Companion Animal Fund Research Projects

Iron status, red blood cell indices, and reticulocyte indices in dogs enrolled in a canine blood donor program

Dr. Jonathan Bach, Department of Medical Sciences

Current standards for human blood donors permit people weighing more than 50 kg (110 lbs) to donate blood every 56 days, with each donation being ~400-450 ml.  Canine blood donor programs typically require dogs to weigh more than 23 kg (50 lbs), but despite lower canine weight standards, donations remain in the range of 400-450 ml.  Initial studies suggested that dogs tolerate donations every 28 days without developing anemia.  However, recent studies have shown evidence of iron deficiency, without overt anemia, in people donating blood only four times annually.  Iron status has not been critically evaluated in canine blood donors.  The objective of this study is to evaluate iron status and incidence of iron deficiency in dogs enrolled in the University of Wisconsin Veterinary Medical Teaching Hospital?s blood donor program.  The results could lead to early intervention protocols or donation recommendations to prevent iron deficiencies in donor dogs.

 

Dr. Ian Duncan

This research project will investigate the genetic basis of a neurologic disease in Weimaraners, with the long-term goal of producing a bench test that will help the breed selectively eliminate the disease, based on their ability to identify dogs that carry the abnormal gene.  The disease presents in the early neonatal period with affected pups developing a severe tremor at 10-12 days of age.  This tremor dissipates with time and is lost when the dog is 4-5 months.  Although not life-threatening, the tremor causes considerable stress to the owner and prevents dogs being placed in homes at the usual age.  It is found across America and in Europe.  Using DNA from two Weimaraner families we will use an approach known as a genome wide association study to map the gene and then fine map the gene and the mutation.  This will allow the development of a DNA test to identify carriers of the mutation, thus allowing future selective breeding.

 

Pharmacokinetics and pharmacodynamics of pimobendan in hispaniolan amazon parrots (Amazona ventralis)

David Sanchez-Migallon Guzman

Congestive heart failure is the most commonly diagnosed cardiac disease in parrots and its treatment has historically been difficult. Pimobendan is a newer inotropic drug that has become the drug of choice in the treatment of congestive heart failure in dogs. We aim to find a clinically practical oral dosage of pimobendan that shows cardiovascular effects that are beneficial for the treatment of congestive heart failure in Amazon parrots. We would also like to characterize the cardiovascular properties of pimobendan in Amazon parrots. First we will study the pharmacokinetic profile of a single oral and intravenous dose of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis). In order to correlate the cardiovascular effects of pimobendan with its plasma concentrations, we will assess the cardiovascular effects of a single intravenous dose.  

 

Translaryngeal Percutaneous Arytenoid Lateralization (TPAL) as a New Minimally Invasive Technique for Treatment of Laryngeal Paralysis in Dogs

Robert J. Hardie, DVM, Dipl. ACVS
Clinical Associate Professor Small Animal General Surgery

Laryngeal paralysis is a relatively common problem in large breed dogs that results in obstruction of the airway due to failure of the vocal cords to open properly during respiration.  Problems resulting from laryngeal paralysis include coughing, gagging, or aspirating while eating, exercise intolerance, respiratory stridor and difficulty oxygenating, and potentially severe respiratory distress and collapse.  Dogs that develop respiratory distress can be challenging to treat and often require emergency intubation to relieve the airway obstruction and break the cycle of respiratory distress that leads to further collapse of the vocal cords.  Emergency intubation is effective for most dogs; however, some fail to stabilize due to persistent swelling of the vocal cords, aspiration pneumonia, or other concurrent conditions and require additional treatment prior to definitive surgery to open the paralyzed vocal cords.  Currently, the only option for relieving the persistent airway obstruction in these dogs is a tracheostomy tube that requires intense management and has been associated with increased mortality when used in dogs with laryngeal paralysis.  The objective of this study is to investigate a new, less-invasive technique called translaryngeal percutaneous arytenoid lateralization (TPAL) which is designed to temporarily hold open the vocal cords and maintain a patent airway so that dogs can be better stabilized prior to definitive surgery for laryngeal paralysis.  The procedure is performed through the mouth and involves placing a suture around one of the vocal cords and tying the suture on the outside of the neck so that the vocal cord is temporarily fixed in an open position thus maintaining a patent airway while the dog is further stabilized.  If successful, this technique has the potential to dramatically improve the way in which dogs with laryngeal paralysis are treated and reduce the morbidity currently associated with the use of tracheostomy tubes in dogs. 

