Companion Animal Fund Research

The Companion Animal Fund is supported by donations from veterinary medical clinics with which the school has established strong ties, as well as individual donors whose animals have been patients at UW Veterinary Care.

Through an annual competitive process, the school uses the funds to award faculty with grants to further research that will enhance the care of companion animals.

In addition to bolstering research, funds support facility and equipment improvements that help UW Veterinary Care clinicians provide enhanced diagnostics and treatments for patients.

Read more about ways the Companion Animal Fund has brought tangible improvements to the care of animals around the world.

Past Projects

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2021 Projects

DOES INCISIONAL LIPOSOME-ENCAPSULATED BUPIVACAINE PROVIDE ADEQUATE ANALGESIA AFTER CANINE ENUCLEATION?

Principal Investigator:
Ellison Bentley, Clinical Professor, Department of Surgical Sciences
Abstract:
Many dogs need eye removal (enucleation) performed due to painful conditions that have resulted in permanent blindness. We have used this model to assess local anesthetic blocks and comparisons of systemic analgesics for enucleation. Specifically, we have published on the efficacy of regular bupivacaine for relief of pain after enucleation when it is administered via an injection behind the eye. This technique requires training and practice, and has risks (e.g. puncture of the eye, etc.), which means some practitioners avoid it. A new formation of bupivacaine (Nocita®) is reported to provide up to 72 hours of analgesia when injected into surgical closure layers, which is a simple technique that requires minimal training. The goal of this study is to assess analgesia in dogs requiring enucleation that have received Nocita® administered during surgical closure compared to an injection of regular bupivacaine behind the eye.

EFFECT OF BODY CONDITION SCORE ON THE PHARMACOKINETICS OF GENTAMICIN IN ADULT HORSES

Principal Investigator:
Alexandra J. Burton, Clinical Assistant Professor, Department of Medical Sciences
Abstract:
Gentamicin is an important, often life-saving antibiotic commonly used in equine and human medicine for the treatment and prevention of infections caused by Gram negative bacteria. In humans, body mass index influences dosage of gentamicin. In overweight and obese people, gentamicin is metabolized differently compared with non-obese patients due to altered drug distribution in the body and pharmacokinetics.

Horses are particularly sensitive to kidney injury (nephrotoxicity) from gentamicin. As with humans, increasingly in the modern world, many horses and ponies are overweight or obese. However the effect of excess body condition on the metabolism of gentamicin has not been assessed in the horse. The aim of this study is to assess the pharmacokinetics (metabolism) of gentamicin in relation to fat mass [body condition score (BCS)] in healthy adult horses.

The goal of this study is to determine if, as with humans, gentamicin dose may need to be adjusted based upon equine BCS in order to maintain effective bacterial killing and enhance the safety of this vital drug.

We hypothesize that there will be a significant difference in the gentamicin concentration at 24 hours. Finally, we hypothesize that an adjusted gentamicin dosage regimen will be required for horses with a BCS of 6/9 or above.

PHARMACODYNAMIC AND PHARMACOKINETIC EVALUATION OF SUBCUTANEOUS METHADONE IN AFRICAN PYGMY HEDGEHOGS

Principal Investigator:
Grayson Doss, Clinical Assistant Professor, Department of Surgical Sciences
Abstract:
African pygmy hedgehogs are frequently presented to veterinarians for a variety of painful or surgical conditions. However, information on effective and safe analgesic (pain-relieving) protocols in this species is significantly lacking. Effective pain management is particularly important in small exotic mammals with high metabolic rates and low stress thresholds, where uncontrolled pain can have serious negative physiologic effects. Currently, the vast majority of recommendations for analgesic drugs in hedgehogs are anecdotal in nature or extrapolated from dissimilar animal orders, like rodents or cats and dogs. Consequently, hedgehogs requiring analgesia are at risk of being treated with ineffective dosages of analgesic drugs, or receiving repeated doses at incorrect dosing frequencies, leading to either lack of pain control or potential adverse effects.

Recently, the pharmacodynamics of subcutaneously administered buprenorphine in hedgehogs have been published and results indicate a very prolonged duration of effect compared to other mammals. Therefore, the evaluation of other analgesic drugs, in particular mu-agonist opioids, is indicated in hedgehogs, in order to avoid extrapolation from other species. The proposed study will evaluate the analgesic efficacy and safety as well as the pharmacokinetic profile of injectable methadone hydrochloride, an opioid analgesic drug commonly used in veterinary medicine, in African pygmy hedgehogs. Veterinarians providing care for hedgehogs can readily apply the results of this study to clinical practice.

PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE-FREE ACID ADMINISTERED VIA INTRAMUSCULAR INJECTION IN WHOOPING CRANES

Principal Investigator:
Barry Hartup, Clinical Instructor, Department of Surgical Sciences
Abstract:
Bacterial infections are a common cause of disease in many birds. Handling larger wild birds, multiple times a day, for treatment due to their higher metabolism can increase stress and risk of accident or injury. Ceftiofur crystalline free acid (CFA) is an extended-release formulation of a broad-spectrum antibiotic that has been studied in a small number of birds, and has shown potential for less frequent administration to treat susceptible infections. Our project aims to study ceftiofur CFA following administration in endangered Whooping Cranes, a species of significant conservation value in Wisconsin and North America. Our goal is to determine an appropriate dosing protocol for ceftiofur CFA in this species, while also improving patient welfare, positive clinical outcomes, and fostering responsible use of antibiotics in non-domestic birds.

FLEA-BORNE PATHOGENS IN FLEAS AND FREE-ROAMING CATS ACROSS GEORGRAPHIC LOCATIONS

Principal Investigator:
Erin Lashnits, Clinical Assistant Professor, Department of Medical Sciences
Abstract:
Recent epidemics of flea-borne diseases in humans, including typhus and cat scratch disease, have been linked to free roaming cats. There are two zoonotic bacteria carried by cats and transmitted by their fleas that are listed as priority pathogens by the National Institutes of Health: Bartonella and Rickettsia species. Free-roaming domestic cats live at the intersection between humans, their pets, wildlife, and the parasites that infest all these animals, creating novel opportunities for pathogens to cross species. Unlike their indoor-only brethren, these cats often have limited or no access to veterinary care, increasing the risk that they carry fleas and transmit disease. Little is known about the risk factors for transmission from these cats and their fleas. In other common vectors of zoonotic disease (ticks and mosquitos), the resident bacterial communities (microbiomes) can affect pathogen transmission. Though co-infection of fleas with multiple pathogenic bacteria has been reported, little is known about the interaction of pathogenic and non-pathogenic bacteria within cat fleas with regard to pathogen transmission.

To address these gaps, we will collect fleas from free roaming cats at multiple geographic locations, determine the presence and abundance of pathogenic and nonpathogenic bacteria using 16S rRNA next-generation sequencing (16S-NGS), and determine the role of flea, host, and landscape-level-factors in pathogen presence in these fleas. To address the role that the microbiome of fleas is playing in transmission of disease among cats, we will also collect samples from the cats to test them for flea-borne disease that may impact their health, as well as human health.

18F-FDG-PET MRI IN CANINE BRAIN TURMOR PATIENTS: A PILOT STUDY

Principal Investigator:
Samantha Loeber, Clinical Assistant Professor, Department of Surgical Sciences
Abstract:
Positron emission tomography (PET) is a diagnostic imaging tool that uses a radioactive drug, called a tracer, to provide metabolic information about tissues in the body. PET imaging has been widely studied in humans and is often used for cancer diagnosis and staging, in combination with computed tomography (CT) and magnetic resonance imaging (MRI). In human brain tumor patients, PET-MRI can be used to differentiate tumor type and grade; however this modality remains relatively novel in veterinary medicine. The aim of this pilot study is to describe PET-MRI imaging characteristics and glucose metabolism of brain tumors in dogs. Preliminary results will serve as a baseline for canine patients and provide data for sample size calculations to support future proposals. Describing the utility of PET-MRI in dogs is an important first step in incorporating this tool into clinical veterinary practice and improving overall patient care.

DISTAL FORELIMB VASCULAR AND SOFT TISSUE EVALUATION IN HORSES WITH STANDING COMPUTED TOMOGRAPHIC VENEOGRAPHY

Principal Investigator:
Jane Lund, Clinical Assistant Professor, Department of Surgical Sciences
Abstract:
Radiographic venography in the distal limbs (everything below the knee and hock) of the horse has been used for decades to evaluate the passage of fluids through tissue (perfusion), guide treatment and monitor the progression of disease. There are inherent limitations with radiography which computed tomography (CT) overcomes. To date, computed tomographic venography in the normal horse has not been described.

The objectives of this study are to accurately describe normal vascular filling patterns of the distal limb during standing CT venography and to describe the soft tissue enhancement of structures within the distal limb during and immediately after CT venography. Standing CT venography has been successfully performed at UWSVM in a few lame and sound horses. Ten normal horses will have standing CT venography with pre-venographic and post-venogram standing CT imaging. Images will be assessed for vascular filling and soft tissue contrast enhancement in CT scans performed prior to, during, and after venography. The goal of this study is to provide a reference of standing CT venography and soft tissue contrast enhancement using a reproducible method in normal horses. This will allow practitioners and researchers to immediately improve their imagining and diagnostic capabilities.

SAFETY AND EFFICACY OF MIRTAZAPINE AS AN APPETITE STIMULANT IN CHINCHILLAS

Principal Investigator:
Christoph Mans, Clinical Associate Professor, Department of Surgical Sciences
Abstract:
Chinchillas are popular companion animals and are increasingly being evaluated by veterinarians for various health problems. Reduced appetite due to underlying disease is the most common presenting complaint in companion chinchillas. Common underlying causes for the reduced appetite include dental disease, liver disease, bacterial infections as well as stress and pain. A prolonged reduction in food intake will result in a negative energy balance, gastrointestinal disturbances, compromised immunity, and impaired liver function. For other companion animals, such as dogs and cats, appetite-stimulating drugs such as mirtazapine and capromorelin have been shown to be safe and effective and are therefore used routinely. However, no such information is available in chinchillas. Thus, in the study proposed here, we aim to determine safe and effective mirtazapine doses in chinchillas. The results of this study will have a broad and immediate impact on the clinical management of chinchillas and will provide veterinarians with information on the efficacy and safety of mirtazapine in chinchillas. Our study’s findings have the potential to reduce morbidity and mortality associated with reduced food intake in this species.

DEVELOPMENT AND VALIDATION OF BEHAVIORAL VISUAL ACUITY AND CONTRAST SENSITIVITY TESTS IN DOGS

Principal Investigator:
Freya Mowat, Assistant Professor, Department of Surgical Sciences
Abstract:
When we humans go to the eye doctor, our vision is tested using a standardized letter chart. The goal of our research is to develop and validate a method to similarly test vision in pet dogs. Pet dogs are emerging as important models for human aging, and our research studies would benefit greatly from understanding how the dog vision system ages in comparison with humans. We have an ongoing project exploring methods to reproducibly and rapidly test vision in dogs, so vision impairment or decline can be detected more easily in patients, and the effect of age on the visual system can be studied.

GENOME-WIDE SIGNATURE OF SELECTION ANALYSIS FOR GENES ASSOCIATED WITH DEGENERATIVE SUSPENSORY LIGAMENT

Principal Investigator:
Peter Muir, Professor, Department of Surgical Sciences
Abstract:
Many diseases in horses have a genetic contribution and are breed-related. Degenerative suspensory ligament desmitis (DSLD) is an untreatable, progressive, crippling disorder that is common in the Peruvian Horse, and the Akhal Teke, and is seen in specific breeding lines. There is a critical need to determine the genetic basis of DSLD. Our long-term goal is to identify the genetic mutation that causes DSLD. We will undertake an association analysis comparing DSLD case and control horses of different breeds using genome-wide markers (SNPs, single nucleotide polymorphisms) to identify a genomic region that is undergoing selection and contains DSLD-associated markers for future discovery of the causal mutation. The research is innovative and significant because it uses a new method for genome-wide association. High impact is also expected as our results will likely discover the genetic basis of DSLD and advance development of genetic testing for DSLD in affected breeds of horse.

MECHANISMS OF CHOP TREATMENT RESISTANCE IN CANINE DIFFUSE LARGE B CELL LYMPHOMA

Principal Investigator:
Xuan Pan, Associate Professor, Department of Medical Sciences
Abstract:
Diffuse large B cell lymphoma (DLBCL) is one of the most common hematological cancers in humans and dogs. The current standard of care for human DLBCL (hDLBCL) and canine DLBCL (cDLBCL) involves extensive chemotherapy. However, almost all of canine responders will relapse within one year of the treatment. Because of the high frequency of relapse and comparable attributes to hDLBCL, cDLBCL offers a powerful comparative model to assess drug resistance mechanisms and develop novel therapeutic strategies to surmount unmet clinical needs. We hypothesize that certain genetic mutations confer advantages in lymphoma cell growth, resulting in clonal expansion of the affected cells after chemotherapy treatment. We aim to establish mechanisms that determine chemotherapy treatment resistance by whole genome sequencing study. Our proposed studies will shed new cellular and molecular insights into the mechanism of chemo resistance, which provide the mechanistic rationale for the development of novel therapeutic strategies in lymphoma.

MODERNIZING CANINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I GENOTYPING

Principle Investigator:
Matt Reynolds, Assistant Professor, Department of Pathobiological Sciences
Abstract:
Dogs share their environments, lifestyles, and genetic predispositions for disease with humans. Major histocompatibility complex class I (MHC-I) molecules are essential components of the immune system, identifying diseased cells. MHC-I genes are incredibly diverse in humans and dogs, necessitating MHC “matching” for organ transplants. The inheritance of specific MHC-I variants, called alleles, also affects susceptibility to inflammatory, infectious, and autoimmune diseases. However, the impact of canine MHC-I genes on disease outcomes is poorly understood. For humans, determining which MHC-I alleles a person possesses, called MHC genotyping, uses sophisticated sequencing techniques. Similar MHC genotyping is not available for dogs. This proposal aims to modernize canine MHC genotyping by adapting it to the Illumina sequencing-by-synthesis platform. We anticipate this method will benefit canine MHC-I disease association studies and determine the impacts of individual MHC-I genes on cancer therapies.

DE NOVO ASSEMBLY OF AN IRISH WOLFHOUND REFERENCE GENOME FOR GENOMIC INVESTICATION OF OSTEOSARCOMA

Principle Investigator:
Susannah Sample, Assistant Professor, Department of Surgical Sciences
Abstract:
We are studying the genomic basis of osteosarcoma in the Irish Wolfhound breed. Osteosarcoma is devastating to the Irish Wolfhound breed, being responsible for over 20% of deaths in this breed. Our long-range goal is to determine the genetic contribution to OSA risk in the young Irish Wolfhound. The funds from our companion animal grant are contributing to the establishment of a reference-grade genome for the Irish Wolfhound, which will be used as the basis of genomic mapping of osteosarcoma. The canine reference genomes, canFam3.1 and canFam4.0, are based on a single Boxer dog and a single German Shepherd Dog, respectively. For canine genomic studies, use of a canine reference genome from a substantially different breed than that under investigation is problematic because of breed-related genomic structural variation. This reference genome will eventually be made available to the wider scientific community, proving a valuable reference for future studies.

