Clinical ophthalmological diagnostic description of 10 healthy sugar gliders (Petaurus breviceps) and prevalence of ocular-related presentations in a larger hospital population.

OBJECTIVE: To provide reference values for ocular examination and diagnostics in ophthalmologically normal sugar gliders (Petaurus breviceps). To retrospectively determine the prevalence of ocular diseases in sugar gliders presenting to a single institution. ANIMALS: Ten client owned and 106 previously evaluated sugar gliders. PROCEDURE: A descriptive study evaluated sugar gliders presented to Colorado State University's Avian, Exotics, and Zoological Medicine Service (CSU-AEZ) from August-2019 to January-2020. A complete ophthalmic examination including Schirmer tear test II (STT II), phenol red threat test (PRTT), intraocular pressure (IOP) via rebound tonometry, fluorescein, and rose bengal stain was performed under anesthesia. Conjunctival aerobic culture swabs and cytology were collected prior to ophthalmic evaluation. A retrospective review of medical records of sugar gliders presented to CSU-AEZ from 2008 to 2018 for ocular disease was performed. RESULTS: Mean values ± standard deviation for selected diagnostics included the following: STT II: 2.2 ± 6.7 mm/min; PRTT: 0 ± 0 mm/15 s; IOP: 12 ± 2.6 mm Hg. Fluorescein and rose bengal staining highlighted corneal abrasions secondary to tear testing. The three most common conjunctival bacterial isolates cultured were Staphylococcus spp. (3/20, 15%), Coryneform spp. (3/20, 15%), and unidentified Gram-positive cocci (3/20, 15%). Retrospective analysis revealed ocular diseases to be the third most common abnormality resulting in sugar glider presentations (13/106, 12.3%). CONCLUSION: This descriptive study gives reference values for IOP, conjunctival microbiology, and cytology for sugar gliders. STT II and PRTT provide little clinical value in sugar gliders. The retrospective study revealed that ocular abnormalities, often secondary to dental disease, are a common reason for presentation.

Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling and progenitor cell characterization.

Canine hemangiosarcomas have been ascribed to an endothelial origin based on histologic appearance; however, recent findings suggest that these tumors may arise instead from hematopoietic progenitor cells. To clarify this ontogenetic dilemma, we used genome-wide expression profiling of primary hemangiosarcomas and identified three distinct tumor subtypes associated with angiogenesis (group 1), inflammation (group 2), and adipogenesis (group 3). Based on these findings, we hypothesized that a common progenitor may differentiate into the three tumor subtypes observed in our gene profiling experiment. To investigate this possibility, we cultured hemangiosarcoma cell lines under normal and sphere-forming culture conditions to enrich for tumor cell progenitors. Cells from sphere-forming cultures displayed a robust self-renewal capacity and exhibited genotypic, phenotypic, and functional properties consistent with each of the three molecular subtypes seen in primary tumors, including expression of endothelial progenitor cell (CD133 and CD34) and endothelial cell (CD105, CD146, and αvß3 integrin) markers, expression of early hematopoietic (CD133, CD117, and CD34) and myeloid (CD115 and CD14) differentiation markers in parallel with increased phagocytic capacity, and acquisition of adipogenic potential. Collectively, these results suggest that canine hemangiosarcomas arise from multipotent progenitors that differentiate into distinct subtypes. Improved understanding of the mechanisms that determine the molecular and phenotypic differentiation of tumor cells in vivo could change paradigms regarding the origin and progression of endothelial sarcomas.

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment.

Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into "IL-8 high" and "IL-8 low" groups. Genome-wide gene expression profiling showed that samples in the "IL-8 high" tumor group were enriched for genes associated with a "reactive microenvironment," including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA.

A dual-radioisotope hybrid whole-body micro-positron emission tomography/computed tomography system reveals functional heterogeneity and early local and systemic changes following targeted radiation to the murine caudal skeleton.

