Degeneration Of Blood Vessels Research Articles

Histopathological, biochemical and molecular studies on a model of systemic autoimmune disease induced by sodium silicate in non-genetically prone rats

Sodium silicate (Na2SiO3) is an inorganic silica salt used in many products. Few studies reported autoimmune diseases (AIDs) due to Na2SiO3 exposure. This study investigates the role of Na2SiO3 exposure by different routes and doses in AID development in rats. We assigned 40 female rats to four groups: G1 control group, G2 rats were subcutaneously injected with 5 mg Na2SiO3 suspension, and G3 and G4 rats were orally administered 5 mg and 7 mg Na2SiO3 suspension, respectively. Na2SiO3 was administered weekly for 20 weeks. Serum anti-nuclear antibodies (ANA) detection, histopathology of kidney, brain, lung, liver, and heart, oxidative stress biomarkers (MDA and GSH) in tissues, Matrix metalloproteinase activity in serum, TNF-α, and Bcl-2 expression in tissues were performed. ANA was significantly increased in silicate groups, especially G2. Creatinine was significantly increased in silicate groups. Histopathology revealed vasculitis and fibrinoid degeneration of blood vessels, a picture of immune-mediated glomerulonephritis in the kidneys, and chronic interstitial pneumonia with medial hypertrophy of pulmonary blood vessels. The activity of gelatinases (MMP-2 and MMP-9) and collagenase (MMP-13), which play role in inflammation, remodeling, and immune complex degradation, were significantly increased in the silicate-exposed groups. Bcl-2 was significantly decreased, indicating apoptosis. Therefore, oral administration and subcutaneous injection of Na2SiO3 induced immune-mediated glomerulonephritis with elevated ANA levels and overexpression of TNF-α in rats.

Automatic Screening of Diabetic Retinopathy Using Fundus Images and Machine Learning Algorithms.

Diabetic Retinopathy is a vision impairment caused by blood vessel degeneration in the retina. It is becoming more widespread as it is linked to diabetes. Diabetic retinopathy can lead to blindness. Early detection of diabetic retinopathy by an ophthalmologist can help avoid vision loss and other complications. Diabetic retinopathy is currently diagnosed by visually recognizing irregularities on fundus pictures. This procedure, however, necessitates the use of ophthalmic imaging technologies to acquire fundus images as well as a detailed visual analysis of the stored photos, resulting in a costly and time-consuming diagnosis. The fundamental goal of this project is to create an easy-to-use machine learning model tool that can accurately predict diabetic retinopathy using pre-recorded digital fundus images. To create the suggested classifier model, we gathered annotated fundus images from publicly accessible data repositories and used two machine learning methods, support vector machine (SVM) and deep neural network (DNN). On test data, the proposed SVM model had a mean area under the receiver operating characteristic curve (AUC) of 97.11%, whereas the DNN model had a mean AUC of 99.15%.

Deficiency of cystathionine gamma-lyase promotes aortic elastolysis and medial degeneration in aged mice

Enzymatic degradation of elastin by matrix metalloproteinases (MMPs) leads to the permanent dilation of aortic wall and constitutes the most prominent characters of aortic aneurysm and aging-related medial degeneration. Hydrogen sulfide (H2S) as a gasotransmitter exhibits a wide variety of cardio-protective functions through its anti-inflammatory and anti-oxidative actions. Cystathionine gamma-lyase (CSE) is a main H2S-generating enzyme in cardiovascular system. The regulatory roles of CSE/H2S system on elastin homeostasis and blood vessel degeneration have not yet been explored. Here we found that aged CSE knockout mice had severe aortic dilation and elastic degradation in abdominal aorta and were more sensitive to angiotensin II-induced aortic elastolysis and medial degeneration. Administration of NaHS would protect the mice from angiotensin II-induced inflammation, gelatinolytic activity, elastin fragmentation, and aortic dilation. In addition, human aortic aneurysm samples had higher inflammatory infiltration and lower expression of CSE. In cultured smooth muscle cells (SMCs), TNFα-induced MMP2/9 hyperactivity and elastolysis could be attenuated by exogenously applied NaHS or CSE overexpression while further deteriorated by complete knockout of CSE. It was further found that H2S inhibited MMP2 transcription by posttranslational modification of Sp1 via S-sulfhydration. H2S also directly suppressed MMP hyperactivity by S-sulfhydrating the cysteine switch motif. Taken together, this study revealed the involvement of CSE/H2S system in the pathogenesis of aortic elastolysis and medial degeneration by maintaining the inactive form of MMPs, suggesting that CSE/H2S system can be a target for the prevention of age-related medial degeneration and treatment of aortic aneurysm.

