Companion Animal Fund Research Projects

Effects of selected topical ophthalmic medications on IOP, Anterior Segment anatomy and aqueous humor dynamics in normal and glaucomatous cats.
Dr. Ellison Bentley, Department of Surgical Sciences

Glaucoma, a disease that is associated with increased intraocular pressure (IOP), is an important cause of blindness in humans and domestic animals.  In cats, glaucoma is often secondary to other disease processes, including inflammation and tumors.  Medical therapies are vital in preventing or slowing progressive loss of vision and reducing discomfort in affected patients.  Unfortunately, the prognosis for long-term maintenance of vision in cats with glaucoma is poor because glaucoma in cats often goes unrecognized until late in the disease process.  Coupled with this, there is currently a lack of published studies that address the usefulness of conventional medical therapies in glaucomatous cats.  We have established a colony of cats with inherited glaucoma.  This feline model will enable us to determine the efficacy in lowering IOP, mechanisms of action, and potential adverse effects of several commonly used ophthalmic drugs in glaucomatous cats. The results of our investigations will provide a strong foundation of species-specific clinical data, enabling veterinary clinicians to formulate appropriate and effective treatment strategies for feline glaucoma patients.

Cystoscopic, magnetic resonance imaging and histpopathologic evaluation of submucosally injected poluethylene glycol-based hydrogel and bovine cross-linked collagen in the porcine urethra.
Dr. Robert Hardie, Department of Surgical Sciences

Urinary incontinence due to sphincter mechanism incompetence (SMI) is a common problem that affects 20% of all female dogs following ovariohysterectomy. Cystoscopic injection of bovine collagen (BC) as urethral bulking agent is a widely used treatment for SMI.  However, clinical results using BC vary significantly with only 53% of dogs becoming continent after one treatment and the median duration of effect limited to 3 months.  Reasons why BC does not provide a more lasting effect are unknown; however, potential explanations include rapid degradation or deformation of BC within the urethra.   Polyethylene glycol hydrogel (PEGH) is a biocompatible compound that can be formulated with variable viscosity and biodegradability.  Its unique properties offer tremendous potential as a bulking agent that may eliminate many of the limitations seen with BC.  Our hypothesis is that PEGH will generate less tissue response and maintain a more consistent shape within the urethra compared to BC, making it a superior bulking agent.  The objectives of this study are to evaluate and compare the tissue response and degree of degradation and deformation of BC and PEGH in the urethra of 8 dogs.  Standardized submucosal injections of BC and PEGH will be made at two separate locations in the urethra.  The injection sites will be evaluated with cystoscopy, MRI, and histopathology at 30 and 120 days.  Data from this study will be used to support a clinical trial using PEGH as a bulking agent for the treatment of SMI in dogs.

Canine computer tomographic cardiovascular angiography
Dr. Rebecca Johnson, Department of Surgical Sciences

Computed tomographic angiography (CTA) of the heart in human patients is used in emergency and scheduled appointment practice to diagnose many heart disorders such as narrowing of the arteries, abnormalities in the structure of the heart and changes that occur with heart attacks. In addition, CTA is the best way to detect blood clots caught within blood vessels of the lung. The technique is a fast and noninvasive procedure with superior image clarity compared to the imaging techniques currently used. However, CTA requires slow, steady heart rates and breathing patterns to obtain high-quality images, conditions which are not always present in anesthetized companion animal patients. As such, the aim of this project is to establish a short-term anesthetic protocol using drugs to controllably slow the heart rate which will enable advanced imaging of the canine heart and lungs with CTA. With this, the imaging protocol for canine heart and lung CTA will be established and described. Our novel data will provide the basis for future investigations into the usefulness of CTA in the noninvasive diagnosis of heart abnormalities present from birth, acquired heart diseases, and diseases involving the lungs and blood vessels of companion animals.

