Grant Updates: Why Giving Matters

Grant Results

The ACVIM Foundation is committed to communicating results and disseminating knowledge to our donors, the public, and the veterinary community. Below are results from some of our funded studies. We will continue to provide more updates as we receive them.

Grant #06-01R Resident Grant
Dr. Mary Beth Callan: "Evaluation of canine platelet cryopreservation methods"
Study completed

Platelets are needed for blood clot formation and prevention of spontaneous bleeding. A dog with a decreased number of platelets (thrombocytopenia) or platelets with impaired function (thrombopathia) may require a platelet transfusion to control severe or potentially life-threatening hemorrhage. Blood products containing platelets include fresh whole blood (i.e., blood collected from a healthy donor dog and administered to the patient within 8 hours of collection), platelet-rich plasma (PRP), and platelet concentrate (PC). PRP and PC are prepared from fresh whole blood, requiring special equipment and expertise, and are stored at room temperature for up to 5 days. Refrigeration has a damaging effect on platelet viability. Many veterinary clinics do not have ready access to fresh platelet products. Therefore, there has been interest in cryopreserving (freezing using a special protective solution) canine platelets to allow for long-term storage and immediate availability of a platelet product. It is recognized that freezing will inevitably lead to some irreversible platelet damage, but the question is whether cryopreserved platelets have acceptable function and viability to control bleeding in patients.

Two platelet cryopreservative solutions, 6% DMSO and 2% DMSO plus Thrombosol, were evaluated in this study. Platelets were collected from healthy donor dogs. In comparison to fresh platelets, both forms of cryopreserved platelets demonstrated impaired function in vitro, although the frozen platelets did retain an ability to be activated, which may allow formation of normal blood clots in the recipient. The cryopreserved platelets were labeled with a protein (biotin) so that their lifespan could be determined following administration to other dogs. While fresh platelets had a half-life (time at which 50% of transfused platelets are present in the recipient dog's circulation) of almost 4 days, the cryopreserved platelets had a reduced half-life of approximately 2 days. Both cryopreservative solutions evaluated appeared comparable with regard to in vitro function and post-transfusion survival of platelets.

The investigators concluded that while cryopreserved platelets fall short of fresh platelets in terms of post-transfusion survival, either method of platelet cryopreservation may be a reasonable alternative to fresh platelet products in veterinary clinics without ready access to fresh platelet products. Further studies are needed to assess the hemostatic function of the cryopreserved platelets in the bleeding canine patient.

Grant #06-03R Resident Grant
Dr. Jeff W. Tyler: "Efficacy of serum transfusions in reducing mortality in dairy heifer calves"
Study in progress

Transfer of immunoglobulins (antibodies which play an essential role in the body's immune system. They attach to foreign substances, such as bacteria, and assist in destroying them) from the mother cow is important for calf health and survival. In healthy calves, immunoglobulins are passively obtained through ingestion of colostrum (a form of milk) in the first day of life and provide protection from infections. Failure of passive transfer of these antibodies is a factor in half of the neonatal deaths in dairy calves. Previous studies have found that treating calves with serum or plasma intravenously can replace immunoglobulins.

Objective: The investigators are examining the benefits of transfusing serum into newborn dairy calves for preventing mortality. The information they gain will help them understand how to use serum transfusions to treat failure of passive transfer and prevent disease. Ultimately the study results will be used to develop recommendations which may have broad application in the cattle industry.

Grant #06-09R Resident Grant
Dr. Stephanie Kottler: "Prevalence of Staphylococcus aureus and MRSA carriage in three populations"
Study sponsored in partnership with
Year one completed of two-year study

Staphylococcus aureus is a bacterium that lives on people. Dogs and cats usually have other kinds of Staphylococcus bacteria on their skin. These bacteria generally do not cause an infection unless the person or animal is ill or there is a break in the skin. Bacteria can become resistant to antibiotics resulting in serious infection, even death. Methicillin-resistant Staphylococcus aureus (MRSA) is a resistant bacterium. It has been proven that health care workers (medical and veterinary) are more likely to carry MRSA than are other people. Data suggests that MRSA in pets may also be on the rise and there is concern that these animals could develop a severe infection or spread the bacterium to people.

