Melbourne Veterinary School - Research Publications
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ItemBreed is associated with the ABCB1-1 Delta mutation in Australian dogs(Wiley, 2020-03-01)OBJECTIVE: The ABCB1 gene encodes P-glycoprotein (P-gp), a cellular membrane pump. One functional mutation that leads to expression of a less functional form of P-gp, ABCB1-1Δ, has been described in dogs. Individuals with this mutation can have severe adverse reactions to common veterinary pharmaceuticals that are known substrates of this pump. We investigated the detection of this mutation in samples submitted to two Australian diagnostic laboratories. METHODS: A total of 4842 dogs across 27 breeds were tested for the ABCB1-1Δ mutation from buccal swabs or EDTA blood using standard PCR, multiplex PCR, or genotyping chip. Statistical analysis was applied to determine the proportions and odds ratios of the ABCB1-1Δ mutation in herding breeds compared with non-herding breeds. RESULTS: The ABCB1-1Δ mutation was detected in nine breeds. The most commonly affected breeds were collies, Australian shepherds, white Swiss shepherds, and Shetland sheepdogs. Of 32 dogs in 18 non-herding breeds tested, one cocker spaniel and one labradoodle were positive for the mutation, both heterozygous. CONCLUSION: The most frequently affected breeds for ABCB1-1Δ mutation are the collie, Australian shepherd, white Swiss shepherd and Shetland sheepdog. As the mutation is associated with an increased incidence of adverse reactions to commonly used pharmaceuticals, veterinarians need to be aware of the breeds at most risk of carrying this mutation and consider testing these individuals prior to administering these medications.
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ItemComplete upper airway collapse and apnoea during tethered swimming in horses.(Wiley, 2020-05)BACKGROUND: There is limited knowledge of the breathing strategy and impact on the patency of the upper respiratory tract (URT) in swimming horses. OBJECTIVES: To describe the respiratory responses and endoscopic appearance of the URT during tethered swimming in horses. STUDY DESIGN: Prospective descriptive study. METHODS: Ten race-fit horses, with no history of URT obstruction, were examined during tethered swimming. Endoscopic examination, heart rate, sound recordings and above and below water video recordings were obtained. Plasma lactate concentration was measured before and 5 min after swimming and tracheal endoscopy was performed 30 min after exercise to assess for presence of blood or mucus. Four horses also underwent endoscopy during exercise on the track. RESULTS: Mean (±s.d.) breathing frequency was 28 ± 5 breaths/min during swimming, with a brief inspiration (mean ± s.d. TI = 0.51 ± 0.08 s), followed by a period of apnoea (1.59 ± 0.53 s) and then a short, forced expiration (TE = 0.42 ± 0.5 s). During apnoea all horses exhibited complete collapse of the URT including closure of the external nares, nasopharynx and rima glottidis (with bilateral adduction of the arytenoid cartilages and vocal folds) and, in two horses, epiglottic retroversion. No horses had URT collapse during overground exercise. Locomotor-respiratory coupling was not observed during swimming. Median (IQR) plasma lactate post swim was 4.71 mmol/L (2.08-8.09 mmol/L) vs 0.68 mmol/L (0.65-0.71 mmol/L) preswim. Post swim endoscopy revealed grade 1 exercise-induced pulmonary haemorrhage (EIPH) in 2 horses. Median mucus grade was 1 (range 0-3). MAIN LIMITATIONS: Overground endoscopy was not performed in all horses. CONCLUSIONS: Horses experienced complete URT collapse associated with post inspiratory apnoea when swimming. The reason for this is unknown but may be to aid buoyancy or associated with the mammalian dive response - a survival reflex to preserve oxygen stores and prevent water entering the lungs.
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ItemDifferential Response of the Chicken Trachea to Chronic Infection with Virulent Mycoplasma gallisepticum Strain Ap3AS and Vaxsafe MG (Strain ts-304): a Transcriptional Profile(AMER SOC MICROBIOLOGY, 2020-05)Mycoplasma gallisepticum is the primary etiological agent of chronic respiratory disease in chickens. Live attenuated vaccines are most commonly used in the field to control the disease, but current vaccines have some limitations. Vaxsafe MG (strain ts-304) is a new vaccine candidate that is efficacious at a lower dose than the current commercial vaccine strain ts-11, from which it is derived. In this study, the transcriptional profiles of the trachea of unvaccinated chickens and chickens vaccinated with strain ts-304 were compared 2 weeks after challenge with M. gallisepticum strain Ap3AS during the chronic stage of infection. After challenge, genes, gene ontologies, pathways, and protein classes involved in inflammation, cytokine production and signaling, and cell proliferation were upregulated, while those involved in formation and motor movement of cilia, formation of intercellular junctional complexes, and formation of the cytoskeleton were downregulated in the unvaccinated birds compared to the vaccinated birds, reflecting immune dysregulation and the pathological changes induced in the trachea by infection with M. gallisepticum Vaccination appears to protect the structural and functional integrity of the tracheal mucosa 2 weeks after infection with M. gallisepticum.