Dr. Fig. Progressive paralysis and syphilis. Progressive Paralyse und Syphilis Correspondenzblatt f. Schweizer Aerszte, 1907

The question of the relationship of progressive paralysis to syphilis has not yet been resolved. The author asks the question: is there a histological difference between the pathological picture of syphilis and progressive paralysis? It follows from his research that progressive paralysis is a disease sui generis. The histological picture of the cerebral cortex is typical. This is a special form of cerebral syphilis. Painful process - chronic inflammation - degeneration of blood vessels stands out especially sharply.

Histopathological, immunohistochemical and biochemical alterations in liver tissue after fungicide-mancozeb exposures in Wistar albino rats.

ABSTRACTPurpose:To evaluate the histopathological, immunohistochemical, and biochemical effects of liver changes after mancozeb administration.Methods:Rats were divided into groups–the control group (n=7) and the mancozeb group (n=7)–, given 500 mg/kg mancozeb dissolved in corn oil daily for four weeks by an orogastric tube. Caspase-3 and tumor necrosis factor-alpha (TNF-α) primary antibodies were used for immunohistochemical analysis.Results:Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values of the mancozeb group increased significantly than ones of the control group. Venous dilatation, inflammation, hepatocyte degeneration, TNF-α, and caspase-3 expression scores increased significantly in the mancozeb group. In the mancozeb group, intensive caspase-3 expression was observed in hepatocyte cells around the central vein in the center of the liver lobule, and there was an increase in TNF-α expression in the inflammatory cells around the enlarged central vein and Kupffer cells and apoptotic hepatocyte cells.Conclusions:Subacute mancozeb exposure in rats leads to elevated toxicity with impaired liver function, increased inflammation in tissue and increased apoptosis due to cellular damage in the liver, and decreased liver regeneration ability due to congestion and degeneration of blood vessels.

A radiação X não afeta a polpa dentária: um estudo morfológico em ratos

Introduction: Radiotherapy is one of the methods used as a treatment for ma-lignant tumors in the head and neck region and it can cause tissue damage in the irradiated areas. In head and neck radiotherapy, teeth are often included within the irradiation area and, consequently, the dental pulp; which receives high doses of radiation. Objective: To evaluate the effects of ionizing radiation on the pulp tissue of rat teeth. Methodology: A double-blind experimental as-say with 35 Albinus Wistar rats divided into seven groups was performed; one control group, three groups irradiated with 15 Gy, and three groups irradiated with 25 Gy. The irradiated groups were submitted to a single dose of radiation and sacrificed 24 hours, 7 days, and 22 days after irradiation, respectively. The samples were evaluated for the morphological presence of inflammatory infil-trate, edema, necrosis, fibrosis, and degeneration of blood vessels. Statistical analysis was performed using the Kruskal-Wallis and Dunn tests with p

Therapeutic Biomaterial Approaches to Alleviate Chronic Limb Threatening Ischemia.

Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non‐healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so‐called “no option patients” which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro‐angiogenic nucleic acid, protein, and stem cell‐based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.