Objective: This study has been designed to determine if cats and dogs that live with health care workers are more likely to carry MRSA than cats and dogs that live with non-health care workers and if the bacteria came from the same source.

Grant #06-11R Resident Grant
Dr. Cheryl A. London and Dr. Melanie McMahon: "Investigating the Biologic Activity of Gemcitabine in Canine Osteosarcoma"
Study sponsored in partnership with Chase Away K9 Cancer Campaign and the Sacramento Valley Dog Fanciers Association Pilot study completed

The investigators are continuing their work in Grant #07-29R/Chase: "Clinical Evaluation of Carboplatin plus Gemcitabine in Canine Osteosarcoma"

Osteosarcoma (OSA) is the most common bone tumor in dogs occurring primarily in the long bones resulting in bone destruction, pain and lameness. Treatment involves amputation of the affected limb followed by chemotherapy, as nearly all dogs have microscopic spread of the cancer at the time of diagnosis. Despite the use of chemotherapy, 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 kills cells by incorporating into DNA, eventually leading to cell death. With support provided by the ACVIM Foundation, the investigators have generated data demonstrating that gemcitabine is capable of killing canine OSA tumor cells in the laboratory. Furthermore they evaluated the interactions of gemcitabine in combination with compounds known to have activity against OSA, including the bisphosphonate pamidronate, the chemotherapeutic carboplatin, and a small molecule inhibitor of hepatocyte growth factor receptor. No additive or synergistic effects on tumor cell kill are noted when gemcitabine is combined with pamidronate or the small molecule inhibitor of hepatocyte growth factor receptor. Alternatively, when gemcitabine is combined with carboplatin, killing of tumor cells is significantly greater than when either drug is used alone.

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.

Grant #06-17D/M Diplomate Grant
Recipient of the Dr. Mary Rose Paradis Multi-Center Grant
Dr. Ramiro Toribio: "Endocrine dysregulation in foal sepsis: the role of arginine vasopressin in neonatal septicemia and foal survival"
Year one completed of two-year study

Sepsis (blood poisoning) is a condition where bacteria can multiply in the blood and set up widespread infection throughout the body and is the most common cause of death in foals. The clinical signs and consequences of sepsis can include multiple organ failure and loss of the normal hormonal functions/mechanisms that regulate cardiovascular and metabolic function and this includes the hormone arginine vasopressin (AVP). Only preliminary has been done to investigate the actual role of AVP in sepsis.

Objective: The investigators are comparing the levels of AVP in normal and septic foals. The information they gain will help them assess the role of AVP in foals and may support the therapeutic use of AVP for the treatment of sepsis in foals and may possibly impact survival rates.

Grant #06-20D Diplomate Grant
Dr. Nicholas Frank: "Improved diagnosis and monitoring of equine endocrine disorders"
Study in progress

Horses can develop health problems when they experience hormonal changes, and there are two common hormone disorders that affect middle-aged and older horses. The first is called equine metabolic syndrome (EMS), and it is similar to diabetes in obese people. Horses with this disorder tend to be overweight and are prone to laminitis (also called founder; inflammation of the lamina, the innermost layer of the hoof wall). They have higher than normal levels of the hormone insulin in their blood, so the disorder can be diagnosed by testing a blood sample. The other disorder is called Equine Cushing's disease, or pituitary pars intermedia dysfunction (PPID) and it causes older horses to lose weight and develop a long haircoat. This disorder also makes the horse more prone to develop laminitis and it is diagnosed by detecting high levels of a hormone called adrenocorticotropin hormone in the blood.

