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Your Donations At Work
From developing a new blood test to screen for certain types of cancer to investigating the safety and effectiveness of topical ointments used to treat skin infections, OVC researchers continue to advance veterinary health care with support from Pet Trust.
The following research projects were funded in the Fall 2011 research competition
Time Series analysis of feline retroviral infections
Dr. Olaf Berke
Viral infections in cats leading to leukemia (FeLV) and immunodeficiency (FIV) are serious. These infections have significant impact on the length and quality of life of infected cats. While FeLV prevalence is thought to have declined over the last 20 years, FIV prevalence has been reported at steady levels. Important risk factors for these infections are age, sex and features associated with increased cat-to-cat contact (outdoor lifestyle, sexually intact status). While both retroviruses are readily inactivated by many environmental conditions, they are maintained within the environment by infected cats. A temporal analysis of these infections has not been reported before. Evidence of a temporal trend or seasonal variation will yield further insight into risk factors of the respective diseases. Indeed a preliminary data analysis indicates the presence of two different temporal upward trends for FIV and FeLV infections. A thorough time series analysis is required to properly investigate the emergence of retroviral infections in cats diagnosed by the Animal Health Laboratory at University of Guelph.
Serum and urine neutrophil gelatinase-associated lipocalin concentrations in dogs with sepsis and dogs with neoplasia- Dr. Shauna Blois
Chronic kidney disease (CKD) is a common and progressive disorder in dogs. Average survival times after diagnosis of CKD in dogs is less than 2 years. Early identification of CKD enables introduction of appropriate monitoring and therapy that may help delay the progression to end stage kidney disease. The best way to assess kidney function is by determination of the glomerular filtration rate (GFR), but this test is not routinely performed due to technical challenges, the need for specialized equipment, and expense. Current methods of diagnosing CKD include identifying elevations in blood kidney markers such as creatinine in conjunction with persistently dilute urine.
Unfortunately, these methods are limited as a large portion (>75%) of renal function must be lost before CKD is detected. A better marker of CKD to enable earlier and easier detection of CKD is warranted in veterinary medicine. Our research group is currently investigating neutrophil gelatinase-associated lipocalin (NGAL), a protein that is gaining use in the diagnosis of kidney disease in human medicine. NGAL concentration has been shown to strongly correlate with GFR values and allows for easier and earlier detection of human kidney disease compared to other blood kidney markers. To use NGAL for further research, our group is establishing a reference range for NGAL in healthy dogs.
Additionally, we are measuring NGAL concentrations in dogs with CKD and comparing these levels to current methods of evaluating kidney function such as creatinine concentrations and GFR. Recent human studies have shown that other diseases, including inflammatory conditions and cancer, may mildly increase NGAL concentrations. The utility of NGAL for early diagnosis of kidney disease in dogs will be highest if other diseases do not cause false positive results. It is anticipated that inflammatory conditions and cancer will cause mild elevations of NGAL concentrations in affected dogs compared to healthy dogs. However, it is thought that the magnitude of such NGAL elevations will be less than those observed with CKD. At this time, there are no studies describing NGAL concentrations in groups of dogs with cancer or inflammatory disease, and this study will offer unique information to the veterinary community.
Can silver-coated urinary catheters reduce the rate of bacteriuria and acquired catheter-associated urinary tract infections in clinical canine patients at the OVC-HSC. Dr. Brigitte Brisson
Catheter associated urinary tract infections (CA-‐UTIs) are common in veterinary practice with a reported incidence of 19% in 137 dogs treated at the OVCHSC over a period of 1 year (Ogeer-‐Gyles 2006). Fourteen dogs in this study had a long term (≥3 days) urinary catheter and 11 of these 14 dogs (79%) developed a UTI which suggests that catheterization of 3 or more days commonly results in CA-UTI in our hospital setting. CA-‐UTI represents a significant problem in referral practice where highly resistant bacteria can be found as part of the patients’ endogenous microflora (the main source of bacteria causing UTIs) as well as the hospital environment. These infections can be particularly difficult and expensive to treat. Many catheterized patients receive antimicrobial therapy for concurrent disease processes making them more prone to bacterial resistance if an acquired UTI develops. Patient discomfort and further expense for recheck culture, recheck appointments and prolonged antibiotic therapy must also be considered. In humans, silver and antibiotic coated urinary catheters have been shown to delay the acquisition of UTI thereby reducing the rate of CA-‐UTI (Beattie 2011). Overall, it has been shown that the difference in cost between performing one (or more) culture +/-‐ the cost of antibiotics outweighs the additional cost of using silver coated urinary catheters. The objective of this study is to compare the rate of catheter-‐associated bacteriuria and CA-‐UTI in clinical dogs catheterized with silver-‐coated or non silver-‐coated urinary catheters and to determine if the use of silver coated urinary catheters delays (# days) the development of bacteriuria and UTI compared to an uncoated catheter in clinical dogs. We believe that silver-‐coated urinary catheters will delay and reduce bacteriuria and CA-‐UTI in clinical patients which will change the recommendations for standard of care of veterinary patients requiring urinary catheterization and in turn reduce the rate of hospital acquired UTI and the costs associated with this condition.
