Medical Research Council for grants which have helped the cost of this research, though this has been also much financed from University sources. We are grateful to Dr. M. C. Manifold for help with some of the preliminary observations and to Dr. A. N. Drury, Dr. L. Colebrook, and Mr. E. Rock Carling for their interest. We also wish to thank Mr. Marsden for technical assistance with the histology.

A method is presented for the immunohistochemical localization of Cx-reactive protein in rabbits, based on the use of a defined antiserum and rigorous fixation techniques requisite for this antigen. In animals in which inflammatory lesions and CxRP response were induced by intramuscular injection of typhoid vaccine, Cx-reactive protein was localized only in the area of local inflammation within muscle fibers showing morphologic evidence of necrotic change. Within such altered fibers, CxRP was observed in peripheral segments of myofiber or in subsarcolemmal sarcoplasm, in scattered deposits in sarcoplasm, and in vacuolar inclusions. No CxRP was found at any time in polymorphonuclear or mononuclear cells in the inflammatory lesion, nor in contralateral muscle, regional or distal lymph nodes, liver, spleen, thymus, heart, or kidney, except as traces in lumens of vessels or interstitium. CxRP was first detected in necrotic myofibers at the inflammatory site after a latent period of 8 to 10 hours following injection of the inflammatory stimulus and could be demonstrated in these sites for the 48 hours of the experiment. It could not be observed at the inflammatory site before appearance in the blood. Identical histologic localization in necrotic myofibers at the site of the local lesions was found following induction of granulocytopenia with nitrogen mustard. These findings are consistent with the hypothesis that CxRP is formed locally at the site of inflammation from tissue elements undergoing necrotic change. Alternatively, secondary deposition from the blood at the inflammatory site cannot be excluded, but is considered less likely in view of the failure to obtain evidence of a cellular localization of CxRP in other organs.

1. The problems of diagnosis in liver injury, the lack of correlation between laboratory findings, biopsy and autopsy studies and the rapid clinical deterioration resulting in death in three cases are presented. 2. Biopsy studies in Case 1 (V.K) showed minimal necrotic changes which were neither severe nor diffuse enough to cause the marked hepatocellular dysfunction present. 3. Case II (G.C.B.) was cirrhosis clinically in an advanced stage, but even after autopsy and histopathologic studies, changes in the liver could not be placed under any particular category relating to cirrhosis of the liver. In spite of extensive bile thrombi there was no clinical jaundice. 4. In Case III (D.R.), there were signs of marked liver damage without signs of portal hypertension. The biopsy studies showed extensive necrotic changes with widespread commencing fibrosis encircling single cells and groups of cells in other places, fitting into the group of liver injury in children who seem to have a relentless, progressive liver damage with no remission which allows the regeneration and the formation of pseudo-lobules.

The response of the intestine to infection with a pathogenic serotype of E. coli was studied by light and electron microscopy in germ-free and gnotobiotic pigs to provide criteria for assessment of tissues from conventional animals. An acute exudative inflammatory reaction occurred in the lamina propria and some animals died. Survivors continued to show the acute reaction histologically, despite apparent recovery. The cellular response of the lamina propria involved mainly macrophages, lymphocytes and polymorphonuclear leucocytes in the cores of villi, and macrophages, lymphocytes and plasma cells in the intercryptal lamina. Plasma cells were not found in the villus' cores. Degenerative and necrotic changes in the tunica media of arteries and arterioles of the submucosa gave rise to ischaemia of adjacent villi. The nutrition of epithelial cells was severely impaired in this way and by the inflammatory reaction at their bases. They became vesiculated and/or vacuolated, showed loss of volume and could apparently be separated from the underlying villus core, though this may have been an artefact. The evidence suggests that all the major pathological changes were induced by metabolic product(s) of the organism, since microbial invasion from the gut appeared to stop at the epithelial cell.

1. In a considerable number of cases of tuberculous meningitis, transverse myelitis may occur and localization of bacilli in the medulla spinalis is primarily due to direct extension. 2. Myelitis appears in cases of prolonged and incomplete therapy of tuberculous meningitis and mainly when intraspinal injections of streptomycin have been administered for a long time. 3. Sulfone J.51 has a considerable therapeutic effect on meningomyelitis, and especially when administered before complete degeneration and necrosis of a spinal segment. 4. Histologic changes of myelitis consist of degenerative and necrotic changes of white and grey matter, accompanied by development of tubercles as well as extensive changes in the subarachnoid cavity vessels.

SUMMARY The suggestion that pulmonary oedema following the introduction of fluids into the bronchial tree is due to damage to the pulmonary alveolar capillaries has been investigated in electron microscopic studies of rabbits' lungs after intratracheal injections of hydrochloric acid solution, water and saline solution. Introduction of all three fluids produced comparable structural changes in affected parts of the lung, involving dehiscence of the endothelial layer of the alveolar-capillary membranes and minor changes in the other layers. In the presence of acid, but not of water or saline solution, neutrophil cellular accumulation and necrotic changes occurred in the alveolar tissues. The relevance of these observations to the production of Mendelson's syndrome is considered.

