CAUSE OF DEATH, PATHOLOGY, AND CHRONIC WASTING DISEASE STATUS OF WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) MORTALITIES IN WISCONSIN, USA.

White-tailed deer (WTD; Odocoileus virginianus) are a critical species for ecosystem function and wildlife management. As such, studies of cause-specific mortality among WTD have long been used to understand population dynamics. However, detailed pathological information is rarely documented for free-ranging WTD, especially in regions with a high prevalence of chronic wasting disease (CWD). This leaves a significant gap in understanding how CWD is associated with disease processes or comorbidities that may subsequently alter broader population dynamics. We investigated unknown mortalities among collared WTD in southwestern Wisconsin, USA, an area of high CWD prevalence. We tested for associations between CWD and other disease processes and used a network approach to test for co-occurring disease processes. Predation and infectious disease were leading suspected causes of death, with high prevalence of CWD (42.4%; of 245 evaluated) and pneumonia (51.2%; of 168 evaluated) in our sample. CWD prevalence increased with age, before decreasing among older individuals, with more older females than males in our sample. Females were more likely to be CWD positive, and although this was not statistically significant when accounting for age, females were significantly more likely to die with end-stage CWD than males and may consequently be an underrecognized source of CWD transmission. Presence of CWD was associated with emaciation, atrophy of marrow fat and hematopoietic cells, and ectoparasitism (lice and ticks). Occurrences of severe infectious disease processes clustered together (e.g., pneumonia, CWD), as compared to noninfectious or low-severity processes (e.g., sarcocystosis), although pneumonia cases were not fully explained by CWD status. With the prevalence of CWD increasing across North America, our results highlight the critical importance of understanding the potential role of CWD in favoring or maintaining disease processes of importance for deer population health and dynamics.

Splenic T-cell lymphoma in a North American River Otter (Lontra canadensis).

Background: Splenic lymphoma is commonly reported in domestic ferrets (Mustela putorious furo), but very rarely reported in wild Mustelidae species, including otters. One report described B-cell splenic lymphoma in an Asian small-clawed otter (Aonyx cinerea) that metastasized and was the primary reasoning for humane euthanasia (Stedman and Mills, 2014). Case Description: The current report describes a case of splenic T-cell lymphoma in a captive North American river otter (Lontra canadensis). The otter died several weeks after splenectomy and no evidence of metastasis was found on gross necropsy or histopathological evaluation. Conclusion: The splenectomy performed on this individual was presumptively curative for its splenic lymphoma. Extensive myocardial fibrosis was found, and suspected to have caused severe cardiac arrhythmia leading to acute death.

Recurrent Subcutaneous Teratoma in an Adult Red-crowned Amazon Parrot (Amazona viridigenalis).

An approximately 42-year-old, wild-caught, red-crowned Amazon parrot (Amazona viridigenalis) was evaluated for a subcutaneous mass to the right of the keel. Cytologic examination of a fine needle aspirate of the mass were suggestive of granulomatous inflammation. The mass was surgically excised, and the parrot was treated with oral nonsteroidal anti-inflammatory drugs. Histologically, the mass was diagnosed as a teratoma with stratified squamous epithelial and neuroectodermal components. Tumor cells extended to surgical margins. Two years later, the neoplasm recurred, with regrowth of only the neuroectodermal component. The neoplasm was again removed surgically, but it recurred again 14 months later, necessitating a third surgery. Histopathologic examination confirmed recurrence of the original neoplasm in both instances, with incomplete margins on both excisions.

Case-control study of risk factors for granulomatous meningoencephalomyelitis in dogs.

OBJECTIVE: To identify environmental and other variables associated with a diagnosis of granulomatous meningoencephalomyelitis (GME) in dogs. DESIGN: Case-control study. ANIMALS: 31 dogs that received a histologic diagnosis of GME (case dogs) from January 2003 to January 2014 and 91 age- and breed-matched dogs. PROCEDURES: Data were obtained from each dog's medical records regarding home address, signalment, body weight, body condition score (BCS), vaccination history, and date of diagnosis (case dogs) or visit (control dogs). Home address data were used to determine the human population density in each dog's geographic region. Seasonal distributions of GME diagnoses in the case group were evaluated for differences. Case and control dogs were compared with respect to the remaining variables. RESULTS: For case dogs, no significant difference was identified among seasons in the distribution of GME diagnoses; however, such diagnoses were more common in the spring than in other seasons. No significant differences were identified between case and control dogs in age, body weight, BCS, human population density, season of diagnosis or visit, or time of last vaccination. Although females appeared more likely than males to have a GME diagnosis, this association was not significant and did not change when BCS, time since last vaccination, or human population density was considered. CONCLUSIONS AND CLINICAL RELEVANCE: None of the evaluated factors, including investigated environmental triggers, were associated with a GME diagnosis in the dogs of this study. Additional research is warranted involving dogs from a broader geographic area.