It seems straightforward that high levels of these hormones indicate disease, but the situation is more complicated because other factors also raise hormone concentrations in healthy horses. This makes it difficult to decide when disease is present, which discourages veterinarians from using these measurements.

Objective:To measure hormone levels in blood collected from horses and ponies over a 12-month period from different geographical locations being fed different rations to determine the best way of collecting blood samples, the extent to which hormone levels vary within the same horse, and the effects of season and diet on blood hormone concentrations. Results will be used to better define the cut-off points for determining the presence of a hormonal disorder and to establish normal guidelines for diagnosis and treatment monitoring.

Grant #06-29D Diplomate Grant
Dr. Jill Beech: "Evaluation of Endogenous Alpha MSH Concentrations at Different Seasons and in Response to TRH in Normal Horses and Those with Pituitary Hyperplasia"
Study in progress

Equine Cushing's disease, pituitary pars intermedia dysfunction (PPID) is a common endocrine disease of horses often associated with severe laminitis (also called founder; inflammation of the lamina, the innermost layer of the hoof wall. This is also the condition which lead to the racehorse Barbaro's death) and recurrent infections. This disease can only be diagnosed when a horse has developed these life-threatening conditions and then it may be too late to initiate successful treatment. More sensitive and specific diagnostic tests are needed to diagnose the disease in its early stages.

In PPID horses, levels of several pituitary hormones are increased. However, alpha-MSH is secreted at disproportionately higher levels compared to other pituitary hormones. Previous studies have found that alpha-MSH levels vary with season as well as disease.

Objective: The investigators are comparing the levels of alpha-MSH in normal and PPID horses at various season of the year. The information they gain will help them determine whether alpha-MSH will be useful in early diagnosis and monitoring of PPID.

Grant #05-02R Resident Grant
"Relative Adrenal Insufficiency in Critically Ill Neonatal Foals"
Dr. Michelle Barton and Dr. Kelsey Hart (Resident)
Study completed

Critically-ill humans frequently lose the ability to regulate body metabolism through circulating hormones, contributing to the severity of their illness. In this study, performed by investigators at University of Georgia College of Veterinary Medicine and Hagyard Equine Medical Institute in Lexington, KY, it was discovered that critically-ill foals have a similar problem.

Approximately half of the foals studied were unable to properly regulate their basic circulating hormones, and this condition was strongly associated with sepsis (i.e., uncontrolled bacterial infections, a leading cause of death in foals). Future studies are planned to determine whether abnormal stress hormone regulation is a cause of, or an effect of, sepsis. Additionally, studies are on-going to determine whether artificial regulation of these hormones using drugs can improve the survival of affected foals. Their findings have the potential to have a significant impact on the early detection and management of foals at risk for developing serious disease.

Grant #05-06D Diplomate Grant
Dr. Todd C. Holbrook: "Indicators of Cardiac Damage in Rattlesnake Envenomated Horses"
Year one completed of two-year study

Rattlesnake bites in horses are not uncommon in the southwestern United States. Anecdotally, horseman have noted that once bitten, often these horses are not the same athletes as they were previously. Currently, the specific effect of rattlesnake venom on the horse's heart after the bite is unknown.

Last year, the ACVIM Foundation funded researchers at Oklahoma State University to study the cardiotoxic effect of rattlesnake bites in horses. To date, they have collected data on 16 horses bitten by rattlesnakes. Their research has confirmed that in some horses, cardiac damage does indeed occur. Future research will be aimed at determining the exact components of venom that cause this damage, and investigate preventive approaches.

Abstract presented at the 2007 ACVIM Forum in Seattle, WA

Grant #05-11D Diplomate Grant
"Efficacy of Famotidine for the Prevention of Stress-Induced Gastric Ulcers"
Dr. Michael Davis
Study completed

Sled dogs, like many other human and animal athletes, are prone to develop stomach ulcers during competition. Previous studies have confirmed that human over-the-counter anti-ulcer medications can decrease the severity of stomach ulcers in racing sled dogs. However, medications proven to work under racing conditions are difficult to administer to dogs, and other medications that are easier to administer have not been proven under racing conditions.

