New Grantees Announced

2007/2008 Cycle Grantees

Our congratulations to our newest grant recipients!

Good luck with your projects and thank you for you for helping us build healthier lives for animals.

07-04D Canine. Diplomate. "Determination of urolith composition using CT-generated Hounsfield units." Dr. Barrak Pressler -$15,000.00 (1-year grant). Purdue University.

Urinary tract stones (uroliths) are one of the most common conditions diagnosed by veterinarians, affecting 1.5-3.0% of all dogs. Although not all patients require immediate treatment, most protocols require knowledge of the urolith's mineral composition. Unfortunately there are no accurate, noninvasive methods for determining mineral composition of uroliths prior to removal from patients.

Because some urolith types can be dissolved without invasive or expensive techniques, determining composition would allow some pets and owners to avoid the pain, costs, and risks associated with anesthesia and surgery. In people the mineral composition of surgically removed uroliths has been determined using computed tomography (CT), whereby the 'grayness' of the stone on the CT image is converted to an actual number; the more dense the composition of a urolith, the higher the number. Application of this technique to people with uroliths prior to surgery in many cases allows differentiation between the most common types of uroliths.

In a previous study performed by the principal investigator of this proposal, CT-derived reference ranges were determined for the three most common types of uroliths recovered from dogs. Using these reference ranges the various mineral types could be differentiated with >90% accuracy, sensitivity, and specificity.

Objective: This clinical study is designed to validate the reference ranges for use in dogs with uroliths, determine the accuracy of this diagnostic test, and determine if urolith density based on CT correlates with fragility when removed by laser fragmentation, potentially leading to improved diagnosis and treatment of dogs with urinary tract stones.

07-08D Canine and Feline. Diplomate. "Epidemiological Study of Azotemia Associated with Eating Recalled Pet Food." Dr. Catherine Langston -$14,800.00 (1-year grant). The Animal Medical Center-New York City.

In March 2007, the Food and Drug Administration recalled certain pet (dog and cat) foods because of an association with kidney failure and death in 16 animals. Immediately, veterinarians began to identify other pets with kidney failure who had consumed the recalled foods. Melamine, a compound found in plastics, fertilizer and fire retardants, was identified as a contaminant in the recalled foods.

There is little scientific information about the toxicity profile of melamine in dogs and cats, and further investigation into this emerging pet food safety issue is needed.

Objective: This study will first determine the proportion of pets developing kidney failure during the pet food recall period which will be compared to the proportion of pets developing kidney failure in time periods prior to the pet food recall to determine if a detectable increase in the frequency of kidney failure occurred during the recall period. Second, a dietary survey of pets with and without kidney failure who were cared for at the Animal Medical Center in New York City during the recall period will be performed. This information will be used to determine the magnitude of the association between consumption of recalled food and kidney failure. Finally, in pets without current kidney failure, blood tests that evaluate renal function will be compared between pets that did and did not consume the recalled food to determine if subclinical kidney damage occurred from consumption of recalled pet food.

07-10D Feline. Diplomate. "D-Lactic Acidosis in Feline Gastrointestinal Disease." Dr. Dennis O'Brien -$12,900.00 (1-year grant). University of Missouri-Columbia. Study sponsored in partnership with

Cats with gastrointestinal (GI) disease often suffer from lethargy and a lack of appetite. Loss of appetite in a cat can have serious consequences such as liver failure. Investigators have recently documented profound elevation of D-lactate in the blood of two cats with severe lethargy and coordination loss (encephalopathy) and GI disease.

D-lactate is not normally found in the blood of mammals, and it is thought to be a byproduct of abnormal bacterial growth within the intestines. While these cats showed extreme signs, it raises the question of whether milder elevations contribute to the problem in cats with milder GI disease. This may lead to specific therapies to reverse these effects.

Current diagnostic tests for GI disease in cats are not very sensitive or accurate in determining the underlying cause, thus D-lactate levels may also provide a better test for diagnosing GI disease in cats.

Objective: The investigators will determine if D-lactate levels are elevated in cats with GI disease. If they are, they will determine which factors correlate with the elevation to assess the usefulness of D-lactate as a diagnostic test, potentially improving the diagnosis and treatment of GI disease in cats.