An examination was carried out to investigate the pathology of changes induced in the golden hamster and albino mice infected with toxoplasma of the RH strain; the infection was made to resemble the natural routes as far as possible, and was made through the mouth, nose, conjunctiva, scarified skin, and mucosa of the genital tract; the material was fixed in 10% formalin, and stained in hematoxylin-eosin. The most acute infection followed transmission of the pathogens through the respiratory passages or through the mucosa of the genital tract. The acute course of the disease is determined by the degree of necrotic changes to the site of infection, and by the speed with it gains entrance into the blood causing a generalized infection, and death from alveoseptal pneumonia.

Age-related changes of the anterior cerebral arteries of Wistar rats were studied by electron microscope. Medial smooth muscle cells (SMC) in the young rats often made membranous contact. Myo-endothelial junction was also observed. In the 4-week-old arteries, development of cerebral arteries was almost complete. In the 3-month-old arteries, necrotic changes of the SMC appeared in the media. In aging rats, medial SMC necrosis was characteristically observed in the outer media. The outer surface of the SMC showed irregular shape and necrotic substance derived from the SMC was increased with advancing age. Increase of collagen fibers was seen only in the outer media and the adventitia.

The hemorrhagic necrotic changes occurring in certain endermal infections of rabbits closely resemble those described by Shwartzman. This induced us to examine various species of pathogenic microorganisms as to their capacity to produce the lesion in question. Previously reported experiments1-4 revealed 3 different types of reactions represented by the following bacteria:(1) H. influenzœ, when injected into the skin over the abdomen produces a localized swelling and infiltration. There is no trace of hemorrhagic necrosis to be observed. When, 24 hours after the intracutaneous injection of H. influenzœ, a suspension of H. influenzœ is given intravenously, the site of the dermal infection may be transformed into a bluish hemorrhagic lesion within a few hours. Not only living and heat-killed influenza bacilli but also agar-washing filtrates of B. typhosus, B. coli, or meningococcus may induce the same change. On the other hand, those filtrates may be activated by the intravenous injection of H. influenza. (2...

Intraperitoneal administration of 200 mg/kg body weight of streptozotocin to non-diabetic adult Chinese hamsters, evoked a triphasic blood glucose response. There was a hyperglycemic peak after 3 hours and a hypoglycemic phase with a minimum at 6 hours, after which time there was a rather rapid return to hyperglycemia. Light and electron microscopic examinations during the first 24 hours after the injection of streptozotocin showed pyknosis, vacuolization, marked degeneration and necrosis of the β-cells. Degenerative and necrotic changes were also seen in a few α2-cells. The results denote that in the Chinese hamster streptozotocin has an early and direct cytotoxic action on the β-cells and probably also on a few α2-cells.

BS>Late sequelae in the bladder are described in 22 women who had undergone x-ray or Ra therapy for uterine cancer. In most cases clinical symptoms were absent for many months after treatment, and initially arose as hematuria 9 months to 14 yr later. Incontinence and diminished urinary capacity of the bladder were frequent subsequent signs of damage. In some cases, persistent, long-standing hematuria reflected necrotic changes in the bladder, and in some patients anastomoses between bladder and rectum were formed. In these patients, extirpation of the bladder or plastic surgery was required. Histopathologic studies of these resected bladders showed fibrosis of the connective tissue of the bladder wall and thickening of the overlying epithelial tissue. Muscle cells had been destroyed and replaced by fibroblasts, among which were multinucleated giant cells with bizarre chromatin figures. Inflammatory activity was rarely found and was confined to the upper mucosal layer in ulcerated and necrotic regions. Blood vessels showed cuffing with round cells and occasional stenosis. Large doses of radiation injured the relatively radioresistant muscle tissue, whereas lower doses affected mainly epithelium oi the bladder. (H.H.D.)

The present study was initiated to study the acute inflammatory process in the oyster, Crassostrea gigas (Thunberg), elicited by injection of turpentine into the tissues. Gross examination revealed a small greenish-yellow area of pus present in all oysters 40 hours after the injection. Histologically, the various pathological changes observable after the injection of turpentine were edema, a general leucocytic infiltration of the tissues, and congestion of the small blood channels after 8 hours. By 16 hours there was a marked vascular dilatation with pavementing of the larger vessel walls by leucocytes and a cellular exudation and migration of leucocytes toward the source of irritation at 24 hours. A thick wall of leucocytes around the wound was characteristic after 48 hours. The appearance of multinucleate giant cells began at 64 hours, as did the mass migration of leucocytes across the epithelial borders of the digestive system. By 72 hours, the digestive tubule secretory epithelium was reduced to a low cuboidal epithelium. At this time pus was becoming a prominent feature in the injured area. Necrotic changes in the gonadal area associated with edema, heavy leucocytic infiltration, distention of the gonadal ducts, and walls of leucocytes forming around the necrotic gonadal areas were observed 72 hours after injection. A distinct abscess was first observed after 88 hours and abscesses were found in almost all oysters from 88 hours through 216 hours. The consistent characteristics of the abscesses were a central area of liquefaction necrosis, surrounded by an area of necrotic leucocytes, with an area of viable appearing leucocytes around the periphery of the lesion. The abscesses were usually in the digestive tubule area and in most instances appeared well confined, even though they lacked any observable signs of fibrous encapsulation. Some oysters exhibited an ulceration of the stomach or intestinal lining. This phenomenon was not observed before 88 hours after injection, the same time at which abscesses were first noticeable.

