Melbourne Veterinary School - Research Publications

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    Bayesian Validation of the Indirect Immunofluorescence Assay and Its Superiority to the Enzyme-Linked Immunosorbent Assay and the Complement Fixation Test for Detecting Antibodies against Coxiella burnetii in Goat Serum
    Muleme, M ; Stenos, J ; Vincent, G ; Campbell, A ; Graves, S ; Warner, S ; Devlin, JM ; Nguyen, C ; Stevenson, MA ; Wilks, CR ; Firestone, SM ; Pasetti, MF (AMER SOC MICROBIOLOGY, 2016-06)
    Although many studies have reported the indirect immunofluorescence assay (IFA) to be more sensitive in detection of antibodies to Coxiella burnetii than the complement fixation test (CFT), the diagnostic sensitivity (DSe) and diagnostic specificity (DSp) of the assay have not been previously established for use in ruminants. This study aimed to validate the IFA by describing the optimization, selection of cutoff titers, repeatability, and reliability as well as the DSe and DSp of the assay. Bayesian latent class analysis was used to estimate diagnostic specifications in comparison with the CFT and the enzyme-linked immunosorbent assay (ELISA). The optimal cutoff dilution for screening for IgG and IgM antibodies in goat serum using the IFA was estimated to be 1:160. The IFA had good repeatability (>96.9% for IgG, >78.0% for IgM), and there was almost perfect agreement (Cohen's kappa > 0.80 for IgG) between the readings reported by two technicians for samples tested for IgG antibodies. The IFA had a higher DSe (94.8%; 95% confidence interval [CI], 80.3, 99.6) for the detection of IgG antibodies against C. burnetii than the ELISA (70.1%; 95% CI, 52.7, 91.0) and the CFT (29.8%; 95% CI, 17.0, 44.8). All three tests were highly specific for goat IgG antibodies. The IFA also had a higher DSe (88.8%; 95% CI, 58.2, 99.5) for detection of IgM antibodies than the ELISA (71.7%; 95% CI, 46.3, 92.8). These results underscore the better suitability of the IFA than of the CFT and ELISA for detection of IgG and IgM antibodies in goat serum and possibly in serum from other ruminants.
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    GADOXETATE DISODIUM (GD-EOB-DTPA) CONTRAST ENHANCED MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF HEPATOCELLULAR CARCINOMA IN DOGS
    Constant, C ; Hecht, S ; Craig, LE ; Lux, CN ; Cannon, CM ; Conklin, GA (WILEY, 2016-11)
    Hepatocellular carcinoma is the most common primary hepatic tumor in dogs and is amenable to surgical resection in many cases. Unfortunately, overlap of sonographic findings between benign and malignant hepatic lesions typically requires more invasive diagnostic tests to be performed (e.g., biopsy for histopathology). The availability of a noninvasive diagnostic test to identify hepatocellular carcinoma would be beneficial. The use of a liver-specific magnetic resonance imaging (MRI) contrast agent such as gadoxetate disodium (Gd-EOB-DTPA; Eovist® or Primovist®) has improved lesion detection in human patients. In this descriptive study, gadoxetate disodium contrast-enhanced MRI characteristics in dogs were evaluated in seven dogs (total of eight lesions). The imaging characteristics were variable with the exception of all lesions being hypointense to surrounding normal hepatic parenchyma on 3D T1-weighted gradient recalled echo images at all postcontrast time points. All lesions displayed signal intensity ratios less than 1, consistent with retained but impaired hepatocyte function. Hepatic lesions not identified on previous imaging were found in 3/7 patients which may affect surgical planning. In two patients, several hepatic nodules were identified during surgery which had not been visualized on MRI and were found to be benign on histopathology. This descriptive study reports the MRI characteristics of hepatocellular carcinoma in dogs using the liver-specific contrast agent gadoxetate disodium.
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    The cardiopulmonary effects and quality of anesthesia after induction with alfaxalone in 2-hydroxypropyl-β-cyclodextrin in dogs and cats: a systematic review
    Chiu, KW ; Robson, S ; Devi, JL ; Woodward, A ; Whittem, T (WILEY, 2016-12)
    To systematically review the quality of evidence comparing the cardiopulmonary effects and quality of anesthesia after induction with alfaxalone vs. other anesthetic agents in dogs and cats. Studies published from 2001 until 20th May 2013 were identified with the terms 'alfaxan' OR 'alfaxalone' OR 'alphaxalone' in electronic databases: Discovery, PubMed, ScienceDirect, and Wiley Interscience. The study design and risk of bias of all included studies were assessed. Twenty-two studies from 408 (22 of 408, 5.39%) satisfied the inclusion criteria. Fourteen studies (14 of 22, 64%) focused on dogs and nine (9 of 22, 40%) on cats. One study had both dogs and cats as subjects. (Hunt et al., 2013) Twelve studies were rated an LOE1, and six of these as ROB1. One, seven, and two studies were rated as LOE2, LOE3, and LOE5, respectively. In dogs, strong evidence shows that induction quality with either alfaxalone-HPCD or propofol is smooth. Moderate evidence supports this finding in cats. In dogs, moderate evidence shows that there is no significant change in heart rate after induction with either alfaxalone-HPCD or propofol. In cats, moderate evidence shows no significant difference in postinduction respiratory rate and heart rate between alfaxalone-HPCD and propofol induction. Strong evidence shows dogs and cats have smooth recoveries after induction using either alfaxalone-HPCD or propofol, before reaching sternal recumbency.