EVALUATION OF THE EFFECTIVENESS OF TWO FASCIAL PLANE BLOCKS FOR ABDOMINAL WALL ANALGESIA IN DOGS

Principle Investigator:
Carrie Schroeder, Clinical Assistant Professor, Department of Surgical Sciences
Abstract:
Abdominal surgical procedures are commonly performed in dogs, requiring pain relief by several means. Fascial plane blocks are a type of regional anesthesia that rely on local anesthetic injection into an area that contains multiple nerves, allowing for a large area of pain relief with minimal injection points. Fascial plane blocks that provide pain relief to the abdominal incisions include the transversus abdominis plane (TAP) block and rectus sheath block (RSB). These blocks have been studied in cadavers, but no controlled studies in living patients have been performed. The goals of this foundational study will be to evaluate the spread of injectate following TAP block and RSB in anesthetized dogs and the efficacy of the TAP block and RSB in conscious dogs. Characterization of these novel blocks in dogs will improve the pain control of patients undergoing abdominal surgical procedures and may allow for reductions in opioid usage.

MUTAGENICITY OF ENVIRONMENTAL CHEMICALS FOUND IN THE URINE OF PET DOGS

Principle Investigator:
Lauren Trepanier, Professor, Department of Medical Sciences
Abstract:
Bladder cancer can lead to pain, difficulty urinating, and eventual euthanasia in affected dogs. Bladder cancer in people is caused by environmental chemicals, including tobacco smoke, and we suspect that environmental chemicals in the household cause bladder cancer in dogs as well. We surveyed the urine of healthy dogs and their owners for chemicals that have been associated with bladder cancer, including arsenic, the air pollutant acrolein, and the herbicide breakdown product 4-chlorophenol. We found urinary exposures to these chemicals in most individuals, with a wide range of concentrations. Our goal with this study is to see whether these chemical levels can cause DNA damage in dog and human urinary cells. This will allow us to understand the role of household chemical exposures in urinary DNA damage, which is the first step in bladder cancer development.

STEREOTACTIC RADIOTHERAPY FOR ADVANCED CANINE ANAL SAC ADENOCARCINOMA: A PILOT STUDY

Principal Investigator:
Nate Van Asselt, Clinical Assistant Professor, Department of Surgical Sciences
Abstract:
Anal sac adenocarcinoma (ASAC) is a common tumor diagnosed in the perianal region in dogs.  ASAC is locally invasive, often causing discomfort, as well as highly metastatic (likely to spread) to regional lymph nodes. Treatment of this tumor is complicated and can consist of surgery, radiation and/or chemotherapy. While surgery is the most aggressive and effective means of irradiating cancer, radiation can provide a reasonable alternative when surgery is not possible.  Stereotactic radiation (SRT) is the precise and highly conformal deliverance of large doses of radiation in just a few treatments (often 3).

The goal of SRT is to give ablative doses of radiation while sparing critical organs such as the colon. Our primary goal is to ensure that SRT is safe to use in dogs with anal sac adenocarcinoma.  Our secondary goal is to see how this tumor responds to large doses of radiation.

SERUM AMYLOID A: CLINICAL BIOMARKER TO ASSIST IN IDENTIFYING CATS WITH ANTIBIOTIC-RESPONSIVE ACTURE BACTERIAL KIDNEY INFECTIONS

Principal Investigator:
Katrina Viviano, Clinical Assistant Professor, Department of Medical Sciences
Abstract:
Bacterial kidney infections are a common clinical diagnosis in cats resulting in treatment with antibiotics. Determining which cats’ benefit from antibiotic  treatment remains a clinical challenge as the signs associated with this disease are vague and the recognition that bacterial culture negative kidney infections occur in cats. In people with bacterial kidney infections, serum amyloid A (SAA) concentrations are significantly increased and used to monitor response to treatment. No studies have investigated the use of SAA, the major acute phase protein in cats, as a marker for bacterial kidney infections. The aim of this study is to determine if SAA concentrations in client-owned cats can assist in identifying antibiotic responsive bacterial kidney infections and to determine if SAA concentrations correlate with clinical improvement. The results of this study may support future studies to evaluate the use of SAA in cats with bacterial kidney infections, including individualizing the duration of antibiotics.

PHARMACODYNAMIC PROPERTIES OF THE CALCIMIMETIC AGENT CINACALCET IN HEALTHY DOGS

Principal Investigator:
Michael Wood, Assistant Professor, Department of Medical Sciences
Abstract:
Primary hyperparathyroidism (PHP) is a disease of older dogs where the parathyroid gland oversecretes parathyroid hormone resulting in dangerous increases of blood calcium. The traditional treatment option for PHP is to surgically remove the parathyroid glands, but this procedure is not without complications. Cinacalcet is an oral calcimimetic drug used to lower serum calcium in humans with PHP when surgery is not possible. Cinacalcet may be a viable non-invasive therapeutic option for dogs with PHP. The primary aim of this study is to determine whether cinacalcet decreases blood ionized calcium (iCa), total calcium (tCa), and parathyroid hormone (PTH) concentrations in healthy dogs. We hypothesize that a well-tolerated starting dose of cinacalcet can be established in dogs that leads to clinically relevant decreases in iCa, tCa, and PTH. This pilot study will provide the basis for a prospective clinical trial testing the efficacy and tolerability of cinacalcet in dogs with PHP.

2020 Projects

EX-VIVO EVALUATION OF A PERCUTANEOUS LOOPED THREAD TECHNIQUE FOR TENOTOMY OF NORMAL DEEP DIGITAL FLEXOR TENDONS IN HORSES

Principal Investigator:
Diego De Gasperi, clinical instructor, Department of Surgical Sciences
Abstract:
Tenotomy of the equine deep digital flexor tendon (DDFT) is indicated mostly for chronic refractory laminitis cases. Approaches described for DDFT tenotomy include the mid metacarpal/metatarsal and the mid-pastern approaches. A minimally invasive equine DDFT tenotomy technique that requires no skin incision has not been described in the literature.

Our objective is to describe the feasibility of a minimally invasive technique for tenotomy of the normal equine DDFT. The specific aims of this study are to (1) develop a percutaneous looped thread technique for transection of the equine DDFT, (2) determine the most appropriate site for thread placement, and (3) evaluate completeness of the DDFT transection and potential damage to adjacent structures. We hypothesize that complete transection of normal DDFTs with no injury to the adjacent structures can be performed safely with this novel technique.

Under ultrasonographic guidance, a thread will be percutaneously routed around the DDFT through 2 skin punctures using spinal needles in twenty cadaveric limbs. The tendon will be manually divided by a back-and-forth motion of the thread until the loop emerges from one of the skin puncture sites. Each specimen will be dissected and assessed for completeness of transection and iatrogenic damage under direct visualization. Descriptive statistics will be reported.

If the percutaneous looped thread technique is feasible for tenotomy of the equine DDFT, we plan to evaluate this technique in live, standing clinically normal horses as well as laminitic horses. Information from this study will allow refinement of this technique for use in equine clinical cases.

EVALUATION OF THE APPETITE-STIMULATING EFFECTS OF LORAZEPAM AND CAPROMORELIN IN BUDGERIGARS (MELOSPITTACUS UNDULATUS)

Principal Investigator:
Greyson Doss, clinical assistant professor, Department of Surgical Sciences
Abstract:
Small bird species are common veterinary patients that are routinely hospitalized for treatment. Often, birds eat less while in the hospital, likely due to illness as well as stress. This decrease in food intake can have significant negative impacts on the immune system and wound healing and can result in detrimental metabolic changes in small birds. To correct this anorexia, hospitalized birds must be force-fed using a feeding tube, increasing patient stress and morbidity. This 2020 University of Wisconsin-Madison School of Veterinary Medicine Companion Animal Fund Grant will support research investigating appetite-stimulating drugs in the budgerigar, a popular pet parrot species. The evaluated drugs have been shown to increase appetite in other species such as cats, dogs and rodents. If we can prove efficacy, the ability to provide an oral appetite stimulant to birds would avoid the need for frequent tube-feedings and subsequently decrease the risks associated with the procedure, improving patient welfare.

EVALUATING THE THERAPEUTIC POTENTIAL OF A NOVEL MODIFIED PROSTAGLANDIN ANALOG AS A FIRST-LINE TREATMENT FOR FELINE GLAUCOMA

Principal Investigator:
Seth Eaton, clinical assistant professor, Department of Surgical Sciences
Abstract:
Feline glaucoma is associated with impaired aqueous humor (AH) outflow from the eye, leading to increased intraocular pressure (IOP) which risks discomfort and blindness secondary to degeneration of the optic nerve and retina. Unfortunately, few marketed drugs are well-tolerated or proven to effectively reduce IOP in feline eyes, limiting viable treatment options. Consequently, affected feline eyes must often be surgically removed to alleviate the discomfort associated with chronically increased IOP. Glaucoma also continues to be a therapeutic challenge in human patients, and ongoing development of novel IOP-reducing drugs has recently produced agents that show new promise for successful treatment of cats with glaucoma. One novel drug, latanoprostene bunod (LBD), is a modified prostaglandin analog that reduces IOP via multiple mechanisms including liberation of nitric oxide inside the eye. Nitric oxide increases aqueous outflow by structurally and functionally altering the eye’s aqueous outflow channels and vessels, putatively increasing their functional capacity. In cats, recent work utilizing advanced ocular imaging techniques has contributed to a growing body of research identifying structural abnormalities of these vessels and vessel-like channels in cats with glaucoma, elucidating a potentially contributory pathologic mechanism in this species. The purpose of the proposed study is to evaluate the efficacy of LBD for altering these pathways and reducing IOP in normal and glaucomatous cats. Characterization of the pharmacologic effects of this drug in feline eyes will improve our understanding of its potential as a viable therapeutic in cats and inform future studies in patients with various forms of glaucoma.

 

LYMPHATICOVENOUS ANASTOMOSIS OF THE CAUDAL THORACIC DUCT TO INTERCOSTAL VEIN IN A CANINE MODEL AS A NOVEL TREATMENT FOR IDIPATHIC CHYLOTHORAX IN DOGS

Principal Investigator:
Robert Hardie, clinical associate professor, Department of Surgical Sciences
Abstract:
Idiopathic chylothorax in dogs is a debilitating disease manifested by accumulation of chyle in the thorax. The cause is likely due to obstruction of flow from the thoracic duct (TD) as it enters the systemic circulation resulting in leakage of chyle from the lymphatics in the cranial mediastinum. Ligation of the caudal TD and ablation of the cisterna chyli is the current treatment of choice and is designed to block the flow of chyle to the chest and promote formation of acquired lymphaticovenous anastomosis (LVA) outside the chest bypassing the leaking lymphatics in the cranial mediastinum. The technique is relatively successful but lack of adequate LVA formation serves as a stimulus for development of collateral circulation around the TD ligation and thus recurrence of chylothorax. The goal of this study is to build on our recent cadaveric study and validate the feasibility of anastomosing the TD to an intercostal vein (ICV) with a microvascular coupling device in an experimental model. The rationale for this technique is to eliminate pressure within the abdominal lymphatics and thus the stimulus for collateral circulation around the TD ligation by creating a direct LVA between the TD and ICV. Six dogs will undergo TD to ICV anastomosis and be evaluated for 30 days to determine long-term patency and healing characteristics of the anastomosis via lymphangiography and histopathology. Our hypothesis is that the technique will be feasible, and the anastomosis will remain patent during the healing process. This technique represents a novel approach for the treatment of chylothorax and holds promise for improving outcomes for this challenging disease.

 

EVALUATION OF POST-PRANDIAL CHANGES IN PLASMA URIC ACID LEVELS IN BEARDED DRAGONS (POGONA VITTICEPS): EFFECTS OF PROTEIN SOURCE AND MEAL SIZE

Principal Investigator:
Christoph Mans, clinical assistant professor, Department of Surgical Sciences
Abstract:
In reptiles, blood uric acid is currently the most commonly used parameter to assess kidney function and dehydration. It has been suggested that reptiles do not experience a clinically relevant increase in blood uric acid levels after meal ingestion (post-prandial), unlike what is seen in meat and fish-eating bird species, which share many anatomical and physiological similarities with reptiles. However, recently published pilot data from our research laboratory has demonstrated that bearded dragons (Pogona vitticeps) show a clinically relevant and statistically significant increase in uric acid levels by 24 hours after ingestion of a cricket meal. Therefore, we propose to further evaluate the effects of recent food ingestion on blood uric acid levels in bearded dragons, and evaluate if the type of protein (plant vs animal protein) as well as the meal size affect post-prandial uric acid levels differently. For clinicians and researchers, it is critically important to better understand post-prandial blood uric acid increases in terrestrial reptiles, such as bearded dragons, in order to avoid misdiagnosis of kidney disease in animals which have recently eaten. It is also important to understand how long animals should be fasted before measuring blood uric acid levels, if samples are collected in order to establish normal uric acid blood reference intervals in captive and free-ranging reptile species.

 

GENETIC BASIS OF FIBROTIC MYOPATHY IN THE GERMAN SHEPHERD DOG

Principal Investigator:
Peter Muir, professor, Department of Surgical Sciences
Abstract:
Fibrotic myopathy is an example of a rare canine disease with a marked breed
predisposition in the German Shepherd Dog (GSD). It affects the medial thigh muscles and leads to disabling hindlimb lameness. Treatment of fibrotic myopathy is ineffective. There is a critical gap in knowledge regarding the best approach to investigate rare canine genetic diseases, but new DNA sequencing technologies promise substantial advances. Our long-range goal is to determine the genetic contribution to GSD fibrotic myopathy and then develop a fibrotic myopathy genetic screening test. Our central hypothesis is that GSD fibrotic myopathy is a recessive Mendelian genetic disease. To test this hypothesis, we will pursue the following specific aim: Discover the fibrotic myopathy candidate genetic variant using linked-read whole genome sequencing of case and control GSDs. Linked-reads will be aligned to a new GSD reference genome assembled in our laboratory to enhance calling of genetic variants for case control association. The rationale for this work is that discovery of a fibrotic myopathy genetic variant and development of a genetic test would enable breed improvement and advance screening of at-risk dogs for improved personalized medical care. Our approach is innovative because we will use state-of-the-art DNA sequencing methods to investigate an important disease where genome-wide association is not feasible because of disease rarity. Our results will have a positive translational impact because canine fibrotic myopathy models human idiopathic congenital torticollis. In addition, our results will advance knowledge regarding technical approaches for studying rare diseases in both companion animals and humans.

 

MOLECULAR DETERMINANTS FOR PEVONEDISTAT TREATMENT SENSITIVITY IN DOGS WITH DIFFUSE LARGE B-CELL LYMPHOMA

Principal Investigator:
Xuan Pan, associate professor, Department of Medical Sciences
Abstract:
Canine diffuse large B cell lymphoma (DLBCL), the most common hematologic malignancy of dogs, is associated with poor overall survival. The lack of conventional chemotherapies with sustainable efficacy warrants investigation of novel therapies. Pevonedistat, a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor, is currently undergoing human phase I/II clinical trials for treating various hematologic malignancies. Similar to humans, there is great heterogeneity in canine DLBCL, and the treatment response to cytotoxic chemotherapy or pathway-specific targeted therapy varies between individuals [1]. Following the publication of the canine genome sequencing [2], substantial progress has been made in understanding canine pharmacogenomics. Determining molecular signatures for pevonedistat treatment sensitivity will provide clinical guidance for selecting the most appropriate treatment through a personalized medicine approach. We hypothesize that there is a distinct gene expression profile in pevonedistat sensitive DLBCL and molecular profiling of canine lymphoma samples allows for tailoring medical care to individual needs. Our aim is to establish molecular signatures that determine canine DLBCL sensitivity to pevonedistat treatment. Elucidating the molecular signatures of pevonedistat-associated therapeutic effect and drug resistance will forge new avenues for understanding the cross-talk between different signaling pathways in both canine and human DLBCLs. Our study will provide justification for further clinical application and a pre-treatment patient screening tool for pevonedistat treatment.

