Engineering a superior vaccine to treat canine melanomas
Melanomas are cancers derived from cells known as melanocytes, which produce the black pigment melanin that gives skin, hair and fur its colour. There is a relatively high incidence of melanomas in dogs. Oral malignant melanomas are particularly aggressive and associated with very low survival rates. New therapies are required to improve survival and quality of life. Vaccines that enable a patient's immune system to kill their own tumours are showing great promise. Although there is currently a commercial vaccine available for canine melanomas, the most recently published survival figures are disappointing and nobody has demonstrated an ability to detect melanoma-specific immune responses. The goal of this project is to draw upon expertise in constructing cancer vaccines to make one with the potential to induce melanoma-specific immune responses that can be readily quantified in dogs. The Ontario Veterinary College is honoured to have become a founding institution in a large, collaborative research network called the National Centre of Excellence in Biotherapeutics for Cancer Treatment (BioCanRx). Should this Pet Trust-funded project be successful, BioCanRx has agreed to invest substantial funds into future canine melanoma trials. The long-term goal would be to combine our novel vaccine with the use of cutting-edge immunomodulatory antibodies designed specifically for dogs. These antibodies would be expected to improve both quantitative and qualitative aspects of the melanoma-specific immune response, hence the need to be able to directly measure this parameter.
Evaluating a new test to monitor the effect of the blood thinner clopidogrel (Plavix) in cats
Hypertrophic cardiomyopathy (HCM) is a common heart disease of cats. In this disease the heart muscle becomes abnormally thick and one of the chambers of the heart (the left atrium) becomes enlarged. A severe complication of HCM is formation of a blood clot in the enlarged left atrium which then cuts off the blood supply to the back legs, analogous to a stroke. This condition is given the acronym FATE (Feline Aortic Thrombo-Embolism), which reflects the fact that at least half of cats afflicted by this disorder die. In an effort to prevent FATE, cats are often treated with clopidogrel (Plavix). This is a blood-thinner which blocks the function of platelets, the blood cells responsible for the first steps in blood clotting. The effect of this drug on clotting in cats with HCM, however, has not been well-documented, and unfortunately some cats treated with this drug still die of FATE. In humans, based on platelet function testing, a subset of cardiac patients with “clopidogrel resistance” (i.e. the drug is not effective) has been identified. It is possible the same is true for cats. Historically, the challenge in assessing the effects of anti-platelet drugs in all species was that platelet function testing was restricted to research laboratories. With advances in technology, user-friendly tests have been developed for humans to monitor therapy with blood-thinners. A long-term objective is to provide such monitoring for cats. The specific objective of this project is to see if a new platelet function test for clopidogrel in humans can be used in cats.
Effect of restraint techniques on acute stress and aversion in cats
Regular veterinary care is important to maintain cat health and welfare. However, many cats are fearful and aggressive during veterinary handling, resulting in negative effects on animal welfare and leading to inadequate veterinary care. In response to these concerns, veterinary organizations are recommending changes to handling for cats to reduce stress and encourage positive experiences for both animals and owners. The key recommendation is to minimize restraint whenever possible. This is supported by previous evidence showing that animals respond negatively to restraint. In contrast, other suggestions are based on anecdotal best practice rather than scientific evidence. When higher levels of restraint are needed to ensure human and animal safety, the new guidelines propose that scruffing (firmly grasping the loose skin at the back of the neck) should be avoided and replaced by alternatives such as head holds and towel wraps to reduce cat stress. However, these recommendations may be incorrect. We aim to objectively assess and improve restraint methods for cats to reduce stress during veterinary exams and procedures. We will compare techniques commonly used for restraining cats, including scruffing, head holds, face masks, and towel wraps, to determine which ones reduce stress responses and aversion to handlers. The restraint techniques will be evaluated by examining stress-related responses of cats during and after handling. Because cats vary in sociability, we will also assess how this affects cat responses to restraint. Results will generate science-based recommendations for cat restraint, with the aim of improving cat welfare.