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    Utstein-style guidelines on uniform reporting of in-hospital cardiopulmonary resuscitation in dogs and cats. A RECOVER statement
    Boller, M ; Fletcher, DJ ; Brainard, BM ; Haskins, S ; Hopper, K ; Nadkarni, VM ; Morley, PT ; McMichael, M ; Nishimura, R ; Robben, JH ; Rozanski, E ; Rudloff, E ; Rush, J ; Shih, A ; Smarick, S ; Tello, LH (WILEY-BLACKWELL, 2016)
    OBJECTIVE: To provide recommendations for reviewing and reporting clinical in-hospital cardiopulmonary resuscitation (CPR) events in dogs and cats and to establish nonambiguous operational definitions for CPR terminology. DESIGN: Consensus guidelines. SETTING: International, academia, referral practice, general practice, and human medicine. METHODS: An international veterinary Utstein task force was convened in April 2013 in San Francisco to determine the scope of the project, the variables to be reported, their definitions, and a reporting template. Factors that were essential for meaningful data reporting and were amenable to accurate collection (ie, core variables) and additional variables useful for research projects and hypothesis generation (ie, supplemental variables) were defined. Consensus on each item was either achieved during that meeting or during the subsequent online modified Delphi process and dialogue between task force members. RESULTS: Variables were defined and categorized as hospital, animal, event (arrest), and outcome variables. This report recommends a template for standardized reporting of veterinary in-hospital CPR studies involving dogs or cats. Core elements include the suspected cause(s) and location of arrest, first rhythm identified, the occurrence of return of spontaneous circulation (ROSC) of more than 30 seconds (any ROSC) or more than 20 minutes (sustained ROSC), survival to discharge, and functional capacity at discharge. If CPR is discontinued or the patient is euthanized by owner request, a reason is reported. The task force suggests a case report form to be used for individual resuscitation events. CONCLUSIONS: The availability of these veterinary small animal CPR reporting guidelines will encourage and facilitate high-quality veterinary CPR research, improve data comparison between studies and across study sites, and serve as the foundation for veterinary CPR registries.
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    Outcomes of Limb-Sparing Surgery Using Two Generations of Metal Endoprosthesis in 45 Dogs With Distal Radial Osteosarcoma. A Veterinary Society of Surgical Oncology Retrospective Study
    Mitchell, KE ; Boston, SE ; Kung, M ; Dry, S ; Straw, RC ; Ehrhart, NP ; Ryan, SD (WILEY-BLACKWELL, 2016-01)
    OBJECTIVE: To report outcomes in dogs with distal radial osteosarcoma (OSA) treated with metal endoprosthesis limb-sparing surgery and compare outcomes between 2 generations of endoprosthesis. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Forty-five dogs with distal radial OSA treated with endoprosthesis and chemotherapy. METHODS: Data of dogs treated with either first-generation endoprosthesis (GEN1) or second-generation endoprosthesis (GEN2) were sourced from medical records and radiographs. Surgical outcomes included postoperative lameness assessment and the presence, severity, and time to onset of complications. Oncologic outcomes included presence of local recurrence or metastasis, time to onset of local recurrence, metastasis-free interval (MFI), and survival time. Results for surgical and oncologic outcomes were compared between GEN1 and GEN2. RESULTS: Twenty-eight dogs received GEN1 and 17 dogs received GEN2. There were 39 complications (96%, 14 minor, 29 major) including infection (78%), implant-related complication (36%), and local recurrence (24%). Metastatic frequency was 67% and median MFI was 188 days (95% confidence interval [CI]: 126-250 days). Survival time ranged from 34 days to 6.1 years with a median of 289 days (95% CI: 207-371 days). There was no significant difference in complication severity, frequency, time to complication, MFI, or survival time between dogs receiving GEN1 and GEN2. CONCLUSION: There was no significant difference in outcomes between dogs receiving GEN1 and GEN2 for limb-sparing surgery of the radius. Metastatic frequency and survival time for metal endoprosthesis were similar to that of amputation with curative intent chemotherapy.
