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Biomedical subjects

G E Sandusky

Publications and source records attributed to G E Sandusky.

51 records · Page 3Linked to original sources

Toxicology of indecainide hydrochloride after intravenous administration to rats and dogs.

Subchronic 1-month intravenous toxicity studies on indecainide, an antidysrhythmic agent, were conducted in rats and dogs. Rats (10 males, 10 females/group) were given daily intravenous (i.v.) doses of 0, 3, 6, or 9 mg/kg of indecainide for 1 month. 6 Of 10 males and 1 of 10 females given 9 mg/kg died during the test period. All but 2 animals from the other test groups survived. The high end of these daily doses was close to the acute single lethal dose, and the deaths were not unexpected. There were no treatment-related hematologic or serum chemistry changes in the surviving animals. No treatment-related histopathologic changes occurred in any of the animals. Groups of dogs (2 males, 2 females per group) were given daily i.v. injections of 0, 1.5, 3, or 4.5 mg/kg of indecainide for 1 month. 2 Of 4 dogs died after receiving multiple daily doses of 4.5 mg/kg. No treatment-related histopathologic changes were present in these animals. Dogs given doses of 1.5 or 3 mg/kg tolerated daily injections of the compound with no overt signs of toxicity and without hematologic, serum chemistry or histologic changes. Electrocardiograms revealed prolonged PR, QRS, and QT intervals in dogs from all three dose groups. Rats and dogs tolerated daily intravenous doses of indecainide as high as 6 and 3 mg/kg, respectively, with no evidence of any effect of treatment except the expected pharmacological action on the myocardium.

Animals↗

Immunohistochemical staining for S100 protein in the diagnosis of canine amelanotic melanoma.

Formalin-fixed, paraffin-embedded tissue samples of canine amelanotic melanomas and normal canine tissues were studied immunohistochemically for the presence of S100 protein. Use of the avidin-biotin complex procedure demonstrated variable amounts of S100 protein in the tumor cell cytoplasm and nuclei in 26 of 31 tumors. S100 protein was not observed in some other common canine skin tumors stained by the avidin-biotin complex technique. These were a mast cell tumor, fibrosarcoma, mammary gland adenocarcinoma, histiocytoma, transmissible venereal tumor, and a thyroid gland adenocarcinoma. Among normal tissues the presence of S100 protein was demonstrated in chondrocytes in the trachea, myoepithelial cells in the breast, melanocytes in the skin, some sweat glands and ducts in the skin, stellate cells in the pituitary, and interdigitating reticulum cells in the lymph node and in Peyer's patches. These results indicate that the avidin-biotin complex procedure for demonstrating S100 protein is a useful diagnostic tool in the diagnosis of canine amelanotic melanoma.

Animals↗

Application of the peroxidase-antiperoxidase procedure to the localization of pituitary hormones and calcitonin in various domestic animals and human beings.

Specific cell populations in the pituitary glands of the rat, cat, pig, and human being were positive for thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). When reacted with prediluted rabbit anti-human TSH, LH, and FSH, antisera were not positive for the demonstration of these hormones in the horse, cow, or dog. Immunocytochemical staining was obtained in the horse, cow, and dog by the use of a primary antiserum against a specific beta-subunit of bovine TSH. The immunocytochemical staining of TSH, LH, FSH, adrenocorticotropic hormone, growth hormone, prolactin, and calcitonin was examined by the peroxidase-antiperoxidase method, using standard commercially available kits. All species examined had a strong positive reaction in specific pituitary cell populations for adrenocorticotropic hormone, growth hormone, and prolactin. Sections of normal thyroid gland tissue had positive staining of C cells containing calcitonin at the dilution of 1:100 of the primary antibody in the rat, horse, cow, dog, cat, pig, and human being.

Adrenocorticotropic Hormone↗

Scanning electron microscopy of the canine atrioventricular bundle and moderator band.

The atrioventricular (AV) bundle and the moderator band in the canine heart were examined by scanning electron microscopy. The AV bundle and the moderator band both were comprised of large, cylindrically shaped cells. These cells were highly organized into bundles, with minimal lateral communication between bundles. There was extensive cell-to-cell communication between cells within a bundle. The end branching of individual cells was prominent, with some interbundle communication. These results are discussed in relationship to the electrophysiologic properties of the AV bundle and the conduction velocity.

Animals↗

Congestive cardiomyopathy in a dog associated with pregnancy.

A two-year-old, six-week postpartum female dog was presented with acute congestive heart failure for treatment. The patient collapsed and suddenly died. Postmortem examination revealed an enlarged, dilated heart with thin ventricular walls. Histologically, scattered multifocal areas of myocardial degeneration and necrosis with fibrosis were seen in the myocardium. This case of acute cardiomyopathy in a female dog six weeks postpartum is similar to the well-described, postpartum cardiomyopathy in man. The etiology of this case was not ascertained.

Animals↗

Histological and ultrastructural evaluation of cardiac lesions in idiopathic cardiomyopathy in dogs.

Described are pathological studies of eight dogs which died in congestive heart failure, with a clinical diagnosis of congestive cardiomyopathy. Examination revealed marked dilatation and enlargement of all four chambers of the heart. The ventricular walls were thin with small atrophic papillary muscles. Histological studies on the myocardium revealed scattered areas of myocardial necrosis, especially around the papillary muscles of the left ventricle and random scattered areas of fibrosis. Electron microscopic studies revealed fewer and disoriented myofibrils, myocytolysis, increased numbers of mitochondria with swelling and inclusions, increased glycogen granules and increased numbers of lysosomes, lipofuscin granules and lipid droplets. Mild Z-band abnormalities were found throughout the myofibers.