 

BIOMECHANICAL TESTING OF TITANIUM TRAUMA SPLINT™: A NOVEL, NON-INVASIVE METHOD OF REPAIR OF MANDIBULAR FRACTURES IN DOGS

Principal Investigator:
Graham Thatcher, clinical assistant professor, Department of Surgical Sciences
Abstract:
Mandibular fractures in canine patients are relatively common and are identified in approximately 90% of canine maxillofacial trauma patients. 1-4 Canine mandibular fractures commonly occur at the mandibular carnassial tooth (M1). This area of weakness is a result of the large volume of M1 relative to the mandibular bone, which causes and area of weakness in the mandible.1-3 These fractures are typically stabilized through repair techniques where stabilization is applied in the oral cavity, or by open reduction and rigid internal fixation. Orthopedic repair techniques using plates and screws can be difficult to apply to the mandible without traumatizing vital structures, when attempting to apply tension band principles.5 Minimally-invasive, intraoral repair techniques involve placing wires around teeth at the cervical portion of the crown (interdental wiring) and the application of bis-acryl splints bonded to the tooth crowns, thereby applying tension band principles. Studies have shown that the combination of interdental wiring with composite splints is a stronger form of fixation than either technique used alone.6 Interdental wiring techniques require extensive practice, they are time consuming and cause periodontal trauma resulting in pain and suffering. An alternative splinting product, Titanium Trauma Splint (TTS) may offer a solution to the challenges associated with interdental wiring. This pilot study is designed to investigate two test questions. These questions include: (1) can a mandibular fixation construct with TTS and bis-acryl splint provide similar biomechanical stability for fixation of mandibular fractures compared with traditional, interdental wiring and bis-acryl splint repair technique; and (2), can the use of a TTS and bis-acryl splint decrease the operative time required compared to the traditional interdental wiring and bis-acryl splint repair technique?

 

IMPROVING ANALGESIC EFFICACY AND WELFARE IN SNAKES WITH FENTANYL PATCH APPLICATION

Principal Investigator:
Mary Thurber, clinical instructor, Department of Surgical Sciences
Abstract:
Snakes are commonly kept as pets and educational animals in zoos. While pain management in snakes has been studied extensively, there are no scientifically-proven pain management drugs effective in snakes. The lack of effective pain control is detrimental to snake welfare, leading to decreased activity and mobility, reduced appetite, and failure to thrive. Recent anecdotal evidence suggests that fentanyl patch application (opioid pain medication) provides pain control to snakes, leading to increased food consumption, activity, and mobility. In collaboration with the San Diego Zoo, we will evaluate the impact of fentanyl patches on subjectively painful snakes. The snakes’ behavior will be evaluated using remote video-recording monitoring. Control experiments will be conducted at the UW SVM to evaluate the impact of fentanyl and sham patches on healthy snakes’ behavior. This study may be the first to convincingly demonstrate fentanyl-dependent pain management in snakes, and dramatically improve snake welfare under human care.

 

EVALUATION OF EFFICACY OF AMIODARONE OR DILTIAZEM TO ACHIEVE OPTIMAL HEART RATE CONTROL IN DOGS WITH ATRIAL FIBRILLATION

Principal Investigator:
Sonja Tjostheim, clinical assistant professor, Department of Medical Sciences
Abstract:
Atrial fibrillation (AF) is a common complication of structural heart disease in dogs. Atrial fibrillation is a rapid arrhythmia that, if inadequately treated, contributes to uncontrolled congestive heart failure (CHF) and increased risk of cardiac-related death. Atrial fibrillation is frequently managed with antiarrhythmic medications that lower the heart rate (HR). Recently, it was shown that dogs with AF live longer if their 24-hour average HR are less than 125 beats per minute (termed “strict HR control”). The best drug or drug combination to achieve this HR target remains unknown. Diltiazem and amiodarone are antiarrhythmic drugs that are commonly used for HR control in dogs with AF, however, there is little information about their efficacy for achieving strict HR control. Our objective is to determine if strict HR control can be achieved in dogs with newly diagnosed AF with either diltiazem or amiodarone, or with the combination of the two drugs. Our hypothesis is that treatment with one drug (diltiazem or amiodarone) will not result in strict HR control, however, strict HR control will be achieved with combination treatment of amiodarone and diltiazem. This work is innovative because it is the first to prospectively compare oral amiodarone treatment with oral diltiazem therapy in dogs with naturally occurring newly diagnosed AF, and it has the potential to improve our ability to treat this life-limiting arrhythmia.

 

HYPERHOMOCYSTEINEMIA AND OXIDATIVE STRESS IN GREYHOUND DOGS

Principal Investigator:
Lauren Trepanier, professor, Department of Medical Sciences
Abstract:
Homocysteine is an amino acid involved in the synthesis of methionine and cysteine. Accumulation of homocysteine (hyperhomocysteinemia; HHC) has been associated with redox stress in humans, as well as insidious disorders such as stroke risk, cognitive impairment, and osteoporosis. Greyhounds have been reported to have HHC relative to other dog breeds, with almost 4-fold variability observed among high concentrations in healthy greyhounds. In humans, HHC can be caused by acquired deficiencies in B vitamins such as folate (B9) and cobalamin (B12), or genetic defects in several enzyme pathways. However, the underlying mechanisms for HHC in greyhounds, and its clinical implications, are not understood. The purpose of this study is to determine whether HHC is associated with redox stress in otherwise healthy greyhounds, and with alterations in serum folate, cobalamin, methionine, or cysteine that would implicate specific pathways in the underlying mechanism. The results of this study will refine hypotheses about the mechanism of HHC in greyhounds and may support follow-up studies on genetic mechanisms as well as the effects of folate, cobalamin, or cysteine supplementation on antioxidant status in this unique breed of dog.

2019 Projects

Assessment of Fraction of Inspired Oxygen in Panting Dogs during Nasal Oxygen Administration

Principal Investigator:
Jonathan Bach, clinical associate professor, Department of Medical Sciences

Abstract:
Dogs frequently pant during hospitalization and the effect on their inspired-oxygen-fraction, while receiving supplemental oxygen, is unknown. Dogs with hypoxemia can be administered oxygen several ways including: use of an oxygen cage, use of a facemask, or by placement of a nasal cannula just inside the nose – midway through the nasal passage or further back closer to the trachea. To date, only nasal cannula placed midway through the nasal passages have had their effect on oxygen content objectively assessed. More importantly, the effect of panting, while administering nasal oxygen, has not been determined.

A newer technique for nasal oxygen administration, termed high flow oxygen therapy (HFOT), provides nasal oxygen at much higher flow rates. Because the oxygen is warmed and humidified, HFOT is able to provide much higher oxygen concentrations in people. High flow oxygen therapy has yet to have its effect on oxygen content objectively assessed in dogs.

The purpose of this study is to determine the effect of panting on inspired-oxygen-concentrations while oxygen is administered, via several nasal techniques. Results will directly affect clinicians’ choices when prescribing supplemental oxygen to patients with hypoxemia.

Development of a Novel Oral Phenobarbital Formulation for Management of Feline Epilepsy

Principal Investigator:
Heidi Barnes Heller, clinical associate professor, Department of Medical Sciences

Abstract:
Giving phenobarbital to cats with seizures by mouth twice-daily results in good seizure control; yet, many cats do not like to take medication and may hurt their owners when medications are given. Skipping or missing doses results in more frequent and/or severe seizures, and poor quality of life for the cat. When given twice daily as recommended, phenobarbital blood concentrations are often predictable and stable. Applying medication to the skin, rather than the mouth, is preferable by many cat owners because it is considered easier and safer. However when phenobarbital is absorbed through the skin, blood concentrations are not predictable or stable. The purpose(s) of this study are to evaluate the taste, blood concentrations and side effects of a new phenobarbital paste which can be applied to the fur (to be licked off by the cat.) This approach allows the cat to take the medication by mouth, resulting in predictable blood concentrations without having to give medication directly into a cat’s mouth. Our secondary purpose is to determine the shelf life of product up to 8 weeks. Our hypotheses are that meat flavored paste will be preferred, blood phenobarbital concentrations will be above the lowest recommended concentration (15 µg/ml) after 14 days of treatment, side effects will be few, and shelf-life will be at least 4 weeks.  The results will provide owners a new treatment option, allowing them give medication more easily to their cat, resulting in better seizure control and improved quality of life.

Evaluation of 3D Printed Surgical Cutting Guides

Principle Investigator:
Jason Bleedorn, clinical associate professor, Department of Surgical Sciences

Abstract:
Patient-specific surgical guides have emerged as a novel, useful tool to optimize surgical treatment of many conditions. Despite rapid development, little information exists to guide objective clinical benefits to offset the additional development time and cost for individual patient use. We propose an important foundational project to investigate the use of custom three-dimensional (3D) printed surgical guides for long bone osteotomies. We will assess accuracy, reliability, and efficiency of angled radial osteotomies using 3D printed surgical guides compared to free-hand using an ex vivo canine model. CT images will be obtained preoperatively for guide creation and postoperatively for outcome assessment. We anticipate that guided osteotomies will provide an accurate, rapid, and consistent osteotomy compared to free-hand (current standard of care). Information learned will be immediately useful to direct clinical application of cutting guides for surgical treatment. This work will also provide a basis for innovative research in other relevant sites and cross-collaborative efforts among veterinary specialties and units on campus.

Investigating the Effects of Exercise on Seizure Frequency in Epileptic Dogs

Principal Investigator:
Starr Cameron, clinical assistant professor, Department of Medical Sciences

Abstract:
The purpose of this study is to investigate the role of exercise in epileptic dogs. 80 dogs with seizures will be recruited and fitted with an activity monitor (FitBark™) attached to their collar, which allows investigators to monitor daily activity remotely. After an initial observation period, dogs will be randomly assigned to either the exercise (treatment) group, which will have an increase in baseline exercise, or the control group, which will continue their normal routine. Owners will be asked to keep a seizure log. The seizure frequency during the initial period will be compared to the frequency during the exercise period to see if any difference occurred. A secondary goal of this study is to evaluate the FitBark™ activity monitor as a possible seizure monitoring device. Our goal is to improve the lives of owners and dogs with epilepsy by identifying ways of improving seizure control without additional medications.

Evaluation of Regional Limb Perfusion with Amikacin in Chickens

Principal Investigator:
Lorelei Clarke, clinical assistant professor, Department of Pathobiological Sciences

Abstract:
Pododermatitis (swelling of the toe or footpad) and joint infections are a significant cause of morbidity in avian species, especially in captive, heavier-bodied, ground-dwelling birds such as chickens and waterfowl. Regional limb perfusion (RLP) is an antibiotic administration technique designed to achieve high drug-tissue-concentrations, while avoiding systemic toxic effects. RLP could potentially be used in various avian species, particularly in treatment of limb infections. Amikacin is a widely used drug with RLP; however, its reported nephrotoxic effects and the presence of the renal-portalsystem in birds, have raised concerns regarding its safety in avian patients.

The objective of this proposed study is to investigate the safety of repeated RLP using amikacin in chickens and to determine tissue concentration of amikacin after RLP. Thirty chickens will be randomly divided into two treatment groups and a control group. The animals will undergo three regional limb perfusions 24 hours apart with either amikacin or saline. Blood and tissue amikacin levels will be measured after RLP. The results of this study are novel and could be potentially significant in improving the outcome of birds with infections of the distal pelvic limbs.

The Building Blocks of Companion Animal Pain: Comparative Molecular Studies of Sensory Neurons

Principal Investigator:
LaTasha K. Crawford, assistant professor, Department of Pathobiological Sciences

Abstract:
Treatment of chronic pain in human patients can be challenging, as existing therapies may cause unwanted side effects, lead to addiction, or prove inadequate for many patients. This unmet therapeutic need would benefit from having greater knowledge of pain mechanisms and a better understanding of the heterogeneity of the patient population. Experimental mouse models of pain have begun to provide insight into the pain-induced molecular and morphologic changes that occur in different subtypes of sensory neurons. Despite the knowledge we have gained from these types of studies, novel pain therapies based on laboratory findings are rarely successful in clinical trials. Often we don’t know whether the mechanisms revealed by mouse studies are relevant in other animal species or in human patients, producing a gap in our ability to translate laboratory findings into societal benefit. We believe that study of the sensory system of companion animals can help fill that gap. Using tissue samples from companion animals that have unfortunately passed away, we hope to learn whether the molecular markers that are the mainstay of mouse studies prove to be useful in other species. We will then focus on companion animals that had a history of pain, to determine which mouse mechanisms of pain are universal or species-specific. This understanding can help us narrow down molecular targets for novel drugs that are the most apt to succeed in preclinical and clinical trials. It will also help us identify which types of veterinary patients can benefit from emerging, new pain therapies.

Characterizing Normal Neurologic Examination Findings and Advanced Imaging Anatomy of the Central Nervous System in African Pygmy Hedgehogs (Atelerix albiventris)

Principal Investigator:
Grayson Doss, clinical assistant professor, Department of Surgical Sciences

Abstract:
African pygmy hedgehogs are common exotic companion animals and are regularly evaluated by veterinarians for a variety of disorders. Although this species is often presented for dysfunction of the nervous system, there is limited information regarding normal examination findings or anatomy of the central nervous system in hedgehogs. These limitations impede both neurolocalization and diagnostic capability of central nervous system imaging in these animals. The proposed study will evaluate the normal neuroanatomy of African pygmy hedgehogs using the commonly used advanced imaging techniques of computed tomography and magnetic resonance imaging in order to provide basic anatomical information. This study will also focus on the approach to and findings of the neurologic examination in hedgehogs, including gait analysis, providing much needed information for this species. Veterinarians providing care for hedgehogs can readily apply the findings of this study to clinical practice.

Validation of Two Point-of-care Lipid Meters for Measuring Whole Blood Cholesterol and Triglyceride in Rabbits

Principle Investigator:
Kristen R. Friedrichs, clinical associate professor, Department of Pathobiological Sciences

Abstract:
Various diseases (hepatic, renal, endocrine) as well as sepsis have important effects on lipid metabolism in many species. Experimental studies in rabbits suggest a relationship between lipid metabolism and inflammation. While rabbits are prone to dietary hyperlipidemia (increased plasma total cholesterol and triglycerides), a recent study of companion rabbits demonstrated significant and strong associations between hyperlipidemia and severe infection or sepsis, renal failure, and hepatopathy, independent of diet. With evidence supporting the use of blood lipids as biomarkers of critical disease, there are many benefits to rapid cage-side blood lipid measurement in companion rabbits. Compared to conventional laboratory lipid measurement, point-of-care (POC) lipid meters require much smaller blood volumes, provide faster results, and are less expensive. Clinically, the anticipated increased efficiency and availability of blood lipid measurement could allow for more timely diagnosis and treatment of critically ill rabbits. Lipid POC meters have been validated for use in humans, dogs, cats, horses, and more recently, chickens. Validation experiments involving two POC lipid meters will be performed on blood collected from Watanabe heritable hyperlipidemic (WHHL) rabbits and non-lipidemic New Zealand white (NZW) rabbits. Contingent on successful lipid meter validation, future studies will be aimed at evaluating POC lipid meter diagnostic utility in companion rabbits with critical illnesses.