This study was designed to bridge this gap by testing easy-to-administer anti-ulcer medications under racing conditions. Although the medications were shown to reduce the severity of ulcers, the investigators concluded that the reduction in severity was not as great as desired. Future studies will examine the use of higher doses to determine whether the effectiveness of the medications can be improved.

Grant #05-12D Diplomate Grant
"Mechanism of Exercise-Induced Airway Immunosuppression in Horses"
Dr. Michael Davis
Year one completed of two-year study
Study sponsored in partnership with

Everyone who has exercised outside knows that breathing cold air while exercising can result in irritation and burning of the nose and throat. However, studies in humans, dogs, and horses suggest that repeatedly breathing cold air during exercise can cause chronic changes to airways, leading in some cases to an asthma-like syndrome known as "ski asthma".

In other cases, evidence suggests that breathing cold air may weaken the immune system in the lungs, possibly explaining why the "cold and flu season" is in the winter. Dr. Davis and colleagues are using horses to examine the short-term and long-term effects of cold air on the lungs' immune system.

To date, they have demonstrated that even a single 5 min period of exercise while breathing cold air can activate the immune system and trigger influx of inflammatory cells. Further studies are on-going to determine how long this response lasts, and whether the overall effect is one of decreased resistance to viruses.

Grant #04-04R Resident Grant
"Relationship between surfactant dysfunction and severity of disease in RAO-affected horses"
Dr. Undine Christmann (Resident) and Dr. Virginia Buechner-Maxwell
Year one completed of two-year study

Recurrent airway obstruction (RAO) or "heaves" induces labored breathing in susceptible horses exposed to a typical barn environment containing hay and straw. Airway surfactant (defined as: a fluid secreted by the cells of the alveoli (the tiny air sacs in the lungs) that serves to reduce the surface tension of pulmonary fluids; surfactant contributes to the elastic properties of pulmonary tissue) counteracts airway obstruction by helping to maintain airways open, facilitating mucus removal, and decreasing airway inflammation.

Drs. Undine Christmann (PhD candidate) and Virginia Buechner-Maxwell are investigating surfactant alterations in horses suffering from RAO. They recently demonstrated that horses suffering from RAO have low surfactant levels and changes in surfactant composition. This was true at all disease stages even in remission when RAO horses were free of clinical signs. RAO crisis further exacerbated surfactant alterations. On-going research will evaluate relationships between surfactant composition, function and disease severity.

Dr. Christmann's graduate training research is supported by a grant from the ACVIM foundation.

She was awarded the Joan O'Brien Research Award for outstanding presentation by a graduate student at the Veterinary Comparative Respiratory Society Forum in 2007. She also achieved 1st place in the basic science category at the graduate student research award competition at the Annual Research Symposium held by the Virginia-Maryland Regional College of Veterinary Medicine in 2007.

The ACVIM Foundation is honored to support Dr. Christmann's work.

Grant #04-05D Diplomate Grant
"Mechanism of Postoperative Bleeding in Retired Racing Greyhounds"
Dr. Guillermo Couto
Study completed

Postoperative bleeding appears to be relatively common in retired racing Greyhounds, sometimes requiring life-saving blood transfusions. Most dogs have normal clotting times during and after the bleeding episodes. This study was performed to investigate the prevalence, severity and cause of post-operative bleeding in Greyhounds having surgery at Ohio State University-Veterinary Teaching Hospital.