 

Comparison of pelvic flexure enterotomies closed with a TA-90 stapling device v. hand sewn closure

Dr. Michael Livesey, Department of Surgical Sciences

Up to 7% of calls made by equine veterinarians are to treat horses suffering from colic.  While most respond to medical treatment, <1% have an intestinal accident, requiring abdominal surgery.  This is performed with the horse restrained on its back under general anesthesia.  An incision is made through the abdominal wall to expose the intestines.  Manipulation of the bowel is difficult if it is distended, while pressure exerted on the diaphragm will make it difficult for the horse to breath.  Speed and efficiency are therefore of importance. 

During surgery, the large bowel is exposed, and if distended, is emptied through an incision made in the wall, a hosepipe inserted and water pumped in to soften and flush out the contents.  The incision is closed with two overlapping layers of sutures, providing a water and gas tight seal.  A secure closure that decreased the surgical time would help reduce complications related to the horse lying on its back for an extended period.  Stapled closure of the colonic incision may offer these benefits, provided our study confirms the closure has a similar mechanical strength.

 

Spinal Anesthesia and Analgesia in Red-Eared Slider Turtles

Christoph Mans, med. Vet; Paulo Steagall, MV, MSc, PhD; Stephen M. Johnson, MD, PhD; Kurt K. Sladky, MS, DVM, Dipl. ACZM

Turtles and tortoises commonly present to veterinarians for surgical conditions such as egg binding or penile/cloacal prolapse. Unfortunately, these animals are frequently physiologically compromised due to a delay in care, which can significantly increase anesthetic risk and lead to a poor recovery. Spinally administered anesthesia/analgesia may help alleviate these negative consequences. Therefore, we propose to develop and validate a novel, spinal anesthesia/analgesia technique in red-eared slider turtles. The benefits of spinal anesthesia/analgesia would include a reduction in systemically administered anesthetics and analgesics, minimal cardiorespiratory depression, and improved post-surgical recovery, particularly in compromised patients. This study will be the first of its kind to investigate spinal anesthesia in any reptile species.

 

Identification of a genetic susceptibility in canine cruciate rupture.

Dr. Peter Muir, Department of Surgical Sciences

Cruciate rupture is the most common cause of lameness in dogs.  Ruptures usually occur during normal activity and are not associated with accidental injury.  Traditionally, knee arthritis was thought to be a consequence of joint instability after rupture of the cruciate ligament.  However, recent work suggests this paradigm is incorrect and that development of cruciate rupture is actually a consequence of inflammatory knee arthritis.  Consequently, it has been proposed that cruciate rupture develops because of an inflammatory arthritis and chronic inflammation of the joint lining.  The health of the cruciate ligament tissue is closely related to the joint environment, as the ligament is surrounded by joint fluid and covered by the joint lining.  Although inflammation of the joint lining is typically found in affected dogs, it is unclear whether the immune responses that develop within knee joints with cruciate rupture are abnormal.  In human beings, inflammatory arthritis is often associated with an immunogenetic susceptibility.  This study will determine whether there is an association between major histocompatibility complex genotype and development of cruciate rupture.  Identification of a genetic risk factor for cruciate rupture will confirm that joint immune responses are abnormal, allow early detection of at-risk dogs and facilitate development of selective breeding strategies.

 

Tramadol, but not Carprofen, provides effective alleviation of post-operative pain after canine enucleation

Principal Investigator: Lesley J. Smith DVM, DACVA
Co-Investigator: Ellison Bentley DVM, DACVO