Construction and evaluation of a mucosal vaccine for canine influenza.
Dr. Jorge Osorio, Department of Pathobiological Sciences

The effects of S-Adenosylmethionine on erythrocyle and hepatic glutathione concentrations of clinically normal horses.
Dr. Simon Peek, Department of Medical Sciences

S-adenosyl-L-methionine (SAMe) is a chemical present in cells throughout the body. Studies in people, dogs, rats, mice and rabbits have found that when SAMe is administered in amounts exceeding those that are normally present in the body to individuals with liver disease there is a beneficial antioxidant effect. Furthermore SAMe has been shown to be safe in all species in which it has been tested. Liver disease is relatively common in horses but there are currently few proven therapeutic options. Many of the liver diseases that SAMe is used to treat in people, dogs and cats have striking similarities to the common liver diseases of horses. Given this, SAMe shows potential as an adjunctive therapy to treat liver disease in horses. We propose a study to establish whether these same beneficial anti-oxidant effects can be achieved in red blood cells and liver tissue of normal horses when SAMe is administered orally. Our study would then establish a therapeutic, safe dose for adult horses and thereby improve therapeutic options for horses with liver disease.

Articular cartilage in normal canine cadaveric elbows.
Dr. Susan Schaefer, Department of Surgical Sciences

S-adenosyl-L-methionine (SAMe) is a chemical present in cells throughout the body. Studies in people, dogs, rats, mice and rabbits have found that when SAMe is administered in amounts exceeding those that are normally present in the body to individuals with liver disease there is a beneficial antioxidant effect. Furthermore SAMe has been shown to be safe in all species in which it has been tested. Liver disease is relatively common in horses but there are currently few proven therapeutic options. Many of the liver diseases that SAMe is used to treat in people, dogs and cats have striking similarities to the common liver diseases of horses. Given this, SAMe shows potential as an adjunctive therapy to treat liver disease in horses. We propose a study to establish whether these same beneficial anti-oxidant effects can be achieved in red blood cells and liver tissue of normal horses when SAMe is administered orally. Our study would then establish a therapeutic, safe dose for adult horses and thereby improve therapeutic options for horses with liver disease.

The prevalence of acute lung injury in small animal patients receiving transfusions.
Dr. Elizabeth Thomovsky, Department of Medical Sciences

Transfusion-related acute lung injury (TRALI) is a syndrome that occurs in humans after receipt of a blood or plasma transfusion.  The transfusion induces inflammation in the lungs that leads to infiltrates which cause a variety of clinical signs ranging from none (sub-clinical cases) to an inability to breath, increased heart and respiratory rates, and even death.  TRALI is a subset of acute lung injury (ALI) in humans.  In the veterinary world, ALI has been described in dogs and dogs are regularly given blood and plasma transfusions.  Dogs receiving transfusions do suffer from a variety of complications related in time to the transfusion, some of which are likely attributable to TRALI.  However, TRALI has not been proved to exist in dogs.  The goal of our study is to determine if ALI induced by transfusion does exist in dogs (ie, TRALI).  We will study this by taking chest radiographs (X-rays) before and after transfusions in dogs to look for evidence of infiltrates in the lungs.  At the same time, the patients will have an arterial blood gas analysis conducted which will provide information on the patients’ ability to oxygenate before and after the transfusion.  Our goal is to determine if ALI is induced by transfusion in dogs; if so, it will lend credence to the idea that TRALI exists in dogs.

Is oxidative stress a risk factor for adverse reactions to the anti-thyroid drug methimazole.
Dr. Lauren Trepanier, Department of Medical Sciences

Hyperthyroidism (an overactive thyroid) is a common disease in middle aged to older cats. Methimazole (also called Tapazole®) is the most commonly used drug for this condition, particularly when radioiodine is not available or not affordable. However, methimazole leads to unpredictable adverse drug reactions, including low platelet and white blood cell counts, facial scratching, or liver toxicity, in 2-7% of cats. This study will determine whether antioxidant deficiencies are a risk factor for these drug reactions in cats.  The results of this study may provide a rationale for antioxidant supplementation in cats with hyperthyroidism, with the goal of preventing adverse reactions to the otherwise very effective drug, methimazole.