1. The intradermal injection of H. influenzae in the abdominal wall of rabbits induces inflammation, frequently combined with a central pustule. The corresponding injection of H. pertussis causes a bluish violet discoloration of the skin area involved which undergoes slight hemorrhagic necrotic changes within a few days. 2. The intravenous injection of living H. influenzae, 24 hours after the intradermal inoculation with living H. influenzae, is able to transform the respective skin areas into severe hemorrhagic necrotic lesions within 3 to 5 hours. 3. Heat-killed H. influenzae, if injected intravenously, may produce hemorrhagic-necrotic lesions in areas previously prepared with living or heat-killed H. influenzae. 4. H. pertussis, if injected intravenously, may cause, perhaps to a lesser extent, hemorrhagic necrotic lesions in skin areas 24 hours previously injected with H. influenzae. 5. The normal course of the infection of rabbit skin with H. pertussis is not, or not essentially, influenced by intravenous reinjection of living or killed H. influenzae or H. pertussis. 6. The agar washing filtrate of B. typhosus, if injected intravenously, can produce hemorrhagic necrotic lesions in rabbit skin prepared intracutaneously with living as well as with heat-killed H. influenzae. The intravenous injection of B. typhosus agar washing filtrate has no influence on areas prepared with H. pertussis. 7. Conversely, H. influenzae as well as H. pertussis, if injected intravenously, are able to produce hemorrhagic necrotic lesions in rabbit skin prepared 24 hours previously with B. typhosus agar washing filtrate. 8. The effectiveness of suspensions of H. influenzae apparently is confined to the bacteria themselves rather than to the supernatant fluids. This does not exclude the possibility of producing effective exotoxins under special experimental conditions.

A 20-years young man suffered from the fractures of the both femurs, of the right lower leg and of the right patella. He was given blood-, fructose and aminoacid transfusion. The abnormality of the physiochemical examination in blood and in urine except for anemia was not evident for 5 days.However, symptome of uremia has appeared since the eighth day, with increasing levels of blood urea or non protein and oliguria, and he died of uremia on the fourteenth day. At autopsy, the kidneys became grossly, as large, swollen, and edematous (right 178gr, left 190gr.). Microscopically, the marked hydropic swelling of the epithelium in the proximal portion of the nephron and slight degeneration and necrotic changes of the epithelium in the distal portion of the nephron with the presence of heme cast were foundThe former is “osmotic nephrosis” and the latter is “lower nephron nephrosis”. No changes were observed in the glomeruli. Therefore it is suggested that slight lower nephron nephrosis resulted from the multiple fractures, marked osmotic nephrosis followed from a large quantity of fructose transfusion and functional disturbance of the kidneys has been produced by them.

Na-sulfaacetylthiazole, 0.5g/kg body weight, was injected into immature and adult rats to produce obstructive nephropathy. Necrotic changes in the myocardium were found in all of the 9 adult rats of about 120 days of age, whereas no such changes occured in immature animals of about 40days of age. Thyrocalcitonin, 50mMRC units a day injected subcutaneously for one week, completely inhibited the occurrence of such myocardial lesion in adult animals, as did parathyroidectomy performed one week previously. Serum calcium was decreased from the normal adult level in thyrocalcitonin treated or parathyroidectomized animals but not in untreated immature rats. Thyrocalcitonin appears to have some effect on cardiovascular system in addition to the known effect on the bone.

Summary This preliminary report presents medullary bone changes occurring in pancreatitis. A case of osteolytic lesions occurring in a girl aged eleven in the acute phase of fat necrosis in pancreatitis is described. Subsequently fat necrosis is demonstrated in the pathological specimen of a man who died following an attack of haemorrhagic pancreatitis, and two cases of calcification in the femoral shafts, with one of which there were necrotic changes in the hip joint, in patients with chronic relapsing pancreatitis are described. In the absence of a history of exposure to abnormal pressures, deep sea diving, caisson work, etc., and in the absence of other sources of embolism, it is considered that in these cases these appearances represented calcification in areas of long-standing fat necrosis in bone associated with pancreatitis.

Grosse Gaben von Diphtherietoxin ohne vorhergehende chronischeγ-Strahlung rufen vielfache kleine fuchsinophile Nekrosen in den Fasern des Myocards hervor. Eine solche chronischeγ-Strahlung sensibilisiert das Myocard gegen das Auftreten von Nekrosen vom selben Typus. Dabei erweisen sich kleine Dosen von Diphtherietoxin als pathogen vollig ausreichend, indem sie kleine Brennpunkte der Schadigung bilden und Herde infarktoider Nekrosen verschiedenen Ausmasses.

The main uterine vessels of pregnant rats were clamped on day 14 for 30, 60, or 90 min. The fetal death rate was increased by 60 or 90 min clamping, proportional to duration. Some surviving fetuses showed skeletal retardation, bilateral limb anomalies, and cleft palate when examined on day 21. As early as 3 h after declamping, edema was seen in the mesenchymal tissue of the limbplates, together with a marked dilatation of the fetal vessels. Later this tissue became necrotic. The necrotic changes also involved surrounding mesenchyme including developing bone, which resulted in the observed limb malformations. In addition large blisters and hematomas at the tip of the snout may have caused tongue displacement to such an extent that palate closure was mechanically impaired. The malformations thus apparently resulted secondarily from necrosis of mesenchymal tissues that had been fully differentiated. This pathogenesis may be a common one for various malformations after impairment of fetal nutrition in rats at this particular develop mental stage.