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs.

BACKGROUND: Oxidative stress is associated with a diverse group of liver disorders across species. OBJECTIVES: Determine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8-isoprostanes/creatinine (F2 -IsoPs/Cr) concentrations, correlate with liver GSH. ANIMALS: Thirty-four client-owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs. METHODS: Prospective, observational cross-sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F2 -IsoPs/Cr was measured by gas chromatography/mass spectrometry. RESULTS: All dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F2 -IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F2 -IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Erythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls.

Diagnosis and management of inflammatory bowel disease in a harpy eagle (Harpia harpyja) with suspected fenbendazole toxicosis.

CASE DESCRIPTION A 14-year-old 4.1-kg (9.02-lb) male harpy eagle (Harpia harpyja) was evaluated because of vomiting, anorexia, lethargy, and weight loss (decrease of 0.35 kg [0.77 lb]) of 4 weeks' duration. The bird had previously been treated orally with fenbendazole after the initial onset of clinical signs. CLINICAL FINDINGS An initial CBC revealed marked heteropenia and anemia, but whole-body contrast-enhanced CT images and other diagnostic test findings were unremarkable. Clinical signs persisted, and additional diagnostic testing failed to reveal the cause. During celiotomy, a biopsy specimen of the duodenum was obtained for histologic examination, which revealed lymphoplasmacytic inflammation, consistent with inflammatory bowel disease (IBD). TREATMENT AND OUTCOME Prior to histopathologic diagnosis of IBD, barium sulfate administered via gavage resulted in a temporary improvement of clinical signs. Following diagnosis of IBD, corticosteroid administration was initiated in conjunction with antifungal prophylaxis. Cessation of vomiting and a return to normal appetite occurred within 3 days. Fifteen months after cessation of corticosteroid treatment, the eagle continued to do well. CLINICAL RELEVANCE To our knowledge, this was the first report of diagnosis and management of IBD in an avian species. For the eagle of the present report, results of several diagnostic tests increased clinical suspicion of IBD, but histologic examination of an intestinal biopsy specimen was required for definitive diagnosis. Although successful in this case, steroid administration in avian species must be carefully considered. Conclusive evidence of fenbendazole toxicosis was not obtained, although it was highly suspected in this bird.

Well-differentiated inflammatory liposarcoma with metastasis in a 6-y-old cat.

Liposarcomas are rare malignant tumors showing adipocytic differentiation. We report a well-differentiated liposarcoma in a 6-y-old, male neutered cat with a prominent inflammatory component and metastatic spread to the lungs. The patient was initially presented because of fever, lethargy, and a firm subcutaneous inguinal mass. A Tru-cut biopsy of the mass revealed a mixture of well-differentiated adipocytes and lymphoplasmacytic-histiocytic inflammation, interpreted as panniculitis. The mass was surgically excised but recurred 4 mo later. A second excisional biopsy yielded similar histologic findings. A third recurrence of the mass was associated with lung nodules. Histopathology of the recurring and metastatic masses confirmed the diagnosis of well-differentiated inflammatory liposarcoma with pulmonary metastases. The neoplasm had an intense inflammatory component, which obscured the underlying features of liposarcoma and made differentiation from steatitis difficult. This inflammatory variant of a well-differentiated liposarcoma should be considered as a differential in tumorous steatitis-like lesions.

Paraganglioma, pituitary adenoma, and osteosarcoma in a dog.

