Atrioventricular valvular angiectasis in Sprague-Dawley rats.

Subendothelial heart valve angiectasis has been reported in cows, dogs, pigs, rats, mice, and in human fetuses and newborns. We observed a high incidence (62 in 208 animals examined) of spontaneous angiectasis on the atrioventricular (AV) valves in 10- to 40-week-old Sprague-Dawley rats. The angiectasis was observed predominately on the septal cusp of the right AV valve and located near the AV ostium in 57 of 62 animals. Of the remaining 5 valvular angiectases, 2 were present on the parietal cusp of the right AV valve and 3 were on the left AV valve. The angiectases were single or multiple, ranging from 40 to 300 microm in diameter and were characterized by light microscopy as blood-filled dilatations lined by endothelium. Spontaneously occurring abnormalities in normal laboratory animals, such as the spontaneous valvular angiectasis reported here, need to be differentiated from drug-related lesions.

Hermaphroditism in a Sprague-Dawley rat.

A spontaneous case of unilateral true hermaphroditism was observed during the routine necropsy of a 9-week-old presumed female Sprague-Dawley rat on a repeat-dose toxicity study. There were no drug-related effects observed. True hermaphroditism is rare in rats, and despite the large numbers of rats examined annually, few cases are reported in the literature.

Transforming growth factor beta(2) (TGF beta(2)) produces effective pleurodesis in sheep with no systemic complications.

BACKGROUND: We have recently shown that transforming growth factor (TGF)beta(2) induces effective pleurodesis in rabbits. However, rabbits have a thin pleura while humans have a thick visceral pleura. The effect of intrapleural administration of TGF beta(2) in animals with a thick pleura and its associated systemic effects have not been investigated. This study was undertaken (1) to develop a new animal model for the study of pleurodesis using sheep which have a thick pleura resembling that of humans; (2) to study the efficacy of TGF beta(2) as a pleurodesis agent in the sheep model; and (3) to assess whether histological changes occur in extrapulmonary organs after intrapleural administration of TGF beta(2). METHODS: Twelve sheep were divided into four groups and were given a single intrapleural injection of TGF beta(2) in a concentration of 1.0 microg/kg, 0.5 microg/kg, 0.25 microg/kg or 0.125 microg/kg to the right pleural cavity via a chest tube. The left pleural cavity served as the control. Any pleural fluid that accumulated after the intrapleural TGF beta(2) injection was collected and analysed. The degree of pleurodesis was graded from 1 (no adhesions) to 8 (complete symphysis >50% of chest wall) at day 14 when the sheep were killed. Biopsy specimens were taken from the lungs and extrapulmonary organs. RESULTS: All sheep that received > or = 0.25 microg/kg TGF beta(2) developed excellent pleurodesis (score = 8) while those that received 0.125 microg/kg had a median score of 6. The pleurodesis score did not exceed 2 in the control (left) side of any sheep. Sheep receiving > or = 0.50 microg/kg TGF beta(2) developed large exudative pleural effusions while those receiving a lower dose did not. The production of effusions neither hindered nor was necessary for inducing pleurodesis. There were no significant fibrotic changes in any of the extrapulmonary organs. CONCLUSION: Intrapleural injection of 0.25-1.0 microg/kg TGF beta(2) produces excellent pleurodesis in a new sheep model with no evidence of extrapulmonary fibrosis.

Acute fulminant sarcocystosis in a captive-born rhesus macaque.

A captive-born juvenile female rhesus macaque (Macaca mulatta) was acquired from a commercial breeder and placed in quarantine. Within 8 days of arrival, the animal became anorexic, inactive, and dehydrated. Subsequently, generalized edema and facial ecchymoses developed, and despite supportive therapy, the animal became moribund and was euthanatized. Macroscopic examination showed diffuse stippling and streaking of the myocardium. Histopathologic examination revealed multifocal to coalescing myocardial edema, necrosis, lymphohistiocytic inflammation, and generalized endothelial infection with Sarcocystis sp. Immature and mature schizonts within endothelial cells were most prevalent in the heart. Fewer schizonts were present in the vasculature of other tissues, including skeletal muscle, smooth muscle, adipose tissue, brain, and retina. Mature tissue cysts within muscle fibers were not found in the myocardium but were occasionally seen in skeletal muscle. Analysis of polymerase-chain-reaction-amplified 18s ribosomal RNA gene sequences revealed 96% identity to published sequences of S. hirsuta, S. hominis, and S. fusiformis and 95% identity to S. cruzi and S. tenella. However, sequences did not show complete identity with any organism in the GenBank database. Sequence homology suggests that this is a newly described Sarcocystis sp. Results of antibody tests for simian retrovirus, simian T-lymphotropic virus 1, and simian immunodeficiency virus were negative, suggesting that viral immunosuppression was unlikely to have augmented the pathogenicity of sarcosporidial infection. Clinical and histopathologic findings in this case of fulminant sarcosporidiosis are similar to those described in Dalmeny disease in cattle, which is associated with ingestion of massive numbers of infective Sarcocystis oocysts.