The feeding of chenodeoxycholic acid or lithocholic acid (0.05 or 0.5% of the diet) to rabbits produced cirrhotic and necrotic changes in the liver, accompanied by an increase of secondary bile acids in bile. Animals fed 0.05% lithocholic acid, 0.05% or 0.5% chenodeoxycholic acid, but not those receiving 0.5% lithocholic acid were able to survive for a period of 21 days. The most severe cirrhotic and necrotic changes were observed in the rabbits fed either 0.5% lithocholic acid or 0.5% chenodeoxycholic acid for 6 days or longer. Liver damage appeared to correlate with bile composition. The pathologic involvement was greatest whenever the percentage of lithocholic acid in the bile exceeded 15%. It is concluded that chenodeoxycholic acid (which is not a major constituent of rabbit bile) exerts its hepatotoxic effects largely because it is converted to lithocholic acid by the intestinal bacterial flora.

The nephrotoxicity of the mushroom species Cortinarius speciosissimus was studied in the rat. Dried, homogenized mushroom was given orally via gastric tubing. The development of the kidney damage was followed by both histological and enzyme histochemical methods. The first signs of kidney damage were interstitial infiltrates occurring mainly in the outer medullary zone, observed two days after the administration of the mushroom. Focuses of inflammation, which gradually scarred, appeared after four days. Chiefly necrotic changes occurred in the tubuli of the cortical zone. Valine residue cleaving aminopeptidase disappeared from the necrotic tubuli at a noticeably greater rate than arginine residue cleaving aminopeptidase. A high activity of arginine residue cleaving aminopeptidase was observed in the inflammatory focuses located in the outer medullary zone, showing the important role of this enzyme in kidney inflammation.