An 11-year-old neutered male Alaskan Malamute mixed-breed dog was presented with a complaint of polyuria/polydipsia (PU/PD), weight loss, tachypnea, regurgitation, and a previous history of nontreated osteosarcoma of the right distal radius, diagnosed 21 months prior. On physical examination, an abdominal mass was palpated. The abdominal mass was aspirated and cytologically diagnosed as a neuroendocrine tumor, suspected to be a pheochromocytoma. Laboratory examination revealed a mild anemia and thrombocytopenia, markedly elevated ATP and ALP activities, and moderate hypercalcemia. A low-dose dexamethasone suppression test and endogenous adrenocorticotropic hormone (ACTH) concentration were compatible with pituitary hyperadrenocorticism. On urinalysis, proteinuria was noted as well as a high urine metanephrine/creatinine ratio, consistent with a diagnosis of pheochromocytoma. The dog was treated with supportive care and euthanized 6 months later due to decreasing quality of life. On necropsy, an extra-adrenal pheochromocytoma (paraganglioma) was diagnosed in the caudal abdomen, and a pituitary adenoma and an osteosarcoma of the right distal radius were confirmed.

COMPUTED TOMOGRAPHIC ANATOMY AND CHARACTERISTICS OF RESPIRATORY ASPERGILLOSIS IN JUVENILE WHOOPING CRANES.

Respiratory diseases are a leading cause of morbidity and mortality in captivity reared, endangered whooping cranes (Grus americana). Objectives of this retrospective, case series, cross-sectional study were to describe computed tomography (CT) respiratory anatomy in a juvenile whooping crane without respiratory disease, compare CT characteristics with gross pathologic characteristics in a group of juvenile whooping cranes with respiratory aspergillosis, and test associations between the number of CT tracheal bends and bird sex and age. A total of 10 juvenile whooping cranes (one control, nine affected) were included. Seven affected cranes had CT characteristics of unilateral extrapulmonary bronchial occlusion or wall thickening, and seven cranes had luminal occlusion of the intrapulmonary primary or secondary bronchi. Air sac membrane thickening was observed in three cranes in the cranial and caudal thoracic air sacs, and air sac diverticulum opacification was observed in four cranes. Necropsy lesions consisted of severe, subacute to chronic, focally extensive granulomatous pathology of the trachea, primary bronchi, lungs, or air sacs. No false positive CT scan results were documented. Seven instances of false negative CT scan results occurred; six of these consisted of subtle, mild air sacculitis including membrane opacification or thickening, or the presence of small plaques found at necropsy. The number of CT tracheal bends was associated with bird age but not sex. Findings supported the use of CT as a diagnostic test for avian species with respiratory disease and tracheal coiling or elongated tracheae where endoscopic evaluation is impractical.

Diagnosis and surgical treatment of a malignant trichoepithelioma of the ear canal in a pet rabbit (Oryctolagus cuniculus).

CASE DESCRIPTION: A 10-year-old spayed female Holland Lop-mix pet rabbit (Oryctolagus cuniculus) was evaluated because of purulent-hemorrhagic discharge from the right ear canal and a suspected mass within that ear canal. CLINICAL FINDINGS: Results of contrast-enhanced CT, video otoscopy, and histologic examination of endoscopic tissue biopsy samples indicated severe otitis media and externa and a benign trichoepithelioma of the right ear canal. TREATMENT AND OUTCOME: Total ear canal ablation and lateral bulla osteotomy were performed. Histologic examination of a surgical biopsy sample of the mass indicated malignant trichoepithelioma. Tumor recurrence was detected 22 weeks after surgery. The rabbit was euthanized 33 weeks after surgery because of the large size of the recurrent tumor and declining quality of life. Necropsy findings indicated a malignant trichoepithelioma with local and lymphatic invasion into the right mandibular lymph node. CLINICAL RELEVANCE: This was the first report of the clinical diagnosis, surgical treatment, and outcome for a domestic rabbit with a diagnosis of a malignant trichoepithelioma of the ear canal and associated otitis media and externa. Neoplasia should be included as a differential diagnosis for pet rabbits with otitis externa and media. Although such tumors are typically benign, trichoepitheliomas in rabbits can be malignant. Computed tomography and histologic examination of tissue samples were useful diagnostic techniques, but histologic examination of an endoscopic biopsy sample did not allow identification of malignant characteristics of the trichoepithelioma.

Periocular extracranial cutaneous meningiomas in two dogs.