Standardization of brochoalveolar lavage suction techniques to optimize diagnostic yield of canine lower airway supplies- Dr. Alice Defarges
Bronchoscopy is a technique used to visualize the lower airways in animals and humans. Bronchoscopy can also be used to “wash” the airways (bronchoalveolar lavage = BAL) to obtain cells for diagnostic analysis. Reasons for bronchoscopy and BAL include chronic cough, unexplained changes on lung radiographs, and lung masses. Side effects of bronchoscopy are usually minor and transient in nature. The basic technique for BAL consists of infusion of saline into the bronchi with re-aspiration. There are three basic techniques for re-aspirating the fluid: 1) suction through a handheld syringe attached directly to a bronchoscope (MA); 2) suction through a handheld syringe attached to a sterile tube which is passed through the bronchoscope (MAPT); 3) aspiration by suction pump (SPA). Each of these techniques is used, but which one is best is unknown. Excessive suction during aspiration may result in airway collapse and limited fluid retrieval, in particular in animals with airway disease. In turn, limited fluid retrieval may hamper the diagnostic utility of BAL. Hence, in this study we will compare 1) SPA and MA in healthy dogs and 2) SPA and MA in dogs with respiratory disease. Identifying a BAL protocol that works well in healthy and diseased dogs will then allow for broad application by internists and general veterinary practitioners alike.
Comparison of Azostix Reagent Test Strips With Standard Automated Biochemical Analyzer for Blood Urea Nitrogen/Urea in Ferrets Dr. David Eshar
The domestic ferret is a common small mammal pet which is seen frequently in clinical practice and in which renal insufficiency and renal failure are common medical conditions. Early detection is crucial for maintaining a good quality of life. The purpose of this research is to determine whether the Azostix ® Reagent Strip is a reliable indicator of renal function in the ferret in order to make science-based recommendations for the use of this product in the clinical medicine of this species.
Quantification of circulating growth factor/cytokine profiles to aid dose optimization of receptor tyrosine kinase inhibitors toceranib and masitinib in canine cancer patients-Dr. Anthony Mutsaers
The recent approval and application of receptor tyrosine kinase inhibitors toceranib (Palladia®) and masitinib (Masivet®, Kinavet®) for the treatment of aggressive canine mast cell tumours has been described as the beginning of a new era of targeted cancer therapy in veterinary oncology. Despite notable successes, there are still a number of unanswered questions regarding the optimal use of these kinase inhibitors in veterinary cancer patients. One important question and emerging controversy surrounds the optimal dose and schedule to be used in the clinic. The recommended label dose for toceranib is 3.25 mg/kg given orally every 48 hours, which is based on studies by Pfizer that indicate this to be the maximum tolerated dose in dogs. However, there is mounting clinical evidence that toceranib may retain efficacy at lower doses, such as 2.5 mg/kg given orally 3 times per week. Furthermore, the lower dose is often better tolerated by dogs, as it is associated with fewer side effects. This translates into higher owner compliance and better likelihood that dogs will continue treatment without
requiring a break period. As the targets of toceranib are similar for masitinib, we see that the same challenges may potentially exist with its use as well. What is needed to address this issue is an objective biomarker of drug dose optimization. Based on previous work involving PI Mutsaers studying the structurally-related human oncology drug sunitinib (Sutent®), it is possible that certain growth factor elevations in canine plasma and serum may provide such a biomarker for dosing toceranib and/or masitinib in cancer-bearing dogs. Of particular interest are vascular endothelial growth factor (VEGF) and stem cell factor (SCF), as both are direct targets of these drugs. The research proposed in this application will determine whether such growth factor changes occur in dogs treated with the lower 2.5 mg/kg dose of toceranib. Furthermore, this project will provide insight into the kinetics of treatment-induced growth factor changes, and the ideal sample types (plasma or serum) to collect for this and future cytokine biomarker studies.