Clinical and clinicopathological assessment of serial phlebotomy in the Sprague Dawley rat.

Two studies, designed to mimic a single-dose, cross-over pharmacokinetic protocol, were conducted to gain a better understanding of the rat's response to multiple, frequent blood sampling. Parameters evaluated included body weight, clinical signs of disease, hematologic and serum biochemical analytes, organ weights, and histopathologic features. Study groups consisted of either 6 or 8 male, viral antibody-free, Sprague Dawley rats. These included controls and blood-collection groups that represented withdrawal of 10, 15, 20, 30, and 40% of estimated total blood volume. Volume of blood collected per time point was based on the total volume to be withdrawn divided by the 13 samples that were collected over 24 h. This regimen was repeated 2 weeks later. Samples were taken for clinical pathologic evaluation on the days subsequent to blood collection for both studies as follows: 0, 1, 2, and 3 days; 7, 8, or 9 days; and either 13 or 14 days. In Study 1, samples were also taken on either days 15 or 16, and on 17 or 18 after the second blood collection. Approximately 2 weeks after the second blood collection regimen, animals were euthanized. Animals in one study were necropsied, and selected tissues were taken for histologic examination. Analysis of variance, based on changes from baseline, was used to assess group differences. Results indicate that the rate of body-weight gain for the bled groups was not significantly different from that of the controls. Group differences in multiple hematologic parameters were significant. Changes were typical of acute blood-loss anemia, with positive or negative trends relating to the volume of blood removed. In addition, these changes were characterized by recovery to control values within approximately 14 days. Few statistically significant group differences were detected in serum biochemical values, and those detected were not biologically relevant. Although organ weights of bled groups were similar to those of controls, minimal to mild splenic hematopoiesis was present in all bled groups, compared with controls. These data indicate that removal of up to 40% of a rat's total blood volume over a 24-h period, and repeated 2 weeks later, caused no gross ill effects.

Characterization of the effects of tebufelone on hepatic cytochromes P450 in the beagle dog.

Tebufelone (1-[3,5-bis(1,1-dimethylethyl)-4-hydroxy-phenyl]-hex-5-yne-1-one) is an investigational ditertiary butylphenol nonsteroidal anti-inflammatory drug. The purpose of the present study was to assess the effects of tebufelone on hepatocyte ultrastructure and hepatic cytochromes p450 (P450s) in the beagle dog after 2 weeks of oral administration at dose levels of 0, 5, 15, 50, and 100 mg/kg/day (N = 1/sex/dose level). Hepatic tissue was obtained at necropsy for histologic, ultrastructural, and biochemical evaluation. Hepatocellular hypertrophy was observed in only a single tebufelone-treated dog (50 mg/kg). Electron microscopic evaluation, however, revealed marked dose-dependent increases in smooth endoplasmic reticulum in all of the tebufelone treatment groups. Biochemical indicators suggested that tebufelone produced mixed effects on hepatic P450s. p-Nitroanisole O-demethylase and, to a greater extent, ethoxyresorufin O-deethylase activities were decreased with increasing tebufelone dose. The precise mechanism by which tebufelone decreased ethoxyresorufin O-deethylase activity in dogs in unknown, but it was not by competitive inhibition, P450 inactivation, or reduced CYP1A expression. Tebufelone treatment increased NADPH-dependent cytochrome c reductase, total P450, and indicators of CYP2B11 (chloramphenicol covalent binding and immunochemically determined 2B11) and CYP3A12 (erythromycin N-demethylase, triacetyloleandomycin spectral complex formation, testosterone 6 beta-hydroxylase, and immunochemically determined 3A12). The largest increase in the 2B11 and 3A12 markers occurred in the 50 or 100 mg/kg treatment groups. The greatest increase in CYP2B11 markers produced by tebufelone treatment ranged from 2- to 3-fold, whereas the increase in CYP3A12 markers ranged from 5- to 10-fold. The changes in hepatic ultrastructure and increases in CYP2B11 and CYP3A12 markers produced by tebufelone in dogs are similar to that reported for phenobarbital.