Cutaneous meningiomas are rare tumors in human beings and animals. Two canine cases of cutaneous meningiomas affecting the eyelid are described in the current study: the first from a 5-week-old female Springer Spaniel dog with an 8 cm in diameter congenital mass expanding the left upper eyelid and medial canthus; the second from a 10-year-old female spayed Maltese-Poodle mix dog with 3 firm subcutaneous nodules affecting the right upper eyelid. All masses were removed surgically. Histologically, tumors were composed of spindle-to-epithelioid cells arranged in small lobules forming solid concentric whorls. Neoplastic cells were positive for vimentin and S100 and negative for pancytokeratin, glial fibrillar acid protein, and neurofilament. Transmission electron microscopy revealed meningothelial cells with convoluted interdigitating processes, desmosomes, and hemidesmosomes, and moderate numbers of cytoplasmic microfilaments. None of the cases presented a primary neuroaxial meningioma. The first case presents clinicopathological features consistent with human type I (congenital) cutaneous meningioma. The second case is consistent with a type II (acquired ectopic) tumor, and both are hypothesized to arise from ectopic arachnoid cells displaced during development.

Clinical, histologic, and computed tomographic features of oral papillary squamous cell carcinoma in dogs: 9 cases (2008- 2011).

Medical records of dogs diagnosed with oral papillary squamous cell carcinoma between December 2008 and April 2011 were reviewed. Information abstracted included signalment, tumor location, tumor size, computed tomographic (CT) features, evidence of metastatic disease based on cytologic examination of lymph node aspirates and thoracic radiography, treatment, surgical margins, histologic features, and treatment outcome. Dogs included in the study were all sexually altered, predominantly large breed dogs with a mean age of 3.9-years (range, 0.5 to 9.0-years). The most common location was the rostral maxilla. Invasion of underlying bone and lymphadenopathy were evident on CT imaging in most dogs. No evidence of metastasis was found on mandibular lymph node cytology and thoracic radiography. Histologic analysis revealed similar morphologic findings for all surgically resected tumors. Surgical excision with 1-2 cm margins was complete in all cases, with a mean tumor-free interval of 12.1-months.

Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene.

N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague-Dawley rats were dosed (i.p.) with 230 µmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S(2)-S(3) segments) while DCVCS primarily affected the outer cortical proximal tubules (S(1)-S(2) segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37°C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity.

Bilateral ureteropelvic junction stenosis causing hydronephrosis and renal failure in an adult cat.

A 3.5-year-old male neutered cat was presented for investigation of renomegaly appreciated during a routine physical examination. Marked renomegaly due to bilateral hydronephrosis was detected and further testing identified International Renal Interest Society stage 2, non-hypertensive, non-proteinuric chronic kidney disease. Ten months later the cat was evaluated for acute lethargy; severe azotemia with oliguria was documented. Medical therapy failed to result in clinical improvement and the cat was euthanased. Necropsy revealed bilateral marked hydronephrosis secondary to a tortuous proximal ureter consistent with proximal ureteropelvic junction stenosis. This is the first report of this disorder leading to progressive renal failure in a cat.

Intramedullary epidermoid cyst in the thoracic spine of a dog.

A 5 yr old female spayed mastiff was evaluated for a 3-4 mo history of paraparesis and 3 days of acutely worse paraparesis and incontinence. On magnetic resonance imaging, a spinal cord lesion was present at the ninth thoracic vertebra. The lesion was hyperintense on T2-weighted images (T2-W), and a hyperintense rim was present on T1-weighted postcontrast images. Histologic examination showed a cystic mass lined by squamous epithelial cells. Histopathologic diagnosis was an intramedullary epidermoid spinal cyst. Epidermoid cyst should be a differential diagnosis in young dogs with a myelopathy and an intramedullary spinal cord lesion on magnetic resonance imaging examination.

Elodontoma in captive southern red-backed voles (Myodes gapperi).

Five southern red-backed voles (Myodes gapperi) of the first generation of a wild-caught breeding colony were presented with lesions at the maxillary incisors consistent with elodontoma. The affected animals had a history of chronic weight loss, were >16 months of age, and were siblings. Radiographs of the head showed multiglobular to irregularly outlined mineral opacity masses at the apices of the maxillary incisors. On necropsy, maxillary incisor teeth were not grossly visible, and a gingival ulceration was observed at the expected site of eruption. Microscopically, the apical region of the maxillary incisors was thickened or replaced by irregular dental tissue masses consistent with elodontoma. This is the first report to describe elodontoma in red-backed voles.

Pulmonary carcinoma in a great horned owl (Bubo virginianus).