Hemostasis in cats with hypertrophic cardiomyopathy at diagnosis and following therapy with anti-platelet drugs- Dr. Tony Ogg
Hypertrophic cardiomyopathy (HCM) is the most 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 this disease 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 treated with either acetylsalicylic acid (Aspirin®) or clopidogrel (Plavix®). These are blood-thinners which block the function of platelets, the blood cells responsible for the first steps in blood clotting. Unfortunately many cats treated with these drugs still die of FATE. Although there have been some studies that have looked at the effects of these
drugs in normal cats, and some studies that have looked at the blood clotting system in cats with HCM with or without FATE, no study has actually examined the effects of Aspirin or clopidogrel in cats with HCM to see if platelets are actually being blocked. Indeed, a recent survey of veterinary cardiologists revealed that the treatment of HCM in general is surprisingly based on little scientific evidence. The purpose of this study aims to investigate whether abnormal platelet function can be detected in cats with HCM in contrast to healthy cats, and to determine whether the use of Aspirin or clopidogrel in cats with HCM blocks platelet function. Platelet function will be measured using gold-standard methods used in specialized laboratories as well as simpler methods available to all veterinary clinics.
Pharmacology of the Oral Acting Factor Xa inhibitor rivaroxaban in normal dogs and cats pilot studies
Dr. Tony Ogg
The formation of an abnormal blood clot (thromboembolism) in dogs and cats is a severe andoften fatal disorder. In dogs this occurs most often in the form of a clot in the lungs (pulmonary thromboembolism), which is a common complication of immune-mediated hemolytic anemia, a disorder where the immune system attacks a dog’s own red blood cells. In cats thromboembolism occurs most often in the form of a clot in the blood supply to the back legs (distal aortic thromboembolism), which is a common complication of hypertrophic cardiomyopathy, a disorder where the heart muscle becomes too big. In both conditions the drugs used to prevent clots are less than ideal. The drugs used most often are acetylsalicylic acid (Aspirin®) and clopidogrel (Plavix®), which have anti-platelet activity. Platelets are small blood cells responsible for the first step in blood clotting. These drugs are used primarily because they may be given by mouth, and not because of proven benefit. Drugs that block the second step (coagulation) in blood clotting may be more effective, but are not used because 1) use requires frequent blood testing (warfarin); 2) use carries a high risk for bleeding (warfarin), or 3) the drugs can only be given by injection (heparin and low-molecular weight heparins). New bloodthinners (anti-coagulants) have been developed for humans to avoid injection, reduce risk for bleeding and reduce the need for repetitive blood testing. One of these drugs is rivaroxaban (Xarelto, Bayer), which blocks one of the clotting factors, Factor X. Previous studies in normal dogs have documented that the absorption and elimination of the drug is similar to humans, but no studies of the effect of the drug on clotting tests have been done. Previous studies in cat blood samples have shown effect on clotting tests, but there is no information on the absorption and elimination of the drug.
COX-2 Expression in Uveitic Eyes and the Ocular and Systemic Effects of Topical NSAIDs in Cats-Dr. Chantale Pinard
One in four cats presenting to the OVC-VTH Ophthalmology Service over the last 10 years had intraocular inflammation (uveitis) as a primary process or secondary to other systemic or ocular causes. Uveitis causes substantial pain, and can cause glaucoma, cataracts and retinal detachment that lead to blindness if inadequately treated. Prompt aggressive therapy to reduce inflammatory mediators, particularly prostaglandin (PG) synthesis, is required to avoid these serious sequelae.