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ItemImmunohistochemical analysis of laryngeal muscle of horses clinically affected with recurrent laryngeal neuropathy(WILEY, 2020-10-27)Background As myosin heavy chain (MyHC) profile of muscle fibres is heavily influenced by neural input, changes in MyHC expression are expected in horses clinically affected with recurrent laryngeal neuropathy (RLN) yet, this has not been thoroughly investigated. Objectives To describe the changes in MyHC and fibre diameter in left cricoarytenoideus dorsalis (L-CAD) muscle of horses with clinical signs of RLN. Study design Observational cohort study. Methods Immunohistochemistry was used to assess the MyHC-based fibre-type proportion, size and grouping in the L-CAD of 10 Thoroughbred horses, five clinically affected with RLN and five unaffected controls based on resting endoscopic examination. The Mann-Whitney U test was used to compare the two groups. Results Compared to controls (of mean age 3.0 ± 1.7 years) which only expressed type I, IIA and IIX MyHC, the L-CAD of affected horses (of mean age 2.8 ± 0.8 years) had obvious fibre-type grouping, and despite apparent compensatory hypertrophy of a small number of fibres, a decrease in overall fibre diameter (median difference −35.2 µm, 95% CI −47.4 to −7.9, P = .02) and diameter of type IIA fibres (median difference −46.8 µm, 95% CI −52.1 to −5.0, P = .03) was observed. Anti-fast MyHC (MY32) cross-immunoreacted with embryonic-MyHC. Whereas MY32-positive fibres were identified as type IIX in controls, in affected horses these fibres were less than 50 µm diameter with internal nuclei and were MYH3-positive for embryonic myosin indicating depletion of type IIX fibres, yet active regeneration and fibre renewal. Main limitations Small sample size that did not include subclinical cases. Fibre size and appearance rather than staining colour were relied upon to differentiate embryonic from type IIX MyHC. Conclusions Horses clinically affected with RLN have overall atrophy of fibres, loss of IIX fibres and expression of embryonic myosin indicating regenerative capacity. Despite hypertrophy of some remaining fibres, the overall decline in the bulk of fibres, including those most fatigue-resistant, may be the critical change that results in failure to maintain arytenoid abduction during exercise although direct comparison to subclinical cases is needed to confirm this.
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ItemDifferences in the clinical practice of small animal CPR before and after the release of the RECOVER guidelines: Results from two electronic surveys (2008 and 2017) in the United States and Canada(Wiley, 2020-11)Objective To assess whether the clinical approach to CPR has changed following the publication of the Reassessment Campaign on Veterinary Resuscitation (RECOVER) guidelines in 2012. Design Internet-based survey. Setting Academia and referral practice. Subjects Four hundred and ninety-one small animal veterinarians in clinical practice in the United States and Canada. Interventions An internet-based survey assessing the clinical approach to small animal CPR was circulated with the assistance of veterinary professional organizations on 2 separate occasions: prior to (2008) and following (2017) publication of the 2012 (RECOVER) guidelines. Survey questions identical to both surveys solicited details of clinician approaches to CPR preparedness, basic life support (BLS), and advanced life support (ALS). Respondents were grouped into level of expertise (board-certified specialists [BCS, n = 202] and general practitioners in emergency clinics [GPE, n = 289]), and year of response to the survey (2008, n = 171; 2017, n = 320). Measurements and Main Results Compliance with the RECOVER guidelines pertaining to CPR preparedness (P < 0.01), BLS (P < 0.01), and ALS P < 0.01) was consistently higher in respondents to the 2017 survey compared to those of the 2008 survey. Being a BCS was associated with significantly higher compliance with the RECOVER recommendations than GPE in the domains of preparedness (P = 0.02), BLS (P < 0.01), and ALS (P < 0.01). Increases in age of the respondent had a negative effect on compliance with the BLS guidelines (P < 0.01), while gender had no effect. Conclusions Compared to 2008, current practices in small animal CPR in the North American emergency and critical care community shifted toward those recommended in the RECOVER guidelines across all CPR domains. This supports the notion that uptake of the RECOVER guidelines among veterinary emergency or critical care clinicians was sufficient to lead to a change in the practice of CPR.