Investigating a new nasal breathing support system in healthy dogs to assess ease of delivery, comfort and ability to support breathing compared to standard treatment
Veterinary patients are frequently hospitalized for breathing difficulties from for example pneumonia or trauma. Oxygen supplementation is a standard therapy for these patients. When traditional oxygen supplementation fails, a new nasal breathing support system may be able to help these patients beyond that achieved by standard oxygen therapy. This new nasal breathing support system delivers supplemental oxygen, via the nose, at high flow rates which provides mild pressure (CPAP) to the airway. This pressure can bolster the respiratory system. This bolstered breathing support system may reduce the need for more aggressive forms of breathing support, such as intubation and artificial breathing. This new breathing support system has been well received in human medicine because it makes breathing easier and it is easy to apply, better tolerated, associated with less trauma than other systems and has a lower cost compared with other CPAP delivery systems. In veterinary medicine a bolstered breathing system that can be used in awake patients has not been identified. This study aims to evaluate the new breathing system in healthy dogs to: 1) identify modifications needed to meet veterinary needs 2) measure whether pressure (CPAP) is successfully achieved in the dog's long muzzled airway 3) identify whether advantages are appreciated in both breathing and comfort parameters when the support system is compared to traditional oxygen therapy 4) identify tolerable oxygen flow rates for the interface and patient size for safety.
Evaluating a new nasal breathing support system in dogs presenting to the OVC Health Sciences Centre with respiratory disease whose symptoms are not alleviated by current standard therapy
Dogs develop breathing difficulties that require oxygen administration from a variety of diseases including airway obstruction, pneumonia and trauma. Dogs with severe disease and in whom standard oxygen therapy does not alleviate breathing difficulties require anesthesia and breathing is controlled by a mechanical device (ventilator). Ventilation carries significant risk and high cost. A new form of oxygen supplementation has been implemented in human medicine; high flow nasal cannula (HFNC) oxygen therapy. It is an intermediate intervention that is promising for its adaptability to dogs. This system uses nasal prongs, but the technology allows much higher oxygen flow rates than traditional oxygen therapy. These high flow rates improve oxygen levels in people and provide pressure to the airways known as continuous positive airway pressure (CPAP). CPAP is quite effective in assisting breathing. To date, other human methods of creating CPAP have not been easily applied to veterinary patients. There is also a second potential application of HFNC. Brachycephalic dogs (short nosed, flat-faced dogs [eg, Bulldogs]) are high-risk postoperative patients due an anatomically disfigured airway and a large tongue that contribute to airway obstruction. Whenever these breeds undergo anesthesia, muscles relax and the airway obstruction worsens. The application of HFNC and CPAP to these dogs in the anesthetic recovery period may improve air flow by gently pushing swollen or injured tissue open. The application of HFNC for these patients is expected to help breathing similar to people with at home CPAP machines for the treatment of sleep apnea. This study aims to determine whether HFNC: 1. in dogs failing traditional therapy improves oxygen levels and alleviates respiratory distress, preventing the need for intubation and ventilation in some patients. 2. improves the recovery of brachycephalic dogs from general anesthesia compared to traditional therapy.
Investigating the constructs of compassion fatigue and burnout in veterinarians and veterinary students in Ontario
In recent years, recognition of the importance of the human-animal bond to the pet owning public and veterinary profession has increased expectations that veterinary care be compassionate and comprehensive, as well as client and patient-centered. Whilst undoubtedly important, this emphasis on honouring the bond likely adds to the multiple demands and stressors faced by veterinary care providers. In other countries, veterinarians have been demonstrated to experience higher levels of anxiety, depression, burnout, and stress, and have 4 times the risk of suicide, compared to the general population. Compassion fatigue is a further documented issue faced by veterinarians; contributing factors may include exposure to traumatic situations (e.g. euthanasia or animal abuse), as well as the daily strains associated with providing care to clients and patients. Regrettably, the mental health toll on veterinarians in Canada is largely unknown; however, our research group very recently investigated depression, anxiety, compassion fatigue, burnout, and resilience in Ontario veterinarians, providing first-time Canadian data. Preliminary results are alarming: one-third and roughly 10% of participants met the case classifications for anxiety and depression, respectively, and 45% met the criteria for emotional exhaustion (one of the three components of burnout). Besides the obvious human health importance, veterinarian mental health is likely also important from the human-animal bond, client- and patientcare, and practice management standpoints, although research is required to confirm. In human medicine however, an association of physician burnout with decreased patient satisfaction, decreased patient adherence and decreased empathy has been demonstrated. Given the similarities between human and veterinary medicine, it is reasonable to expect comparable negative impacts on veterinarians’ care provision. More research is urgently required to understand the impact of common mental health issues on veterinarians, and how these impact patient-care, the human-animal bond, and the economic health of practices. As such, the objective of this study is to fully characterize the lived experiences of depression, anxiety, burnout, compassion fatigue and resilience in practicing Ontario veterinarians. To this end, both quantitative (survey using validated mental health scales) and qualitative (key informant interviews and thematic analyses) methods will be employed. In addition to this contribution to collective knowledge, this project will inform development of evidence-based resources for veterinarians and student veterinarians that will allow them to cope better with the strains of practice that can lead to depression, anxiety, burnout and compassion fatigue. Not only will this have direct health benefits to veterinarians, it could enhance veterinarian client interactions, patient-care, practice efficiency and effectiveness, and ultimately support the human-animal bond.