Effects of Intravenous and Topical Lidocaine Administration on Heart Rate, Blood Pressure, Rima Glottidis Surface Area, and Quality of Tracheal Intubation in Rabbits

Principal Investigator:
Rebecca A. Johnson, clinical associate professor, Department of Surgical Sciences

Abstract:
When placing a tracheal tube during anesthesia in rabbits, their airways can spasm, ultimately leading to respiratory issues including death. Lidocaine is a local anesthetic that mitigates laryngeal spasm in dogs and cats. However, the effects of lidocaine on tracheal intubation have not been studied in rabbits. The specific objective is to investigate whether topical (on the larynx) or intravenous administration of lidocaine relaxes the laryngeal cartilages and facilitates tracheal intubation in rabbits. A small endoscope will be used to visualize the larynx and quantify the area of tracheal opening between the two laryngeal cartilages; ease of intubation will also be assessed. We hypothesize that intravenous and topical lidocaine administration will significantly increase the area of the tracheal opening and improve intubation quality. These studies may greatly affect the clinical management of our rabbit patients and may improve mortality rates associated with this common pet species.

Regional Auricular Anesthesia for Otoscopic Procedures in Dogs: Effect on Anesthetic Drug Usage and Pain Scores

Primary Investigator:
Elizabeth A. Layne, clinical instructor, Department of Medical Sciences

Abstract:
Video otoscopy is a commonly performed procedure at UW Veterinary Care in dogs suffering from otitis externa and media. This procedure is considered moderately invasive; therefore, adequate perioperative pain control is essential. In dogs, and other species, preferred analgesics are a combination of opioids, non-steroidal anti-inflammatory drugs, and the use of local anesthesia to block the sensory input of the nerves that supply the ear. While a technique has been described for regional nerve blocks in cadavers, there is no description of the effectiveness of these blocks in live dogs undergoing video otoscopy. The goal of this study is to compare the effect of a regional nerve block technique with local anesthestic to the same technique with saline (placebo) on opioid consumption and quality of recovery in client-owned dogs undergoing video otoscopic procedures. We believe the use of regional anesthesia for dogs undergoing video otoscopy will allow decreased use of systemic opioid analgesics, which are shown to have dose-dependent adverse effects in dogs, including respiratory depression, loss of appetite, and excitement during recovery. The knowledge gained from this proposed study will directly improve the care provided to canine patients at UW Veterinary Care and other veterinary hospitals.

Effect of Cisapride on Fecal Output in Chinchillas with Experimentally-induced Gastrointestinal Hypomotility

Principal Investigator:
Christoph Mans, clinical assistant professor, Department of Surgical Sciences

Abstract:
Chinchillas are popular companion animals and are therefore increasingly being evaluated by veterinarians for a variety of health problems. Reduced or lack of fecal output is a frequent presenting complaint in chinchillas and is usually secondary to gastrointestinal stasis, which can be induced by pain, stress, opioid or anesthetic drug use or systemic disease. While veterinarians frequently use the promotility drug Cisapride as part of the treatment protocol for GI stasis in chinchillas, there is currently no evidence that this drug, at the recommended dosage, has any beneficial clinical effects. In the study proposed we aim to evaluate the effect of Cisapride in chinchillas utilizing two different experimentally-induced gastrointestinal hypomotility models. In a series of experiments, the effect of Cisapride on fecal output will be evaluated at the currently recommended dosage (0.5 mg/kg PO q8h) as well as at higher dosage (which will be determined to have no clinical relevant adverse effects.) Thefindings of this study will have a wide and immediate impact on the clinical management of chinchillas and will provide veterinarians with the currently lacking evidence on the efficacy of Cisapride in this species.

The Effect of Heel Elevation on Strain in the Digital Flexor Tendons in the Equine Forelimb

Principal Investigator:
Samantha Morello, clinical associate professor, Department of Surgical Sciences

Abstract:
“No foot, no horse” is a common saying among horsemen and veterinarians, as the foot is the most important part of what keeps the equine musculoskeletal system sound and functional.  Laminitis, navicular disease, and tendon problems are all common causes of lameness that rely on the use of orthotics, applied to the foot, for the treatment of disease. Orthotics can alter the biomechanical function of tendons in the limb and around the foot to modify disease and help promote healing. Acoustoelastography (AEG) is a novel ultrasound-based technique that can quantify stiffness and strain in tendons in live horses, therefore providing an ideal platform for investigating the effects of orthopedic shoeing. This study will use AEG to investigate the effects of hoof orthotics on flexor tendons in the distal limb of horses, to help direct veterinarians on how best to treat various lameness in the horse.

Dissecting Breed-specific Genomic Structural Variation in Dogs to Enhance Discovery of Genetic Architecture of Disease

Principal Investigator:
Peter Muir, professor, Department of Surgical Sciences

Abstract:
Many diseases in dogs have an important genetic contribution and are breed-related. The canine reference genome, canFam3.1, is the only assembly available and is built from a single Boxer. It provides no information regarding genetic variation in the genome of other breeds. This problem, therefore, limits genetic discovery as substantial genomic differences between breeds are expected. This important knowledge gap limits studies of the genetics of disease, particularly analysis of whole genome sequencing projects. We will assembly a West Highland White Terrier (WHWT) genome without using the canFam3.1 assembly (de novo assembly). We will compare the WHWT assembly with the Boxer reference, and de novo reference assemblies from two other breeds with a different evolutionary background that we have constructed. Completion of this work will allow us to move rapidly towards our long-term goal of advancing genetic discovery through studies of breed-related canine diseases and improving genetic screening in dogs.

Point-of-care Glucose Testing in Critically Ill Neonatal Foals

Principal Investigator:
Amelia Munsterman, clinical assistant professor, Department of Surgical Sciences

 Abstract:
Neonatal foals have limited endogenous glycogen stores and high tissue metabolism, which combine to impair glucose homeostasis, particularly in critically ill neonatal foals. Glycemic disturbances are therefore common in critically ill foals, and both hypoglycemia and hyperglycemia at hospital admission have been identified as poor prognostic indicators. Hypoglycemia at admission has also been associated with sepsis, increased likelihood of a positive blood culture, and systemic inflammatory response syndrome.

Optimal management of critically ill foals requires frequent blood glucose monitoring and strict glycemic control. Blood glucose levels guide fluid therapy, insulin administration, and nutritional support. Point-of-care (POC) or stall side glucometry is commonly used in equine neonatal intensive care units. In human medicine, capillary (fingerstick) POC measurements were traditionally used for monitoring, given the ease of sample collection. More recently, studies have demonstrated the inaccuracy of this method, especially in patients with poor peripheral tissue perfusion and shock. Currently, standard of care in human medicine requires arterial or venous specimens. As is the case with humans, capillary samples are easily obtained from neonatal foals and are often utilized for glucose monitoring in equine neonatal intensive care units, including at the UW. Capillary samples are often preferred, as they prevent damage to veins, and are particularlyuseful when dextrose solutions are being infused through an intravenous catheter, which can alter the glucose concentration in blood taken from the catheter. This warrants a prospective investigation of the accuracy of capillary POC samples for glucose monitoring in the critically ill neonatal foal.

Incidence and Risk Factors for Bacteremia Secondary to Gastrointestinal Endoscopy in Dogs with Gastrointestinal Disease

Principal Investigator:
Jessica Pritchard, clinical assistant professor, Department of Medical Sciences

Abstract:
Dogs undergo colonoscopy for reasons similar to humans, to help diagnose and treat diseases of the colon. It is suspected that in some dogs the injured colon combined with the pressure from the scoping procedure allows bacteria to enter the bloodstream during the colonoscopy, a condition called bacteremia. In humans undergoing colonoscopy, bacteremia is known to occur in up to half of patients. No study has evaluated how commonly bacteremia occurs in dogs undergoing colonoscopy. This study will use two tests for detecting bacteremia, blood culture and next-generation-sequencing, on dogs undergoing colonoscopy before and after their procedure. Data gathered will describe how many dogs develop bacteremia and if they share any common characteristics. We will use this information to help drive future studies to identify dogs at risk for bacteremia and establish if antibiotics are necessary for this procedure to protect the dogs at risk.

Defining the Neurophysiologic Basis of Late-Onset Laryngeal Paralysis in the Labrador Retriever

Principal Investigator:
Susannah Sample, assistant professor, Department of Surgical Sciences

 Abstract:
Late-onset laryngeal paralysis (LOLP) is a serious and sometimes fatal late-onset condition of older dogs that results from peripheral neuropathy. Labrador and Golden Retrievers are commonly affected. Airway obstruction from LOLP affects a dog’s ability to breathe and weakness due to the generalized involvement of peripheral nerves. There is little known regarding the neuropathology of LOLP. Studies of nerve conduction velocity (NCV) and electromyography (EMG) are essential for classifying peripheral nerve disease pathology.

Our long-term goals are to identify LOLP’s genetic basis and establish its neuropathologic basis. The objective of the study is to define the neurophysiologic abnormalities of LOLP in the Labrador. Our hypothesis is that Labrador LOLP is due to generalized age-dependent peripheral nerve axonal loss. We will accomplish our objective by undertaking NCV and EMG studies on affected Labradors and age-matched controls. This study will address the neurophysiologic basis of LOLP in a single uniform population of pure-bred Labradors, which is essential for development of a treatment strategy.

Pharmacokinetics of Ceftazidime in Leopard Frogs (Lithobates pipiens): A Two-dose Comparison between Subcutaneous and Topical Administration

Principal Investigator:
Kurt K. Sladky, clinical associate professor, Department of Surgical Sciences

Abstract:
Antimicrobial use in amphibians is commonly performed with little or no pharmacokinetic (PK) data to support antibiotic selection, route of administration, or dose frequency, even though frogs (anurans) and salamanders (caudates) are widely used as laboratory animals, housed in zoological institutions and commonly maintained as pets.

Ceftazidime, a 3rd generation cephalosporin is frequently used in anurans. As with most antimicrobials used in amphibian medicine, dosing is typically extrapolated from reptile publications or anecdotal reports. Published PK data in anurans exist only for enrofloxacin, gentamicin, oxytetracycline, and metronidazole, all those studies have varying routes of administration, methodological flaws and confounding PK data. No published studies exist comparing PK data between transcutaneous (delivered across the skin) and injectable medication administration in amphibians. The transcutaneous route is a viable option in amphibians, as their skin readily absorbs any applied chemicals. Transcutaneous administration eliminates the stress of manual restraint and a hypodermic needle insertion.

Therefore, we propose a two-part pharmacokinetic study using a commonly studied frog species, the leopard frog. Results of this study will directly impact and improve amphibian clinical medicine by systematically evaluating the pharmacokinetics of a commonly used antibiotic for which no data currently exist. This study will serve as a primary research project for Dr. Hawkins, a first-year resident in Zoological Medicine.

Biomechanical Testing of a Resorbable Bone Adhesive for Noninvasive Fracture Repair of Mandibular Fractures in Dogs

Principal Investigator:
Christopher J. Snyder, clinical associate professor, Department of Surgical Sciences

Abstract:
The largest chewing tooth in the lower jaw of dogs is a common location for jaw fractures to occur.   Fractures at this location can be particularly challenging to repair due to the presence of tooth roots, small amount of available bone and a limited number of locations to safely place different forms of repair devices.  This study will mechanically test a new resorbable bone adhesive as a fracture repair option for jaw fractures in dogs.  This technology involves a novel material that is currently being evaluated for various purposes in humans. The project will evaluate the biomechanical strength of the material in simulated fractures in cadaver bones.  We will be testing how this technique compares to other traditionally performed fracture repair techniques.  Successful implementation of this technology may facilitate quicker healing and decrease anesthesia time for treatment of clinical patients.

Optimization of Cell Reprogramming to Derive Transgene-free Canine Induced Pluripotent Stem Cells for Disease Modelling and Cell-based Therapy

Principal Investigator:
Masatoshi Suzuki, associate professor, Department of Comparative Biosciences

Abstract:
Adult cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by inducing reprograming genes. iPSCs have tremendous regenerative potential as they can create various cell types in the body. Traditional reprogramming methods permanently alter the target cell DNA, which can possibly cause genetic mutations or tumor formations. This presents an important problem that must be overcome for before iPSCs can be safely transplanted into veterinary patients. Recent techniques in humans use ‘foot-print free’ viruses or transient gene expression to create iPSCs with minimal genetic alteration. Our long-term goal is to streamline the method for production canine iPSCs for future clinical uses and to establish a stem cell bank. To achieve this goal, our specific objective in this proposal is to optimize protocols for efficient generation of unedited canine iPSCs from blood and skin cells. ‘Transgene-free’ canine iPSCs carry less risk for tumor formation and are safer for clinical trials. Our rationale is that this project will have a broad impact on regenerative medicine in dogs. To accomplish our objective, we will take blood and skin cells from normal dogs and reprogram them into iPSCs using either Sendai virus or the transient gene expression using plasmid vectors. This study is significant because it will advance knowledge of canine iPSCs and open new areas of research, such as disease modelling and transplantation studies. Our proposed work is innovative as creation of canine iPSCs using transgene-free approaches with blood cells has never been performed.

Biotransformation of Immunosuppressive and Antineoplastic Drugs by Glutathione S-transferases in Dogs

Principal Investigator:
Lauren Trepanier, professor, Department of Medical Sciences

Abstract:
There are several drugs that are useful in treating dogs that have certain cancers or immune disorders. However, some dogs will develop unacceptable side effects during treatment, while other dogs may not improve with a standard dose of the drug. This study will try to find out why individual dogs respond differently to the drugs azathioprine (Imuran), cyclophosphamide (Cytoxan), cisplatin, lomustine (CCNU), and chlorambucil. We will find out how these drugs are broken down in dogs, focusing on an enzyme pathway (GSTs) that can vary between individual dogs. These results will help us understand how genetic defects in these enzymes, found in some dogs, might be used to predict drug response and adjust dosing before treatment. The overall goal is to make these important drugs safer and more effective in dogs.

The Role of Pre-irradiation Dental Care in Dogs Underdoing Radiotherapy for Head and Neck Tumors: A Pilot Study to Explore the Feasibility of a Future Prospective Trial

Principal Investigator:
Michelle Turek, assistant professor, Department of Surgical Sciences

Abstract:
Radiotherapy is the cornerstone for treatment of head and neck tumors in both people and dogs. In people, it is well known that pre-existing dental disease worsens radiation-induced oral complications including mucositis, periodontal attachment loss, and tooth decay. Boney structures exposed to radiotherapy are often abnormal, so future treatments such as dental extractions or other oral surgery can lead to osteonecrosis. To prevent these short and long-term complications, pre-irradiation dental care, including management of periodontal disease, is crucial for human head and neck patients. Given the strong relationship between periodontal disease and oral health after radiotherapy in people, it is surprising that little is known about the effect of radiotherapy on oral health in dogs. The prevalence of periodontal disease in dogs is frequent, yet the relationship between radiotherapy and oral health has not yet been investigated. The proposed pilot study is aimed at establishing an experimental protocol and collecting preliminary data documenting oral health after radiotherapy, including periodontal changes, severity of mucositis and measures of quality of life, in dogs with nasal tumors. These data will be used to support a proposal for a future prospective study. If a relationship between periodontal disease and radiation therapy ultimately is found, pre-radiation dental scaling and polishing as well as maintenance of oral health after radiation therapy will be emphasized in radiation patients for the purpose of improving quality of life and decreasing morbidity associated with radiation.