The purpose of this study was to develop a longitudinal non-invasive functional imaging method using a dual-radioisotope hybrid micro-positron emission tomography/computed tomography (PET/CT) scanner in order to assess both the skeletal metabolic heterogeneity and the effect of localized radiation that models therapeutic cancer treatment on marrow and bone metabolism. Skeletally mature BALB/c female mice were given clinically relevant local radiation (16 Gy) to the hind limbs on day 0. Micro-PET/CT acquisition was performed serially for the same mice on days -5 and +2 with FDG and days -4 and +3 with NaF. Serum levels of pro-inflammatory cytokines were measured. Significant differences (p < 0.0001) in marrow metabolism (measured by FDG) and bone metabolism (measured by NaF) were observed among bones before radiation, which demonstrates functional heterogeneity in the marrow and mineralized bone throughout the skeleton. Radiation significantly (p < 0.0001) decreased FDG uptake but increased NaF uptake (p = 0.0314) in both irradiated and non-irradiated bones at early time points. An increase in IL-6 was observed with a significant abscopal (distant) effect on marrow and bone metabolic function. Radiation significantly decreased circulating IGF-1 (p < 0.01). Non-invasive longitudinal imaging with dual-radioisotope micro-PET/CT is feasible to investigate simultaneous changes in marrow and bone metabolic function at local and distant skeletal sites in response to focused radiation injury. Distinct local and remote changes may be affected by several cytokines activated early after local radiation exposure. This approach has the potential for longer-term studies to clarify the effects of radiation on marrow and bone.

Hepatic insufficiency in two juvenile dogs with histoplasmosis.

A 9-month-old female intact toy poodle and a 1-year-old female intact Labrador retriever mix presented to separate teaching hospitals for chronic histories of malaise and clinicopathologic evidence of hepatic dysfunction. The signalment and clinical histories of these dogs prompted consideration of a congenital portosystemic shunt as a primary differential. However, microscopic evaluation of peritoneal effusion, pleural effusion, and peripheral blood samples from the dogs revealed round to ovoid yeast organisms morphologically most compatible with Histoplasma capsulatum. Additional testing confirmed histoplasmosis in each case. The poodle underwent a computed tomography (CT) study, which showed hepatomegaly with a spleno-gonadal shunt, pancreatic and gastric wall edema, and marked peritoneal effusion, findings compatible with portal hypertension and secondary acquired shunt formation. The dog was later humanely euthanized due to clinical deterioration, and on necropsy hepatic histoplasmosis was verified, with additional affected tissues comprising lungs and spleen. The Labrador Retriever mix responded clinically and clinicopathologically to antifungal therapy, though no abdominal imaging was performed to definitively exclude the possibility of a congenital portosystemic shunt. In retrospect, several features were more compatible with histoplasmosis than portosystemic shunt in these cases, including hyperbilirubinemia, effusion, and hepatomegaly. These findings serve as a reminder of the need to interpret serum biochemical findings in the context of the totality of the clinicopathologic data and imaging findings, as well as the diagnostic value of microscopy in the evaluation of hematologic and body cavity fluid samples.

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats.

Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity.

Accuracy of US-guided FNA of focal liver lesions in dogs: 140 cases (2005-2008).

Medical records from dogs having abdominal ultrasound (US) performed between March 2005 and October 2008 were reviewed for detection of focal liver lesions (FLL) with both cytologic and histologic sampling. Samples were classified as to either the presence or absence of major categories of pathologic processes, including malignant neoplasia, inflammation, hyperplasia/benign neoplasia, vacuolar change, extramedullary hematopoeisis, cholestasis, necrosis, and no microscopic abnormalities. Evaluation of selection bias was performed by review of the relative distribution of cytologic diagnoses for cases with histology compared with cases excluded from the comparison analysis because histology results were not available. Cytology had the highest sensitivity for vacuolar change (57.9%), followed by neoplasia (52.0%). Cytology had the highest positive predictive value (PPV) for neoplasia (86.7%) followed by vacuolar change (51.6%). Cytology had lower sensitivity and PPVs for inflammation, necrosis, and hyperplasia. The ability of cytology to characterize disease in canine FLL varies by pathologic process. Clinicians can have a high degree of confidence when a cytologic diagnosis of neoplasia is given; however, cytology is less reliable for excluding the potential for neoplasia. Cytology has a low sensitivity and PPV for inflammation and a limited diagnostic performance for the diagnosis of vacuolar change.