Non-invasively standardizing the diagnosis of canine epilepsy by examining electrical activity in the brain
Epilepsy is a chronic brain disease characterized by a predisposition to generate epileptic seizures. It is the most common brain disease in dogs. This high rate is extremely concerning as epileptic dogs have a significantly increased risk of euthanasia and premature death compared to unaffected dogs. Current diagnostic tools for canine epilepsy are weak, being based primarily on the age of onset, the description of the episodes, physical and neurological examinations between episodes, and advanced imaging studies (e.g. magnetic resonance imaging - MRI), none of which can adequately assess brain function to confirm seizure activity. Electroencephalography (EEG), the recording of spontaneous electrical activity arising from the brain's cortical surface, is the best real-time assessment of brain function. In humans, EEG plays a critical role in diagnosing specific epileptic disorders based on the characteristics of the EEG recording. The identification of such syndromes directly influences the type of anti-epileptic treatments and the prognosis. While more than 30 epileptic syndromes have been defined in human medicine only a few have been characterized for canine patients illustrating the lack of knowledge about canine epilepsy and partly explaining the failure of many treatments. This is likely due to the fact that EEG use in veterinary neurology is rare because of the lack of protocol standardization. A key unknown is precisely what region of the cortex each EEG electrode on the canine scalp detects. This makes it difficult to compare EEG recordings from the same dog, between dogs, or between facilities. We propose to significantly improve the diagnosis and characterization of canine epilepsy by describing precisely and standardizing the placement of EEG electrodes on the canine head using a novel, non-invasive method. Collecting extra data from dogs undergoing medically required MRIs of the head region at the OVC will allow "virtual dissection" using specific software to find out how the scalp electrodes map to the underlying brain surface. The resulting model of the "average" canine head for EEG electrode placement in dogs will guide clinicians in consistent electrode placement, thus advancing our ability to diagnose, monitor and treat canine epilepsy more appropriately.
Correlation of small molecules in blood and tumour cells in dogs with lymphoma
Lymphoma represents one of the most common cancers diagnosed in dogs and has significant overlap with the human disease. The most frequent presentation of this tumor in dogs is an aggressive multicentric form, in which patients present with multiple enlarged lymph nodes. Diagnosis is routinely determined by microscopic assessment of lymph node cells or tissue and further testing may be pursued to assess the extent of disease. Lymphoma is a systemic disease and therefore chemotherapy is the most appropriate course of treatment. Remission with chemotherapy can be achieved, but we are unable to predict which individuals may benefit from this therapy prior to its initiation. MicroRNAs (miRNAs) are small, non-coding RNA molecules found inside cells that are released within the body and play a role in regulating numerous biological processes. Alternations in circulating and cell specific miRNAs have been associated with the presence of cancer and other disease states. Our research goal is to characterize whether the miRNA profile from blood and lymph nodes may be of diagnostic value and can assist in predicting response to therapy for canine multicentric lymphoma patients. We hypothesize that altered miRNAs circulating in blood will correspond with those in lymph nodes, which would suggest they are produced and released from the cancer cells themselves. In addition, we will further investigate changes in the miRNA profile that occur in response to chemotherapy and how these specific miRNA may play a potential role in resistance.
Computed tomography evaluation of sentinel lymph nodes in dogs with oral neoplasia using peritumoral injection of iodinated contrast medium
In the field of veterinary oncology, identification of metastatic disease is critical for determining the extent of disease, prognosis, and for developing treatment plans. For many cancer types, metastasis occurs via the lymphatic system and the status of the draining lymph nodes is an important part of the pre- and intraoperative evaluation. The sentinel lymph node (SLN) is the primary lymph node draining the tumour and although one might expect that it is the first lymph node down stream from the tumour, this is not always true. Failure to identify and assess the sentinel lymph node can lead to incomplete treatment, worse prognosis and poor patient outcome. Currently there is minimal literature and no developed technique for SLN evaluation in veterinary patients. The ability to better identify the most relevant lymph nodes to remove would decrease the effect on the patient while not compromising treatment. The purpose of this study is to evaluate the use of injection of a contrast medium around the tumour for identification of SLN on CT. Routine surgery and histopathology of the LN will then be performed based on the current standard of care.