Pilot study: evaluation of CD19 as a potential immunotherapeutic target for the treatment of canine and feline lymphoma.
Dr. David Vail, Department of Medical Sciences

In the past twenty years, no improvement in cures have been made in the treatment of dogs and cats with lymphoma, the most common form of white blood cell cancer. Approximately 90% of our companions continue to die from this disease. Despite newer forms of chemotherapy, improvements in curing lymphoma in people did not occur until the development of antibodies (a form of immunotherapy) that attack the cancerous white blood cell were developed about 10 years ago.  Unfortunately, the antibody that recognizes and helps kill human cancerous white blood cells does not recognize the dog and cat cancer cell.  This study will seek to identify and test a new set of antibodies that will be designed to recognize the cancerous white blood cells found in dogs and cats. It is hoped that, as it has for people, this new immune therapy will be successful in increasing the cure rate for lymphoma in our companion animals.

Digital Radiographic Evaluation of the Psittacine (Parrot) Gastrointestinal Tract in Normalcy and Disease.
Dr. Chess Adams, Department of Surgical Sciences

Gastrointestinal disease in parrots is common, leading to dehydration, weight loss and death if not identified and treated in a timely manner. Parrots with disease affecting the gastrointestinal tract present with anorexia, regurgitation, vomiting, or abnormal feces, and may sustain enlargement of the affected organ(s). Among the many causes of gastrointestinal disease, Neuropathic Gastric Dilation (NGD) is the most notorious and feared due to the inevitably fatal outcome and risk of spread to other parrots. Thus, differentiating NGD from other gastrointestinal disease is extremely important. Historically gastric enlargement has been subjectively assessed on radiographs. In a recently published study, we introduced the proventriculus (stomach):keel ratio in parrots. This study described the ratio as an objective method for assessment of stomach diameter, successfully differentiating 100 normal parrots from 19 with stomach disease.

In this study we will further evaluate and validate this ratio by investigating the effects of anesthesia, positional rotation, and size fluctuations over time on radiographs of the gastrointestinal tracts of healthy parrots. We will also evaluate the use of the ratio for radiographs of parrots with a gastrointestinal tract disease. Here we hope to validate the ability of the ratio to differentiate between different diseases.  This study will be facilitated by the outstanding detail and scale of contrast attainable with our recently installed digital radiographic equipment.  Digital radiography is rapidly becoming available in private practice, so practical advantages of this new technology will be explored in the historically challenging setting of the very small patient with little inherent abdominal contrast.

Molecular Characterizaion of Methicillin-Resistant Staphylococcus intermedius of Veterinary Origin.
Faye Hartmann, Department of Pathobiological Sciences

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of hospital-acquired and more recently community-acquired infections in humans.  They are resistant to the antibiotic methicillin (and related antibiotics) and are often resistant to other classes of antimicrobials used to treat staphylococcal infections.  Since 2004, methicillin-resistant S. intermedius (MRSI) has become a significant cause of infections in dogs and cats. Human beings can also develop infections from MRSI and probably acquire the microorganism from colonized pets.  Both MRSI and MRSA produce an altered protein which has reduced affinity for methicillin and related antibiotics and is encoded by a gene called mecA.  The mecA gene is carried on variants of a structurally complex mobile genetic element (SCCmec) that can be transferred between various species of staphylococci.  This study will provide new information about the variants of SCCmec harbored by MRSI from pets, will help in determining the origins of methicillin resistance in S. intermedius, and provide additional information about this potential zoonotic pathogen. 

Seasonal Variation of Fecal Coritcosterone concentrations in Wisconsin Sandhill Cranes (Grus canadensis).
Dr. Barry Hartup, Department of Surgical Sciences

I will use a proven non-invasive technique to evaluate corticosterone, the stress hormone of birds, in stool samples from wild cranes for the first time.  Samples will be collected at roost sites of a well studied population of sandhill cranes in south-central Wisconsin during different seasons to determine normal hormone levels.  I expect corticosterone concentrations will increase as the cranes shift from a non-breeding, sedentary condition in summer to migratory condition in fall.  The reference information gathered by this study will be used to evaluate the impacts of social, behavioral and environmental stressors on the health of this population in future studies.  The findings of this study will also have a broader application: sandhill cranes are a recognized biological model for several endangered cranes worldwide.  Use of this technique would provide a non-invasive tool for assessing the health of imperiled crane populations and their ecosystems worldwide where traditional methods of health assessment are impractical.