Topical and systemic corticosteroids are commonly used to treat uveitis but are contraindicated when concurrent corneal ulceration is present. Corticosteroids are also contraindicated in diabetic patients, patients with suspected lymphoma, and uveitis secondary to suspected infectious disease. These concurrent disease states occur in 45% percent of cats presenting with uveitis. As such, treatment with non-steroidal anti-inflammatories (NSAIDs) should be used in a large proportion of uveitis cases. NSAIDs act by inhibiting cyclo-oxygenase (COX) enzymes. COX produces prostaglandins and other mediators of inflammation from arachidonic acid precursors liberated from cellular membranes. Cyclo-oxygenase-2 (COX-2) is thought to be induced by inflammation, and has been shown to be increased in a multitude of inflammatory conditions of the canine eye. The role of COX-2 in feline ocular disease is currently unclear. Oral administration of NSAIDs can produce serious adverse effects on the kidney, liver and gastrointestinal tract. This is particularly true in cats because of limited capacity for hepatic glucuronidation and metabolism of some drug classes. In other species, topical NSAIDs are a mainstay in treating uveitis, while not producing significant adverse effects. Due to their limited metabolism of NSAIDs, however, it is therefore important that this be verified in cats. The systemic absorption and potential for adverse effects of topical NSAIDs has not been evaluated in cats, and no topical NSAID products are currently licensed for use in cats. Although one goal of topical therapy is to limit systemic absorption, a proportion of topically applied medications is systemically absorbed. Studies in humans and rabbits have suggested that the majority of systemic absorption of topical medications occurs by way of the conjunctiva and via drainage through the nasolacrimal duct, leading to nasal mucosal and gastrointestinal absorption. Little is known about the therapeutic effects and ocular and systemic adverse effects of topical NSAIDs in cats. If systemic absorption approaches that seen with topical ocular drugs in rabbits and people the result could be serious renal and liver dysfunction in cats. A concurrent and important goal of this project is to evaluate the ocular adverse effects of NSAIDs, as increased intraocular pressure has been reported secondary to topical NSAID use and has been reported in dogs and cats. Corneal lesions, ranging from very mild to vision threatening, have been documented in the human literature. However, no data exists on the effects of repeated administration of topical NSAIDs on tear production and quality, corneal sensitivity, and corneal health in the cat. A common NSAID prescribed in dogs and humans is topical ophthalmic diclofenac. Diclofenac has been shown to be superior to other topical NSAIDs in dogs, and may be an ideal agent for use in cats. In previous feline and canine studies, the only documented ocular effect associated with diclofenac administration has been a transient mild rise in intraocular pressure. Corneal lesions, ranging from infiltrates to melting corneal ulcers, have been documented in the human literature following topical diclofenac therapy.
Quantifying the upregulation of cyclooxygenase (COX) enzymes in the eye will strengthen the rational for the use of topical NSAIDs in cats with uveitis. Evaluating the ocular and systemic adverse effects of topical NSAIDs will determine whether this route of administration and class of drug can be used safely to treat this common problem in cats.
A Molecular Investigation of Dilated Cardiomyopathy in Doberman Pinschers- Dr. Glen Pyle
Up to 60% of Doberman Pinschers die of an inheritable form of heart failure called dilated cardiomyopathy (DCM). Although the age of onset can vary, once the condition manifests clinically as overt congestive heart failure (CHF), dogs experience a rapid and devastating decline: average survival time is 14 days. Despite the high prevalence of DCM in the Doberman population, little is known about the underlying mechanisms of this disease. Work in other hereditary forms of DCM has found that mutations in genes encoding for the group of contractile proteins collectively known as “myofilaments” are the most common cause of heart failure. Interestingly, the most effective treatment for DCM in Doberman Pinschers is a group of drugs called calcium sensitizers that alter myofilament function. Together these data have led us to hypothesize that abnormal cardiac myofilament function is the underlying cause of DCM in Doberman Pinschers. To test this hypothesis we are working in collaboration with Dr Lynne O’Sullivan and the clinical cardiology service at the Veterinary Teaching Hospital at the Ontario Veterinary College to measure myofilament function in normal and diseased heart tissue. Moreover, we will examine the composition and modification of myofilament proteins to determine if changes in myofilament proteins occur with DCM. Using calcium sensitizers that target unique regions of the myofilaments we will be able to map any dysfunction to a specific region of the myofilament complex, permitting us to identify a subset of candidate genes that may be altered in this genetically transmitted form of heart failure. Calcium sensitizers are a highly effective treatment for canine DCM, increasing life expectancy. Despite the ability of this class of drugs to prolong the life span of dogs suffering from DCM, they do not cure the disease. Our results will determine if calcium sensitizers are effective because they correct a functional defect, or simply mask dysfunction. The use of calcium sensitizers that target different regions of the myofilaments will also allow us to compare the effectiveness of compounds in this drug class, and evaluate whether changing current therapeutic protocols might improve survival and quality of life for our DCM patients. Finally, our assessment of the effects of different calcium sensitizers on cardiac myofilament function will create a functional “map” that will allow us to determine the region of the myofilaments that are responsible for altered function. Overall our work will simultaneously test the rationale and effectiveness of currently used therapies, while searching for the cause of this naturally occurring and devastating disease.