Premature parturition, edema, and ascites in an alpaca infected with Anaplasma phagocytophilum.

An 8-year-old alpaca was presented for fever, anorexia, edema, ascites, and premature parturition. She was determined to have Anaplasma phagocytophilum infection based on positive blood polymerase chain reaction (PCR) and positive acute and convalescent serum titers. Antibiotics and supportive therapies were administered and the alpaca made a complete recovery.

Parturition prématurée, œdème et ascite chez un alpaga infecté parAnaplasma phagocytophilum. Un alpaga femelle âgé de 8 ans a été présenté pour une fièvre, de l'anorexie, de l'œdème, de l'ascite et une parturition prématurée. On a déterminé qu'elle avait une infection à Anaplasma phagocytophilum en se fondant sur le résultat positif d'un test d'amplification en chaîne par la polymérase (PCR) effectué sur un échantillon sanguin et des titres sériques aigus et convalescents positifs. Des antibiotiques et des thérapies de soutien ont été administrés et l'alpaga s'est rétabli complètement.(Traduit par Isabelle Vallières).

Retrospective evaluation of fluid production at the time of thoracostomy tube removal following elective and emergency surgery in dogs (2010-2017): 185 cases.

OBJECTIVE: To report the rate of fluid production at the time of removal of thoracostomy tubes placed intraoperatively and to determine the association of this rate with specific patient factors, surgical factors, or clinical diagnosis. The secondary objective was to determine whether identification of pleural effusion within 2 weeks of thoracostomy tube removal was associated with the same variables. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: One hundred eighty-five client-owned dogs with thoracostomy tubes placed intraoperatively between January 2010 and March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thoracostomy tubes were removed at a median fluid production of 0.09 mL/kg/h (range, 0-7.0 m L/kg/h). Median fluid production at the time of thoracostomy tube removal was significantly higher in dogs with preoperative pleural effusion compared to dogs without preoperative pleural effusion (0.21 vs 0.05 mL/kg/h; P = 0.0001) and in dogs that had a median sternotomy compared to dogs that had a lateral thoracotomy (0.14 vs 0.09 mL/kg/h; P = 0.04). Of the 169 dogs available for follow-up, 12 (7.1%) had pleural effusion within 2 weeks of removal of the thoracostomy tube. Detection of pleural effusion during the follow-up period was significantly associated with the presence of preoperative pleural effusion (P = 0.0019) and the diagnosis (P = 0.01). A greater proportion of dogs with a lung lobe torsion (4/9, 44.4%) and idiopathic chylothorax (2/7, 28.5%) had pleural effusion within 2 weeks compared to other diagnoses. Reintervention was performed in 4.7% of dogs. CONCLUSIONS: Thoracostomy tubes were removed at pleural fluid production rates that frequently exceeded current veterinary guidelines. However, the fluid production rate at the time of thoracostomy tube removal was not associated with the detection of pleural effusion within 2 weeks of thoracostomy tube removal, and the overall need for reintervention following thoracostomy tube removal was low (4.7%).

Advances in the diagnosis of acute pancreatitis in dogs.

In the last 20 years, the diagnosis of pancreatitis has become more frequent as a result of improved diagnostic modalities such as abdominal ultrasound examination, advanced imaging, and immunoassays for the measurement of pancreatic lipase. Our aim is to provide a state-of-the-art overview of the clinical diagnosis of acute pancreatitis (AP) in dogs with a particular focus on pancreatic lipase assay validation and clinical performance, in addition to advanced imaging modalities. We also discuss the potential indications for cytology and histopathology in dogs with suspected AP.

Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma.

BACKGROUND: The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. METHODS: We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR. RESULTS: Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma). CONCLUSIONS: The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.