Of 88 Greyhounds that were spayed or neutered, 26% had moderate to severe bleeding 36-48 hours after surgery. None of these dogs required transfusions. There were no differences in clotting between the "bleeders" and "non-bleeders". However, a few tests suggested that the "bleeders" may be breaking down blood clots sooner than "non-bleeders". This would explain why the bleeding is seen 1-2 days after surgery rather than during surgery. The "bleeders" were more anemic and had lower platelet counts after surgery, which is expected with blood loss.

While this study showed that 26% of Greyhounds had post-operative bleeding, the lack of difference in clotting times before and after surgery between the "bleeders" and "non-bleeders" makes it unlikely to be caused by a clotting disorder. None of the routine clotting tests were able to predict if a dog was likely to have post-operative bleeding. The data obtained from this study may help future surgical care and treatment of Greyhounds.

Abstract presented at the 2007 ACVIM Forum in Seattle, WA

Grant #04-18D Diplomate Grant
"Magnetic resonance imaging in boxers with arrhythmogenic right ventricular cardiomyopathy" Dr. Mark Kittleson and Dr. Sarah Miller (Resident)
Study completed

Several forms of cardiac disease in dogs are inherited - though some may not become apparent until animals reach adulthood. In boxer dogs, this is true of arrhythmogenic right ventricular cardiomyopathy - often referred to as boxer ARVC. The traditional screening technique - a 24-hour electrocardiogram - usually yields a diagnosis only after most affected dogs have been bred and passed on the disease .

In this study magnetic resonance imaging (MRI) was used for the first time ever in clinically affected dogs as a new diagnostic screening tool. The hope: to identify boxers affected with ARVC earlier in their lives and before they are bred. Longer-range goals include developing a possible genetic test for ARVC, and, of course, eliminating this deadly and devastating disease forever.

Grant #03-16D Diplomate Grant
"Real-Time RT-PCR Based Detection of the Prevalence of Feline Calicivirus Urinary Tract Infections in Cats with Idiopathic Cystitus" Dr. John M. Kruger
Study completed

Feline idiopathic cystitis (FIC) is a bladder disorder of unknown cause that is characterized by bloody, painful and frequent urinations, house soiling, and life-threatening urinary blockage. The disorder is believed to affect a quarter to half million cats in the United States annually. As of yet, there is no effective therapy.

Feline calicivirus (FCV) is best known as a cause of upper respiratory disease in domestic cats. However, there is increasing evidence that FCV may have a causative role in feline idiopathic cystitis (FIC). Previous studies have been hindered by lack of a rapid and sensitive means of identifying FCV urinary infections. The aim of this study was to determine the prevalence of FCV urinary tract infection in cats with and without FIC by using a new rapid, specific, and sensitive test for detection of FCV in urine developed by the investigators.

The results confirmed urinary shedding of FCV in cats with and without respiratory signs. Although urine shedding of FCV was not observed in asymptomatic control cats, there was not a significant difference in the prevalence of FCV urinary tract infection. These results did not conclusively establish a causative role of FCV in idiopathic cystitis, but thanks to the initial work funded by the ACVIM Foundation, the investigators were able to secure further funding to continue with a large-scale study of the epidemiology of FCV urinary tract infection in cats with idiopathic cystitis.

Pending analysis of other explanatory variables, results of the large-scale study indicate increased exposure of cats with FIC to FCV compared to asymptomatic controls. These results clearly indicate the need for additional investigations into the pathogenic role of FCV in feline idiopathic cystitis. Results from such studies could lead to the development of specific antiviral drugs, more effective vaccines, reduction of severity or duration of clinical signs and life-threatening complications which would be of substantial value to affected cats and their owners.

Abstract presented at the 2007 ACVIM Forum in Seattle, WA

Grant #02-07D Diplomate Grant
"Evaluating the effect of pamidronate with bone resorption markers and dual energy X-ray absorptiometry in canine osteosarcoma" Dr. Timothy Fan
Study completed

Osteosarcoma is the most common bone tumor of large-breed dogs, typically affecting the long bones. Traditionally, removing the source of pain requires amputation of the affected limb or palliative radiation therapy. Innovative medical treatment options which decrease bone destruction may also provide pain relief.