Our collaborative research group has successfully employed the canine model of eye removal for studies of analgesics in dogs that present to the UW VMTH for medical conditions requiring this procedure.  To date, we have used this model to publish studies on specific local anesthetic blocks. Many veterinary practitioners, however, are not comfortable with the competency required to perform these techniques. A popular non-steroidal anti-inflammatory oral analgesic used for canine post-operative pain is the drug carprofen, which is similar to the drug ibuprofen. Carprofen has potential side effects, including damage to the renal and gastrointestinal systems. A second oral analgesic that is gaining popularity in veterinary medicine is tramadol. Tramadol has mechanisms of action that make it a potentially superior analgesic with fewer side effects, but studies of its efficacy in clinical models of canine pain are lacking.  Specifically, tramadol acts as a morphine-like drug, but also provides analgesia by inhibiting specific neurotransmitter reuptake in the spinal cord, so its mechanisms of action are more diverse and ?multimodal? than the non-steroidal anti-inflammatory drug carprofen. The goal of the study proposed here is to compare analgesia in dogs, requiring eye removal, that have received either carprofen or tramadol orally prior to surgery.  The hypothesis of this study is that tramadol will provide more effective analgesia than carprofen in the post-operative period and that fewer dogs receiving tramadol will require additional analgesia. Results of this study would provide valuable information to veterinarians about the comparative analgesic benefits of these drugs.

 

Comparison of image quality of the dog maxilla obtained by cone beam computed tomography or medical grade computed tomography

JASON W. SOUKUP, DVM, DAVDC
RANDI DREES, Dr. med. vet., DACVR, DECVDI
CHRISTOPHER SNYDER, DVM, DAVDC
LISA J. KOENIG, B.CH.D., D.D.S., M.S.

Successful surgical planning of maxillofacial pathology in companion animals requires high-resolution, three-dimensional pre-operative imaging. A new imaging modality, cone beam computed tomography (CBCT), has been shown to provide high-detail, high-resolution two- and three-dimensional images in humans. Given the steady movement toward the use of CBCT as the primary imaging modality of the orofacial region in humans, validation of CBCT in companion animals is needed. The primary objective of our research is to determine the feasibility and potential benefits of CBCT imaging of the canine maxilla, when compared to traditional imaging modalities.  Our future goals are to evaluate the capacity of CBCT to: quantify bone loss from periodontal disease; facilitate diagnosis and treatment success of endodontic disease; support planning of surgical and non-surgical treatment of orthodontic disease; and improve diagnosis and treatment planning of invasive oral pathology and maxillofacial trauma.

 

Bacteriologic and clinical cure rates of short duration
 trimethoprim-sulfamethoxazole therapy versus long duration
 ?-lactam therapy in female dogs with uncomplicated bacterial cystitis

Principal Investigator:  Katrina R. Viviano PhD, DVM, DACVIM
Co-Investigators:  Sharon Clare PhD, DVM and Faye A. Hartmann, M.S., MT (ASCP)

Urinary tract infections are a common clinical problem in women and female dogs.  In women, research supports short duration trimethoprim-sulfonamides (TMS) versus long duration ?-lactams.  Short duration TMS is used in women without clinically significant drug hypersensitivity reactions, a rare adverse reaction of sulfonamide antibiotics.  In contrast, long-duration ?-lactams are routinely used in dogs.  A cure rate of 45% was recently reported in dogs treated with cephalexin for 14 days, suggesting ?-lactams may not be ideal therapy in dogs.  The goals of this study are to compare the response to treatment with short-term TMS to long-term ?-lactam therapy in female dogs with urinary tract infections and determine the frequency of clinically significant sulfonamide hypersensitivity reactions in dogs treated for 3 days. We hypothesize that short-term TMS therapy will be safe and effective in the treatment of urinary tract infections in female dogs while minimizing cost, antibiotic exposure, and bacterial resistance.   

 

Apoptosis - not just for nucleated cells

Karen Young, Clinical Professor, Department of Pathobiological Sciences

Red blood cells (RBCs) circulate in the blood stream and provide oxygen to all tissues of the body. The lifespan of circulating RBCs is tightly regulated, and an "old" cell undergoes alterations that result in its removal, whereas replacement RBCs are made in the bone marrow. In healthy animals, the exact nature of the alterations in RBCs and the mechanisms used to recognize and remove them are areas of active investigation. In immune-mediated hemolytic anemia (IMHA), RBCs are destroyed or removed from the blood stream early and in excess of what the bone marrow can produce; thus, the animal's ability to deliver oxygen to the tissues is compromised. This disease can be severe and
is often life-threatening in dogs with a reported mortality rate of 40%. Efforts to improve diagnosis and management of IMHA have long focused on the immunologic components of the disease. Recent data suggest that a closer look at changes in RBCs themselves is warranted. We will systematically evaluate changes in RBC membranes and signaling events hypothesized to contribute to their increased interaction with the immune system and removal from circulation. This has the potential to identify alterations in the RBCs that may serve as diagnostic aids or therapeutic targets in the future.