Effect of pancreatic tissue sampling on serum pancreatic enzyme levels in clinically healthy dogs.

Little is known about the potential consequences of pancreatic tissue sampling in dogs. The goal of the present study was to evaluate changes in serum trypsin-like immunoreactivity and canine-specific pancreatic lipase after pancreatic fine-needle aspiration and surgical biopsy in 27 clinically healthy dogs. Presurgical, ultrasound-guided aspiration of the pancreas was performed with the dogs under sedation. Subsequently, all the dogs underwent intraoperative pancreatic fine-needle aspiration and clamshell biopsy. After euthanasia, pancreata were sectioned for histopathologic evaluation. Serum pancreatic enzyme levels were measured at 3 time points: baseline, after ultrasound-guided aspiration, and after intraoperative aspiration and biopsy. No significant differences were detected among mean serum pancreatic lipase values at any point (P > 0.05). Serum trypsin-like immunoreactivity did not change from baseline (18.2 +/- 2.1 microg/dl; mean +/- standard error) after ultrasound-guided aspiration (13.6 +/- 2.2 microg/dl) but increased significantly after intraoperative sampling (44.8 +/- 1.9 microg/dl; P < 0.0005). After surgical biopsy, the 20 dogs that had both ultrasound-guided and intraoperative sampling had a higher mean (SE) serum trypsin-like immunoreactivity (44.8 +/- 1.9 microg/dl) than the 7 dogs that had only intraoperative samples taken (36.4 +/- 4.1 microg/dl; P < 0.05). All 27 pancreata were grossly normal before intraoperative sampling. Pancreatic sampling was associated with increased serum trypsin-like immunoreactivity and mild, peracute necrosis, inflammation, hemorrhage, and fibrin deposition. Tissue damage from sampling was not sufficient to cause an elevation in canine-specific pancreatic lipase in the time frame evaluated. Further studies are needed to determine longer-term effects of pancreatic sampling on enzyme levels and clinical outcome.

Nasal rhinosporidiosis in two dogs native to the upper Mississippi river valley region.

Two dogs, 4 and 7 years of age, were presented for evaluation and treatment of excessive sneezing. Physical examinations in both cases were within acceptable limits except for the presence of a single mass in the left nasal passage in the first case and left-sided nasal discharge in the second case. Rhinoscopy was used to visualize the nasal masses, and in both cases a single mass was surgically removed. Impression smears and histopathology submitted from each mass revealed lymphoplasmacytic and neutrophilic inflammation with spores typical of Rhinosporidium seeberi. These are the first reported cases of nasal rhinosporidiosis in two dogs native to the Upper Mississippi River Valley area with no travel history outside the region.

Diagnosis of canine renal lymphoma by cytology and flow cytometry of the urine.

Lymphoma is a common hematopoietic neoplasm of dogs. A definitive diagnosis typically requires the collection of samples via fine-needle aspirate or biopsy. A unique case of canine renal T-cell lymphoma diagnosed using urine sediment microscopy with flow cytometry and PCR for Antigen Receptor Rearrangement (PARR) is presented. A fresh urine sample was collected via a urinary catheter and immediately prepared for cytologic examination, flow cytometry, and PARR. The flow cytometric study revealed that 83% of the cells were large CD3+ CD8+ T cells, while PARR identified a clonally rearranged T-cell receptor gene, supporting the flow cytometry findings. Despite supportive care, the patient progressed to anuric renal failure and was humanely euthanized. A necropsy was performed, and tissues from the upper and lower urinary tracts were collected. Histologically, the right and left kidneys were infiltrated by a neoplastic round cell population effacing the cortex and medulla. Immunohistochemistry for the T- and B-cell antigens CD3 and CD20, respectively, revealed that the neoplastic population within the kidney demonstrated diffuse, strong, membranous to intracytoplasmic CD3 expression while lacking CD20 expression. These results confirmed the diagnosis of renal T-cell lymphoma. This is the first known report of canine lymphoma diagnosed using either urine flow cytometry or clonality testing. Therefore, in select cases, urine flow cytometry and/or PARR are feasible to perform on urine-derived cells as a quick and cost-effective means to aid in the diagnosis of urinary tract lymphoma.

