Coccidioidomycosis presenting as a heart base mass in two dogs.

Two atypical cases of canine coccidioidomycosis presenting as heart base masses are described. An echocardiogram performed in one of the two dogs revealed a large mass at the base of the heart and a computed tomography scan showed that the mass compressed the bronchi, left atrium, aorta and pulmonary arteries. A firm, white or pale yellow mass was found at the base of the heart at necropsy examination in both cases. Microscopical examination of the masses revealed severe, chronic, locally extensive granulomatous or pyogranulomatous inflammation with intralesional spherules consistent with Coccidioides spp. The diagnosis was further confirmed by immunohistochemistry and in-situ hybridization. Coccidioides spp. have been reported to cause pericarditis in dogs, but this is the first description of coccidioidomycosis mimicking a heart-based tumour in dogs.

The lesions of hepatic fatty cirrhosis in sheep.

During a natural outbreak of hepatic fatty cirrhosis (HFC) in western Texas, 500 2-6-year-old Rambouillet ewe sheep were sequentially studied to determine the pattern of lesion development. All sheep developed lesions of HFC. Grossly, changes first began in the subcapsular hepatic parenchyma along the porta hepatis and spread peripherally until, in the final stages of the disease, approximately 80% of the liver was affected. Ascites, hydropericardium, and acquired hepatic vascular shunts were present in sheep with severe HFC. Light microscopic lesions initially appeared as accumulations of fine lipid droplets in the cytoplasm of periacinar hepatocytes but, with time, involved all hepatocytes of the lobule. The fat vacuoles in the periacinar hepatocytes coalesced to form larger vacuoles; and after rupture of adjacent fat-laden hepatocytes, fatty cysts appeared. Fibrosis began in the periacinar zone associated with the ruptured fatty cysts and continued until there was widespread bridging periacinar fibrosis. Islands of regenerating hepatocytes were frequently sequestered within the bands of fibrous tissue. Characteristically, the hepatic and posterior mediastinal lymph nodes, lung, and spleen contain ceroid. No lesions of hepatic encephalopathy were found in any animal. HFC is a progressive, chronic disease of sheep, and the morphology of the hepatic lesions is similar to lipotrope-deficient forms of nutritional cirrhosis. These findings are discussed in relation to similar nutritional deficiencies and toxicoses in sheep.

Inhibition of copper-associated erythrocyte ghost membrane lipid peroxidation by hepatic cytosolic low molecular weight proteins.

Male weanling Fischer rats were injected ip once daily with either 12.5 mg/kg body weight cupric chloride or 2 ml/kg body weight saline for up to 70 days. As the hepatic cytosolic copper increased in copper-treated rats, copper bound to proteins of different molecular weights; this was determined by gel filtration chromatography. Hepatic cytosolic copper from rats treated with cupric chloride for 14 days eluted in 3 peaks. These included a 150,000 + dalton peak, a 29,000 dalton peak and an 11,000-12,800 dalton peak. In addition to these peaks, hepatic cytosolic copper from rats treated with cupric chloride for greater than or equal to 28 days also eluted in a 4th, but shorter, 6,000-7,000 dalton peak. Hepatic cytosolic copper from saline-treated rats eluted only in a single 29,000 dalton peak. Experiments using an erythrocyte ghost membrane model of copper-associated lipid peroxidation demonstrated that incubation of membranes with protein-bound copper eluted in the 11,000-12,000 dalton peak was associated with less lipid peroxidation than incubation of membranes with cupric chloride or protein-bound copper eluted in the 150,000+ dalton peak. Experimental results suggest that the ability of copper to catalyze lipid peroxidation is significantly reduced by binding with hepatic cytosolic low molecular weight proteins but not by binding with hepatic cytosolic high molecular weight proteins.

The isolation and identification of steroidal sapogenins in Kleingrass.

Kleingrass (Panicum coloratum L) has been reported to cause hepatogenous photosensitization in sheep and goats in West Texas since 1973. The toxin in Kleingrass has been suspected of being a steroidal saponin as Kleingrass produced characteristic birefringent crystals similar to those produced by saponin-containing plants such as Agave lecheguilla and Tribulus terrestris. In this present study, steroidal saponis were isolated from Kleingrass and their sapogenins were identified as diosgenin and yamogenin by means of thin-layer chromatography and infrared spectrophotometric analysis.

Influence of variable content of dietary zinc on copper metabolism of weanling foals.