Heavy Metal (Ni, Fe) Concentration in Water and Histopathological of Marine Fish in the Obi Island, Indonesia.

This study aims to determine the content of nickel (Ni) and iron (Fe) as well as histopathological analysis of marine fish in Obi Island waters as a bioindicator of pollution. Besides, water quality conditions were carried out in-situ and ex-situ observations. The parameters observed were temperature, brightness, salinity, pH, dissolved oxygen, nitrate, orthophosphate, ammonia, iron (Fe), and nickel (Ni). The results showed the temperature range between 26.48 ℃ to 27.99 ℃ below the quality standard or low temperature. The brightness of the relationship between 12 m and 13 m is under quality standards. The salinity range between 31.01 ppt to 32.13 ppt below the quality standard. The pH range is from 8.6 to 8.7 in high or alkaline conditions. Ammonia range between 0.4 mg / L to 0.7 mg / L exceeds the quality standard. The range of nitrate between 0.009 mg / L to 0.012 mg / L exceeds the quality standard. The range of phosphate between 0.016 mg / L to 0.019 mg / L exceeds the quality standard. The DO range between 3.68 mg / L to 3.77 mg / L lower than the quality standard. The metal range of 0.6 mg / L to 0.9 mg / L exceeds the quality standard. The range of Ni metal between 0.06 mg / L to 0.09 mg / L exceeds the quality standard. Histopathological analysis showed that the liver had a hemorrhage, degeneration of blood vessels, vacuolate degeneration, necrosis, or cell death. The muscles experience edema, degeneration of muscle fibers, atrophy of muscle bundles, vacuolar degeneration of muscle Bundles, hemorrhage, infiltration of lymphocytes, and necrosis. The intestine experience infiltration of lymphocytes, melanomacrophages, and necrosis. While P. tayenus fish ovaries showed necrosis structure oocytes. This research can be a reference for warning of heavy metal pollution in Obi Island waters, binding to the nature of heavy metals that can accumulate in fish tissue.Keywords: Water quality; Heavy Metal; Pollution; Histopathological; Obi Island.

Evaluation of serum electrolytes and their relation to glycemic status in patients with T2DM

Diabetes mellitus is a chronic disease that requires long-term medication to limit the development of its ruinous complications. The complications of diabetes are metabolic imbalance, blood vessel degeneration; effect on electrolyte concentration can offset the proportion of electrolytes. Since there is a direct association of serum electrolytes with diabetes mellitus (DM), the study was planned to investigate the electrolytes disturbance and their association with glycemic status in T2DM patients. This was cross-sectional hospital-based study; 60 participants who were diagnosed to have T2DM between the age group 30 to 60 years were recruited. Fasting glucose, glycated hemoglobin and serum electrolytes such as sodium, potassium, calcium and magnesium were estimated. Descriptive statistics was expressed as mean & SD. Pearson’s correlation analysis was performed to find the association and degree of relationship between serum electrolytes and glycemic status in T2DM. All the biochemical parameters were altered in T2DM patients. There was no significant association between FBS, HbA1c and serum electrolytes. The present study showed an alteration in electrolytes status, but there was no statistically significant association between fasting blood glucose, glycemic control and serum electrolytes consideration of the multifactorial origin of electrolyte imbalance, a cause-specific treatment is required to avoid any risk.