Evaluation of serum cardiac troponin I concentration in dogs with renal failure.

OBJECTIVE: To determine whether dogs with renal failure have higher serum cardiac troponin I (cTnI) concentrations than healthy dogs. DESIGN: Case-control study. ANIMALS: 31 dogs with renal failure and 51 healthy dogs. PROCEDURES: Serum concentrations of creatinine and cardiac troponin I, urine specific gravity, and systolic arterial blood pressure were measured for all dogs. Dogs underwent a standardized physical examination, and any dog with evidence of cardiovascular disease or other nonrenal disease was excluded from final analyses. Dogs were considered to be in renal failure when the serum creatinine concentration was >or= 3.0 mg/dL, urine specific gravity was between 1.007 and 1.030, and renal failure had been clinically diagnosed. RESULTS: Dogs with renal failure had significantly higher serum cTnI concentrations (median, 0.35 ng/mL) than did healthy dogs (0.20 ng/mL). The renal failure group also had a significantly higher median systolic blood pressure (156 mm Hg) than did healthy dogs (138 mm Hg), although serum cTnI concentration was not correlated with systolic blood pressure in dogs with renal failure. There was no significant difference in age between dogs with renal failure and healthy dogs, but dogs with renal failure had significantly higher serum creatinine concentration and lower urine specific gravity. CONCLUSIONS AND CLINICAL RELEVANCE: Although dogs with renal failure did not have overt clinical signs of cardiac disease, they had high serum cTnI concentrations, which may have been associated with subclinical cardiovascular disease. The cause of the high serum cTnI concentration in these dogs requires additional investigation.

Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses.

In addition to its role as an energy storage depot, adipose tissue is now recognized as a complex endocrine organ. Adipose tissue releases a variety of factors, termed adipokines, that regulate energy metabolism, cardiovascular function, reproductive status, and immune function. Some of the better-studied adipokines include leptin, adiponectin, and components of the renin-angiotensin system such as angiotensinogen. The function of more recently discovered adipokines such as resistin are under intense scrutiny. Abnormal production or regulation of adipokines occurs in obese individuals and is implicated in the development of a variety of associated co-morbidities including metabolic syndrome, type 2 diabetes, atherosclerosis, heart disease, and cancer in people, although evaluation in domestic species is just beginning. Adipokines are now being examined as potential biomarkers for risk assessment for development of complications related to obesity. This article summarizes the function and regulation of some better-characterized adipokines. It also reviews the current information on the characterization of adipokines in some domestic species in which rates of obesity and obesity-related disorders are increasing, such as the dog, cat, and horse.

Sexual dimorphism of acute doxorubicin-induced nephrotoxicity in C57Bl/6 mice.

Doxorubicin (DOX) is a chemotherapeutic agent that has been reported to cause nephrotoxicity in rodent models and to a lesser degree in cancer patients. Female rodents have been shown to be protected against several features of DOX-induced nephrotoxicity. Nevertheless, the underlying mechanisms of this sexual dimorphism are not fully elucidated. Therefore, in the current study, we investigated the sex and time-dependent changes in pathological lesions as well as apoptotic and fibrotic markers in response to acute DOX-induced nephrotoxicity. We also determined the effect of acute DOX treatment on the renal expression of the sexually dimorphic enzyme, soluble epoxide hydrolase (sEH), since inhibition of sEH has been shown to protect against DOX-induced nephrotoxicity. Acute DOX-induced nephrotoxicity was induced by a single intra-peritoneal injection of 20 mg/kg DOX to male and female adult C57Bl/6 mice. The kidneys were isolated 1, 3 and 6 days after DOX administration. Histopathology assessment, gene expression of the apoptotic marker, BAX, protein expression of the fibrotic marker, transforming growth factor-ß (TGF-ß), and gene and protein expression of sEH were assessed. DOX administration caused more severe pathological lesions as well as higher induction of the apoptotic and fibrotic markers in kidneys of male than in female mice. Intriguingly, DOX inhibited sEH protein expression in kidneys of male mice sacrificed at 3 and 6 days following administration, suggesting that induction of sEH is not necessary for acute DOX-induced nephrotoxicity. However, DOX-induced inhibition of renal sEH in male mice may protect the kidney from further DOX-induced injury in a negative feedback mechanism. We also observed lower constitutive expressions of TGF-ß and sEH in the kidney of female mice which may contribute, at least in part, to sexual dimorphism of DOX-induced nephrotoxicity.