Assessment of Seriological Tests to Detect Avian Bornavirus Infection- Dr. Dale Smith
Proventricular dilation disease (PDD) is a devastating and frequently fatal disease of psittacine birds (parrots) that was first identified in macaws imported from South America in the late 1970s. The disease has since spread around the world and has been diagnosed in over 50 species of parrots. Until a novel avian bornavirus (ABV) was identified as the cause of PDD in 2008, there was no specific method of identifying affected birds. This discovery has allowed the development of a now commercially available PCR test to identify the virus in the tissues and secretions of infected birds. Unfortunately, infected birds do not shed virus on regular or reliable schedules, thus we still underestimate the prevalence of disease in populations, and can fail to diagnose infected individuals. Our intention is to develop a test for antibodies to ABV, which will provide us with an additional tool for diagnosis of exposed and infected birds. This in turn will assist in preventing the spread of ABV from infected to uninfected birds, and in reaching our ultimate goal of eliminating ABV from the pet parrot population.
Preliminary Evaluation of Fecal Bacteriotherapy (Stool Transplantation) for Treatment of Inflammatory Bowel Disease- Dr. Scott Weese
Chronic diarrhea is a highly frustrating condition in dogs. There are various potential causes, yet a definitive diagnosis is often not made. While the causes are poorly understood, there is evidence from human medicine and laboratory animals that the bacterial population of the intestinal tract (the intestinal microbiome) plays an important role in causing and/or potentiating inflammation in the intestinal tract. Accordingly, manipulating this population may be a critical control measure, yet successful treatment using standard methods such as antimicrobials, antiinflammatories and dietary modification is often elusive. Recently, stool transplantation (also known as fecal bacteriotherapy) has gathered much attention in humans. Astounding success is being reported with recurrent C. difficile infection, a potentially debilitating disease with a low cure rate. Large trials are underway based on these highly encouraging findings, and study of other chronic or recurrent gastrointestinal disorders is also being undertaken. Given the success that this approach seems to be producing with a range of inflammatory and infectious enteric diseases, it is a promising area for the treatment of IBD in dogs.
Role of the Protein C Pathway in Pathogenesis of Dogs with Inflammatory Bowel Disease Dr. Darren Wood
Canine inflammatory bowel disease (IBD) is a poorly characterized disease whose cause remains largely unknown. As a result, this disease remains a nuisance to veterinarians and a financial burden for the owners. Obtaining a diagnosis involves a physical exam, blood work, x-rays and stomach and/or intestinal biopsies with evidence of inflammation. Treatment typically involves long term anti-inflammatory, anti-bacterial, anti-parasitic, and immunosuppressive drug therapy along with dietary modification. These treatments do not always work. Recent evidence shows that dysregulation of the protein C pathway plays a major role in human IBD and that treatment with recombinant protein C suppresses the exuberant inflammatory response seen in intestinal endothelial cells grown in the lab. This research is aimed at improving our understanding of the cause of canine IBD by assessing the role of the protein C pathway and linking changes in this pathway to disease outcome. Quantifying the genes and proteins that make up the protein C pathway in tissue from biopsies, and comparing them to unaffected control animals will accomplish this. If the protein C pathway is similarly dysregulated in the canine patient, restoration of this pathway using canine recombinant protein C may be an improved treatment modality.