The influence of variable zinc content (29.1, 250, 1,000 and 2,000 mg/kg of dry weight) in a basic diet containing 7.7 mg of copper/kg on the ability of weanling foals to maintain normal copper balance was investigated. Serum copper and zinc concentrations were monitored, and terminal hepatic copper and zinc contents were measured in 4 weanling foals fed the basic diet containing 29.1 mg of zinc/kg and in 2 foals each fed the higher-zinc diets. Foals fed the lower-zinc diets (29.1 and 250 mg/kg) maintained normal serum copper and zinc concentrations for 14 to 15 weeks, whereas those fed the 2 higher-zinc diets became hypocupremic within 5 to 6 weeks and were lame within 6 weeks, owing to cartilaginous disease characteristic of osteochondritis dissecans. Serum zinc concentration in the foals fed the 2 higher-zinc diets increased to greater than 2 micrograms/ml within 2 weeks. Foals fed the high-zinc diets became lame after serum copper concentration had remained at 0.3 micrograms/ml for greater than 1 week. Serum copper concentration in these arthritic foals was less than or equal to 0.2 micrograms/ml at the end of the study. In lame foals, fractures of the cartilage of the articular and growth physes occurred through the zone of hypertrophic cells, and varied from bilateral to unilateral and from small to large. Free masses and flaps of cartilage attached to one side were numerous.

The developmental toxicity of an isolate from the plant Solanum dimidiatum (potato-weed) in Syrian golden hamsters.

The developmental toxicity of an ethanol extract from Solanum dimidiatum was investigated in date-bred Syrian golden hamsters. Neural tube defects were seen in three Syrian golden hamster fetuses, from one litter out of 12, at a maternal dose of 1.52 mg of plant isolate per g of body weight. Other malformations observed were syndactyly in a single fetus, from one litter out of ten, in the 0.45 mg/g dose group and gastroschisis in a single fetus, from one litter out of nine, in the 1.01 mg/g dose group. These findings suggest minimal developmental toxicity for this plant isolate.

Kleingrass-associated hepatotoxicosis in horses.

Chronic hepatic disease was diagnosed in 6 horses with history of anorexia and weight loss. These horses consistently had abnormally high serum gamma-glutamyltransferase activities, total and direct bilirubin and blood ammonia values, and sulfobromophthalein clearance times, whereas serum iditol dehydrogenase, aspartate transaminase, and alkaline phosphatase activities were variable. In the 6 horses, histologic examination of the liver revealed lesions of chronic hepatitis with varying degrees of fibrosis. All 6 horses had ingested kleingrass (Panicum coloratum) for variable periods. Three healthy horses fed kleingrass hay for 90 days developed hepatic lesions and increases in serum gamma-glutamyltransferase activities similar to those in the 6 horses with chronic hepatitis. Characteristic hepatic lesions in both groups of horses included bridging hepatic fibrosis, cholangitis, and hepatocellular regeneration.

Experimentally induced cartilaginous fractures (osteochondritis dissecans) in foals fed low-copper diets.

Four Thoroughbred foals were weaned from their dams when they were 1 day old and were fed a liquid milk-replacer diet containing approximately 1.7 micrograms of copper/g from plastic buckets for 4 to 7 months. They were kept in stalls with fiberglass walls and asphalt floors covered with rubber pads. Serum copper and zinc concentrations were determined 3 times/week by atomic absorption spectrophotometry, and liver copper and zinc concentrations were determined similarly after acid digestion of tissues taken at necropsy. The amount of soluble collagen in articular cartilage and aortic tissue was determined after necropsy. Clinical signs of illness, particularly evidence of lameness, were monitored daily. The foals were weighed weekly, and growth rate was monitored by measurement of height at the withers. Packed cell volumes and total and differential WBC counts were measured each time blood was drawn for copper and zinc concentration determinations. The foals were examined by necropsy at the end of the experiment, and the tissues were examined histologically. The foals developed intermittent, but nondebilitating, diarrhea with the onset of low serum copper concentrations. Considering the totally liquid diet, the foals grew well. Serum copper concentrations decreased to less than 0.1 micrograms/ml in 13 to 16 weeks. Lameness was evident 2 to 6 weeks after serum copper concentrations decreased to their lowest value (less than 0.1 micrograms/ml). All foals developed stilted gaits and ultimately walked on the front of their hooves. Major hematologic changes and alterations of hair color were not evident. Soluble collagen of articular cartilage and aortic tissue increased from 340 to 600% greater than that of control foals.(ABSTRACT TRUNCATED AT 250 WORDS)

Kleingrass (Panicum coloratum L.) poisoning in sheep.

Twenty-four lambs grazing pastures of Panicum coloratum developed photosensitization secondary to hepatic dysfunction. Lesions were necrosis of scattered hepatocytes, obstruction of small bile ducts and bile canaliculi by small aggregates of birefringent crystals, and accumulation of birefringent crystals in phagocytes within sinusoids. The number of crystals in livers of affected sheep varied, depending on the amount of time of exposure to toxic plants and severity of hepatic abnormalities. Crystals in the liver were soluble in acidified ethyl alcohol, acetic acid, pyridine, chloral hydrate, and methanol, but not in xylene, petroleum ether, diethyl ether, acetone, water, or cold ethyl alcohol. Crystals were not stained by oil red O. There was necrosis of epithelial cells in renal distal convoluted tubules, papillary muscles of the heart, and the adrenal cortex. Lesions of Panicum coloratum-associated disease are similar to those associated with photosensitization induced by Tribulus terrestris, Agave lecheguilla, and Nolina texana.