Characterization and therapy for experimental infection by Helicobacter mustelae in ferrets.

BACKGROUND: Numerous clinical trials evaluating the efficacy of various antimicrobial compounds against Helicobacter pylori infection have been performed in humans. A convenient animal model for Helicobacter infection would facilitate the evaluation of novel therapies. These experiments were performed to evaluate the use of ferrets as a model of Helicobacter infection. MATERIALS AND METHODS: Ferrets were infected experimentally with Helicobacter mustelae and subsequently treated with bismuth subsalicylate (BSS) triple therapy (BSS, metronidazole, and amoxicillin), or left untreated. The status of infection and serology was assessed during treatment and for 8 weeks posttreatment. Seven ferrets successfully treated with triple therapy were challenged with H. mustelae and monitored for infection for an additional 5 weeks. RESULTS: Infection of ferrets by H. mustelae was accompanied by gastritis and a specific antibody response. Treatment of H. mustelae-infected ferrets with BSS suppressed bacterial growth in four of nine animals but did not eradicate infection. Triple therapy eradicated infection in all nine ferrets with a reduction in gastric inflammation. No relapse of infection occurred up to 8 weeks posttherapy. Challenge with H. mustelae of ferrets successfully treated with triple therapy resulted in a 100% rate of reinfection. CONCLUSIONS: H. mustelae infection can be eliminated by triple therapy, but this does not result in protective immunity against reinfection by H. mustelae. This model, using a strain of Helicobacter indigenous to the host, may be useful for assessing therapeutic efficacy of novel therapies for the treatment of human infection by H. pylori.

Volume overload hypertrophy in a closed-chest model of mitral regurgitation.

Chronic volume overload hypertrophy as seen in mitral regurgitation in humans eventually may cause left ventricular dysfunction. Longitudinal study of the mechanisms leading to such dysfunction is difficult in humans and more easily performed in an animal model. In this study, we describe a canine model of volume overload hypertrophy produced by mitral regurgitation. An arterially placed grasping forceps was used to disrupt mitral chordae or leaflets; thus mitral regurgitation was produced without the need for thoracotomy. Eleven of 22 dogs had severe mitral regurgitation (regurgitant fraction greater than 0.50) and survived for greater than or equal to 3 mo (average 9.2 +/- 6 mo) after the production of mitral regurgitation. At 3 mo, end-diastolic volume increased from 48 +/- 9 to 85 +/- 19 ml, P less than 0.01. Left ventricular mass increased from 71 +/- 13 to 90 +/- 10 g, P less than 0.01. Left ventricular end-diastolic pressure increased from 9 +/- 3 to 19 +/- 6 mmHg, P less than 0.01. Cardiac output decreased from 2.3 +/- 0.61 to 1.80 +/- 0.64 l/min, P less than 0.05. The mass-to-volume ratio decreased from 1.44 +/- 0.17 to 1.09 +/- 0.13, P less than 0.01. We conclude that this closed-chest model of chronic mitral regurgitation produces significant eccentric cardiac hypertrophy. Despite a doubling of end-diastolic volume, there was a fall in cardiac output and a rise in left ventricular end-diastolic pressure, suggesting cardiac decompensation.

Metastasis of a well-differentiated liposarcoma in a dog and a note on nomenclature of fatty tumours.

A slow-growing mass in the left thigh of a 7-year-old spayed female fox terrier dog was originally diagnosed as an infiltrative lipoma by surgical biopsy. Necropsy findings one year later revealed multiple masses made up of well-differentiated adipocytes in the spleen, liver, lungs and a lymph node. The final histopathological diagnosis of these masses and, in retrospect, for the initial leg mass was well-differentiated liposarcoma. This case illustrates some of the confusion in current nomenclature of fatty tumours. Tumours made up of well-differentiated adipose cells which show no tendency toward invasion of surrounding tissue should be designated lipomas. We suggest that fatty tumours characterized by local tissue invasion and/or metastasis should be classified as liposarcomas. Liposarcomas may be further subdivided into well-differentiated and poorly-differentiated types.

Pigeon herpesvirus: inclusion body hepatitis in a free-ranging pigeon.