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    Exercise-induced inhibition of remodelling is focally offset with fatigue fracture in racehorses
    Whitton, RC ; Mirams, M ; Mackie, EJ ; Anderson, GA ; Seeman, E (SPRINGER LONDON LTD, 2013-07)
    UNLABELLED: Bone remodelling is inhibited by high repetitive loading. However, in subchondral bone of racehorses in training, eroded surface doubled in association with fatigue fracture and there was greater surrounding trabecular bone volume suggesting trabecular modelling unloads the bone focally, allowing damage repair by remodelling. INTRODUCTION: Remodelling replaces damaged bone with new bone but is suppressed during high magnitude repetitive loading when damage is most likely. However, in cortical bone of racehorses, at sites of fatigue fracture, focal porosity, consistent with remodelling, is observed in proportion to the extent of surrounding callus. Focal areas of porosity are also observed at sites of fatigue damage in subchondral bone. We hypothesised that fatigued subchondral bone, like damaged cortical bone, is remodelled focally in proportion to the modelling of surrounding trabecular bone. METHODS: Eroded and mineralizing surfaces and bone area were measured using backscattered scanning electron microscopy of post-mortem specimens of the distal third metacarpal bone in 11 racehorses with condylar fractures (cases) and eight racehorses in training without fractures (controls). RESULTS: Cases had a two-fold greater eroded surface per unit area at the fracture site than controls (0.81 ± 0.10 vs. 0.40 ± 0.12 mm(-1), P = 0.021) but not at an adjacent site (0.22 ± 0.09 vs. 0.30 ± 0.11 mm(-1), P = 0.59). Area fraction of surrounding trabecular bone was higher in cases than controls (81 ± 2 vs. 72 ± 2 %, P = 0.0020) and the eroded surface at the fracture site correlated with the surrounding trabecular area (adjusted R (2) = 0.63, P = 0.0010). CONCLUSION: In conclusion, exercise-induced inhibition of remodelling is offset at sites of fatigue fracture. Modelling of trabecular bone may contribute to unloading these regions, allowing repair by remodelling.
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    Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions.
    Hussey, GS ; Goehring, LS ; Lunn, DP ; Hussey, SB ; Huang, T ; Osterrieder, N ; Powell, C ; Hand, J ; Holz, C ; Slater, J (Springer Science and Business Media LLC, 2013-12-05)
    Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.
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    Cats, Cancer and Comparative Oncology.
    Cannon, CM (MDPI AG, 2015-06-30)
    Naturally occurring tumors in dogs are well-established models for several human cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous cancers developing in an immunocompetent animal sharing the same environment as humans, shorter lifespan allowing more rapid trial completion and data collection, lack of standard of care for many cancers allowing evaluation of therapies in treatment-naïve populations), but have not been utilized to the same degree in the One Medicine approach to cancer. There are both challenges and opportunities in feline compared to canine models. This review will discuss three specific tumor types where cats may offer insights into human cancers. Feline oral squamous cell carcinoma is common, shares both clinical and molecular features with human head and neck cancer and is an attractive model for evaluating new therapies. Feline mammary tumors are usually malignant and aggressive, with the 'triple-negative' phenotype being more common than in humans, offering an enriched population in which to examine potential targets and treatments. Finally, although there is not an exact corollary in humans, feline injection site sarcoma may be a model for inflammation-driven tumorigenesis, offering opportunities for studying variations in individual susceptibility as well as preventative and therapeutic strategies.
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    Gallbladder mucocoele: A review.
    Smalle, TM ; Cahalane, AK ; Köster, LS (Medpharm Publications, 2015-12-09)
    Gallbladder mucocoele (GBM) is an abnormal, intraluminal accumulation of inspissated bile and/or mucous within the gallbladder. Older, small- to medium-breed dogs seem to be predisposed, but no sex predilection has been identified. Clinical signs are often non-specific and include vomiting, lethargy, anorexia, abdominal pain, icterus and polyuria-polydipsia. Results of a complete blood count may be unremarkable, but serum biochemistry usually reveals increased liver enzymes. The ultrasonographic appearance is diagnostic and well described in the literature. Surgical intervention for the treatment of GBM remains the therapeutic gold standard, with short- and long-term survival for biliary surgery being 66%. The worst outcome is seen in those dogs requiring cholecystoenterostomy. With GBM becoming an apparently increasingly common cause of extrahepatic biliary disease in canines, it is essential that clinicians become familiar with the current literature pertaining to this condition. Numerous predisposing factors are highlighted in this review article and the role of certain endocrinopathies (e.g. hyperadrenocorticism and hypothyroidism) in the development of GBM is touched upon. Furthermore, the aetiopathogenesis of this disease is discussed with reference to the latest literature. Cholecystectomy remains the treatment of choice, but other options are considered based on a current literature review.
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    SYSTEMIC INFECTION DUE TO CANDIDA PARAPSILOSIS IN A DOMESTIC FERRET (MUSTELA PUTORILIS FURO)
    Mancinelli, E ; Meredith, AL ; Stidworthy, MF (ELSEVIER SCIENCE INC, 2014-01)
    An 18-month-old castrated male ferret (Mustela putorius furo) was presented to the veterinary hospital for acute collapse but died despite initiation of emergency treatment. The body was submitted for a complete postmortem examination. The pathologist determined the ferret was suffering from severe necrotizing encephalitis, necrogranulomatous mediastinal lymphadenitis, and ulcerative dermatitis attributable to systemic Candida parapsilosis. This is the first report of systemic Candida parapsilosis in a ferret.