Chromobacterium violaceum Infection in a Horse

Chromobacterium violaceum is an opportunistic pathogen of mammals that produces characteristic violet pigment in bacterial culture. We report pneumonia and septicaemia caused by C. violaceum in a horse. Necropsy examination was performed on a 3-year-old Quarter Horse stallion with a history of recurrent episodes of pneumonia, fever, dyspnoea and sanguineous nasal discharge. The lungs were not collapsed, but they contained dark red foci mixed with white areas, and multiple nodules of firm consistency. Within the liver and kidney there were randomly distributed, multifocal, white pinpoint lesions (0.1-0.5cm diameter) in the capsule and extending into the parenchyma. The brain and spinal cord contained numerous petechiae. Microscopically, the lung had severe multifocal to coalescing infiltration of degenerate neutrophils within the alveoli and parenchyma associated with extensive areas of necrosis and haemorrhage. Rod-shaped bacteria were often present in the centre of the lesions. There was intense intra-alveolar exudation of fibrin and fibrinoid degeneration of blood vessels associated with thrombosis and ischaemic necrosis adjacent to areas of severe haemorrhage. Similar lesions were present in the liver and kidneys. A pure culture of C. violaceum was obtained from samples of the lung and liver. The identity of the organism was confirmed by amplifying and sequencing the 16S rRNA gene with subsequent analysis of sequence similarity.

Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats

A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague–Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin−/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin−/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin−/type IV+ acellular strands to levels observed in the control group. However, the lectin−/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage.

Brown spider venom toxins interact with cell surface and are endocytosed by rabbit endothelial cells

Bites from the Loxosceles genus (brown spiders) cause severe clinical symptoms, including dermonecrotic injury, hemorrhage, hemolysis, platelet aggregation and renal failure. Histological findings of dermonecrotic lesions in animals exposed to Loxosceles intermedia venom show numerous vascular alterations. Study of the hemorrhagic consequences of the venom in endothelial cells has demonstrated that the degeneration of blood vessels results not only from degradation of the extracellular matrix molecule or massive leukocyte infiltration, but also from a direct and primary activity of the venom on endothelial cells. Exposure of an endothelial cell line in vitro to L. intermedia venom induce morphological alterations, such as cell retraction and disadhesion to the extracellular matrix. The aim of the present study was to investigate the interaction between the venom toxins and the endothelial cell surface and their possible internalization, in order to illuminate the information about the deleterious effect triggered by venom. After treating endothelial cells with venom toxins, we observed that the venom interacts with cell surface. Venom treatment also can cause a reduction of cell surface glycoconjugates. When cells were permeabilized, it was possible to verify that some venom toxins were internalized by the endothelial cells. The venom internalization involves endocytic vesicles and the venom was detected in the lysosomes. However, no damage to lysosomal integrity was observed, suggesting that the cytotoxic effect evoked by L. intermedia venom on endothelial cells is not mediated by venom internalization.

Novel System for Degeneration of Blood Vessels by UV Irradiation and Subsequent Regeneration Using Chick Bone Marrow Cells

Recently, many results have been reported regarding the pluripotency of bone marrow cells (BMCs) with the aim of benefiting regenerative medicine for humans. Particularly, vessel formation by hematopoietic stem cells or vascular endothelial stem cells which were derived from bone marrow has received considerable interest, since the mechanism of vessel formation has been found to be involved in neoangiogenesis of serious diseases such as cancer. Most work on neoangiogenesis and regeneration has involved mammalian experimental systems, however the avian model is useful since the process of neoangiogenesis and regeneration of vessels can be observed with the whole embryo culture system. We have established a novel system using early chick embryos, where a portion of blood vessels are degenerated by UV irradiation, and vessel regeneration is then studied. Incubated embryos were partially covered with aluminum foil, from the embryonic body to the dorsal marginal vein, and irradiated with UV for 1 min. Donor BMCs were obtained from the femurs and tibias of chicks aged 10 days, fluorescently labeled with PKH26 and injected into the anterior vitelline vein of the recipients. In BMC-treated embryos the donor BMCs were observed around the UV-degenerated vessels, and regeneration of blood vessels occurred, in contrast to the untreated embryos. These results indicate that avian BMCs have the ability to participate in vessel regeneration, and the avian model used here may be a useful tool for studies of vessel neoangiogenesis and repair.

Transforming growth factor beta1 induction of vascular endothelial growth factor receptor 1: mechanism of pericyte-induced vascular survival in vivo.