 

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

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

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

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

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

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

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

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

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

Articular cartilage in normal canine cadaveric elbows:
Comparison of CT arthrography with MRI and MR arthrography.
Dr. Susan Schaefer, Department of Surgical Sciences

The elbow is a common site for the development bone and cartilage lesions, often referred to as elbow dysplasia in young growing dogs. Articular cartilage erosions, fissures or fragmentation are often found at the time of arthroscopic surgery in dogs with elbow dysplasia and are believed to negatively affect long-term outcome.  It would be helpful if these lesions could be identified without the need for arthroscopic surgery. Radiography, Commuted Tomography (CT), and Magnetic Resonance Imaging (MRI) are diagnostic tools that can evaluate bony lesions and secondary degenerative changes, but fail to allow visualization of the articular cartilage. Arthrography, the use of a contrast medium in a joint, in combination with radiography, CT or MRI, is required for the accurate evaluate the articular cartilage. CT and MR arthrography are utilized in the diagnosis of cartilage lesions of the human elbow but no previous work has validated these imaging modalities in the canine elbow. The purpose of this investigation is to establish the optimum technical parameters for CT arthrograms of the canine elbow and to determine which imaging modality, CT or MRI, is most accurate in the measurement of articular cartilage thickness.   Canine cadaver elbows will be used for this study. Confirmation of a reliable technique for cartilage evaluation in the dog will significantly enhance our ability to identify abnormalities and prevent needless surgeries in our patients.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Pharmacokinetics and efficacy of liposomal extended-release buprenorphine in a rat model of neuropathic pain
Dr. Dale Bjorling
Department of Surgical Sciences

Animals do not like frequent injections and it may be difficult for owners to give dogs and cats pills at home. Morphine-like medications (opioids) are used to treat pain from many causes, but may be abused by people or accidentally ingested by children. Buprenorphine is an opioid drug commonly used in animals. It is one of the few drugs that can be used to treat pain in cats. Our laboratory has developed a formulation of buprenorphine that lasts for 2 weeks in rats using liposomes (LE-Bup). Liposomes are small, artificial membranes that form into hollow spheres. Drugs may be loaded into these hollow spheres, and the liposomes leak the drug slowly into the body. We will test the release rate of more LE-Bup formulations in rats, and determine their effectiveness at treating rats in a standard model of pain from nerve injury. This study would provide preliminary data to develop LE-Bup for clinical use in animals and people.

In vivo evaluation of acultoelastic strain gauge in the normal equine superficial digital flexor tendon
Dr. Sabrina Brounts
Department of Surgical Sciences

The superficial digital flexor tendon (SDFT) is a commonly injured soft tissue structure in performance horses. Injury of this structure happens to occur mainly in the mid-portion of the SDFT. Prognosis for return to full athletic function is guarded due to the fact that horses are placed back into work to soon and re-injury of the tendon occurs. Therefore it is important to be able to assess quantitatively the mechanical property of tendons under load before the horse returns to full athletic use. At the University of Wisconsin a novel technique called ?Acoustoelastography (AE) was developed, which interrelates the ultrasound wave propagation to the local tissue biomechanical stiffness. Pathological diseased tendon has less stiffness than normal healthy tendon. AE can assess this in virtually real-time without knowing/recording tissue loads or performing extensive numerical analysis on images. The goal of this project is to determine whether AE can measure mechanical properties and strains non-invasively in normal equine tendons and secondly establish a reproducible method of applying AE to the equine SDFT in vivo. The ability to evaluate the degree of tendon injury via its function would revolutionize diagnosis, monitoring, and treatment of musculoskeletal injury. By identification of weak areas within the tendon before overt changes in tendon anatomy are appreciated, rehabilitation programs could be specifically tailored for the patient reducing the rate of re-injury. In addition, a more specific prognosis for soundness after return to a high level of athletic competition may be determined. Degenerative tendon changes may be detectable earlier, allowing identification of high-risk animals before a career ending injury occurs.