Identification of improved tools for molecular diagnosis, prognosis and therapy of canine osteosarcoma
Osteosarcoma (OSA) is the most common primary bone tumor in dogs, and often spreads (metastasizes) to other organs in the body. Metastatic OSA responds poorly to current available therapies, commonly resulting in patient death. It is not well understood what drives metastasis and therapy-resistance in OSA. Therefore, it is imperative to improve our understanding of the mechanisms of OSA metastasis and treatment resistance, to be able to identify new and improved treatments. Our previous Pet Trust-funded research generated data to suggest that a molecule highly enriched in the bone environment where OSA originates, named transforming growth factor beta (TGF-beta), plays a role in canine OSA aggressiveness. TGF-beta has been previously implicated in metastasis and treatment resistance in different cancer types, in part by promoting a stem cell-like behavior in tumor cells. Two other molecules, known as TAZ and YAP, are necessary for tumor cell's response to TGF-beta, and have also been implicated in cancer metastasis and therapy resistance. Based on this and preliminary data, this research aims to demonstrate that intracellular communication between the latter two molecules (TAZ and YAP) and TGF-beta drives OSA malignancy and this communication can be targeted to treat OSA. Our ultimate goal is to identify novel therapeutic targets to improve treatment outcomes in metastatic canine OSA, and enhance the quality of life of canine patients afflicted by this disease.
Determination of important causes of morbidity and mortality in psittacine birds submitted to the Ontario Veterinary College Teaching Hospital: Management and treatment implications
The increasing popularity of macaws, parrots, cockatoos, parakeets and other psittacines as pets has led to a dramatic increase in the numbers of veterinarians specializing in pet bird medicine with a concurrent need for knowledge about diseases that threaten the health of these birds. The ability to diagnose common diseases among psittacine birds is essential to determining more efficacious treatment strategies and making constructive husbandry recommendations in terms of disease prevention. Thus, diagnostic services such as postmortem and biopsy, together with laboratory techniques are becoming increasingly important, with avian veterinarians and bird owners depending on pathologists to make accurate diagnoses as prognostic indicators, to determine suitable treatment regimes, and to understand disease outcomes and epidemiology. Furthermore, accurate disease diagnoses and awareness is paramount to maintaining healthy captive breeding populations, as this practice is becoming increasingly popular and feeds directly into the pet bird trade. Despite the increased importance of pet bird medicine as a veterinary specialty, comprehensive information about disease conditions in psittacine birds is limited and available resources are often fragmentary, incomplete, or scattered throughout the scientific literature. This project aims to perform a complete review of diagnoses among psittacine birds submitted for post-mortem investigation and biopsy at the Ontario Veterinary College (OVC) and Animal Health Laboratory (AHL) over the past 20 years (1995-2015) in order to: 1) Determine the varied prevalence of diseases diagnosed at a teaching hospital/diagnostic laboratory in the captive psittacine population in Ontario; 2) Review the presentation (e.g., history, clinical signs, clinical pathology findings, and treatment) of such cases while linking these data with pathology and laboratory results; 3) Conduct additional laboratory investigations to formulate a more accurate and complete diagnosis in cases for which a complete diagnosis was not previously reached; 4) Assess whether various management issues (e.g., treatment and husbandry protocols) can be improved to prevent or minimize diseases and their spread among companion psittacines; and 5) Determine whether there are temporal patterns to indicate if past treatment schemes or husbandry tactics have aided in minimizing or exacerbating diagnosed diseases, thereby affecting disease prevalence and case outcomes. The goal of this study is to improve the overall health status of captive psittacines in Ontario by characterizing commonly diagnosed diseases to then provide guidelines and recommendations to avian clinicians and pathologists.