Utility of diagnostic tests for and medical treatment of pulmonary blastomycosis in dogs: 125 cases (1989-2006).

OBJECTIVE: To compare results of the most common diagnostic tests for pulmonary blastomycosis in dogs, identify factors associated with outcome, and determine response to various antifungal treatment protocols. DESIGN: Retrospective case series. ANIMALS: 125 dogs with pulmonary blastomycosis. PROCEDURES: Medical records were reviewed, and information was obtained regarding diagnostic methods, results of routine laboratory testing, and radiographic response to antifungal treatment. RESULTS: 79 dogs survived, 38 died, and 8 were euthanized. Transthoracic fine-needle aspiration and transtracheal lavage were the most common diagnostic methods. Results of an agar gel immunodiffusion test for antibodies against Blastomyces dermatitidis were negative in 12 of 24 (50%) dogs. Only 3 of 94 (3.2%) dogs in which cytologic or histologic examination or bacterial culture of pulmonary samples were performed had any evidence of concurrent bacterial infection. The half-time for radiographic resolution of pulmonary infiltrates did not vary significantly with antifungal treatment, and use of a loading dosage of itraconazole was not associated with significant improvements in outcome or time to disease resolution. Dogs that died had a higher number of band neutrophils at initial examination, compared with those that survived. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the agar gel immunodiffusion test should not be used as the sole diagnostic test for pulmonary blastomycosis in dogs, that concurrent bacterial pneumonia was uncommon in dogs with pulmonary blastomycosis, and that the rate with which pulmonary infiltrates resolved did not vary significantly among antifungal treatments.

Correlation between cytologic and histopathologic diagnoses of bone lesions in dogs: a study of the diagnostic accuracy of bone cytology.

BACKGROUND: The diagnostic value of cytology compared with histopathology varies by tissue, but there is little information regarding this comparison involving canine bone. OBJECTIVES: The objective of this retrospective study was to compare primary pathologic processes for cytology and histopathology of canine bone lesions. We adopted a proposed standardized format for reporting studies of diagnostic accuracy. METHODS: A computer search of canine medical records at the University of Minnesota Veterinary Medical Center from September 2002 through October 2006 identified 52 bone cytology samples that had incisional (IncB) and/or excisional (ExcB) biopsy performed. The primary pathologic process was determined by evaluation of original reports. Cytologic vs IncB and cytologic vs ExcB were compared pairwise for agreement. Agreement was compared for neoplastic and non-neoplastic processes using the combined IncB/ExcB data, which included all ExcB (n=21) and IncB when that was the only biopsy available (n=31). Combined data were used to determine the effect of cytology cellularity on the diagnostic correlation. RESULTS: The correlation in primary process between cytology and IncB was 71%, and for ExcB was 71%. For lesions with a cytologic diagnosis of neoplasia compared with the combined IncB/ExcB data set, cytology and histopathology agreed in 92% of cases, which was significantly greater (P<.0001, chi2) than the 27% for non-neoplastic processes. Cytology cellularity significantly affected rates of correlation (P=.026), with high, moderate, and poor cellularity samples having concordant primary processes in 88%, 77%, and 47% of cases, respectively. CONCLUSIONS: Cytologic diagnosis of neoplasia for samples collected from canine bone correlates better with histopathology than cytologic diagnosis of non-neoplastic proliferative processes or inflammation. Cytologic diagnoses from highly cellular samples are more likely to correlate with histopathology than those from less cellular samples.