2018 Projects

Use of Extended-Release Levetiracetam in Small Breed Dogs

Principal Investigator:
Heidi Barnes Heller, clinical associate professor, Department of Medical Sciences

Abstract:
Epileptic dogs must receive their seizure medications every day, often multiple times daily, otherwise seizures will be poorly controlled and may ultimately lead to early death. Giving drugs by mouth many times daily, every day, is challenging for owners and often leads to poor compliance. There are a limited number of anti-seizure drugs that come in sizes appropriate for dosing small dogs. Levetiracetam is a newer anti-convulsant drug that is effective in controlling seizures in the majority of dogs. There are two forms of levetiracetam: regular-release (IRL) and extended-release. (XRL). XRL tablets are formulated to allow less frequent daily dosing. Use of XRL reduced the dosing frequency from three times to twice daily in large breed dogs, and to once daily in cats. XRL has not been evaluated in small breed dogs. This study’s objectives are: to evaluate blood concentrations of levetiracetam after a single dose of XRL in a healthy small breed dog; to determine the longest frequency that the drug can be given; to determine if blood concentrations remain constant over time; and to document side effects. Our hypotheses are that blood levels will remain within the therapeutic range for at least 12 hours, periodic sampling will demonstrate consistent blood levels, and the drug will be well tolerated. Study results may lead to better treatment of small breed epileptic dogs, with better quality of life through improved treatment compliance.

Assessment of the Efficacy of the Greater Auricular and Auriculo-temporal Nerve Blocks in Rabbits

Principal Investigator:
Cristina De Miguel, clinical instructor, Department of Surgical Sciences

Abstract:
In rabbits, total or partial ear canal ablation (T/PECA) with lateral bulla osteotomy (LBO) is a commonly performed surgical technique at UW Veterinary Care, when medical management of otitis externa and media has failed. These surgeries are considered highly invasive; therefore, adequate perioperative pain control is essential. In other species, preferred analgesics for these procedures are a combination of opioids, non-steroidal anti-inflammatory drugs and the use of local anesthesia to block the sensory input of the nerves that supply the ear. However, there is no description of the technique to carry out these regional nerve blocks in rabbits. The goals of this study are to describe a feasible and effective approach to block the pinna and external acoustic meatus in rabbits with a local anesthetic drugs. The use of regional anesthesia for rabbits undergoing T/PECA-LBO will allow to decrease the use of systemic opioid analgesics, which have shown to have dose-dependent adverse effects in rabbits, including, respiratory depression, sedation and suppression of gastrointestinal motility. The knowledge gained from this proposed study will directly improve the care provided to rabbit patients at UW Veterinary Care and other veterinary hospitals.

Evaluation of the Analgesic Efficacy of Buprenorphine in African Pygmy Hedgehogs (Atelerix albiventris)

Principal investigator:
Grayson Doss, clinical instructor, Department of Surgical Sciences

Co-investigator:
Christoph Mans, clinical associate professor, Department of Surgical Sciences

Abstract:
African pygmy hedgehogs are common exotic pets, but little is known or understood about pain control in this unique species. Most drugs used for treatment of pain in hedgehogs are based on information obtained in distinctly different species, like cats and ferrets. This 2018 University of Wisconsin School of Veterinary Medicine Companion Animal Fund Grant will support research investigating the effectiveness and safety of a commonly-used opioid drug, buprenorphine, in African pygmy hedgehogs. Part of this research will examine if buprenorphine, when administered by injection, will result in improved comfort when an infrared thermal stimulus is applied to a paw. It will also evaluate how hedgehogs tolerate buprenorphine, making sure it does not have dramatic side-effects like decreased food intake or activity levels. This research will help explore basic questions enabling veterinarians to provide the best possible care for hedgehogs through providing adequate and safe pain control in post-operative or ill patients.

Safety of Endotracheal Intubation with Two Different Types of Endotracheal Tubes in Healthy Dogs – the Effects of Cuff Inflation on Tracheal Mucosa and Pulmonary Aspiration

Principal investigator:
Tatiana H. Ferreira, clinical assistant professor, Department of Surgical Sciences

Abstract:
Tracheal intubation is the placement of a flexible tube (endotracheal tube – ETT) into the trachea (windpipe) to facilitate breathing and allow administration of oxygen/inhalant anesthetics to maintain general anesthesia. Intubation protects patients from pulmonary aspiration of gastric contents in case of gastroesophageal reflux. As the incidence of gastroesophageal reflux in dogs can be as high as 57%, tracheal intubation is considered an essential component of general inhalant anesthesia. However, the ETT itself can cause mild to severe injury to the trachea if not appropriately used. Even though this is a routinely performed procedure in dogs, there is a paucity of published research assessing its safety, including physical damage to trachea and potential pulmonary aspiration in this species. The objective of the present study is to evaluate two different types of ETT commonly used clinically and their effects on tracheal integrity and potential pulmonary aspiration in dogs under general anesthesia.

Electromyographic Evaluation and Response to Electrical Stimulation of the Laryngeal Muscles in Dogs with Acquired Laryngeal Paralysis

Principal Investigator:
Robert Hardie, clinical associate professor, Department of Surgical Sciences

Co-investigators:

Helena Rylander, clinical associate professor, Department of Neurology
Alexander Piazza, resident, Department of Surgical Sciences

Abstract:
Acquired laryngeal paralysis (ALP) is a common problem in older, large-breed dogs that results in progressive respiratory obstruction due to degeneration of the nerves that innervate the larynx.  Current treatment for ALP involves surgery to permanently open the larynx, but which unfortunately results in a relatively high rate (20%) of postoperative aspiration pneumonia. Recently, successful use of an implantable pacemaker has been described for the treatment of laryngeal paralysis in dogs. The advantages of using a pacemaker to control the larynx, over current surgical techniques, is that laryngeal motion would be more physiologic and potentially reduce the risk of life-threatening aspiration pneumonia.  Substantial work has already been done to develop this technique; however, previous studies have all used an experimental model of laryngeal paralysis and thus it is not known whether a pacemaker would effectively stimulate the laryngeal muscles in dogs with naturally occurring ALP.

The goal of our study is to describe the electromyographic activity of the laryngeal muscles and determine the responsiveness to electrical stimulation.  Our Hypothesis is that laryngeal muscles will demonstrate changes consistent with a degenerative neuropathy, yet still be responsive to electrical stimulation resulting in measurable motion of the larynx. Our results will determine whether pacemaker technology is a feasible option for treatment of ALP and provide the foundation for future clinical studies establishing this new form of treatment for dogs.

Stimulation of Acupoints Pericardium 6 (PC6) and Stomach 36 (ST36) to Improve Nausea and Vomiting Associated with Intravenous Lidocaine Infusions in Conscious Dogs

Principal Investigator:
Rebecca Johnson, clinical associate professor, Department of Surgical Sciences

Abstract:
Lidocaine is commonly used in dogs to provide non-opioid analgesia (pain relief), stabilize heart rhythms, and enhance gastrointestinal (GI) motility. However, nausea, vomiting and sedation also develop. Acupuncture is an ancient treatment used to reduce nausea and vomiting associated with opioids in dogs. In addition, stimulation of GI acupoints slows GI motility, whereas lidocaine infusions hasten GI transit times. Thus, the specific objective is to study the effects of GI acupuncture and simultaneous intravenous lidocaine infusions on nausea, vomiting and sedation in dogs, and to assess GI motility with these concurrent treatments. Conclusions resulting from these studies may greatly affect the clinical management of our painful patients or patients that require heart rhythm therapy since the dose-dependent side effects of lidocaine may preclude its use in certain canine populations.

Antinociception Without Respiratory Depression in Ball Pythons (Python regius) in a Clinically Relevant Model of Pain

Principal Investigator:
Stephen Johnson, associate professor, Department of Comparative Biosciences

Co-Investigator:
Kurt Sladky, clinical professor, Department of Surgical Sciences

Abstract:
Veterinarians are ethically obligated to relieve pain in their patients, and effective pain management contributes to a more rapid return to normal behavior after trauma or surgery. However, pain management is poorly understood in snakes, and there are no clinically available drugs that have been proven to provide pain relief in snakes. We recently published a study showing that dexmedetomidine (DEX) is a promising candidate drug for providing pain relief in snakes, but DEX also depresses breathing in snakes, which can compromise a snake’s recovery from trauma or surgery. The goal of this study is to test whether DEX provides pain relief in snakes using a standard laboratory model that causes mild pain in reptiles (e.g., relatively common surgical neutering procedure). In addition, drugs will be tested that increase breathing in snakes so as to identify a drug combination (DEX + respiratory stimulating drug) that provides pain relief without decreasing breathing. If successful, this would represent a significant step forward in providing pain relief to snakes, which is important given the increasing popularity of snakes as pets.

Evaluation of a Novel Intrathecal Injection Technique for Spinal Anesthesia and Analgesia in Bearded Dragons (Pogona viticeps)

Principal Investigator:
Christoph Mans, clinical assistant professor, Department of Surgical Sciences

Co-Investigator:
Tatiana H. Ferreira, clinical assistant professor, Department of Surgical Sciences

Abstract:
The goal of this proposed study is to evaluate if spinal anesthesia, which is similar to epidural anesthesia, can be used in bearded dragons, a common pet lizard species. Many pet lizards are treated by veterinarians for tail damage, cloacal prolapse or egg binding. All these conditions require manipulation and/or surgery of these organs under general anesthesia. Because many pet lizards often present in compromised health, they make poor anesthetic candidates. Being able to use spinal anesthesia would allow the amount of drugs used to induce anesthesia, or general anesthesia, to be greatly reduced or even completely avoided. Therefore, the anesthetic complications could be greatly reduced. Our laboratory has previously successfully investigated the use of spinal anesthesia in turtles, which has since then been used in many turtle patients world-wide. We hope that a spinal anesthesia will be equally effective in bearded dragons, in order to allow veterinarians to provide better care for this species and other pet lizards.

Evaluation of the Efficacy of the Chinese Herbal Wei Le San for Treatment of Equine Gastric Ulcers

Principal Investigators:
Fernando Marques, clinical associate professor, Department of Medical Sciences
Amelia Munsterman, clinical assistant professor, Department of Surgical Sciences

Abstract:
Equine Gastric Ulcer Syndrome is a significant cause of morbidity in the domesticated horse. The incidence of gastric ulcers in horses is reported as greater than 80%. However, the occurrence rates are closely linked to the athletic occupation of the horse, with higher rates noted in racehorses and high level sports horses. Gastric ulcers result in significant costs in regards to both treatment and loss of training days.  Current medications work primarily by reducing acid production, but their effects are not always consistent and the duration of treatment is often prolonged. Recently, an herbal medication called Wei Le San has been purported to be efficacious for both the prevention and treatment of gastric ulcers in horses. The main purpose of this study is to assess the effect of the Chinese herbal Wei Le San supplement in horses with ulcers.

Genetics of Primary Angle Closure Glaucoma in the Siberian Husky

Principal Investigator:
Gillian McLellan, associate professor, Department of Surgical Sciences

Abstract:
Glaucoma is a very painful and rapidly blinding disease that leads to irreversible loss of sight in thousands of dogs in the United States and worldwide every year.  Medical and surgical treatments that target the damaging high pressure in the eyes of affected dogs are not able to cure the disease, only control it. And in many dogs with glaucoma, surgical removal of both eyes is needed to control pain.  Research reveals that the Siberian Husky is one of the more commonly affected breeds in both North America and Europe.  With improvements in canine DNA sequencing tools, it is now possible to carry out very detailed sequencing of DNA of individual dogs. These techniques have identified mutated genes responsible for several dog disease. Our study will harness the power of these exciting new sequencing tools and technologies to analyze DNA from Siberian Huskies with glaucoma and compare it to DNA from dogs without glaucoma. Our goal is to identify the mutation (or mutations) in DNA that cause glaucoma and, in turn, develop a genetic test for the disease in this breed and possibly other affected breeds. Due to the current lack of effective treatments for glaucoma, a DNA test would provide an invaluable tool in efforts to fight this disease as dog breeders would be able to avoid carriers of the disease in their breeding strategies and ultimately breeders could eliminate this exceedingly painful, disabling disease from the dog population.

Discovery of Biological Pathways Associated with Degenerative Suspensory Ligament Desmitis in the Peruvian Paso Using RNA-Sequencing

Principal Investigator:
Peter Muir, professor, Department of Surgical Sciences

Abstract:
Degenerative suspensory ligament desmitis (DSLD) is a progressive disease that affects several horse breeds which collectively represent a large number of horses in the USA. DSLD is particularly common in the Peruvian Paso and occurs in specific breeding lines. Affected horses are crippled when ligament rupture causes collapse of fetlock joints. Currently, we do not understand how genetic variation contributes to DSLD in Peruvian Pasos. This knowledge gap is limiting development of new approaches to patient management. In this project, we will identify genes and biological pathways that increase risk of DSLD through sequencing of RNA isolated from tissue biopsies. Completion of this work will allow us to move rapidly towards our long-term goal of identifying genes that could ultimately be targeted with medical treatment to alter the course of the disease. This work will also advance development of pre-emptive genetic screening for disease risk to optimize clinical care.

Measurement of Equine Gastrointestinal Myoelectrical Activity Using Electroinstinography

Principal Investigator:
Amelia Munsterman, clinical assistant professor, Department of Surgical Sciences

Abstract:
Colic is a condition that results in significant losses to the equine industry each year.  In horses treated for colic, the ability of the intestine to return to normal function after illness, is often reduced or delayed, increasing the risk of complications and death. Medications used to treat this condition, known as ileus, have not been consistently efficacious in clinical cases. Recently, a technique called electrointestinography has shown the ability to measure the contractions of the intestines using electrodes placed on the skin surface. By monitoring these contractions from outside the horse, it allows the veterinarian to observe gastrointestinal function without invasive or painful procedures. This study plans to evaluate current medications and novel therapies, including those used in traditional Chinese medicine, for treatment of ileus in horses. The goal would be to identify effective therapies to treat ileus in horses, to shorten hospitalization and improve survival.