Degeneration of vessels precedes and precipitates the devastating ischemia of many diseases, including retinopathy of prematurity and diabetic retinopathy. Ischemia then leads to proliferative retinopathy and blindness. Understanding the mechanisms of blood vessel degeneration is critical to prevention of these diseases. Vessel loss is associated with oxygen-induced suppression of vascular endothelial growth factor (VEGF) and with pericyte (vascular smooth muscle cell) dropout. The molecular mechanism of pericyte protection of the vasculature is unknown. We show that transforming growth factor beta1 (TGF-beta1)-expressing pericytes are specifically found on vessels resistant to oxygen-induced loss. TGF-beta1 potently induces VEGF receptor 1 (VEGFR-1) expression in endothelial cells and thereby prevents oxygen-induced vessel loss in vivo. Vessel survival is further stimulated with a VEGFR-1-specific ligand, placental growth factor 1. TGF-beta1 induction of VEGFR-1 in endothelial cells explains pericyte protection of vessels and the selective vulnerability of neonatal vessels to oxygen. These results implicate induction and activation of VEGFR-1 as critical targets to prevent vessel loss.

Ruptured internal carotid aneurysm resulting from neurofibromatosis: Treatment with intraluminal stent graft

Purpose: This report shows a method of treatment for life-threatening hemorrhage due to rupture of an aneurysm in the cervical internal carotid artery caused by neurofibromatosis. Methods: Ten days after delivery of healthy twins, a 28-year-old woman with known neurofibromatosis had sudden massive swelling in the left neck. After initial tracheostomy, angiography confirmed rupture of the mid cervical internal carotid artery as well as contribution to the resultant pseudoaneurysm from external carotid branches. Treatment began with coil embolization of the external carotid branches. The internal carotid lesion, a defect approximately 1 cm in length, was then closed through use of two stent grafts, each made from Palmaz stents and 3-mm polytetrafluorethylene grafts predilated to 6 mm. The neck hematoma was then evacuated surgically. Results: Completion angiography and computed tomographic scanning confirmed control of the hemorrhage. The patient survived neurologically intact with the exception of cranial nerve deficits caused by the hemorrhage. The tracheostomy tube was removed 3 weeks postoperatively. Follow-up computed tomographic scanning showed a gradual decrease in the size of the cervical soft tissue and no recurrent aneurysm. Conclusion: Neurofibromatosis is a rare cause of aneurysmal degeneration of blood vessels. Repair of a ruptured cervical internal carotid artery aneurysm, though feasible, is difficult with stent grafts; however, this is a better option than surgical intervention in inaccessible vessels. (J Vasc Surg 2000;32:824-8.)

A Case of Sneddon's Syndrome with Positive ANA and Anti‐cardiolipin Antibodies: Primary Anti‐phospholipid Syndrome?

A 22-year-old woman developed ulcerative lesions on the lower extremities which usually exacerbated during the summer. Histological analysis revealed a micro-thrombotic lesion in the deep dermis without inflammatory cell infiltration or fibrinoid degeneration of blood vessels. Magnetic resonance imaging revealed multiple cerebral infarctions. Abnormal laboratory findings included an elevated anti-cardiolipin antibody titer and positive speckled pattern ANA (x80), but without other manifestations or signs of SLE. FACS analysis revealed that the patient's serum reacted with ethanol fixed endothelial cells in addition to keratinocytes and peripheral blood neutrophils. This case was thought to be livedo reticularis and cerebral thrombotic lesions (Sneddon's syndrome) associated with atrophie blanche or livedo(id) vasculitis and may be one clinical subset of primary anti-phospholipid syndrome.

Commentary on the pathogenesis of Alzheimer's disease

A dysfunction of the blood brain barrier and degeneration of the blood vessels in the cortex of the brain seem to be fundamental to the pathogenesis of Alzheimer's disease. It is speculated that the degeneration of blood vessels is caused by some agents affecting the aged blood vessel.