The histological changes of the brain and of the other organs of the patient who was admited to the Psycopathic Hospital de la Magdalena del Mar, has been studied. The patient was admited to the hospital thirty years ago with the diagnosis of Demencia Precox. The discharge diagnosis was Maniac Psychosis. The examination showed lesions of Luetic endoarteritis of the small vessels of the cortex, an entity which was first studied in 1903 by Nissl and Alzheimer. It has been demostrated alterations in the vessels, meninqes, ganglion cells, and gliotic elements of the brain, and structural changes of the other organs. The predominant changes in the meninges are of a chronic and acute character. The former are old "alterations together with vascular sclerosis. The latter are peri-vascular infiltrations of phagocitic wandering cells in which it is frequent to find dense el elements of angular contours with a very rare or no nuclear bodies. This same cells are Frequent in the infiltrations of other organs, such as the Iiver. The dominant character of the typical vascular injury is the proliferation of the adventicial and endothelial cells. It is not unusual, specially in the vessels of large caliber to find alterations of a degenerative nature in the middle layer; these being as a rule of and sclerotic or hialine nature. In these vessels it is quite frequent to find the presence of proliferative and degenerative changes in the intima. The same vascular injuries are found in other organs like the uterus, adrenals, liver etc. Sclerotic changes have been proved to exist in the uterus; calcic concretions and complete calcic occlusions have been found in the vessels of Gasserian ganglion and in the csorcid plexus: hialine degenerations in the media of many vessels of the brain, adrenals, ovary and uterus; and endothelial bridges in the vessels of the ovary are also present. All this shows that the vascular alteration was of a general character. There are two kinds of alterations in ganglion cells, some due to alterations in the vessels and in close relation with these: the necrotic perivascular alterations: others are independent and far related with them: the systematic changes. The exclusive les ion of the cells of the IIIth plate of the cortex (Fig. Nr. 14 and 15) belong to this class, as it is the loss of the Purkinje cells and the deep necrotic changes of nucleus dentatus of the cerebellum. The parts that have a general vulnerability have been intensly affected such as the Cornu Ammonis. Not only in its constitutive insulated elements but also in its architecture. showing considerable changes (Fig. Nr 50). There is evident necrosis of the cells of the spinal cord, specially of the nucleeus propius cornu enterioris and of the nucleus myorabdoticus leterelis, many of these elements. specially those of the first group have disapeared. It is interest to note that some of these changes have not shown relation with the correspondent clinical manifestations. At least until a few before the patient died there were no symptoms of cerebellum or of spinal cord involvement. In adition it must be noted that in the cerebellum there was alterations of basket fibers which gives a resembles with the heredo-cerebellar ataxia of which cerebellar modifications are seperated because the organ mantein the granular layer undemne. Cerebellum changes are common in the desease. It is known that syphilis in all its diferent forms involves large sections of the cerebellum, sometimes entire lobules. With the use of the silver stein of DEL RIO HORTEGA it has been possible to make it easily visible both in the regions of the cortex as well as in the medula oblongata and other formations the most interesant gliotic formations of the astrocytic type, specialy in the periphery of the capilars where the perivascular gliotic rings have been intensly developed. AIso nets of glia of the most complicated weaves and elements have been found in different regions of the nervus systern. The histological examination has confirmed the long believed suposition that the architectural glia of the cortex is heterogeneus and therefore different in its defensive reactions. It would be advisable to study this point both in the normal and patological state. Diferently to what happenes in the general paralysis or in the acute process of syphilis. the microglial reaction has been practical null. The astrocyts has been the prevaling element: this change seems to go with a chronic state of the disease. lt has been found in the dorsal surface of the medula oblongata bodies of the “corpora amilacea" and certain degenerated states of the ganglion cells of the nucleus magnocellularis fumculi posterioris, sustantia reticulatis grisea, nucleus ambigues and nucleus arcuatus, beside gliotic neurophagic nodes. In the ventricles an exudative and proliferative ependimitis has taken place and subependym gliotic elements have penetrated in the inside of the cavity mixing themselves with the morphologic elements of the exudate. At least in some places there is a complete destruction of the ependimary fences; such alterations have often been observed in diferent cases of siphilis. 0ther organs beside the brain have been submited to a close study to determinate its pathological changes in the malady. A large number of the vessels have shown the same alteration as those of the brain, that is adventitial and endotelial proliferation, and degenerated changes in the media of the vessels of medium size. Together with these alterations and as its result, necrosis and degenerations of various kinds have been found in other organs such as the degenerative changes of the parenchyma of the liver and spleen, and of the cells and fibers of the Gasserian ganglion depending these last ones, as it can be seen in the photographs of a calcifing process in the capillairies. It is observed in the liver the different fases of a conective peribiliar proliferation which tend to close the biliar duct, and the particular reaction of the Kuppffer cells. (Fig. N° 64). In the hypophysis, a great increase of the fibrous components, can be seen. Clinically the disease was of a chronic nature: its symptoms of a maniatic Psychosis. The inmediatly cause of death was heart failure; the most notable aspect from the psiquic point of view was the contribution presented by the patient hability to recite a remarkable number of songs of national folklore, old refrains which she was able to remember with extremly fidelity to the last., Se estudia las alteraciones histológicas del cerebro y de los órganos extracerebrales de una enferma que permaneció treinta años en el hospital psiquiátrico de Magdalena del Mar con el diagnóstico de psicosis maniaca, diagnóstico que fué a su ingreso de demencia precoz. El examen muestra que el cambio dominante en el cerebro es la endarteritis de los pequeños vasos de la corteza, tipo endarteritis sifilítica, entidad estudiada por primera vez por NISSL y ALZHEIMER en 1903. Han sido comprobadas alteraciones en los vasos, pía, elementos ganglionares y glióticos, del cerebro, y modificaciones estructurales en los órganos extracerebrales. En la pía dominan los cambios de carácter crónico y agudo. Al primero corresponden viejas alteraciones meningeas en concomitancia, corrientemente, con esclerosis vasculares; al segundo, los infiltrados perivasculares de células de inflamación en los que es frecuente hallar elementos densos de contorno anguloso, con escasa o ninguna evidencia de cuerpo nuclear, de franca cepa conectiva, y muy frecuente también en los infiltrados de otros órganos, del hígado por ejemplo. Carácter dominante de la lesión típica vascular es la proliferación adventicial y endotelial. No es raro encontrar sobre todo en los vasos de calibre mayor, alteraciones degenerativas de la capa media, de carácter hialino o escleroso. En vasos de mayor dimensión es frecuente la presencia de lesiones proliferativas y degenerativas de la íntima. Las mismas lesiones vasculares se hallan en órganos extracerebrales como el útero, cápsulas suprarrenales, hígado, etc. Lesiones de carácter escleroso han sido comprobados en el útero; concreciones y totales oclusiones cálcicas en los vasos del ganglio de Gasser y los plexos coroides; degeneraciones hialinas en la capa media de los vasos medianos en el cerebro, cápsulas suprarrenales, ovario y útero; y, puentes endoteliales en el ovario, todo lo que acusa que el cambio vascular ha tenido carácter general. Hay dos clases de alteraciones ganglionares : unas dependientes de las lesiones de los vasos y en inmediata relación con éstos, las necrosis y alteraciones individuales celulares perivasculares; otras, independientes y muy alejados de los mismos: los cambios sistemáticos. El compromiso exclusivo de las células de la III~ lámina de la corteza (Figs. Nos. 14 y 15), pertenece a esta categoría, lo mismo que la desaparición de las células de Purkinje y las alteraciones necróticas del nucleus dentatus del cerebelo. Territorios que poseen una vulnerabilidad general han sido intensamente comprometidos, como el asta de Ammon. No sólo, aisladamente sus elementos constitutivos, sino su arquitectura muestran considerables cambios: Fig. No. 50. Hay evidente necrosis de grupos celulares de la médula espinal, principalmente del n. proprius cornu anterioris y del n. myorabdoticus lateralis, muchos de cuyos elementos, sobre todo del primero, han desaparecido. Interesante es que estos cambios no han guardado relación con manifestaciones clínicas correspondientes. En ningún momento por lo menos hasta pocos días antes de su muerte, presentó la enferma síntomas cerebelosos o medulares. Además en el cerebelo hay alteraciones de las fibras del canastillo, lo que le da un cierto parecido con la heredo-ataxia cerebelosa, de cuyas modificaciones cerebelosos se aparta por conservarse indemne la capa granulosa. Las alteraciones cerebelosas no son propias de la enfermedad. Es sabido que la sífilis en sus diferentes formas compromete extensos territorios del órgano, a veces lóbulos íntegros. Mediante el empleo de los procedimientos argénticos de DEL RIO HORTEGA se ha logrado hacer visibles tanto en los más apartados territorios de la corteza, como en el bulbo y otras formaciones nerviosas, las más diversas e interesantes formaciones glióticas de tipo astrocitario, sobre todo, en la periferie de los capilares donde se ha desarrollado con particular intensidad los típicos anillos glióticos perivasculares. Además redes de glía de las más variadas tramas, y elementos de esta especie de la mayor diversidad, han sido hallados en distintos territorios del sistema nervioso. El examen histológico confirma la suposición hace mucho tiempo sostenida de ser heterogénea la arquitectura gliótica de la corteza, y, como consecuencia distinta su manera reaccional frente a los agentes alterantes. Convendría estudiar este punto en lo normal y en lo patológico. Al contrario de lo que ocurre en la parálisis general o en procesos sifilíticos de curso agudo, la reacción microglial ha sido casi nula. El astrocito ha sido el elemento dominante, cambio que parece aparejarse con el carácter crónico de la enfermedad. Se ha comprobado en el bulbo: cuerpos amiláceos en las vecindades de la superficie del 4º ventrículo y particulares estados degenerativos de los elementos ganglionares de los núcleos : magno cellularis funiculi posterioris, sustancia reticularís grisea, n. ambiguos, y n. arcuatus. Además nódulos glióticos neuronofágicos. En los ventrículos internos se ha desarrollado una ependimitis proliferativa y exudativa, en muchos sitios ha sido rota la barrera ependimaria, y elementos glióticos subependimarios han hecho su irrupción en la cavidad interna mezclándose con los componentes morfológicos del exudado. Por último en algunos lugares ha sido destruida la barrera ependimaria. Semejantes alteraciones han sido descritas en diversas clases de sífilis. Se ha estudiado diversos órganos extracerebrales con el propósito de averiguar su repercusión en el proceso. Gran parte de los vasos presentan las mismas alteraciones que los del cerebro, esto es las proliferaciones endo y adventiciales, pero aparte de éstas es frecuente hallar cambios degenerativos de la capa media de los de mediano calibre. Junto con tales alteraciones y como su consecuencia, necrosis y degeneraciones de la más variada índole se han hecho presentes en diversos órganos, como las insulares del parénquima hepático y del bazo, las de las células y fibras del ganglio de Gasser, dependientes estas últimas como se ve en las fotografías respectivas, de procesos calcificantes oclusivos de los capilares. Se estudia en el hígado las fases de una proliferación conectiva peribiliar, con tendencia oclusiva por estrechamiento de la luz canalicular; y la particular reacción de las células de Kupffer. Fig. No. 64. Eh la hipófisis se comprueba un desarrollo considerable del componente fibroso que "ahoga" islotes glandulares. CIÍnicamente el curso de la enfermedad fué crónico; sus síntomas los d~ una psicosis maniaca; la causa inmediata de la muerte una cardiopatía rápidamente descompensada; lo más notable en el aspecto psíquico la contribución presentada por la enferma al enriquecimiento del folk-lore nacional por la suma de cantares, consejas y refranes que su memoria había por felicidad conservado.