Seeking veterinary health information and knowledge on the Internet: Exploring behaviours, perceptions and attitudes of students, practicing veterinarians and pet owners
The human-animal bond is recognized by the veterinary profession as an integral component in the decision-making processes of how and why veterinarians and pet owners care for companion animals. More recently there has been a growing recognition that the type and quality of pet health care information presented to pet owners, and indeed veterinarians may also have a profound impact on the human-animal bond, and decisions around companion animal healthcare. It is well accepted that the Internet is the most widely and frequently used source for health information. Recent years have seen an increase of research into, and recognition of the importance in understanding health information seeking behaviour in medical students, doctors and human patients, and the impact this behaviour has on the delivery of human healthcare. However, to date there is a distinct paucity of information about how and why students of veterinary medicine, practicing veterinarians and pet owners seek health care information on the Internet. This research project seeks to develop an understanding of what and why various pet-care stakeholders search for when they seek pet care information online. The consequences of this information seeking behavior may have profound impacts on the decisions made for companion animal care and ultimately the human-animal bond. By investigating the behaviours of all stakeholders, meaningful recommendations may also be made for online seeking behaviour. Specifically this research aims to: 1) To explore veterinary students’ behaviors, attitudes and perceptions of using the Internet to search for pet health information; 2) To explore practicing veterinarians’ behaviors, attitudes and perceptions of using the Internet to search for pet health information; 3) To explore pet owners’ behaviors, attitudes and perceptions of using the Internet to search for pet health information; 4) Based on objectives 1-3, to make preliminary ‘best practice’ recommendations for online pet health information seeking behavior for the various stakeholders.
Investigating methods to increase safety of blood transfusion in dogs and cats
Blood transfusion is an essential part of therapy for critical small animal patients. Veterinary blood products have become widely available due to commercial veterinary blood banks; as a result, transfusion therapy has become more common both inside and outside of the specialty veterinary hospital. Although life-saving for many patients, blood transfusion is not without risk. It is common practice to check the blood type all dogs and cats prior to transfusion, to ensure that patients are given blood of a compatible type. However, transfusion reactions can occur between donors and recipients with the same blood type. Crossmatching (CM) is a method used to test blood compatibility between a blood donor and an intended recipient, prior to blood transfusion. By ensuring compatibility, risk of transfusion reactions in the recipient is decreased. In simple terms, the CM mimics a transfusion by mixing serum and red blood cells from the donor and recipient in tubes or on microscope slides, then assessing appearance of the blood. This helps detect if there are any reactions or incompatibilities between blood, prior to the blood actually being given to a transfusion recipient. It is not common to perform CM in all patients prior to transfusion, but rather to use this test only in patients with a history of previous transfusion as they are considered more likely to have antibodies from previous transfusions (and therefore incompatible CM). However, new information is emerging in veterinary medicine showing that patients naïve to blood transfusion (ie. not previously transfused) still could have incompatible CM results with intended blood donors, placing them at increased risk of transfusion reaction if blood from that incompatible donor is given. Further work needs to be performed to confirm the rate of CM incompatibilities in dogs and cats naïve to transfusion. CM is performed by sending a sample to a reference laboratory, or less often in a clinic using very laborious techniques. As a result, CM is often not performed because results will not be immediately available for patients needing emergency transfusion, or because the test is too time-consuming to perform in the clinic. New point-of-care CM kits are available for cats and dogs to rapidly provide CM results using simple technology and alleviatethese concerns. However, the accuracy of such kits is not known and therefore needs to be explored. This study aims to answer the following questions: 1. What rate of CM incompatibility exists in dogs and cats without a previous history of blood transfusion? 2. Are the new point-of-care CM test kits accurate when compared to the laboratory methods?
Can ‘good’ bacteria prevent recurrent urinary tract infections in cats?
Recurrent urinary tract infections (UTIs) can be frustrating to manage for owners and veterinarians alike, and contribute to significant health problems in patients. UTIs are not uncommon and can be very difficult to eliminate. This study will evaluate a novel approach to prevention of UTIs in cats. It moves away from the concept of ‘all bacteria are bad’ to a realization that some bacteria may be useful for prevention of disease. The study will be based on the hypothesis that since these bacteria have been present in the urinary tract of high-risk patients in the absence of disease, they may be effective at colonizing these devices and/or the urinary tract and effectively exclude disease-causing bacteria that are subsequently encountered. This will include assessing antibiotic resistance, evaluating the presence of antibiotic resistance genes that can be passed to other bacteria and genes that might be associated with increased risk of disease, characterizing the ability of strains to adhere to urinary deices and evaluating whether these strains produce substances that inhibit bacteria that cause UTIs. These characteristics will identify optimal candidates for planned future studies aimed at developing a safe and effective method for preventing UTIs in cats and dogs.