Radiographic anatomy of juvenile bovine limbs
Dr. Randi Drees
Department of Surgical Sciences

The University of Wisconsin-Madison, Veterinary Medicine Teaching Hospital receives referral patients from farms around Wisconsin and even farther afield. Young calves and older cattle patients are frequently radiographed to assess the source of lameness and swelling of their limbs. With the radiographic technology available at the VMTH, we can obtain detailed radiographs of the affected limbs. The reference images available are quite old and are based on images which are much less detailed than those we can obtain today. Our objective is to take radiographs of calves at different points during their development, in order to have an improved reference of normal juvenile bovine limbs. We can then use these images to help diagnose disease in our patients, and also to improve learning resources for our students and a reference for veterinarians in practice.

Efficacy of taurine supplementation as a treatment for canine urinary incontinence
Dr. Heidi Kellihan
Department of Medical Sciences

Twenty percent of spayed female dogs will develop some degree of urinary incontinence, which is the unconscious leaking of urine during sleep or activity. This disease significantly impacts quality of life for these patients and their owners. New therapies are needed that are proven to be effective and safe. One novel therapy is taurine, an amino acid supplement that has many important functions in the body, although all of its physiological roles are not fully understood. Taurine has been safely used in dogs and cats for years for the treatment of heart disease caused by taurine deficiency. We have observed resolution of incontinence in canine patients supplemented with taurine, suggesting that taurine may be a reasonable, alternative therapy for incontinent dogs. The objective of this study is to evaluate the response of incontinent dogs to treatment with taurine, as compared to placebo, in a randomized, blinded clinical trial.

Low temperature blood-free perfusion for prolonged cardiac arrest in small dogs
Dr. Jon McAnulty
Department of Surgical Sciences

The goal of this research is to study methods to utilize very low temperature methods for achieving long term cardiac arrest in small animals. The significance of this research is in development of methods that will allow easier and more successful methods for cardiac surgery in the dog than is currently available with conventional cardiac bypass techniques. The specific studies proposed are an extension of previous work and are targeted at successful implementation of these methods in small dogs which is anticipated to represent the majority of the cases for which these surgeries are needed in the clinic. Small dogs represent a specific challenge with respect to down sizing the pump circuits, fluid volumes and alteration of methods protocols to achieve similar success as seen in larger dogs. We anticipate that success in these studies will lead directly to application of these methods in patient animals.

In vitro biomedical evaluation of four surgical techniques for fusion of the equine distal and tarsometatarsal joints
Dr. Samantha Morello
Department of Surgical Sciences

Osteoarthritis of the distal hock joints is a debilitating cause of lameness in many equine athletes. The disease process results in significant pain for the animal, part of which is believed to arise from instability of the joints. We aim to evaluate the stability of the hock after various surgical treatments designed to promote ankylosis of these distal joints. In particular, we are evaluating the implantation of Kerf-cut cylinders, devices which have been used in both human and equine surgeries to stabilize regions of the spine. The potential exists to implant these devices in horses via a minimally invasive approach saving time and money. We aim to show that the implantation of these cylinders will improve the biomechanical stability of the distal hock joints and thereby may reduce lameness and facilitate fusion. It is hoped that this background study will provided us with enough data to conduct a clinical trial.

Arthroscopic assessment of stifle synovitis in the dog
Dr. Peter Muir
Department of Surgical Sciences

Cruciate rupture is the most common cause of lameness in dogs. Ruptures usually occur during normal activity and are not associated with accidental injury. Traditionally, knee arthritis was thought to be a consequence of joint instability after rupture of the cruciate ligament. However, recent work suggests this paradigm is incorrect and that development of cruciate rupture is a consequence of inflammatory knee arthritis. Consequently, it has been proposed that cruciate rupture develops because of rheumatic disease characterized by chronic inflammation of the joint lining or synovium. The health of the cruciate ligament tissue is closely related to the joint environment, as the ligament is surrounded by joint fluid and covered by the joint lining. Although synovitis is typically found in affected dogs, it is difficult to assess severity of inflammation clinically, particularly in therapeutic clinical trials. Minimally invasive surgery with a rigid fiber optic arthroscope provides a magnified view of the joint lining, with little patient risk. In human beings, the arthroscopic appearance of the synovium is highly correlated with histologic inflammation of the synovium. This study will determine whether there is an association between quantitative arthroscopic scoring of synovial inflammation and histologic markers of synovial membrane inflammation. Arthroscopy promises to be a useful tool upon which individual treatment plans may be based and responses to therapy may be monitored. This knowledge will be used in clinical trials evaluating use of disease-modifying medical therapy for affected dogs.