Fifty-four postirradiation arthropathies were found among 536 patients with radiation-induced osteodysplasias. There were three main types of joint changes: degenerative arthrosis, inflammatory arthritis, and ankylosis. Degenerative arthropathy was the most common. Degenerative and necrotic changes occurred in the cartilage, joint capsule, and bones in the vicinity of the joint. A slowly progressive septic arthritis occurred in some patients, due to infection by bacteria of low virulence. This arthritis led ultimately to ankylosis or amputations. Like bones, joints must be considered to be radiosensitive and their resistance to various insults, especially bacterial infection, is lessened after radiation damage.

This chapter focuses on relative contribution of the three systems of vessels to the blood supply of the long bones. Because of the very large anastomoses, to cause evident changes, vascular suppression must be radical, with the danger of damaging the venous as much as the arterial flow. The chapter presents a study in which 20 animals were used: 15 young and 5 adults. The nutrient vessels were cut, and the blood flow of the bone marrow from the metaphyseal vessels was prevented by plugging the drill holes made at each end of the shaft with the polythene sheath as reported. Necrotic changes appear on the first day following the vascular interruption in the bone marrow cells. All the radii examined showed good filling of the stem of the nutrient artery and of many of its branches.

Malignant melanoma often undergoes spontaneous focal necrosis and ulceration. In conjunction with this gross and microscopic necrosis there appears a wide spectrum of subcellular changes, accompanied by hydrolytic enzyme activity in the cytoplasm of malignant melanoma cells. In die present study, these subcellular changes are described and differentiated from die accelerated subcellular melanogenic activity also occurring in the malignant melanoma cell. Three types of Fortner's hamster melanoma, whose ontogenies include focal necrotic changes like those of their human counterparts, have been investigated electron microscopically and histochemically. The electron microscopic acid phosphatase reaction confirms that the hydrolytic activity occurring in malignant cells of both melanotic and amelanotic melanoma is localized within autophagic vacuoles which are thus shown to be lysosomes. Electron microscopy reveals that the occurrence of microfocal degradation by the segregation of ergastoplasm and mitochondria within lysosomes is closely related to the spontaneous necrosis seen in malignant melanomas. This lysosomal engulfment is also involved in the segregation and degradation of premelanosomes and melanosomes. Increased tyrosinase activity and melanosome production characteristic of malignant melanoma cells proceed concomitantly with the appearance of lysosome formation and hydrolytic activity until the melanoma cells complete their own ontogeny and the ontogeny of the melanosomes which they have synthesized.