07-13D Equine. Diplomate. "Dantrolene Sodium for the Prevention of Anesthesia-Related Myopathy in Horses." Dr. Erica McKenzie -$14,712.00 (1-year grant). Oregon State University.

Hundreds of horses undergo general anesthesia at veterinary institutions around the country every day. Approximately 3 to 10% will develop muscle damage associated with anesthesia, leading to difficult anesthetic recovery, and potentially lameness and nerve damage.

Objective: Dantrolene is a muscle relaxant drug that prevents many forms of muscle damage. The aim of this study is to determine if dantrolene prior to anesthesia prevents muscle damage in horses at risk. Six horses will be treated 60 minutes before anesthesia with either dantrolene or a placebo treatment (saline) both administered by mouth and the effect of dantrolene on the occurrence of muscle damage will be determined via appropriate statistical techniques.

07-20D Canine. Diplomate. "Gene Expression Profiling of Canine T Cell Chronic Lymphocytic Leukemia." Dr. Susan Lana -$11,044 year one; $11,513 year two ($22,557 total for a 2-year grant). Colorado State University.

Canine chronic lymphocytic leukemia is a blood cancer of the white blood cells called lymphocytes. This affects most breeds, but disproportionally affects Golden Retrievers and Shih-tzus. The disease is often unnoticed for a long time as the dogs do not show any overt clinical signs. It is still unclear which subset of dogs will benefit from therapy or if otherwise healthy dogs require expensive and potentially toxic chemotherapy.

Markers (proteins expressed by the cancerous lymphocytes) that would help predict a patient's survival would be useful tools for making such decisions. Gene expression profiling is a method that allows scientists to examine thousands of genes expressed by tumor cells simultaneously. In this study the investigators will use gene expression profiling in dogs with CLL to determine if there are genes associated with good and poor prognosis.

Objective: the overall goal of the study is to develop a simple and inexpensive diagnostic test which will help owners and veterinarians determine the severity of disease and the indications for early therapy in a needed patient.

07-22D Canine. Diplomate. "Characterization of Intravascular Bacteria Isolated from Dogs With and Without Bartonella spp. Infections." Dr. Edward Breitschwerdt -$9,075.00 per year; $18,150.00 total (2-year grant). North Carolina State University.

The vast majority of bacteria that exist on this planet cannot be isolated in a microbiology laboratory using currently available microbiological approaches. Within the past decade, a new genus of bacteria, named Bartonella, has been found in the blood of numerous domestic and wild animal species. It is now obvious that these previously un-culturable Bartonella bacteria have inhabited the blood of animals and people for millions of years.

At times and for reasons that remain unclear, these bacteria occasionally induce disease in the reservoir host. More frequently, disease is induced when a reservoir-adapted Bartonella spp. is transmitted to a non-reservoir host by arthropod and animal bites or by scratches (an example is cat scratch disease caused by Bartonella henselae). Because fastidious bacteria are difficult to detect, the invetigators' research group developed novel diagnostic techniques to enhance detection of Bartonella species and other hard to grow bacteria in the blood of sick animals and people. Some of these bacteria have never been isolated from sick people previously.

Objective: to determine if the isolation medium developed and validated for the detection of Bartonella species in animals and humans allows us to detect novel bacteria that could not be isolated with previous methods. It is possible that these organisms contribute to the development of diseases for which the cause is unknown. To determine the identity of these bacteria, the investigators will obtain the DNA sequence of each isolate and compare their DNA to other bacteria with known DNA sequences.

07-23D Ruminant. Diplomate. "Redefining the role of Chlamydophila spp. associated disease in dairy goats." Dr. Paul Plummer -$14,925.00 (1-year grant). Iowa State University.

Chlamydophila is a bacterial disease known to cause "pink-eye" and abortions in goats. Unfortunately, the difficulty associated with growing this organism in the laboratory has resulted in a lack of knowledge about how the bacteria spreads from animal to animal.

Research in dairy cattle suggest that this bacteria may also be responsible for infections of the mammary gland of cattle, however this issue has never been evaluated in goats. The recent development of a new diagnostic test has, for the first time, allowed scientists to scientifically evaluate these issues.