Clinicopathological study of brain tumor radiotherapy.

A clinicopathological study was made on 45 autopsy cases of brain tumors treated with radiotherapy. Morphological changes after radiotherapy were classified into six categories : 1) tumor disappearance, 2) small residual tumor, 3) extensive tumor necrosis, 4) proliferative tumor growth, 5) mixed glioblastoma and fibrosarcoma, and 6) no remarkable change. When the tumors are primarily radiosensitive, tumor disappearance or small residual tumors might occur. Germinomas, some of lymphomas and medulloblastomas were representative of primary radiosensitivity. When the tumors are secondarily radiosensitive, or tumor cell necrosis is brought about by blood vessel degeneration caused by radiation, there might be extensive tumor necrosis. About one a half of the astrocytic tumors and glioblastomas were thought to have a combination of primary and secondary radiosensitivity. One case of oligodendroglioma, two cases of ependymoblastoma, two cases of malignant lymphoma and two cases of metastatic tumor also showed extensive tumor necrosis. The other half of the astrocytic tumors and glioblastomas showed proliferative tumor growth. They seemed to be less radiosensitive. Two cases of glioblastoma at the time of the operation changed into mixed glioblastoma and fibrosarcoma in the autopsy. No remarkable changes were observed in cases of teratoma and pineocytoma which were mature benign tumors with little blood vessel supply. No definite correlations were observed between the pathological changes and therapies such as the degree of resection, doses of irradiation and chemotherapy in astrocytic tumors and glioblastomas. There were, however, some tendencies for small residual tumors and extensive tumor necrosis to be brought about by extensive tumor resection, full courses of radiotherapy and intensive chemotherapy.

Haemorrhagic Septicaemia in the LampreyGeotria australisGray

The early upstream migrants of the lamprey, Geotria australis, were occasionally found dead in the field and suffered a very heavy mortality when held in the laboratory. The clinical signs exhibited by dying animals included the production of massive amounts of mucus, petechial haemorrhage of the skin and fins, and both haemorrhage and oedema around the eyes. Necropsy also revealed haemorrhage and oedema in various internal structures and in one case thrombosis and degeneration of blood vessels in the gill. The disease was attributed to infection with Aeromonas hydrophila and Pseudomonas fluorescens which were cultured from the organs of diseased animals. No signs of this disease occurred when the aquaria water was treated with chlortetracycline immediately after the introduction of each new batch of animals.

Acute haemorrhagic leuco-encephalitis.

SummaryTwenty‐three cases of acute hæmorrhagic leuco‐encephalitis have been described in the literature under this title. The clinical and pathological features of these cases have been reviewed.The condition is characterized by the sudden onset of speech disturbances, motor paralyses and urinary incontinence. Rapid progression to coma and death has occurred in all cases.The illness generally follows a respiratory infection after a short latent interval. It may also arise spontaneously, or follow the administration of certain drugs or chemical agents.At autopsy, the lesions in the cerebral hemispheres are almost entirely confined to the white matter. Elsewhere in the central nervous system, this predilection is not obvious. The lesions consist of areas of hæmorrhage, perivascular exudate, fibrinoid degeneration of blood vessels, especially of small veins, together with focal and perivascular areas of demyelination and microglial proliferation.Present evidence suggests that the condition may result from hypersensitivity—a cerebral Arthus phenomenon, and that this state may be induced by different allergens. Auto‐sensitization may be involved.The relationship of this condition to various types of “hæmorrhagic encephalitis”, and to acute disseminated encephalo‐myelitis is discussed. It would appear that what is known as acute hæmorrhagic leuco‐encephalitis in Australia, the United Kingdom and certain parts of Europe, is called acute necrotizing hæmorrhagic encephalopathy in the United States.The use of cerebral biopsy in an attempt to obtain a definitive diagnosis during life is advocated.The early administration of cortisone in the diagnosed case is suggested.