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ItemStudy design synopsis: Designing and performing pharmacokinetic studies for systemically administered drugs in horses(WILEY, 2020-09)The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than the PK data analysis itself.
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ItemInfectious disease and emergency conservation interventions(WILEY, 2020-08)
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ItemEffect of a second treatment of prostaglandin F2α during the Ovsynch program on fixed-time artificial insemination conception rates and luteolysis in split-calving, pasture-fed dairy cows(WILEY, 2020-05)OBJECTIVE: To compare fixed-time artificial insemination (FTAI) conception rates and serum progesterone concentrations at the time of FTAI for cows treated with the original Ovsynch program (OV) with those treated with a modified Ovsynch (MO) program. DESIGN: This was a randomised clinical trial. METHODS: The study used five split-calving, pasture-based dairy herds in Southwest Victoria, Australia. Controls (n = 851) received the OV program: day 0 gonadotropin-releasing hormone, day 7 prostaglandin F2α (PGF), day 9 gonadotropin-releasing hormone and FTAI at day 10. The treatment group (n = 852) received a MO program with an additional prostaglandin injection on day 8. Subsets of cows from each group were sampled for blood progesterone at the time of FTAI. RESULTS: The treatment group demonstrated FTAI conception rates that were 7% (95% confidence interval 2%-12%) greater than the control group. After adjusting for the effect of age, days in milk at Mating Start Date and herd, the odds of conception using FTAI was 1.36 (95% confidence interval 1.12-1.66) times greater for treatment group cows compared with control group cows. The variability of serum progesterone concentrations at the time of FTAI was significantly less for treatment group cows compared with control group cows. CONCLUSION: For Holstein-Friesian and Holstein-Friesian cross-bred cows managed in pasture-based dairy herds in southern Australia, a MO protocol, including a second injection of prostaglandin F2α on day 8, increased FTAI conception rates compared with cows receiving the OV protocol.
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ItemFibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs(ELSEVIER SCI LTD, 2020-04)Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.
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ItemThe Effect of Pet Insurance on Presurgical Euthanasia of Dogs With Gastric Dilatation-Volvulus: A Novel Approach to Quantifying Economic Euthanasia in Veterinary Emergency Medicine(FRONTIERS MEDIA SA, 2020-12-08)Euthanasia of companion animals in veterinary emergency medicine is a common cause of death. Euthanasia is economic when it is the consequence of the pet owner's inability to afford essential treatment while a viable medical alternative to euthanasia exists. Gastric dilatation-volvulus (GDV) is an acute life-threatening emergency condition of dogs; if left untreated, rapid death is highly likely. Surgical treatment leads to survival of around 80-90% of dogs; however, such treatment is costly. Therefore, pre-surgical euthanasia may be largely economically motivated. Having pet insurance, a financial instrument to reduce the burden of unforeseen veterinary medical costs on pet owners, would be expected to abolish the risk for pre-surgical economic euthanasia. We therefore aimed to determine whether pet insurance attenuates the risk of pre-surgical economic euthanasia in dogs with GDV. Non-referred dogs (n = 260) with GDV and known insurance status seen at 24 emergency clinics over a 2-year period were included. Relevant data (e.g., insurance status, age, comorbidities, outcome) were retrospectively extracted from a pet insurer's claim records (insured animals) or from electronic medical records of participating hospitals (non-insured animals). Forty-one percent of dogs (106 of 260 dogs) did not survive to hospital discharge; 82 (77%) of non-survivors died before surgery, all through euthanasia. The pre-surgical euthanasia rate was 10% in insured and 37% in non-insured dogs (p < 0.001). When adjusted for the effect of age, deposit size, comorbidities, and blood lactate concentration, the absence of insurance increased the odds of pre-surgical euthanasia by a factor of 7.4 (95% CI 2.0 to 37; p = 0.002). Of dogs undergoing surgery, 86% survived to hospital discharge. Overall, 80% of insured animals and 53% of non-insured animals survived to hospital discharge (p < 0.001). Thus, insurance was associated with a marked decrease in risk of pre-surgical euthanasia indicating that the cause of pre-surgical euthanasia of dogs with GDV is predominantly economic in nature. The rate of pre-surgical euthanasia in dogs with GDV may emerge as a suitable marker to quantify economic decision making of pet owners and to measure the impact of financial interventions aimed at mitigating economic duress associated with cost of veterinary emergency care.