Pamidronate is a drug that prevents bone mineral loss, and minimizes local bone pain caused by tumors that spread to the bone in human cancer patients. This study evaluated the clinical and biologic effects of pamidronate in dogs with primary bone cancer. Eleven of the 41 dogs treated experienced clinical pain relief for greater than 4 month's duration. A significant increase in primary tumor bone mineral density was also observed in these 11 dogs.

The investigators concluded that pamidronate was well-tolerated by all canine patients, and the dosages evaluated exert bone remodeling effects as demonstrated by reductions in urine N-telopeptide and enhanced bone mineral density. This study may lead to new treatment techniques for canine osteosarcoma and may improve the quality of life of patients.

Published: "Evaluation of Intravenous Pamidronate Administration in 33 Cancer-Bearing Dogs with Primary or Secondary Bone Involvement" Journal of Veterinary Internal Medicine, January-February 2005 "Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone Pain" Journal of Veterinary Internal Medicine, May-June 2007

Grant #02-18D Diplomate Grant
"Systemic endocrine and immune effects of an inhalant steroid in cats"
Dr. Carol R. Reinero
Study completed

Feline bronchial disease, sometimes called feline asthma, is commonly treated with oral glucocorticoids (OGC). These drugs, of which prednisone in the most commonly used, may cause complications in cats with infections and/or certain conditions such as diabetes mellitus, heart disease or kidney disease. Inhalant glucocorticoid (IGC) treatment has been used in an attempt to try and reduce the inflammation in the airways without exposing the rest of the body to the medication.

This study compared an IGC, and OGC and a placebo. Six healthy cats received each medication for 2 weeks. Comparisons were made for hormone levels and immune function between both forms of treatment and the placebo. While both treatments affected hormone levels, the IGC treatment showed significantly less effects on the overall immune system. The knowledge obtained from this study may help improve treatment of feline asthma.

Published:
"Inhaled Flunisolide Suppresses the Hypothalamic-Pituitary-Adrenocortical Axis, but Has Minimal Systemic Immune Effects in Healthy Cats"
Journal of Veterinary Internal Medicine, January-February 2006

Grant# 02-21D Diplomate Grant
"In Vitro Effects of N-Acetylcysteine Against Canine Hemangiosarcoma"
Dr. Douglas H. Thamm
Study completed

Canine hemangiosarcoma (HSA) is a very aggressive blood vessel lining cancer affecting several body organs. Most commonly reported anatomic sites in dogs include spleen, liver, heart and skin. In most cases depending on the clinical stage at the time of diagnosis, the overall survival is shorter with surgery and chemotherapy. On the contrary, a longer survival is anticipated in dogs where the tumor is limited to skin only.

Due to overall shorter survival in visceral HSA, novel therapies are desperately needed. Since the tumor is derived from the blood vessels, it appears that antiangiogenic (restricting tumor blood supply) therapies may be uniquely efficacious for HSA. In this study, the investigators have shown efficacy of an antioxidant N-acetylcysteine (NAC) against HSA cells. N-acetylcysteine is a potent free radical scavenger.

The results have demonstrated that the antioxidant NAC was capable of significantly inhibiting angiogenic factor production by canine HSA cells, although a higher concentration of NAC was required. Unfortunately, based on these results it appears that it is unlikely that NAC will have a meaningful anti-tumor effect.

Through this study we learned that use of NAC does not carry any clinical value in dogs, leaving us with other unanswered questions. It is possible that more potent antioxidants could prove clinically useful for the treatment of canine HSA in the future. Our scientists will keep looking into more innovative approaches until a remedy is unraveled for such an aggressive malignancy.

Research abstract presented at 2005 ACVIM Forum in Baltimore, MD and published:
Journal of Veterinary Internal Medicine, May-June 2006

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