Investigation of Prognostic Markers in Canine Mammary Tumours Using Tissue Microarray
Dr. Geoffrey Wood
Canine inflammatory bowel disease (IBD) is a poorly characterized disease whose cause remains largely unknown. As a result, this disease remains a nuisance to veterinarians and a financial burden for the owners. Obtaining a diagnosis involves a physical exam, blood work, x-rays and stomach and/or intestinal biopsies with evidence of inflammation. Treatment typically involves long term anti-inflammatory, anti-bacterial, anti-parasitic, and immunosuppressive drug therapy along with dietary modification. These treatments do not always work. Recent evidence shows that dysregulation of the protein C pathway plays a major role in human IBD and that treatment with recombinant protein C suppresses the exuberant inflammatory response seen in intestinal endothelial cells grown in the lab. This research is aimed at improving our understanding of the cause of canine IBD by assessing the role of the protein C pathway and linking changes in this pathway to disease outcome. Quantifying the genes and proteins that make up the protein C pathway in tissue from biopsies, and comparing them to unaffected control animals will accomplish this. If the protein C pathway is similarly dysregulated in the canine patient, restoration of this pathway using canine recombinant protein C may be an improved treatment modality.
Ten research projects will share in $207,508 allocated in OVC Pet Trust’s fall 2009 research competition:
Comparison of a point-of-care blood typing kit with laboratory gel-based blood typing in dogs – Dr. Shauna Blois
This project aims to validate a canine blood typing test kit. Blood transfusions are an increasingly important part of veterinary medical care, and are available at many primary care and referral veterinary practices. Similar to people, animals have unique blood types. Giving a mismatched blood type to a dog may lead to transfusion reactions.
To help ensure that blood transfusion is as safe as possible, it is recommended that both the blood donor and the patient receiving the blood transfusion are blood typed prior to the transfusion. Currently, the best method of blood typing available is through a specialty laboratory. The results of blood typing are therefore not immediately available, and can it take a day or more for these results to reach a private practice.
Therefore, it is desirable to have a quick, in-clinic method of blood typing available to veterinarians. A new blood typing cartridge for dogs is available to veterinarians. However, it is not known how accurate the results of this cartridge are when compared to laboratory blood type testing. The goal of this study is to compare the results of blood typing cartridges to the results obtained from laboratory testing.
If successful, this study will identify a relatively inexpensive, quick, and easy-to-use method of blood typing that is available to perform in any clinic and gives results within minutes. This will help ensure that the critically ill patients receiving blood transfusions have a decreased risk of transfusion reactions.
Establishment of a canine reference range for thromboelastrography – Dr.Shauna Blois
Thromboelastography and platelet mapping are novel, point-of-care tests of blood clotting that show the interaction of platelets and coagulation factors in the formation of a blood clot. Platelet mapping is a modification of thromboelastography that isolates platelet function. Conventional laboratory clotting tests measure an isolated part of the clotting system and are insensitive for detecting increased tendency for blood clotting (hypercoagulability).
Hypercoagulability can occur in conjunction with various diseases in veterinary patients and can lead to abnormal blood clots forming in places in the body such as the lungs and aorta. These clots are difficult to treat and are often fatal. Recent studies have shown that thromboelastography can be used to detect hypercoagulability in dogs with various underlying conditions. However, there is little information in the veterinary literature about the use of platelet mapping. In human medicine platelet mapping is used extensively to measure platelet function, monitor the efficacy of antiplatelet drug therapy and plan surgery and other interventions. In theory, platelet mapping in animals could be used for the same purposes.
Currently a thromboelastography machine is in use in the OVC Hemostasis Laboratory; however the platelet mapping function of the machine has not been utilized. To use platelet mapping for further research it will be necessary to establish values for normal dogs on this machine. At this time, there are no trials describing platelet mapping in a group of normal dogs, and this study will offer unique information to the veterinary community.
Transcatheter arterial chemoembolization for the treatment of canine appendicular osteosarcoma – Dr. Sarah Boston
Transcatheter arterial chemoembolization is a novel technique for the treatment of tumors in people. The technique involves the mapping and visualization of the blood supply to a tumor using X-ray. Once the blood supply is visualized and selected, chemotherapy and a material that will destroy the blood supply is selectively administered to the tumour.
This technique is relatively new, but has been reported for liver tumours in people that are not surgically removable and for osteosarcoma. This technique has been used successfully in people with minimal to no side effects.
Anecdotally, this technique has also been used in dogs with boney tumors of the skull. The purpose of this study is to develop this technique so it may be used to treat clinical cases of bone cancer in canine patients.