Evaluation of the Pharmacodynamic Effects of the NEDD8-Activating Enzyme (NAE) Inhibitor Pevonedistat in Dogs with Diffuse Large B-cell Lymphoma

Principal Investigator:
Xuan Pan, assistant professor, Department of Medical Sciences

Abstract:
Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy in dogs. This aggressive disease is associated with poor overall survival with traditional multi-drug chemotherapy treatment.  This mandates the great need for investigating novel therapies to treat this disease.  Pevonedistat is a potent and selective small molecule NEDD8-activating enzyme inhibitor and has been shown to induce human activated B cell-like (ABC) DLBCL cell cycle arrest and apoptosis by inhibiting NEDD8-regulated protein degradation.  Our prior data show that pevonedistat treatment induces cell cycle arrest and apoptosis in canine DLBCL cells.  Furthermore, pevonedistat treatment of mice bearing canine DLBCL xenograft tumors resulted in complete tumor regression.  Although phase 1 clinical trials showed a great safety profile of pevonedistat in people with DLBCL, there has been no pharmacodynamic studies in dogs.  As canine and human DLBCLs serve as comparative models to each other in evaluation of new therapeutic drugs, our study aims to assess the safety and pharmacodynamic effects of pevonedistat in pet dogs diagnosed with DLBCL.  We will assess the expression levels of 8 pevonedistat inducible genes in blood of dogs with DLBCL and will evaluate NRF-2 and CDT-1, substrates of pevonedistat-mediated protein degradation, in primary canine DLBCL samples upon pevonedistat treatment.  Our study will serve as a pilot study for a phase I clinical trial and will help to refine an optimal dosing regimen of pevonedistat in future phase II efficacy trials in dogs with DLBCL.

Investigation of Regulatory B Cell Content, Phenotype and Function in Dogs with Primary Immune-Mediated Hematologic Disorders

Principal Investigator:
Jessica Pritchard, clinical assistant professor, Department of Medical Sciences

Abstract:
Immune-mediated hematologic disorders (IMHD) are diseases in which a dog’s own immune system destroys their blood cells. They result in life-threatening symptoms such as bleeding and anemia, and have high rates of mortality and relapse. Because drugs to treat IMHD can be costly and have life-threatening side effects, more specific and safer treatments are necessary. In humans, changes in the number or function of a type of immune cell, the B regulatory cell (Bregs), are a possible contributor to IMHD. In mice with autoimmune disease, administration of Bregs leads to remission of disease. We hypothesize that as in humans, Bregs are deficient in number or function in dogs with IMHD compared to healthy dogs. In this study, we will compare Breg number and function between dogs with IMHD and healthy dogs. Our results will expand knowledge of the causes of IMHD and serve as the initial support for administration of Bregs to treat IMHD.

Effectiveness of Liposome-Encapsulated Bupivacaine for Extended Analgesia of the Maxilla in Dogs

Principal Investigator:
Lesley Smith, clinical professor, Department of Surgical Sciences

Abstract:
Evaluation of the nasal cavity using an endoscope is commonly performed in dogs to diagnose cancer, fungal infection, presence of foreign bodies, etc. This procedure is extremely painful and requires a deep plane of anesthesia, which can be associated with a higher rate of anesthetic complications. Additionally, management of post-procedure pain is challenging, as dogs are at risk of inhaling fluid contents that remain in their oral cavity. Thus, use of large doses of systemic pain medications (narcotics) are generally avoided because they depress the gag reflex, making aspiration pneumonia a high risk factor. These patients often recover in the critical care unit because they need to have their respiratory function monitored, adding cost to the owner. A novel liposome-encapsulated local anesthetic (bupivacaine) [LEB] has been shown effective for about 72 hours of pain relief in dogs when infiltrated into the surgical site. The goal of this study is to evaluate pain control and plasma levels of LEB when it is administered via a modified nerve block to desensitize the maxillary nerve in dogs. The maxillary nerve supplies sensation to the nasal cavity and oral cavity. Our hypothesis is that LEB will provide about 72 hours of desensitization of the nose, soft palate, and gums of the upper jaw, without side effects such as tongue trauma or depression of the gag reflex. We expect plasma bupivacaine levels to be undetectable within 24 hours of receiving the block. If our hypothesis proves true, using LEB as a nerve block will offer an attractive novel alternative for pain management in dogs undergoing nasal endoscopy or other invasive procedures involving the upper jaw and associated structures.

Derivation of Canine Induced Pluripotent Stem Cells for Future Application to Disease Modelling and Cell-based Therapy

Principal investigator:
Masatoshi Suzuki, associate professor, Department of Comparative Biosciences

Co-investigators:
Timothy Menghini, resident, Department of Surgical Sciences
Peter Muir, professor, Department of Surgical Sciences
Igor I. Slukvin, professor, Department of Pathology and Laboratory Medicine

Abstract:
Stem cell technology holds great promise for regenerative medicine. Induced pluripotent stem cells (iPSCs) are generated from adult cells by cellular reprogramming. Pluripotent stem cells can differentiate to form any cell in the body and can be renewed indefinitely, hence iPSCs represent a valuable cell resource for disease modeling and cell-based therapies. The proposed project aims to create canine iPSCs from blood and skin samples. We will take blood and skin cells from adult dogs and reprogram them into iPSCs using novel methods that do not integrate into the host genome. This pioneering technology can avoid the concerns of traditional virus-based approaches to creating iPSCs, such as disrupting the host genome through integration and increasing the risk of tumor formation. Our study will significantly advance understanding of companion animal iPSC technology by allowing future disease-specific stem cells to be created for use in disease modelling, drug testing and for patient-specific cellular therapies to be developed.

Clinical Outcome of Subclinical Bacteriuria in Dogs Following Surgical Decompression of Hansen Type I Thoracolumbar Intervertebral Disc Herniation

Principal Investigator:
Katrina Viviano, clinical associate professor, Department of Medical Science

Abstract:
Intervertebral disc herniation (IVDH) is the most common acute spinal cord injury in dogs.  IVDH often requires surgery and medical management of secondary urinary dysfunction. Many dogs develop subclinical bacteriuria (SBU), a culture positive urine without signs/symptoms, resulting in the use of antimicrobials to reduce the risk of complications. In human spinal cord patients using antimicrobials for SBU has not been shown to prevent recurrence or secondary complications. Most IVDH dogs regain neurological and urinary function following surgery. SBU may self-resolve with return of urinary function suggesting that antimicrobials may be overused.  In this era of increasing antimicrobial resistance, identification of clinical populations where antimicrobials may be unnecessary is critical. The purpose of this study is to describe the clinical outcome, in the absence of an antimicrobial intervention, of canine SBU following surgical decompression of IVDH.  The results of this study may suggest a clinical population of dogs in which antimicrobials are unnecessary but commonly prescribed.

An Association Between Urine Fibrinogen and Canine Enterococcus Spp. Urinary Tract Infection

Principal Investigator:
Michael Wood, assistant professor, Department of Medical Sciences

Abstract:
In 7 percent of dogs with recurring urinary tract infections (UTI), the defect allowing bacterial re-colonization  cannot be effectively managed, and often leads to cyclical infection, antibiotic treatment and ultimately the emergence of antibiotic resistant infections. Enterococcus spp. bacteria are particularly prone to antibiotic resistance which necessitates using alternate non-antimicrobial therapeutic development. In humans, increased urinary fibrinogen concentrations are vital for Enterococcus spp. UTI. Therapies blocking Enterococcus spp./fibrinogen interactions are promising alternative therapies. Whether similar therapeutics would be effective in dogs is unknown as fibrinogen’s role in canine Enterococcus spp. UTI is unexplored. This study will test the hypothesis that dogs with recurrent Enterococcus spp. UTI have persistently increased urinary fibrinogen concentrations. To test this hypothesis, we will measure fibrinogen in the urine of dogs with recurrent Enterococcus spp. UTI before and after UTI treatment. Persistent elevations of these molecules will identify a potential mechanism that Enterococcus spp. may exploit to promote recurrent UTI.

FELINE HEALTH FUND

Linking Feline and Human Temporal Lobe Epilepsy: Clinical Signs, Magnetic Resonance Imaging Findings, and Pathological Changes in Epileptic Cats

Principal Investigator:
Starr Cameron, clinical assistant professor, Department of Medical Sciences

Abstract:
Temporal lobe epilepsy (TLE) has been well described in several species and is the most common cause of epilepsy in humans. Over 50% of cats with epilepsy have seizure symptoms similar to humans with TLE, including: hypersalivation, staring, dilated pupils, and facial twitching. We will correlate magnetic resonance imaging (MRI) findings and pathological changes in epileptic cats compared to normal cats. In cats that fail to respond to treatment or die spontaneously, we will look for specific microscopic changes within the hippocampal portion of the brain using special staining techniques to compare and contrast feline TLE to human TLE. This project will improve our understanding of seizures in cats, thus broadening treatment options for these cats and improving their quality of life. Finally, our results in cats will advance our understanding of TLE in humans.

2017 Projects

Evaluation of transcutaneous carbon dioxide monitoring in dogs at risk of hypoventilation

Principal Investigator
Jonathan Bach, clinical associate professor, Department of Medical Sciences

Abstract
Hypoventilation is a condition in dogs caused by failure to breathe rapidly or deeply enough, resulting in low blood oxygen levels and high blood carbon dioxide (CO2) levels. Dogs with conditions that may cause hypoventilation, such as obesity, are at risk for sudden death without proper monitoring. Currently available monitoring methods are cumbersome and technically challenging. A continuous, noninvasive method of monitoring CO2 is not readily available. Transcutaneous CO2 is a method that is safe and allows continuous and noninvasive CO2 monitoring. This study will enroll dogs that are at risk of hypoventilation. By  placing a CO2 transcutaneous monitor on each dogs’ chest over a 48-hour time span, transcutaneous CO2 and venous blood CO2 values will be obtained every 4 hours, allowing comparison of multiple measurements. We hypothesize that transcutaneous CO2 will reliably predict venous blood CO2 in dogs and serve as a reliable, noninvasive monitoring option for dogs at risk of hypoventilation.

Tick-borne Powassan virus surveillance in dogs in Wisconsin

Principal Investigator
Kristen Bernard, professor, Department of Pathobiological Sciences

Abstract
With increasing frequency, the tick-borne Powassan virus (POWV) is causing sporadic human disease in several Midwestern states, including Wisconsin. POWV causes inflammation of the central nervous system (CNS), resulting in a high fatality rate.  In dogs, there has not been an in-depth investigation, with no recent studies published. The related tick-borne encephalitis virus is known to cause severe CNS inflammation in people and dogs in Europe, thus we hypothesize that POWV is a risk to dogs in North America.  Our objective is to study dogs from Wisconsin and adjacent areas who visit UW Veterinary Care by firstly examining healthy dogs for previous POWV infection and screening for dogs with CNS inflammation for evidence of current POWV infection.  We will then correlate POWV exposure with exposure to other tick-borne pathogens, and conclude by mapping our data with available data from ticks collected in Wisconsin. The resulting geographic surveillance data will demonstrate the potential exposure of dogs to the Powassan virus and will warrant further investigation of this virus as a potential novel canine pathogen.

Serum levetiracetam concentrations following multiple oral dosing of extended release levetiracetam in healthy cats

Principal Investigator
Heidi Barnes Heller, clinical assistant professor, Department of Medical Sciences

Abstract
Giving feline medications by mouth is challenging for many cats and their owners. To avoid seizures, cats must receive multiple doses of medication at the same time every day. To be effective, common anti-seizure medications must be given 2-3 times daily. Missing doses increases risk of seizures, which can be harmful to the cats and upsetting to owners. Levetiracetam, a new anti-seizure drug, has few side effects in cats. There are two formulations of levetiracetam, however, only the regular duration formulation has been evaluated in cats. The long-acting formula is given less frequently, and has fewer side effects in people and dogs. The purpose of this study is to evaluate blood levels and side effects in cats receiving long acting levetiracetam (once daily for 10 days). Our hypothesis is that blood concentrations of this drug will stay above 5 mcg/ml throughout the day, and that side effects will be similar to side effects noted with regular duration levetiracetam. The results of this study will benefit cats with seizures who are resistant to receiving oral anti-seizure medications multiple times a day. Reducing anxiety about taking medication will increase compliance and improve the overall well-being of cats and their owners.

Developing Novel Surgical Methods for Spinal Stabilization in Teacup and Toy Breeds

Principal Investigator
Guillaume Leblond, clinical instructor, Department of Medical Sciences

Abstract
Atlantoaxial instability is a serious condition affecting the first two vertebrae in the neck, which can predispose affected patients to sudden death. This anomaly is best-treated surgically by placing metal implants to prevent vertebral luxation. Unfortunately, this disease occurs in dogs of very small size (teacup and toy breeds), which makes accurate implant positioning extremely challenging and potentially life threatening using currently available tools. Our long-term research goal is to develop novel surgical methods of spinal stabilization that are safe and easy to perform. The current study will focus on analyzing the 3D motions within this specific anatomical region using advanced biomechanical testing and state of the art 3D tracking technology. Understanding these complex motions is essential to be able to develop computer software capable of realigning displaced vertebrae prior to performing the surgery. This data is also necessary to design novel tools optimizing implant placement accuracy.

Exploiting biological priors identified by RNA-Seq to enhance cruciate ligament rupture quantitative trait locus discovery in dogs by genome-wide association

Principal Investigator
Peter Muir, professor, Department of Surgical Sciences

Abstract
Breed and knee inflammation both influence risk of cruciate ligament rupture (CR) in dogs, a major cause of ill-health. CR is a heritable complex disease in which both genetic and environmental factors influence risk of disease. Currently, there is an important gap in understanding how genetic variation disturbs ligament maintenance and repair to increase risk of rupture. This knowledge gap is limiting development of new approaches to patient management. In this project, we will identify biological pathways that influence risk of CR in dogs and use this knowledge to advance discovery of associated genes that ultimately could be targeted using medical treatment to alter the course of the disease. This is an innovative project that will use state-of-the-art RNA sequencing to identify genes with altered expression in cranial cruciate ligament tissue from dogs with CR. Knowledge of differentially expressed genes will then be used to find genetic variants associated with CR using existing genome-wide genetic marker data. Completion of this work will allow us to move rapidly toward our long-term goal of improved treatment for the disease and development of genetic screening for disease risk.

Evaluation of novel small molecule targeted therapy AZD1480 and CYT387 on canine B cell lymphoma

Principal Investigator
Xuan Pan, assistant professor, Department of Medical Sciences

Abstract
Non-Hodgkin Lymphoma (NHL) is the most commonly occurring hematologic malignancy in both human and canines.  Similar to humans, the majority of canine NHL (60-80%) are of the B cell immunophenotype, with most being diffuse large B cell lymphomas (DLBCLs).  Although the majority of canine DLBCL patients will initially respond to traditional chemotherapies, fatality rate of this disease is over 90%.  A new therapeutic drug is needed for canine DLBCL patients. The JAK/STAT signaling pathway has been shown to play a critical role in cancer biology in humans, but has not been extensively studied in canine lymphoma patients.  AZD1480 and CYT387 are novel JAK1/2 inhibitors.  We will investigate the therapeutic efficacy and the underlying mechanisms of AZD1480 and CYT387 in canine DLBCLs. Our study will create new opportunities for novel anti-cancer therapies in the future.

Defining laryngeal paralysis phenotypes in dogs by histological assessment of peripheral nerve pathology through predictive genetic markers

Principal Investigator
Susannah Sample, assistant scientist, Department of Comparative Biosciences and clinical instructor, Department of Surgical Sciences

Abstract
Acquired laryngeal paralysis polyneuropathy (ALPP) is a serious late-onset condition of older dogs. The disease causes degeneration of nerves throughout the body. Labrador and Golden retrievers are commonly affected. ALPP affects a dog’s ability to breathe. Profound changes in a dog’s mobility also develops, as ALPP is part of a generalized disease of nerves. Currently, there is little understanding of the specific nerve pathology that causes ALPP. Through a genome-wide association study, our laboratory has identified genetic markers that can predict development of ALPP in the Labrador. Our long-term goal is to identify the genetic basis for ALPP and understand the pathology of the disease. Our research objective is to study how nerve degeneration in canine ALP develops over time. We will accomplish our objective by performing a detailed histologic assessment, including high-resolution imaging, of nerve biopsies collected from pre-clinical cases and controls. This work is innovative because pre-clinical case and control dogs will be identified using recently discovered genetic markers for ALPP. This knowledge is expected to advance understanding of human inherited motor neuron disease, which canine ALPP models. Our results will also provide essential data for development of a novel disease-modifying treatment and for pre-clinical drug treatment studies that would benefit both dogs and humans.