Nociceptive Assessment and Pharmacodynamics of Nalbuphine HCL in Amazon Parrots.
Dr. Joanne Paul-Murphy, Department of Surgical Sciences

Is the presence of bacterial nucleic acids associatged with chrinic synovitis in horses.
Dr. Alberto Serena, Department of surgical Sciences

Increased filling of the hock (tarsocrural joint) with synovial fluid is often referred to as “bog spavin”. Many horses that develop bog spavin are not lame. However, the observation that a horse has boggy hocks may raise concerns about the horse’s joint health and future soundness, or bother the owner who has intentions of showing the horse. The veterinarian who is asked for advice is then prompted to investigate the underlying cause of the increased joint filling. Often, diagnostic tests do not reveal a definitive underlying pathology. In this case, the veterinarian will use the term “idiopathic bog spavin” or “aseptic synovitis” to describe the condition. In addition, most of the treatments, such as bandaging, hydrotherapy or draining the joint fluid and subsequent injections with steroids, only yield a temporary improvement.
Using a molecular biology technique called PCR-polymerase chain reaction-, our laboratory has recently shown a link between the presence of bacterial DNA in stifle joints and concurrent joint disease in dogs.
The purpose of our project is to find out if latent bacterial DNA can trigger joint inflammation and swelling in horses. We will collect joint fluid from horses affected with bog spavin and from normal horses, and our hypothesis is that we will find bacterial material in boggy joints much more frequently than in normal joints.

We believe that our research will help to increase the knowledge about the disease process but also permit us veterinarians to focus on a more effective treatment strategy to control and cure “idiopathic synovitis” in its early stages.

Epidural administration of ammonium sulfate gradient-loaded liposomes containing hydromorphone provides hindlimb analgesia for greater than 1 week in an animal model of stifle arthritis.
Dr. Lesley Smith, Department of Surgical Sciences

The goals of this study are to assess the analgesic effects, and duration of said effects, of epidurally administered liposome-encapsulated hydromorphone in arthritic rats. Hydromorphone is a potent opioid analgesic that has a duration of approximately 6-8 hours when administered epidurally in people. In general, encapsulation of opioids into liposomes increases the duration of drug release and effect. Recently, we collected pilot data in dogs after epidural administration of liposomes containing hydromorphone and found that pain relief after injury to the cruciate ligament of the stifle was profound and lasted more than 7 days. The purpose of the study proposed here is to examine the duration of analgesic effect after epidural administration of liposome-encapsulate hydromorphone in a rodent model of stifle arthritis.  We will use the change in thermal latency time to assess the analgesic effect of our epidurally administered drugs. We will test relative weight bearing of the arthritic and normal (control) hind limb using an incapacitance meter, which is a force plate specifically made for rats.  Additionally, we will test changes in mechanical threshold using Von frey hairs.  Animals will be divided into 4 groups including two different doses of liposome-encapsulated hydromorphone, one dose of standard hydromorphone and one dose of blank liposomes.  The scientific significance of this research is that, if liposome-encapsulated hydromorphone proves to have a long duration (i.e. 7 or more days) of analgesic effect after epidural administration in arthritic rats, it offers a cost-effective and clinically effective means to provide superior analgesia for many potential medical and surgical conditions in animals and in people.

Infraorbital dental nerve blocks with mepivacaine decrease the anesthetic requirement of isoflurane in dogs undergoing dental procedures.
Dr. Lindsey Snyder, Department of Surgical Sciences