Comparison of hemilaminectomy and pediculectomy in dogs with thoracolumbar IVDD using MRI and CT – Dr. Luis Gaitero
Intervertebral disc disease, also called disc herniation or IVDD, is the most common cause of back pain and hind limb weakness in dogs. Small breeds are more commonly affected due to a specific degeneration of their intervertebral discs. Those degenerated discs are not able to resist forces on the spine properly, so they can suddenly blow up expulsing their inner material. That expulsed material usually hits and compresses the spinal cord, causing back pain and/or weakness in the hind limbs.
Surgery is the treatment of choice for many affected dogs. The two most common surgical techniques performed, pediculectomy and hemilaminectomy, have different advantages and disadvantages. Some patients do not improve properly after the surgery and one factor that may contribute is the amount of disc material left at the time of surgery.
We would like to compare the ability of hemilaminectomy and pediculectomy to remove disc material in 20 patients, to identify if remaining disc material can cause a lack of improvement, and under what circumstances either surgical procedure is better suited. Additional data obtained using MRI and CT scans would provide vital information that would guide us to decide between any of both techniques in every particular case.
Effects of acepromazine or medetomidine on cardiopulmonary preference and fentanyl pharmacokinetics during recovery from isoflurane/fentanyl anesthesia in the dog and cat – Dr. Carolyn Kerr
Anesthesia in dogs and cats is associated with a risk of anesthesia related mortality of approximately 0.17 to 0.24% respectively, values unfortunately considerably higher than the approximately 0.0001 to 0.002% reported in humans. Failure of the cardiovascular or respiratory systems was identified as the primary cause of anesthetic-related mortality in the most recent large study in dogs and cats. The time of the greatest risk for morbidity or mortality to occur was end of the anesthesia period when the animal was recovering.
To date, there is little information regarding the cardiovascular and respiratory effects of the sedative and analgesic drugs we routinely administer to dogs and cats during the recovery of anesthesia. The goals of this study are to evaluate the effect of different drug regimes on cardiovascular and respiratory function during recovery from anesthesia in dogs and cats. The information obtained from this study will help improve the way veterinarians manage the recovery phase of anesthesia in dogs and cats.
Validation of serum collage XXVII A-1 as a screening assay for canine hemangiosarcoma – Dr. Gordon Kirby
Hemangiosarcoma is a highly aggressive cancer of dogs, developing as a cancerous growth of abnormal blood vessels and occurring most commonly in the spleen of large breed dogs over the age of six years. These cancers are often not obvious to their owners until late in the development of the disease when the cancerous vessels rupture and the dog bleeds into the body cavities. By this time, the cancer is very advanced and often has spread to other parts of the body.
It would be useful to detect hemangiosarcoma early on, before the tumor has grown large and has spread as it would then be possible to remove the spleen including the small tumors and begin chemotherapy earlier, when it is most effective. Unfortunately, the only available method for early detection is ultrasound imaging, which is expensive, requires special training to perform and is usually only available through veterinary referral clinics. A blood test that could rapidly screen for early evidence of hemangiosarcomas would be clinically very useful, inexpensive and readily available to most veterinary practitioners.
This proposal describes two studies in which veterinary researchers from the Ontario Veterinary College and three veterinary referral hospitals in Toronto and Ottawa plan to confirm whether a recently identified blood protein found at high levels in dogs with hemangiosarcoma is useful in screening for the presence of this cancer. The studies will compare levels of the blood protein with ultrasound evidence of the cancer both at early stages of development and when the cancer reappears after surgical removal and chemotherapy. This so-called “validation” study is a necessary step before the blood test is made available commercially.
Utility of speckle tracking strain in the assessment of global systolic and diastolic cardiac function in the dog – Dr. Michael O’Grady
Heart disease continues to be a common cause of death and sickness in dogs. In almost all cases after a relatively short course of illness (weeks to 1.5 years), it is inevitably fatal. Additionally, response to our best therapies is highly variable. Therefore it is important to find tests that identify heart disease earlier, assist with selection of the best therapies, and that predict outcome all to enable us to better empower owners with accurate expectations.
Speckle tracking strain analysis provides new echocardiographically parameters that evaluate the function of the heart. It is easy to perform and in people offers outstanding promise as the best non-invasive test to identify early disease and accurately predict the severity of heart disease. We expect it will be similarly helpful to assess heart disease in the dog.
Prior to adopting and using any test it is imperative to establish the accuracy and reliability of the test. The present study will establish the accuracy and reliability of the non-invasive speckle strain in dogs when compared with the invasive gold standard parameters. The research dogs used in this study will be provided the care and respect afforded client dogs and will be adopted to families at the completion of the study.