Evalutation of alfaxalone-morphine and, dexmedetomidine-morphine-midazolam for sedation in Poison Dart Frogs (Dendrobates spp.)

Principal Investigator
Kurt Sladky, Clinical Professor, Department of Surgical Sciences

Co-Investigators
Taylor Yaw, resident, Zoological Medicine
Christoph Mans, clinical assistant professor, Department of Surgical Sciences

Abstract
There is a general lack of information regarding the safety and effectiveness of anesthetic and sedative drugs in most amphibian species. Because of this, clinicians and researchers must rely on published information from unrelated species – such as birds, reptiles, and mammals, in order to guesstimate appropriate drug dosages and frequency of drug administration. Therefore, it is important to develop new, species-specific anesthetic and sedative protocols for use in amphibians. Poison dart frogs (Dendrobates spp.) are ideal subjects because they are commonly kept in zoological collections, educational facilities, and are popular in the pet trade. Sedation or light anesthesia is required for a variety of clinical procedures in poison dart frogs, such as X-rays and blood sample collection as well as minor surgical procedures. This proposed study will evaluate the sedative effects and safety of two different anesthetic drug combinations (alfaxalone-morphine and dexmedetomidine-morphine-midazolam) at different dosages in poison dart frogs. The quality of sedation will be determined based on behavioral observations as well as the monitoring of heart and respiratory rates. The protocols developed from this study will allow for safe sedation and anesthesia of Dendrobates spp. for routine diagnostic and treatment procedures. Veterinarians providing care for these species will be able to apply the results from this study in clinical practice and in research settings.

Blood markers of free radical damage in cats with chronic kidney disease

Principal Investigator
Lauren Trepanier, professor, Department of Medical Sciences

Co-investigator
Allison Leuin, resident, Small Animal Internal Medicine

Abstract
People with kidney disease have evidence of free radical damage (oxidative stress), which can do even more damage to the kidneys over time. Cats also develop kidney disease, and it worsens despite treatment; however, the reasons for this are not known. Isoprostanes (IsoPs) are chemical products of free radical damage, and can be measured in the blood or urine. These chemical products are believed to contribute to kidney damage in humans, but it is not known whether they are important in cats. The purpose of this study is to measure both blood (plasma) and urine IsoPs in cats with different stages of kidney disease severity. We predict that plasma IsoPs will increase as kidney disease worsens but that urine IsoP concentrations will no longer follow plasma levels as more kidney cells are lost. This study may provide better tools for veterinarians to monitor cats with chronic kidney disease, and to determine whether specific treatments, such as antioxidants or special kidney diets, are effective in decreasing oxidative stress and in slowing kidney damage.

C-reactive protein: A biomarker of therapeutic response in dogs with aspiration pneumonia

Principal Investigator
Katrina Viviano, clinical associate professor, Department of Medical Sciences

Co-Investigators
Monica Chwala, resident, Small Animal Internal Medicine
Faye Hartmann, Clinical Pathology
Kenneth Waller III, clinical assistant professor, Department of Surgical Sciences

Abstract
Canine aspiration (bacterial) pneumonia is a common condition that is treated with antibiotics.  The length of antibiotic treatment in these cases is a challenge, as no consensus has been reached in veterinary medicine.  Most clinicians treat for 2-6 plus weeks based on comfort level and experience.  In human medicine, short duration antibiotics (5-7 days) are recommended for patients with bacterial pneumonia based on clinical markers, including C-reactive protein (CRP), a biomarker detected in the blood that becomes elevated associated with tissue inflammation.  Only recently, has CRP been receiving attention in the veterinary field.  For example, CRP levels are higher in dogs with bacterial pneumonia compared with respiratory diseases of other causes, but the use of CRP to direct antibiotic therapy has not been investigated in dogs.  Identifying an objective (measureable) marker of active disease would aid in optimizing treatment.  The goals of this study are to see if CRP levels correlate with clinical and radiographic resolution of aspiration pneumonia in dogs and if point-of-care (portable) canine CRP testing correlates with the “gold standard” send-out canine CRP assay to facilitate real time treatment decisions.  The results of this study may support the use of CRP as an objective tool to shorten the duration of antibiotic treatment in dogs with pneumonia.  Shorter antibiotic treatments lessen exposure to antibiotics leading to less adverse effects, lower cost, improved compliance, and less antibiotic resistance of respiratory bacteria.

Comparison of Two Intramuscular Sedation Protocols for Feline Blood Donation

Principal Investigators
Julie Walker, clinical assistant professor, Department of Medical Sciences
Lesley Smith, clinical professor, Department of Surgical Sciences

Co-Investigators
Susanna Solbak, resident, Department of Medical Sciences
Marcella Granfone, resident, Department of Medical Sciences

Abstract
A cat owner’s desire to help other cats sometimes leads them to offer their own cats as feline blood donors. Therefore, maximizing safety and comfort for donor cats is of utmost importance. Cats are sedated before blood collection to reduce stress and the likelihood of injury. Standard –of-care sedation protocols are currently used, but occasionally they cause inadequate sedation and/or low blood pressure.

An intravenous anesthetic drug called alfaxalone was approved for use in cats in the United States in 2012. When given by intramuscular (IM) injection, alfaxalone produces sedation in healthy cats while having minimal adverse effects on heart rate and blood pressure. Low-dose IM alfaxalone combined with an opioid (butorphanol) provides adequate sedation for roughly 40 minutes with a rapid onset of action and a smooth post-sedation recovery.

In a pilot study, a combination of alfaxalone and butorphanol was administered intramuscularly to sedate six healthy cats for blood donation. The results of this study suggest that this combination is safe and effective for use in cats when up to 20% of the blood volume is collected. Although preliminary data suggests that a combination of alfaxalone and butorphanol is suitable for feline blood donation, a larger study comparing this protocol to standard-of-care protocols in blood donor cats is needed. The aim of this study is to compare the depth and duration of sedation, cardiovascular safety, and quality of recovery of a butorphanol and alfaxalone IM combination compared to our present standard-of-care IM protocol in healthy blood donor cats.

Early Indication of the Bacterial Origins of Pyothorax in Canines Using Polymerase Chain Reaction for rapid Diagnosis

Principal Investigator
Joel Weltman, clinical instructor, Department of Medical Sciences

Abstract
Pyothorax is a condition where infectious fluid surrounds the lungs, causing severe compromise of breathing in dogs. This can lead to death if not treated promptly and appropriately. Migrating foreign objects and chest wall trauma are the most frequently proposed inciting factors for canines. Bacteria vary and patients often suffer from multiple types. Early identification of causative agents may help determine the origin of the pyothorax and guide appropriate medical and surgical management.

Traditional diagnostic evaluation includes cytology and bacterial culture and susceptibility; however, these tests are time consuming and may delay appropriate management of these critical cases. Early application of empirical broad-spectrum antimicrobials while awaiting culture and susceptibility results leads to ineffective and inappropriate use of antibiotics. Surgical management of pyothorax carries significant morbidity and cost and is traditionally guided simply by advanced imaging and response to therapy. The early identification of bacterial organisms implicated in pyothorax can assist clinicians in both selection of antimicrobials, but also may provide additional information regarding surgical need.

Our study proposes the use of polymerase chain reaction (PCR) as a rapid and accurate method of diagnosing organisms underlying pleural infection. Data from this study will allow us to improve patient management providing early, directed therapy in this life threatening condition. Additionally early identification of causative bacteria will improve compliance with the current recommendations for antimicrobial stewardship by limiting the use of broad spectrum, anecdotal antimicrobial selections while awaiting results from bacterial susceptibility.

2016 Projects

Genomic, Phylogenetic, and Recombinational Characterization of Feline Herpesvirus Field Isolates Using Deep-Sequencing Technology

Principal Investigator
Ellison Bentley, clinical professor, Department of Surgical Sciences

Abstract
Feline herpesvirus is an extremely widespread cause of eye and respiratory disease in cats. Some estimate that over 90% of cats have been exposed to herpesvirus, and half of those continue to shed virus intermittently. Half of those shedding may have recurrent eye problems, some of which are painful and blinding. Treatment has been frustrating as there is a wide spectrum of disease and susceptibility to treatment. This study will collect samples from a geographically diverse area and then compare genomes between different virus strains. Genomic difference may contribute to differences in virulence and response to treatment, which will allow us to develop better prevention and treatment strategies.

An Investigation of Slow CT to Assess Respiratory Motion in Dogs with Pulmonary Lesions for Use in Radiation Therapy Planning

Principal Investigator
Neil Christensen, clinical instructor, Department of Surgical Sciences

Co-Investigator
MacKenzie Pellin, resident, Radiation Oncology

Abstract
Accurate identification of cancerous targets is required for radiation therapy. When treating areas of motion like lung or abdomen, traditional CT scans cause distortion of the target. In humans, may be partially responsible for high rates of lung tumor recurrence after radiation therapy. Four-dimensional CT is used to image high motion areas in humans; however, the cost of this technology is too expensive for veterinary medicine.

Slow CT scanning (sCT) is an alternative imaging method that can be performed on any CT scanner. Preliminary research using models at the UW School of Veterinary Medicine suggest that sCT may give an accurate depiction of target motion compared to traditional CT. Our study aims to evaluate the effectiveness of sCT for determining
target motion in dogs with lung tumors as compared to fluoroscopy. The possible impact on radiation dose and normal tissue toxicity will be compared between radiation plans created using traditional CT and sCT.

Canine Exposure to Ebola Virus in Uganda

Principal Investigator
Tony Goldberg, professor, Department of Pathobiological Sciences

Abstract
Domestic dogs have been implicated as hosts for Ebola. This idea became famous after the controversial forced euthanasia of an Ebola patient’s pet dog in Spain in 2014. As a result, dogs have become maligned in affected areas of Africa, and mass forced canine euthanasia is being considered as part of Ebola emergency response plans in Africa,
Europe, and North America. These draconian measures are not evidence-based. To date, only one assessment of exposure of dogs to Ebola virus has been conducted, and the diagnostic methods were non-specific. We propose to conduct the first specific assessment of canine Ebola virus exposure in an outbreak zone. In 2008, Ebola struck the village of Bundibugyo, Uganda, near the PI’s long-term research site. We will sample dogs from households of Ebola victims, matched controls from unaffected households, and dogs from three control populations. We have the commitment of The United States Army Medical Research Institute of Infectious Diseases (USAAMRIID) for this study. USAAMRIID has a new “virus scanning” assay that detects antibodies to panels of viruses, including Ebola and its relatives, with very high sensitivity and specificity. Their involvement allows us to avoid biological hazards.

Our results will have important implications for canine health and welfare. If dogs do indeed show evidence of specific exposure to Ebola, this must be studied further and considered in response planning. If not, then this knowledge could prevent the unnecessary euthanasia of thousands of domestic dogs around the world.

Ventilation, Thermal Nociception, Food Intake, and Fecal Output FollowingAdministration of a Novel, High-Concentration Buprenorphine Preparation (Simbadol) in Rats

Principal Investigator
Rebecca Johnson, clinical associate professor, Department of Surgical Sciences

Co-Investigator
Molly Allen, resident, Anesthesia and Pain Management

Abstract
Buprenorphine (Buprenex) is a widely used peri-operative analgesic in animals, including rats. Side effects of buprenorphine administration include mild to moderate respiratory depression, impaired gastrointestinal motility, and pica (consumption of bedding), resulting in gastrointestinal impaction and reduced weight gain. Recently, high-concentration (1.8 mg/mL) buprenorphine in a 5% dextrose vehicle (Simbadol) was approved for up to 24 hours of post-operative analgesia in cats when administered at a high dose (0.24 mg/kg once daily versus the Buprenex dose of 0.02 mg/kg every 6-8 hours); this new formulation is not yet associated with adverse reactions seen with other sustained release buprenorphine preparations (e.g. Buprenex SR). Given the efficacy of Simbadol in cats and the disadvantages of repeated rodent injections (i.e., stress of handling, interference with experimentation, pica, diminished food intake/body weight), a once daily dosing regimen using Simbadol in rats is a realistic and attractive prospect.

Adult rats will be used to test the effects of Simbadol (0.15, 0.30 and 0.60 mg/kg) on ventilation, analgesia, and food intake/fecal output. Our techniques have proven effective in previous studies, and these studies will be the first to assess this novel, long-lasting buprenorphine preparation in rats. These studies may provide an appealing alternative for the veterinary medical professional to deliver long-lasting analgesia to companion and laboratory rodents without repeated dosing or the side-effects associated with sustainedrelease preparations, vastly improving post-operative care and reducing patient morbidity associated with painful states.

Dexmedetomidine-dependent Effects on Nociception and Respiration in Ball Pythons (Python regius)

Principal Investigator
Stephen Johnson, associate professor, Department of Comparative Biosciences

Abstract
Snakes are increasingly more popular as household pets. Unfortunately, when snakes require surgery or need to undergo potentially painful procedures, there are no drugs available that clearly provide long-lasting pain relief. In general, pain management in reptiles is poorly understood, particularly for snakes. Previously, we showed that morphine provides pain relief in turtles and lizards but not in snakes, even though extremely large dosages were tested. Several other morphinelike drugs were tested in snakes, but there was no evidence of pain relief. Consequently, we explored other non-morphine-like drugs and found that dexmedetomidine appears to provide pain relief with minimal depression of breathing in pilot studies. This study will carefully test whether dexmedetomidine can be used clinically in ball python snakes and possibly other snake species. If successful, this would represent a significant step forward in providing pain relief to snakes.

Development of a Dehydration–Rehydration Model in Lizards: Improving the Standard of Care for Dehydrated Reptile Patients

Principal Investigator
Christoph Mans, clinical assistant professor, Department of Surgical Sciences

Co-Investigator
Lily Parkinson, resident, Zoological Medicine

Abstract
Dehydration is a very common consequence of many serious diseases seen in animals,and therefore providing patients with fluids when ill or injured is a cornerstone of
treatment. Unfortunately for reptile patients, no research has been conducted to identify the best types of fluids for these unique animals. This study will be the first to investigate reptile fluid therapy. It will test different dosages of the diuretic drug furosemide, which has been used extensively in mammals but has yet to be studied in reptiles. Furosemide will be used to dehydrate the bearded dragons in the current experiment, but information from this study can be applied to the treatment of diseases such as heart failure in reptile patients. Overall, a plethora of new information will be gained by monitoring these bearded dragons’ blood parameters as they receive furosemide and fluids with far-reaching impacts on the future of reptile medicine.