The isolated perfused rat liver has previously been used to demonstrate an increase in the basal resistance to blood flow in the liver following CCl4 intoxication. The data indicated the presence of a biphasic response to CCl4. The effects of hypophysectomy and spinal cord transection have now been studied. Livers for perfusion, were obtained from hypophysectomized or cord-transected animals, 3 and 12 hours after treatment with CCl4. Pressure-flow responses were employed to assess changes in basal vascular resistance. Hypophysectomy blocked the increase in resistance normally seen 3 hours after CCl4, but had no effect on the 12-hour effect. Hypophysectomy also blocked the usual increase in hepatic triglyceride, while having no effect on necrotic changes. Cord-transection had the same overall effect as hypophysectomy if the animals were kept normothermic. However, if the animals were allowed to become hypothermic, not only were the triglyceride and necrotic changes blocked, but so were the circulatory changes at both 3 and 12 hours. These data are consistent with the idea of a biphasic response to CCl4, the early and late responses being due to different mechanisms.

1. Watery vacuolation in the acinar cells of the rat submandibular gland is described. The vacuoles are cytoplasmic, membrane-walled, and 2-20 μ in diameter. They are visible in living cells and appear to contain a watery fluid. 2. Vacuolation occurred regularly in the following experimental situations: (1) in vitro—under anoxic conditions (2) post mortem—in animals killed by anoxia, and (3) in vivo—during secretion. 3. By in vitro experiments it was shown that vacuolation occurs only when the cells are both anoxic and exposed to an excess of extracellular fluid containing calcium and bicarbonate. It was further shown that vacuolation is reversible in oxygen and that both its development and recovery are temperature dependent. 4. Evidence is presented that the vacuolation is not a degenerative or necrotic change, that it is accompanied by the entry of fluid into the cells, and that it is not caused by simple osmosis. 5. The mechanism of vacuolation and its possible relation to secretion are discussed. It is suggested that vacuolation represents an imbalance between the ingestion and secretion of water and salts. 6. Similar vacuoles, apparently produced by the same mechanism, were observed in the acinar cells of the parotid gland and the pancreas of the rat. 7. The close similarity of this vacuolation to that previously described in rat liver cells was noted.

Summary The adenohypophysis of a total of 73 adult rabbits was studied, 56 (37 males and 19 females) had been submitted to orthostatic collapse and 17 (10 males and 7 females) served as controls. The animals either died from collapse or were sacrificed at regular periods of time up to 8 months following it. The first change observed was vacuolar alteration of the glandular cells seen 30 minutes after the collapse. This change is possibly related to a nutritive disturbance mainly hypoxic in nature due to shock. The next change seen was nuclear pyknosis, and at 6 or more hours following collapse necrosis of the glandular cells was found. This necrosis was slight, involving isolated cells or groups of them, and complete regeneration of the adenohypophysis occurred 2 months later.

During an outbreak of Salmonella abortion in mink farms receiving food from a central feed plant, sulphamezathine (a 16 % solution of sulphadimidine sodium) was added to the food to combat the infection. After 3 days of medication, some males of the Aleutian type developed severe urinary bleedings. The serum concentration of the drug was not above the recommended value in 2 severely affected animals (1.5 and 1.7 mg/100 ml, respectively). Screening tests for the extrinsic (Thrombotest and Normotest) and intrinsic (cephalin time) coagulation mechanism, fibrinogen assay, fibrinolysis (plasma clot lysis time), and platelet count were not much different from normal. Coagulation or platelet defects did not therefore seem to be the cause of the bleedings. Some of the diseased animals died, and the only necropsy finding was a greatly distended urinary bladder filled with clotted blood. Histologically, hemorrhages and necrotic changes of varying severity were found in the vesical wall. In several cases, the arteries were the structures most evidently affected, indicating that the hemorrhages were due to vascular injury (Fig. 1). The damaged vessels were sporadically occluded by thrombi. The lesions were often most evident in subserosal arteries and in the relatively large arteries situated between the inner circular and the outer longitudinal muscular layer, whereas the submucosal structures were obscured by massive extravasations of red blood cells. Occasionally, the necrotic arteries were surrounded by incipient circumferential cellular accumulations, predominantly mononuclear cells, but some eosinophils were also present (Fig. 2). Thus, in these cases the vascular damage was similar to vascular lesions frequently accompanying viral plasmacytosis (periarteritis nodosa). The possibility exists that the animals were in an early developmental stage of plasmacytosis, but no extravesical changes suggesting plasmacytosis were discovered during the microscopic examination. Although other sulphonamides have occasionally shown toxic properties when administered to mink, this preparation has not, to the authors’knowledge, previously been recorded as injurious to this species. The following experiment was performed to elucidate the toxicity of sulphadimidine sodium to male Aleutian mink.