Dental nerve blocks, modeled after human dental techniques, can be used for pain management in animals undergoing painful dental procedures such as extractions.  General anesthesia, using gas anesthetics, is required for immobilization of dogs when performing dental cleanings.  Gas anesthetics are associated with dose-dependant adverse effects on the cardiovascular and respiratory systems.  The objective of this study is to evaluate the effects of routinely used dental nerve blocks on the gas anesthesia requirements needed for general anesthesia in dogs.  Dogs will be anesthetized with gas anesthesia and the minimum amount of gas anesthesia needed to keep them from responding to a painful stimulus will be determined.  A well established method of stimulating the nerves located within teeth will provide the stimulus in this study.  After the minimum amount of gas anesthesia needed to keep the patient immobilized in response to stimulus has been established, a dental nerve block will be performed.  The minimum amount of anesthetic will again be established with the addition of the dental nerve block.  Cardiovascular and respiratory parameters will be recorded throughout the study.  We expect to prove that dental nerve blocks can reduce the amount of gas anesthesia required to keep the patient asleep and pain-free during dental procedures and therefore improve the safety of anesthesia by reducing the dose-dependant cardiovascular and respiratory side effects. Results of this study would provide additional support for widespread use of dental blocks in dogs undergoing dental procedures and subsequently minimize risks of general anesthesia in these patients.

Effect of antioxidant supplementation on intracellualr glutathione, urine isopostanes, clinical score, and survival in clinically ill dogs.
Dr. Katrina Viviano, Department of Medical Sciences

Oxidative damage has been implicated in the ageing process and considered a contributing factor in many diseases.  The body’s primary natural defense against oxidative damage is antioxidants.  Glutathione is one of the many natural antioxidants that is pivotal in protecting cells from oxidative damage.  Evidence supporting excessive oxidative damage or oxidative stress include decreased antioxidant levels and increased oxidative products generated from cell damage termed lipid peroxidation.  Antioxidant depletion, specifically glutathione, has been reported in many systemic disease states in humans including the critically ill and associated with poor clinical outcomes.  Plasma or urine 8-isoprostane concentrations are considered a specific marker for lipid peroxidation with levels correlating with disease severity in humans.  Antioxidant supplementation as a means of modulating oxidative stress has been studied using many antioxidants with varying degrees of success in humans.  In particular, the antioxidant N-acetylcysteine has been used to replete intracellular glutathione.  In veterinary medicine therapeutic antioxidant intervention is primarily empirical or extrapolated from human medicine as limited objective scientific therapeutic trials are undertaken.  A previous study in our laboratory documented decreased glutathione levels in ill dogs with the degree of depletion correlating with disease severity.  The purpose of this study is to objectively evaluate the effect supplementation with N-acetylcysteine has on normalizing red blood cell glutathione, decreasing urine 8-isoprostane concentrations, improving clinical score, and impacting outcome in a group of glutathione deficient clinically ill dogs.  The results of this study may provide a therapeutic rationale for antioxidant therapy in clinically ill dogs.  

Plasma atrial natriuretic peptide and brain natriuretic peptide concentrations in hyperthyroid cats.
Dr. Jonathan Bach, Department of Medical Sciences

Determination of the effect of 3-bromopyruvate on canine normal and tumor cell lines.
Dr. Ruthanne Chun, Department of Medical Sciences

Identification of cancer stem cells in canine melanoma.
Ilene Kurzman, Department of Medical Sciences

Studies in low temperature blood-free perfusion for prolonged cardiac arrest in the dog.
Dr. Jonathan McAnulty, Department of Surgical Sciences

Estimation of bacterial copy number in stifle joint tissues in dogs with chronic inflammatory arthritis and degenerative cranial cruciate ligament rupture.
Dr. Peter Muir, Department of Surgical Sciences

Pilot study to address the treatment of iron overload in common marmosets using oral chelation therapy and dietary modification.
Dr. Joanne Paul-Murphy, Department of Surgical Sciences

The development of standardized anatomic landmarks for magnetic resonance imaging of the canine shoulder.
Dr. Susan Schaefer, Department of Surgical Sciences

Magnification radiography in large animal patients.
Dr. Tobias Schwarz, Department of Surgical Sciences

Effect of initial fluid resuscitation and intravenous plasma administration on colloid osmotic pressure in critically ill neonatal foals.
Dr. Susan Semrad, Department of Medical Sciences

Evaluation of meloxicam for treatment of arthritic pain in the parrot.
Dr. Kurt Sladky, Department of surgical Sciences

Non-invasive assessment of cardiac response to naturally-occuring systemic hypertension in dogs.
Dr. Rebecca Stepien, Department of Medical Sciences