Objective: This study will utilize this new diagnostic test as a means of determining how many animals are infected with these bacteria, a necessary step in the design of additional studies focused on the specifics of the disease. The second portion of this project will evaluate the role of these bacteria in the development of mammary gland infections. The results obtained by this study will provide much needed basic information regarding this disease in dairy goats and will provide a platform for improved diagnosis, treatment and management recommendations.

07-25D Canine and Feline. Diplomate. "Multi-drug resistance and virulence patterns in canine and feline urinary E. coli." Dr. Julie Fischer -$14,981.00 (1-year grant). University of California-Davis.

Bacterial urinary tract infections (UTI) are common in companion animals, usually starting in the bladder, but sometimes spreading to the kidneys, causing severe, potentially fatal illness.

Escherichia coli (E. coli) causes most bacterial UTI, and the E. coli which produce UTI often possess adaptations that enhance their ability to cause disease. Relative ability to cause disease is called "virulence" and genes affecting virulence can be identified and described. The ability of bacteria to survive in the presence of antibiotics is called "resistance." The more resistant a bacterial strain, the fewer antibiotics are available for treatment. Traditionally, E. coli have shown either virulence or resistance, but human and preliminary dog/cat studies show the emergence of UTI-derived E. coli that show both virulence and broad resistance.

Treatment of such infections frequently requires hospitalization and/or specific injectable medications. This intensive treatment can radically increase the cost and complexity of therapy, as well as the impact of medical management on both pet and owner.

Objective: This study will describe current virulence and resistance patterns of dog and cat UTI-derived E. coli, and will place these bacteria into the E. coli "family tree." Comparison of animal and human data will delineate common and species-specific characteristics of dog, cat, and human E. coli. Documentation of virulent and resistant E. coli strains indicates need for further study of effective and economical treatment for these potentially devastating organisms. Characterization of virulence/resistance patterns in these strains may indicate fruitful, possibly species-specific, alternative treatment options for further investigation.

Multi-Center Grants:

07-15D/M Equine. Diplomate. "The Effect of Season, Latitude and Breed on Equine Pituitary Function." Dr. Dianne McFarlane -$19,953 year one; $18,938 year two ($38,891 total for 2-year grant). Oklahoma State University.

Equine Cushing's Disease (ECD) is the most common hormone disease of aged horses and ponies. Horses with ECD often develop life-threatening complications including founder and infections, therefore early diagnosis is critical to prevent these devastating conditions from occurring.

Diagnosis of ECD is complicated by seasonal increase in the activity of the pituitary gland. Due to normal seasonal activation of the pituitary gland, horses that are tested for ECD in the fall often have false positive results and are therefore incorrectly diagnosed with ECD. It is unknown when in the year this seasonal change begins that triggers the increased activity of the pituitary gland.

Objective: The investigators hypothesize that hormone release from a healthy horse is regulated by seasonal change in day length. They will measure hormone concentrations in horses once a month for one year and they will also examine geographical effects (location in relation to distance from the equator) and breed impact on the levels of hormone concentration. Results from this study may help veterinarians to more accurately diagnose Equine Cushing's Disease.

07-21D/M Equine. Diplomate. "Real-Time RT-qPCR for Detection of Equine Infectious Anemia Virus." Dr. Brett Sponseller -$20,000 year one; $5,100 year two ($25,100 total for 2-year grant). Iowa State University.

Equine Infectious Anemia (EIA) is a disease regulated by the United States Department of Agriculture (USDA). Infection with Equine Infectious Anemia Virus (EIAV) results in a lifelong, persistent infection. In 2003, the USDA estimated that serosurveillance of nearly 2 million samples cost horse owners in the United States in excess of $48 million.

Laboratories accredited by the USDA use a testing scheme that detects the presence of serum antibody to the virus. The agar gel immunodiffusion (AGID) test, or "Coggins test", developed by Dr. Leroy Coggins, provided the first efficient serological test for detection of antibody to EIAV and it remains a USDA accepted test. In addition, there are 4 licensed enzyme-linked immunosorbent assays (ELISAs) that test for antibody to EIAV.