An adult male pigeon (Columba livia) was presented to the Wildlife Service at the University of Pennsylvania School of Veterinary Medicine for depression, cachexia, and diarrhea. Five days after the initial presentation, the bird died and was necropsied. Gross lesions included opaque air sacs and multiple 1-mm yellow-white foci on the epicardial surface of the heart. Histopathologic lesions included a pericarditis, epicarditis, and multifocal hepatic necrosis accompanied by eosinophilic inclusion bodies. Ultrastructural examination of the hepatic inclusions revealed viral particles consistent with a herpesvirus. The gross, light microscopic, and electron microscopic findings are consistent with pigeon herpesvirus infection.

Ureteral fibropapilloma in a dog.

A fibropapilloma was found to involve the left ureter in a 7-year-old castrated male Doberman Pinscher dog. Severe unilateral hydronephrosis and hydroureter were associated with the ureteral mass. Treatment consisted of unilateral nephrectomy and ureterectomy. This case represents an additional type of primary ureteral neoplasm found in the dog.

Calcifying epithelial odontogenic tumours in three cats and a dog.

Neoplasms histologically similar to calcifying epithelial odontogenic tumour (CEOT) of man are described in three cats and a dog. The diagnostic features of these neoplasms are their occurrence in the jaw and the histological appearance of cords of epithelial cells, amyloid spherules and foci of calcification. The histogenesis and behaviour of the tumour are discussed.

Choroidal melanomas in dogs.

The clinical and morphological features of intraocular melanocytic masses that originated in the choroid of five dogs were compared. Two of the cases had been reported previously and the authors have examined the pathological material. Histologically, the choroidal melanocytic tumors had several features in common and appeared to be entities distinct from melanocytic tumors of the anterior uveal tract or the epibulbar region. The tumors were well-delineated with tapered edges. They occurred in the posterior quadrant and two tumors had infiltrated the optic nerve. The tumors contained plump, strap-like polyhedral cells, with minimal nuclear anaplasia and no mitotic figures. The retina overlying the tumor mass was detached, and the retinal pigment epithelium in this area was swollen and contained intracytoplasmic autofluorescent lipopigment. In two cases, the basement membrane of the retinal epithelium was disrupted by the tumor and pigmented cells infiltrated into the retina, the subretinal space, and the posterior chamber. In one case, retinal detachment was complete and accompanied by intraocular hemorrhage. Melanocytic tumors of the canine choroid have features in common with choroidal nevus and melanocytoma in human eyes.

Craniopharyngioma in a dog.

Craniopharyngiomas are rare in dogs. A 3 cm suprasellar craniopharyngioma in a 13-month-old male mongrel dog is described. The mass consisted of multiple microcysts and solid areas with mesenchymal proliferation in areas of transition. Tumour cells were arranged in solid sheets or separated into islands by thick bands of collagen. Squamous differentiation of tumour cells with keratin formation and a focus of osseous metaplasia were present. Occasionally, tumour cells were arranged in rosettes. Cysts were lined by a single layer of cuboidal to low columnar epithelium and contained proteinaceous fluid with numerous cholesterol clefts. The diagnosis was based on age of occurrence, location and histological appearance.

Canine multilobular osteosarcoma of the skull with metastasis.

A 6-year-old crossbreed dog had recurring nodular masses on the dorsum of the head which were diagnosed as multilobular osteosarcoma. At necropsy, metastases were present throughout the lungs. Histological features of the masses included multiple islands of cartilage and bone separated by a dense fibrovascular stroma. These tumours are slow growing malignant neoplasms which may metastasize.

Feline basal cell tumors: a review of 124 cases.

Basal cell tumors from 124 cats of six breeds which represented 4.2% of feline neoplasms and 10.9% of feline cutaneous neoplasms are characterized. The mean age of cats affected was 9.6 years, and an increased risk was correlated positively with increasing age (rxy = +0.85). Males, females, and castrates were affected equally. Long-haired breeds were at higher risk (p less than 0.01) for development of basal cell tumors which had two major histologic types--solid and cystic. No site predilection was apparent.

Clinical and pathologic features of canine ocular melanomas.

Ocular melanomas in 40 dogs were reviewed and classified by site of origin and cytologic features. An apparent correlation existed between site, cytologic classification, and prognosis. Limbal melanomas and intraocular melanomas classified as spindle A or spindle B were less aggressive and had a more favorable prognosis than intraocular melanomas classified as a mixed-cell type or epithelioid.