Animals↗

Congenital cardiac anomalies in calves.

Seven cases of congenital cardiac anomalies in calves were reviewed from the files of the Ohio Veterinary Diagnostic Laboratory. The collection of material occurred during a six-month period from June 1977 to January 1978. The major clinical signs were dyspnoea, failure to gain weight and sudden death in young animals. The cardiac defects included two patent ductus arteriosus, two anomalies of the coronary vessels, one persistent truncus arteriosus, one transposition of the aorta and pulmonary artery and one ventricular septal defect.

Animals↗

Morphologic variations and aging in the atrioventricular conduction system of large breed dogs.

The microscopic anatomy of the atrioventricular node, bundle of His, both bundle branches and surrounding fibrous cardiac skeleton was studied in 40 large breed dogs of various ages. In the AV conduction system of all dogs over five years of age there was an increase of fibrous connective tissue, an infiltration of adipose tissue, loss of conduction fibers and focal fibrosis extending from the central fibrous body. Fibrosis was seen in the summit of the interventricular septum posterior to the AV node in dogs of all ages. Chondroid metaplasia was consistently observed in the central fibrous body and the root of the aorta in large breed dogs, including ten Doberman Pinschers of all ages. This metaplasia varied from a few chondroblasts and chondrocytes to mature chondrocytes with mineralization. Bone formation was seen in eight dogs. These changes appeared in close approximation to the cardiac conduction system above the bundle of His. No degenerative changes were seen in the AV bundle. Approximately one-half of the large breed dogs five years of age and older had thickened medial and intima proliferation in the small coronary arterioles supplying the AV node. The results of this study suggest that the presence of cartilage and bone in the central fibrous body is a normal occurrence in large breed dogs at all ages.

Aging↗

Anomalous left coronary artery in a calf.

An anomalous left coronary artery was seen arising from an ostium in the pulmonary artery in a 4-month-old Hereford calf. Endocardial fibrosis was found in the left atrium and left ventricle. The mitral valve was dilated and thickened. A normal right coronary artery originated from the aorta.

Animals↗

Oak poisoning of cattle in Ohio.

Fourteen cases of oak poisoning were diagnosed at the Ohio Veterinary Diagnostic Laboratory, Reynoldsburg, Oh, in the fall of 1976. The poisoning was attributed to ingestion of oak shrubs, oak leaves, and acorns. Clinical signs included anorexia, rumen atony, hemorrhagic diarrhea, subcutaneous edema, and abnormal renal function. Perirenal edema and hemorrhage, ascites, hydrothorax, and hemorrhagic enteritis were frequently encountered pathologic changes. Histologic examination of the kidney revealed multifocal necrosis of the proximal convoluted tubules, which is a characteristic feature of this type of poisoning.

Animals↗

Small intestinal submucosa as a vascular graft: a review.

Continuing investigations of vascular graft materials suggest that unacceptable graft complications continue and that the ideal graft material has not yet been found. We have developed and tested a biologic vascular graft material, small intestine submucosa (SIS), in normal dogs. This material, when used as an autograft, allograft, or xenograft has demonstrated biocompatibility and high patency rates in aorta, carotid and femoral arteries, and superior vena cava locations. The grafts are completely endothelialized at 28 days post-implantation. At 90 days, the grafts are histologically similar to normal arteries and veins and contain a smooth muscle media and a dense fibrous connective tissue adventitia. Follow-up periods of up to 5 years found no evidence of infection, intimal hyperplasia, or aneurysmal dilation. One infection-challenge study suggested that SIS may be infection resistant, possibly because of early capillary penetration of the SIS (2 to 4 days after implantation) and delivery of body defenses to the local site. We conclude that SIS is a suitable blood interface material and is worthy of continued investigation. It may serve as a structural framework for the application of tissue engineering technologies in the development of the elusive ideal vascular graft material.

Animals↗

Inhibition of glycinamide ribonucleotide formyltransferase results in selective inhibition of macrophage cytokine secretion in vitro and in vivo efficacy in rat adjuvant arthritis.

OBJECTIVE: To determine the effects of a glycinamide ribonucleotide formyltransferase (GARFT) inhibitor on macrophage inflammatory processes and in vivo in rat adjuvant arthritis. METHODS: GARFT inhibitors, LY309886 (6S-2',5'-thienyl-5, 10-dideazatetrahydrofolic acid) and LY329201 (R)-N-[[5-[2-(2-amino-1,4,5,6,7,8-hexahydro-4-oxopyrido[2,3-d]pyrimidin-6-yl)ethyl]-2-thienyl]carbonyl]-L-glutamatic acid disodium salt, were investigated in vitro and ex vivo on primary murine peritoneal macrophages and in the RAW macrophage cell line for both purine depletion and inhibition of LPS induced monokine secretion. In vivo efficacy following GARFT inhibition was evaluated in modified rat adjuvant arthritis. RESULTS: LY309886 inhibited purine biosynthesis in the RAW cell line with an EC50 of 90 nM, an effect readily reversible with exogenous hypoxanthine. LY309886 and LY329201 also inhibited LPS induced TNF alpha and MIP1 alpha in these cells and in primary macrophages. A similar effect could be demonstrated ex vivo with mice dosed for two days with 3 mg/kg of LY329201. LY329201 as well as methotrexate demonstrated a dose dependent reduction in both paw and spleen weight and improved joint histology following 2 weeks of dosing in a rat adjuvant arthritis study. CONCLUSION: These results suggest that GARFT inhibitors should be tested in the treatment of rheumatoid arthritis by considering their mechanism of action, here successfully tested on activated macrophages.

Adenosine Triphosphate↗