Within North America, seropositive horses must be quarantined and/or euthanized. While the antibody-based means of serosurveillance are effective, they have their shortcomings. Indeed, direct detection of viral genetic material by PCR has become the preferred method of diagnosis for a variety of viral pathogens. To date, such a USDA approved diagnostic assay is unavailable for EIAV.

Objective: Investigators at Iowa State University and the USDA-National Veterinary Services Laboratories (Diagnostic Virology Laboratory) propose to develop an assay that detects the genetic material for EIAV. A first step includes an analysis of the genetic variation of EIAV to determine suitable genetic sequences to target in the diagnostic assay. Once they develop the assay, they will compare this assay, which detects viral genetic material, with the currently approved tests which detect antibodies. This work may possibly lead to an improved testing method for Equine Infectious Anemia Virus.

Chase Away K9 Cancer Grants-Funded by the Chase Away K9 Cancer Campaign:

Osteosarcoma (OSA) is the most common bone tumor in dogs occurring primarily in the long bones resulting in bone destruction, pain, lameness and metastasis primarily to the lungs. Treatment involves limb amputation followed by chemotherapy. Despite the treatment, approximately 90% of dogs with OSA will die of metastasis within 2 years of amputation. Therefore, it is critical that more effective treatments be developed.

Gemcitabine is a chemotherapy drug that incorporates into the cell DNA, eventually leading to cell death. In a previous study funded by the ACVIM Foundation, the investigators have generated data demonstrating the efficacy of gemcitabine against canine OSA tumor cells in the laboratory. They have also demonstrated that when gemcitabine is combined with carboplatin, killing of tumor cells is greater than when either drug is used alone.

Objective: based on these encouraging preliminary findings, as well as evidence for superior clinical activity of combined gemcitabine and carboplatin for the treatment of human cancers, the investigators have initiated a clinical trial to determine whether gemcitabine administered in combination with carboplatin will improve outcome in dogs with OSA. In this study, 50 dogs with appendicular OSA will undergo limb amputation followed by four treatments with carboplatin and gemictabine administered on the same day. Dogs will then be followed to determine whether the combination of these two drugs is capable of significantly prolonging 1 year survival rates in affected dogs.

This clinical trial, funded by the ACVIM Foundation's Chase Away K9 Cancer Campaign, represents a joint effort between the Ohio State University Veterinary Teaching Hospital and the New England Veterinary Medical Oncology Group in Waltham, MA.

07-33D/Chase. Diplomate. "Developing novel single chain targeted agents for canine hemangiosarcoma." Dr. Nicola Mason - $30,314.00 year one; $17,000.00 year two ($47,314.00 total for 2-year grant). University of Pennsylvania.

Canine hemangiosarcoma is an aggressive cancer of blood vessels that commonly affects large breed dogs. Currently, available chemotherapeutic regimens results in a median survival time of approximately 6 months. Recently, adjuvant immunotherapies (treatments to stimulate or restore the ability of the immune (defense) system to fight infection and disease) have extended the survival times but mortality rates remain high and novel targeting approaches for the treatment of this disease are needed. The use of target specific antibodies to directly target the tumors has shown promising results in human clinical trials. For the antibodies to be effective they first need to recognize the enemy that is the antigen. In dog models this immunotherapy approach has a great limitation because in dogs the tumor antigens have not been identified.

Objective: In this proposal, the investigators aim to use molecular techniques developed in their laboratory to generate a specific antibody from canine patients with hemangiosarcoma and screen them to identify an antibody that specifically targets cancerous blood vessel cells (antigens in this case). This work aims to break the self-tolerance (where the antibodies will not destroy the normal cells) and generate antibody responses against their own tumors in dogs.

Extended Multi-Year Projects:

06-09R Canine and Feline. Resident. "Prevalence of Staphylococcus aureus and MRSA carriage in three populations." Dr. Stephanie Kottler. University of Missouri. Study sponsored in partnership with

06-17D/M Equine. Diplomate/Multi-Center. "Endocrine dysregulation in foal sepsis: the role of arginine vasopressin in neonatal septicemia and foal survival." Dr. Ramiro Toribio. The Ohio State University. Recipient of the Dr. Mary Rose Paradis Multi-Center Grant

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