The role of lysosomes in the pathogenesis of copper-induced hepatotoxicity: morphological studies.

Copper-induced hepatotoxicity was evaluated in beige and conventional mice which were injected intraperitoneally with aqueous copper chloride (8 mg per kg body weight per day). Hepatic lesions developed more quickly and were more severe in beige mice and consisted of karyomegaly, progressive accumulation of lipofuscin within hepatocytes and Kupffer cells, acute necrosis of random hepatocytes, and aggregation of leukocytes within the sinusoids. In both groups of mice the hepatic lesion had a centrilobular distribution and closely paralleled the appearance and distribution of copper within hepatocytes. Overall, beige mice had more severe copper-mediated hepatotoxicity, suggesting that normal lysosomes have protective effects for hepatocytes by sequestering copper from other cytoplasmic constituents.

Considerations of copper metabolism in osteochondrosis of suckling foals.

Of 8 Thoroughbred foals in which osteochondrosis developed before weaning, 7 had serum copper and ceruloplasmin concentrations below normal. Three foals on one farm had serum zinc content high enough to suggest zinc toxicosis, and the liver of each foal contained abnormally high content of zinc. Four foals from the second farm had extremely low serum copper content, but normal serum zinc content. Evidence of environmental exposure to excess zinc was not found on either farm. The lesions in the zones of endochondral ossification of the afflicted foals were similar in many respects to those found in other species of animals with molybdenum-induced copper deficiency and with inhibition of the function of copper-dependent lysyl oxidase by beta-aminopropionitrile, a toxic component of Lathyrus odoratus known to cause osteolathyrism.

Stage A prostatic carcinoma and repeat transurethral resection: a reappraisal 5 years later.

The treatment of patients with stage A prostatic carcinoma demands precise pathological review. In an attempt to evaluate these patients thoroughly earlier reports from our institution recommended repeat transurethral biopsy. Recent studies have reaffirmed the benign nature of stage A1 disease. To examine the efficacy of this procedure a referee pathologist reviewed 8 years of experience with patients with stage A prostatic carcinoma from our institution. Clinical followup was more than 5 years in most cases. Of the 40 patients who underwent repeat transurethral biopsy the tumor in 38 remained stage A1 pathologically. While 1 patient died of the tumor the the remainder are without clinical disease. This low incidence of upstaging does not support the routine use of repeat resections.

The role of lysosomes in the pathogenesis of copper-induced hepatotoxicity. II. Intracellular distribution of copper in hepatocytes.

The effects of altered lysosomal function on the pathogenesis of copper-induced hepatotoxicity were studied in C57B1/6 bg/bg (beige) and C57B1/6 bg/+ (conventional) mice. Copper loading was accomplished through daily ip injections of aqueous copper chloride at a dosage rate of 8 mg/kg body weight for 1, 2, and 4 weeks. The subcellular distribution of copper in copper-treated beige mice was significantly different than that in conventional mice. Beige mice had consistently higher levels of copper in the nuclear and cytosolic fractions with lower levels in the heavy and light mitochondrial fractions. The copper levels were lowest in the microsomal fractions of both groups of copper-treated mice and remained similar throughout the 4-week experiment. Levels of total hepatic copper were similar in both groups of mice receiving parenteral copper except at Day 14, when beige mice had higher levels.

Toxicity of Cassia occidentalis in the horse.

Three Shetland ponies were given a single oral dose of ground Cassia occidentalis seeds in aqueous suspension. The clinical signs observed resembled those seen in naturally occurring and experimental cases in cattle. The syndrome was characterized by an afebrile course, incoordination, recumbency and death. Elevations of blood alkaline phosphatase, CPK, LDH, and SGOT were observed. Although muscle lesions were not seen grossly, microscopic lesions included segmental necrosis of skeletal muscle fibers. The findings were regarded as sufficiently characteristic of C. occidentalis poisoning to be useful in differential diagnosis. When Cassia poisoning is suspected, access of the affected horses to the plant should be demonstrated.

Photosenitization of sheep on kleingrass pasture.

The clinical appearance and serum gamma-glutamyl transpeptidase (GGT) activity were studied in 5 groups of sheep (12 per group) on kleingrass (Panicum coloratum) pasture plots and in 1 group of sheep (10 animals) on native buffalograss (Buchloë dactyloides) pasture. Eleven sheep (at least 1 from each group on kleingrass pasture plots) had elevated serum GGT activity. Seven of 11 sheep with elevated serum GGT activity developed signs of photosensitization. None of the sheep on buffalograss pasture developed signs of photosensitization or elevated GGT activity. The pathologic findings were similar in the sheep that had signs of photosensitization. Grossly, there was icterus and subcutaneous edema. The livers had tapeworms (Thysanosoma actinioides) in the bile ducts, were slightly swollen, and varied in color from yellow to ochre in severe cases of biliary system derangements. Microscopically, there was cholangitis.