Oral and Intravascular Contrast-Enhanced Computed Tomographic Evaluation of Small Pet Birds

Principal Investigators
Christoph Mans, clinical assistant professor, Department of Surgical Sciences
Jackie Williams, clinical assistant professor, Department of Surgical Sciences

Abstract
Small pet birds are commonly treated at UW Veterinary Care. Diagnostic imaging is frequently used in conjunction with blood testing to investigate underlying disease. Internal organs most often affected by disease in pet birds include the gastrointestinal tract, liver, and reproductive tract. Complete evaluation of internal organs in computed tomographic (CT) studies can be hindered due to the avian patient’s small size and poor internal detail. Orally and intravascularly administered positive contrast media can aid in identifying internal disease. In our study, we will use cockatiels to develop imaging protocols that will allow veterinarians to increase the diagnostic value of CT scans performed in small pet birds. The results of this study will have an immediate clinical application for avian patients presented to UW Veterinary Care and to any other clinicians who use CT for the evaluation of internal disorders in birds.

A Comparison of the Effects of Alfaxalone and Propofol on Laryngeal Function and Quality of Laryngeal Examination in Normal Dogs

Principal Investigator
Lesley J. Smith, clinical professor, Department of Surgical Sciences

Co-Investigator
Robert J. Hardie, clinical associate professor, Department of Surgical Sciences

Abstract
Laryngeal paralysis is an acquired disease of older dogs that results in respiratory difficulty and exercise intolerance due to obstruction of the larynx. In severely affected dogs, respiratory distress can become life threatening, requiring hospitalization, sedation, and endotracheal intubation to relieve the airway obstruction. Definitive diagnosis is made via laryngeal examination, and treatment involves surgically “tying back” the cartilage of the larynx to create a larger opening for breathing. Accurate diagnosis is critical prior to surgery, as laryngeal function is permanently affected, and the risk of aspiration of food and water is increased after tie-back surgery. The anesthetic propofol is commonly used for laryngeal examination in dogs. Although it is a safe option, propofol is not ideal because it can cause dogs to stop breathing (apnea) for periods of time, making it challenging to assess laryngeal function and potentially risk inaccurate diagnosis. A new anesthetic, alfaxalone, is recently available in the U.S. Alfaxalone has potential advantages over propofol for laryngeal examination, including lower risk of apnea and fewer cardiovascular side effects. It has not been evaluated for its effects on laryngeal function in dogs. The goal of this study is to compare propofol and alfaxalone for their effect on laryngeal function and the quality of laryngeal examination. Our hypothesis is that alfaxalone has less effect on laryngeal function and provides a better quality of laryngeal examination. Our data will determine which of these anesthetic drugs is most appropriate for use for laryngeal examination, thus minimizing the risk of misdiagnosis of laryngeal paralysis prior to surgical treatment.

Half-Body Radiotherapy in Combination with Chemotherapy for Canine Multicentric Lymphoma: A Recruitment Feasibility Study

Principal Investigator
Michelle Turek, assistant professor, Department of Medical Sciences

Abstract
The treatment for canine lymphoma has remained unchanged for 15 years. Chemotherapy is the therapy of choice. Initial remission rates are high, and dogs in remission enjoy an excellent quality of life. However, relapse is common, and cures are rare. As one of the most common and uniformly fatal diseases in dogs, effective new therapies are in great demand. Radiation is an effective treatment for select forms of lymphoma in people. To answer the long-standing question about the benefit of radiotherapy as a treatment in dogs with lymphoma, a clinical trial is necessary. The integrated oncology service at UW Veterinary Care is well-suited to execute such a multi-disciplinary trial. To investigate the feasibility of a successful partnership between medical oncology, radiation oncology, and regional private practices, we propose a recruitment and feasibility study. Ten dogs with lymphoma will be recruited to receive radiation in conjunction with chemotherapy. If recruitment and protocol execution are successful, we will be in a position to propose a larger comparative trial to determine if radiotherapy has a role in the treatment of this uniformly fatal disease.

2015 Projects

Efficacy And Tolerability Of Transdermal Phenobarbital For Seizure Control In Cats

Principal Investigator
Heidi Barnes Heller, Department of Medical Sciences

Abstract
Reliable administration of anti-seizure drugs, like phenobarbital, is critical to maintain seizure control in cats. Unfortunately administering oral phenobarbital to cats can be
difficult, resulting in inconsistent dosing, stress to the cat and injury to the owner. Furthermore, a missed dose of anti-seizure medications can result in a seizure. The purpose of this study is to compare blood levels achieved using topical phenobarbital to levels achieved using oral phenobarbital in cats with seizures. Additionally, we will compare side effects and ease of administration between oral and topical administration of phenobarbital. Cats will receive oral medication for three months, followed by topical phenobarbital for three months. Our hypothesis is that topical phenobarbital will achieve comparable serum levels to oral phenobarbital, owners will be more satisfied with the topical administration, and that side effects will be minimal and similar to known side effects of phenobarbital.

The Role Of Urothelial Glycosaminoglycans In The Development Of Canine Recurrent Urinary Tract Infections

Principal Investigators
Sara Colopy, Department of Surgical Sciences
Michael Wood, Department of Medical Sciences

Abstract
Recurrent urinary tract infections (UTI) are common in dogs and are associated with poor quality of life due to frequent and painful urination. Repeated courses of antibiotics lead to development of drug-resistant infections. Treatments targeted at preventing UTI would be ideal to avoid the poor quality of life and drug resistance associated with recurrent infections. Glycosaminoglycans (GAGs) lining the bladder surface have been shown to be important in maintaining a tight barrier to bacteria in the urine. Treatment with GAGs in the bladder reduces the rate of UTI in people. The role of GAGs in development of canine UTI has not been evaluated. The goal of this study is to compare the GAG content in the urine of dogs with and without recurrent UTI. Results of this study would lay the groundwork for future clinical studies evaluating the efficacy of GAG treatment in preventing canine UTI. Gastrointestinal Transit Time Following Intravenous Lidocaine Infusions In Conscious

Dogs Assessed With Barium-impregnated Polyethylene Spheres (BIPS)

Principal Investigator
Rebecca Johnson, Department of Surgical Sciences

Abstract
Lidocaine is a commonly used drug in veterinary medicine for analgesia (pain relief) and to decrease cardiac arrhythmias. In horses, lidocaine is also used to increase gut motility. However, despite the frequent use of lidocaine in dogs, no studies have assessed its effects on their gastrointestinal system. Our specific objective focuses on answering a clinically-important, yet untested question: Do intravenous lidocaine infusions at routine doses decrease gastric and intestinal emptying times in the conscious dog? We will feed barium-infused polyethylene spheres (BIPS) to dogs followed by radiographic BIPS tracking throughout the gastrointestinal tract at various time points to assess this question. All information and inferences gained from these experiments will be novel and may greatly impact the clinical management of our painful patients or patients that require antiarrhythmic therapy since the dosedependent side effects of lidocaine CRI may preclude its use in certain canine populations.

Evaluation of Gastrointestinal Contract Fluoroscopy In Red-tailed Hawks (Buteo Jamaicensis)

Principal Investigator
Christoph Mans, Department of Surgical Sciences

Abstract
Red-tailed hawks are the most commonly treated birds of prey in wildlife rehabilitation centers as well as the most common species used for falconry in North America. Gastrointestinal (GI) disorders are common in birds of prey, but the work-up of these diseases using diagnostic imaging tools is limited by the lack of established “normal.” Indeed, while contrast fluoroscopy studies are commonly used in parrots for work-up of GI disorders, their use in birds of prey is rare, as normal GI transit, have not yet been established. The aim of this study is to determine the normal GI transit times in healthy red-tailed hawks fluoroscopy following oral administration of a contrast media. In addition, since hooding is a very common technique used in birds of prey to calm and immobilize, the effects of this technique on GI transit times will also be assessed.

Angiotensin Receptor Blockers As A Novel Therapeutic Approach For Glaucoma In Cats: A Pilot Study

Principal Investigator
Gillian McLellan, Department of Surgical Sciences

Abstract
Glaucoma is a leading cause of blindness in animals and humans. We have identified increased amounts of a specific protein (TGFβ) within the eyes of cats with glaucoma. This growth factor may also contribute to worsening of glaucoma in people. In recent years, a widely available blood pressure medication, losartan, has shown promise in treating children with Marfan syndrome, a life-threatening condition in which high levels of TGFβ have also been identified. Our objective is to determine if losartan is effective in slowing or preventing progressive loss of vision in cats with glaucoma. A favorable response to treatment in cats will help to establish an exciting new approach to the treatment of glaucoma, as well as other diseases in which altered TGFβ signaling has been identified, in companion animal and human patients.

Detection Of Copy Number Variants In The Canine Genome And Examination Of Their Association With Canine Cruciate Rupture

Principal Investigator
Peter Muir, Department of Surgical Sciences

Abstract
Cruciate ligament rupture (CR) is a common disabling condition of the knee in dogs that is economically important. CR occurs through a non-contact mechanism and is common in the Labrador Retriever, affecting 5.79% of the breed. CR is a complex trait in which both genetic and environmental factors influence disease risk. Copy number variations (CNVs) are alterations to the DNA of the genome that result in duplication of DNA segments. CNV is associated with disease. In this project, we will analyze the genomes of Labrador Retriever CR cases and controls for the presence of CNVs. We will then determine whether specific CNVs are associated with risk of CR. Comprehensive understanding of the genetic contribution to the CR condition will enable development of a genetic test for disease. Because the genetic contribution to CR consists of many sites in the genome with small effects, genomic selection will likely be needed.

Determination Of Blood Lactate In Healthy And Hospitalized Neonatal Cria And Examination Of Its Association With Survival In Septic And Non-Septic, Critically Ill Neonates

Principal Investigators
Simon Peek, Department of Medical Sciences
Ana Moreira, Department of Medical Sciences

Abstract
Alpacas are the most popular New World Camelid in North America and an important part of the caseload at UW Veterinary Care (UWVC.) Sepsis is the most significant cause of illness and death during the first 30 days of life and early identification of high-risk crias and implementation of intensive care are crucial for a successful outcome. Equine and human medicine lactate values are linked with disease severity and determine the odds of survival for a number of common illnesses seen in intensive care facilities. Lactate levels have also been used as a prognostic indicator and as a tool for monitoring treatment in other species for conditions such as sepsis and colic. No such data exists in alpacas. This study aims to establish normal ranges for alpaca crias and to investigate the diagnostic and prognostic value of blood lactate in sick crias presented for treatment at the UWVC.

The Influence Of Axial Grooves On The Dislodgement Resistance Of Prosthetic Metal Crowns In Dogs

Principal Investigator
Jason Soukup, Department of Surgical Sciences

Abstract
Dental fractures affect nearly 30% of all dogs, many of which require metal crowns in order to properly restore health and strength to the tooth. However, the dislodgement rate of metal crowns in dogs is suboptimal (10-20% dislodgement rate) when compared to humans (1% dislodgement rate). In order to place a metal crown on a tooth, some tooth structure must be removed. This process is referred to as crown preparation. The shape of the tooth after tooth preparation and the specific design of the preparation influence the long-term retention of the metal crown on the tooth. Some preparation design features are known to increase retention in humans. However, these design features have not been evaluated on the unique shape of dog teeth. This study will evaluate the influence of grooves cut into the walls of the tooth during crown preparation on the retention of metal crowns. We hope to develop a more intelligent preparation design that enhances the retention of metal crowns in dogs.

Evaluating ROR2 Inhibition In Canine Malignant Melanoma

Principal Investigator
Timothy J Stein, Department of Medical Sciences

Abstract
Canine malignant melanoma is a highly aggressive malignancy associated with poor overall survival due to local disease recurrence, high metastatic rate, and poor response to conventional anti-cancer therapies. Recent studies suggest that disease recurrence,metastasis, and chemoresistance may be due in part to the presence of a subpopulation
of tumor-initiating cells. The non-canonical Wnt signaling pathway, including the ROR2 receptor, has been implicated in contributing to a phenotype consistent with these tumor-initiating cells. We aim to determine the impact of specifically inhibiting ROR2 activity on tumor-initiating cell formation in canine malignant melanoma cell lines. As noted above, the lack of sustainable disease control warrants investigation of novel therapies. It is possible therapies aimed at ROR2 may be capable of reducing the
aggressiveness of canine melanoma cells as well as inhibiting tumor-initiating cells, thereby improving patient outcomes relative to currently available treatments.

Association Of Relative Regulatory T-Cell Frequency With Progression-Free Survival In Dogs With B-Cell Lymphoma

Principal Investigator
M. Suresh, Department of Pathobiological Sciences

Abstract
Nearly half of all dogs over 10 years old will die of cancer, and B cell lymphoma (BCL) is one of the most common types. Although treatment with chemotherapy may extend
survival, it is currently impossible to reliably predict which dogs will respond to chemotherapy. This clinical study aims to improve our ability to predict how dogs with BCL will respond to chemotherapy. Patients respond to tumors by producing immune cells that kill tumor cells. However, cells known as regulatory T lymphocytes (Tregs) can “turn off” this immune response, allowing the tumor to grow unchecked. Our study will measure both of these cell types in dogs with BCL, to identify patterns associated with dogs that respond well to chemotherapy. We expect this information to help clinicians determine the prognosis and best treatment options for dogs with BCL, and to identify potential new targets for treating this common disease.

Evaluation Ff Stereotactic Radiotherapy For Canine Sinonasal Tumors Using Helical Tomotherapy

Principal Investigator
Michelle Turek, Department of Medical Sciences

Abstract
Sinonasal tumors are aggressive cancers of the nasal passages of dogs that cause nosebleeds, nasal congestion, and pain. Radiotherapy is the treatment of choice to alleviate
symptoms and extend life expectancy. Radiation side effects commonly affect normal tissues surrounding the tumor. Specialized radiation equipment, including
TomoTherapy®, has made it possible to deliver radiation more precisely, reducing these harmful effects. Since TomoTherapy® allows radiation delivery with fewer
complications, it raises the question; can dose to the tumor be safely increased to improve tumor control? Stereotactic radiotherapy is a precision-delivery approach that
delivers high-dose radiation in fewer treatments compared to conventional protocols. We will evaluate the safety and efficacy of stereotactic radiotherapy for sinonasal
tumors using TomoTherapy®. We hypothesize that it will be safe and at least as effective as conventional protocols. By providing a shorter treatment with fewer anesthestic episodes, stereotactic radiotherapy may alter the treatment paradigm for sinonasal cancer.

Ultrasonographic Acoustoelastography Characteristics And Contrast Enhanced Enhancement Pattern Of Splenic Nodules In 50 Dogs

Principal Investigator
Ken Waller, Department of Surgical Sciences

Abstract
Ultrasonography is non-invasive diagnostic tool used to evaluate for abdominal disease. Splenic nodules and masses are a relatively common finding in dogs of all age ranges and when seen, the lesion may be benign or malignant. Acoustoelastography (AEG) and contrast harmonic ultrasonography (CEUS) have independently proven to help differentiate some types of malignancy from benign lesions. To the investigators knowledge, splenic AEC results have not previously been correlated with the CEUS patterns of similar lesions. The purpose of this study is to prospectively evaluate splenic nodules or masses using AEG techniques, to characterize these lesions and any concurrent metastatic hepatic lesions with CEUS and to correlate these patterns with cytology/histopathology results. The ultimate goal is not to replace cytological sampling, yet it is to establish more refined non-invasive parameters to minimize unnecessary sampling of benign lesions and maximizing sampling of lesions with a higher probability of malignancy.