Epidural analgesia is extended when dexmedetomidine is added to buvicaine in dogs undergoing hindlimb orthopedic procedures
Dr. Lesley Smith
Department of Surgical Sciences

Epidural administration of opioids (e.g. morphine) or local anesthetics (e.g. bupivacaine) provides analgesia of varying durations for hindlimb and lower abdominal procedures. Epidural analgesia is used commonly at the UW VMTH for dogs that undergo hindlimb orthopedic surgery. Use of epidurals for post-surgical pain management is also common in general practice. Bupivacaine and morphine are the most common drugs chosen for epidural use in veterinary medicine. Studies from human medicine suggest that alpha-2 agonist drugs, including dexmedetomidine, have benefits when added to the epidural analgesics, including better quality of analgesia and an extended duration compared to when single drugs are used alone. In addition, morphine is a controlled substance, whereas dexmedetomidine and bupivacaine are not controlled, thus are routinely available to general practitioners. No scientific studies have been reported in veterinary medicine on the analgesic use of epidural dexmedetomidine. . The goal of this study is to compare the duration of epidural analgesia attained from bupivacaine alone, bupivacaine + morphine, and bupivacaine + dexmedetomidine. Our hypothesis is that addition of dexmedetomidine to the epidural will provide longer and more effective analgesia than when bupivacaine is administered alone or in combination with morphine. If our hypothesis proves correct, dogs that receive epidural dexmedetomidine and bupivacaine will have lower pain scores and will require less additional analgesia in the post-operative period. Results of this study would provide valuable information to veterinarians in both general and referral practice about the duration and comparative analgesia of these drugs when administered epidurally to dogs.

Characterization of beta catenin expression and pathway activity in canine malignant melanoma
Dr. Tim Stein
Department of Medical Sciences

Canine oral melanoma is a highly aggressive cancer associated with a poor overall survival due to local disease recurrence as well as spread to other organs. Similar to advanced melanoma in humans, canine oral melanoma is poorly responsive to conventional anti-cancer therapies. The lack of sustainable disease control warrants investigation of novel therapies, preferably targeting features specific to the tumor and different from normal cells. Perturbation in a cellular signaling pathway - the Wnt/?-catenin pathway - has been implicated in the progression of human melanoma. Our preliminary data indicate ?-catenin (a protein) is expressed in canine oral melanomas, and we propose to further evaluate this pathway?s potential to serve as a therapeutic target. We hypothesize that the Wnt/?-catenin signaling pathway will be active in a subset of canine oral melanomas. The results of our study will indicate whether further research is warranted to determine the prognostic and therapeutic relevance of the Wnt/?-catenin signaling pathway in canine oral melanoma.

Health Assessment of Endangered Whooping Cranes in the Central Flyway
Dr. Barry Hartup
Department of Surgical Sciences and International Crane Foundation

The North American whooping crane (Grus americana) was successfully returned from the brink of extinction, but remains highly endangered. Despite highly publicized reintroductions, the only self-sustaining flock remains the original migratory population that breeds in Wood Buffalo National Park, Canada and winters at the Aransas National Wildlife Refuge in coastal Texas. This population remains at risk: total mortality for the 12 months following April, 2008 equaled 57 birds (21% of the population of 266 cranes). A newly authorized study will involve capture, marking and tagging of whooping cranes from this population with conventional and satellite telemetry for the next 3 years. My study is designed to provide health assessments from whooping cranes during the last 2 years of captures at the Aransas NWR. Together with development of a dataset of marked individuals and detailed telemetry, follow-up investigations of migration health risks and mortality factors will be possible, where previously only scant opportunistic information was available. The results of this investigation will be used to develop science-based strategies to prevent losses of whooping cranes in the decades to come and contribute to the recovery of the species.