Cytarabine (cytosine arabinoside) was utilized in the treatment of a patient with chronic lymphocytic leukemia who developed symptomatic progressive multifocal leukoencephalopathy (PML) after a 12-year course of lymphoproliferative illness. An immediate and impressive degree of neurologic improvement occurred with the institution of antiviral chemotherapy, but clinical benefit was not sustained and the patient died of his neurologic disorder. On gross examination at postmortem, necrotic changes in the demyelinated areas of the brain were seen. Light and electron microscopic studies showed changes characteristic of PML and virus-like particles abundant in glial cells. Cytarabine may have some influence on the course of the illness, but the quality of therapeutic effect needs further investigation. ( JAMA 229:1313-1316, 1974)

Many studies of experimental nephritis are reported in the literature, notably those which concern the injection of the salts of the heavy metals, uranium and tartrates, into rabbits and dogs. There seems to be no mention of nephritis caused by the injection into rabbits of relatively large amounts of monobasic sodium phosphate. In the course of certain experiments with rabbits, injections of solutions of this salt were made and in the examination of the kidney tissue, necrosis of the cells lining the convoluted tubules and the loops of Henle was observed. Other experiments were made to confirm this observation, and in each instance depending in severity largely on the length of time that the rabbit was poisoned by the injections, there are necrotic changes in the cells of the renal tubules mentioned. Blood to be used for determining the hydrogen ion concentration and the carbon dioxid combining power was drawn

The normal range of activity of transaminase in human serum was first described in 1953 (1). Since then the clinical implications of alterations in serum transaminase activity in disease of the heart (2, 3), liver (3-6), and skeletal muscle (7) have been well documented. The large amounts present in these organs as compared to normal serum levels suggest that increases in serum levels are associated with tissue injury. This association has proved to be well founded (5, 6). Serum glutamic pyruvic transaminase activities can play an important part in the detection and diagnosis of active liver cell damage and necrosis before any other abnormality is shown by other liver function tests (8). The collection and analysis of sufficient data on the serum transaminase levels in Pu239-burdened dogs will allow one to detect early necrotic changes induced by the deposition of Pu239 in the liver of these dogs.

Soon after the discovery of X-rays it was realized that these penetrating radiations induced striking alterations in living tissue, and in 1903 Albers-Sch6nberg (1) described radiation damage to the testis. Numerous investigations followed his initial report, and a voluminous literature has accumulated (for reviews, see refs. 2-4). Regaud and Blanc (5) were the first to realize the changes in sensitivity that accompany development of the different cell types, a subject which has received various interpretations (2, 6-13). The weight of experimental evidence indicates that spermatagonia are more sensitive than spermatocytes, spermatids, and sperm. Depletion of spermatogonia results in disappearance of cells in the order of their developmental sequence and eventually results in loss of sperm (2, 5, 8, 10, 11). However, a few type A (dusty) spermatogonia survive and eventually repopulate the germinal epithelium (8, 11-15). Therefore, both initial depletion and subsequent regeneration of spermatogenic elements depend on the response of spermatogonia. Paradoxically, it is the effect of radiation on spermatogonia that is the least understood. Regaud and Blanc (5) recognized the extreme sensitivity of spermatogonia, and Schinz and Slotopolsky (2) observed necrotic changes in spermatogonia as early as 2 hours after irradiation, with cessation of spermatogonial degeneration by 4 days. Regaud and Lacassagne (16), von Wattenwyl and JoMl (17, 18), and HIertwig (8) also considered necrosis of spermatogonia to be important. However, more recent reports have claimed that degenerative cells are rare (4, 11-13, 19, 20). On the basis of failure to observe degeneration, Eschenbrenner et al. (19) suggested that depletion of the germinal epithelium after irradiation was due to inhibition of mitosis of the most primitive cells, namely, the type A spermatogonia. A subsequent experiment with acute doses of X-rays was interpreted as supporting evidence for the hypothesis of mitotic inhibition (11). However, this hypothesis is in disagreement with the data of Langendorff (21), who observed a return to normal mitotic

Leukopenia accompanies numerous infectious and toxic conditions. However, the diminution in the number of the white corpuscles is oftentimes only transitory, and the drop in the leukocyte count, although it may have considerable prognostic significance, is not regarded as anything more than a symptomatic indication of a variety of disorders. Recently, however, a condition has been described in which the outstanding characteristic, persisting until death of the patient, is the disappearance from the circulating blood of the polymorphonuclear leukocytes (granulocytes), the erythropoietic and lymphopoietic systems being but slightly affected. The clinical picture of the disease, as described by various authors, resembles that of a severe infection with fever accompanied by necrotic changes in various mucous membranes, particularly those of the buccopharynx. The patients, in the majority of instances women, not uncommonly develop jaundice. The disease is fatal in about 90 per cent of the cases. Blood cultures during life or

SUMMARY Lesions in turkey poults naturally infected with Arizona hinshawii were found to be comparable to lesions induced by salmonella and paratyphoid organisms. Most organs had inflammatory, degenerative, and/or necrotic changes. Changes were acute in central nervous and ocular tissue, and subacute in tissues of other organs. Streptomycin and penicillin medication probably prevented intestinal lesions. The central nervous and ocular tissues were apparently infected by way of the blood stream.