Investigation of cytotoxicity of essential oils, biocides and topical antimicrobials – Dr. Scott Weese
Skin infections are a very common problem in dogs and a common reason for veterinary visits and antimicrobial therapy. Typically, skin infections or other superficial infections (wound infections, surgical incision infections) are treated with oral antibiotics. However, this approach does not always work. Long-term or repeated treatment may be required, which becomes problematic because of difficulty treating some animals, cost of treatment and the potential for side effects such as diarrhea, vomiting, and anorexia. Further, there has been a tremendous increase in highly drug resistant skin infections, which can be very difficult to treat. Therefore, alternative options are needed to supplement or replace oral antibiotics.
One approach is the use of topical treatments. Various options are available, including topical antibiotics, biocides (antiseptic solutions) and essential oils. These substances can have good efficacy against bacteria and are appealing options but there is inadequate information about safety. Topical treatments must be both effective against the infection and have no negative consequences on the body’s tissues.
Tissue damage is a potential concern with these substances and information about tissue damage is required to determine which of these options should be used and at what concentrations. This study will evaluate the cell-damaging effects of various compounds on canine skin cells, using a range of concentrations that could be achievable during treatment.
Development and characterization of recombinant canine activated protein C – Dr. Darren Wood
Sepsis is common in dogs and often results in morality despite treatment. More effective therapy for canine sepsis is thus needed. In humans, activated protein C (APC) is an effective treatment for severe sepsis. APC is derived from protein C (PC) in plasma and has anti-coagulant, anti-inflammatory, pro-fibrinolytic, and cytoprotective effects.
Reduced PC levels are associated with mortality in humans with sepsis.
Currently, recombinant human activated protein C (rhAPC) is the only US FDA-approved therapy that increases survival in adult patients with high-risk, severe sepsis. Similar to humans, PC activity is significantly decreased in canine sepsis and such decreases predict mortality.
Success in treating sepsis in humans with rhAPC provides a rationale for treating septic dogs with APC. However, rhAPC is highly antigenic in dogs, rending it inappropriate for canine use, and knowledge of PC biology in dogs is limited. Therefore, canine-specific PC needs to be isolated or genetically engineered and better characterized before intervention with the PC pathway in septic canine patients is attempted.
We propose a study that examines the anti-coagulant, anti-inflammatory, pro-fibrinolytic, and cytoprotective effects of PC purified from canine plasma. Canine PC is expected to have similar biological properties as its human counterpart. The results from this study will provide a basis for developing and characterizing recombinant canine protein (rCnAPC).
Preclinical evaluation of potential of Nabidiolex to attenuate nausea/vomiting/anorexia in dogs undergoing chemotherapy treatment – Dr. Paul Woods
Malignant lymphoma is the most common hematopoietic neoplasm in the dog. Without treatment lymphoma is a fatal disease with usually rapid rate of progression and an average survival of about 30 days. With serial sequential chemotherapy complete re-missions rates of 60 to 80% with median survivals of six to 12 months have been reported.
OVC has a busy caseload, treating approximately150 lymphoma cases each year with standard chemotherapy protocol. However, dogs undergoing chemotherapy treatment for lymphoma often experience nausea, vomiting, and anorexia for which current treatments may be ineffective in relieving these signs.
Considerable evidence indicates that the psychoactive compound found in the marijuana plant, Δ9-tetrahydrocannabinol (THC), attenuates nausea and vomiting in animal models. However, the marijuana plant contains over 60 cannabinoid compounds other than THC, including the non-intoxicating compound, cannabidiol (CBD). CBD has no reported intoxicating effects and recently it has been shown to have a number of therapeutic effects in animal models and clinical trials with humans. The Parker laboratory has provided considerable evidence showing that CBD, like THC, attenuates nausea and vomiting in animal models. CBD has been shown to inhibit toxin-induced vomiting in the musk shrew (Suncus murinus) and to suppress toxin-induced nausea in rats. In addition, CBD has also been shown to prevent the expression of anticipatory nausea in the shrew and nausea in rats. CBD may be a potential non-intoxicating alternative to medical marihuana in the treatment of nausea and vomiting.
This project seeks to evaluate the effectiveness of CBD to attenuate nausea and vomiting in dogs undergoing chemotherapy treatment.