Pulmonary carcinoma was diagnosed in an 18+-year-old captive female great horned owl (Bubo virginianus). The owl presented with a history of progressive weakness and sudden onset of frank blood in the droppings. On physical examination, the owl had multiple white to yellow plaques in the oral cavity, decreased air sac sounds on the right side, dyspnea (during manual restraint), and reduced pectoral musculature. Whole-body radiographs revealed obliteration of the right-sided air sacs, a soft tissue plaque/density in the left caudal thoracic air sac, soft tissue opacity over the coelomic organs, and increased medullary opacity in the distal right humerus. The owl died during anesthetic recovery, and the body was submitted for necropsy. Although the clinical signs, physical examination results, radiographic signs, and gross pathology supported a diagnosis of mycotic infection, such as aspergillosis, histopathology confirmed pulmonary carcinoma with metastases to the air sacs and humerus.

Combined ascorbate and glutathione deficiency leads to decreased cytochrome b5 expression and impaired reduction of sulfamethoxazole hydroxylamine.

Sulfonamide antimicrobials such as sulfamethoxazole (SMX) have been associated with drug hypersensitivity reactions, particularly in patients with AIDS. A reactive oxidative metabolite, sulfamethoxazole-nitroso (SMX-NO), forms drug-tissue adducts that elicit a T-cell response. Antioxidants such as ascorbic acid (AA) and glutathione (GSH) reduce SMX-NO to the less reactive hydroxylamine metabolite (SMX-HA), which is further reduced to the non-immunogenic parent compound by cytochrome b (5) (b5) and its reductase (b5R). We hypothesized that deficiencies in AA and GSH would enhance drug-tissue adduct formation and immunogenicity toward SMX-NO and that these antioxidant deficiencies might also impair the activity of the b5/b5R pathway. We tested these hypotheses in guinea pigs fed either a normal or AA-restricted diet, followed by buthionine sulfoximine treatment (250 mg/kg SC daily, or vehicle); and SMX-NO (1 mg/kg IP 4 days per week, or vehicle), for 2 weeks. Guinea pigs did not show any biochemical or histopathologic evidence of SMX-NO-related toxicity. Combined AA and GSH deficiency in this model did not significantly increase tissue-drug adduct formation, or splenocyte proliferation in response to SMX-NO. However, combined antioxidant deficiency was associated with decreased mRNA and protein expression of cytochrome b (5), as well as significant decreases in SMX-HA reduction in SMX-NO-treated pigs. These results suggest that SMX-HA detoxification may be down-regulated in combined AA and GSH deficiency. This mechanism could contribute to the higher risk of SMX hypersensitivity in patients with AIDS with antioxidant depletion.

Urogenital leiomyosarcoma in an alpaca.

A mass in the pelvic canal of a 4-year-old pregnant alpaca hembra diagnosed as leiomyosarcoma of the urogenital tract was confirmed by biopsy. Following a tube cystotomy, the alpaca was presented 33 d later, 2 d after the tube cystotomy had been dislodged. A dead cria was delivered by caesarean section.

Computed tomography-assisted management of a mandibular dentigerous cyst in a dog with a nasal carcinoma.

CASE DESCRIPTION: A 6-year-old neutered male Boston Terrier was examined to determine the cause of sneezing, bilateral nasal discharge, nasal congestion, lethargy, and coughing of 2 months' duration. CLINICAL FINDINGS: An undifferentiated nasal carcinoma was diagnosed. During computed tomography (CT) evaluation of response to tomotherapy radiation treatment, a mandibular dentigerous cyst, associated with an unerupted left mandibular first premolar, was monitored for expansion. TREATMENT AND OUTCOME: The dog had a profound response to radiation treatment, and the nasal carcinoma totally resolved. It was determined on the basis of CT that the rate of expansion of the dentigerous cyst was placing the dog at risk for mandibular fracture and loss of vitality to the surrounding teeth. The unerupted left mandibular first premolar and associated dentigerous cyst were surgically removed and submitted for histologic evaluation. CLINICAL RELEVANCE: Images obtained during sequential CT evaluations performed after radiation treatment of nasal carcinoma should be examined for evidence of the primary neoplasm as well as to detect unrelated lesions of the orofacial region that can compromise the quality of life. Findings of CT evaluations can be used to determine when and how to initiate treatment for dentigerous cysts in regard to the patient's response to radiation treatment.