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Completed Clinical Studies

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This section highlights our completed clinical trials and studies, with publication information if applicable. Publication links will take you to PubMed.

Clinical Pathology
Emergency and Critical Care
Large Animal Medicine and Surgery
Small Animal Medicine
Small Animal Surgery


Structural and functional cardiovascular changes and their consequences following interventional patent ductus arteriosus occlusion in dogs: 24 cases (2000-2006)

Principal Investigator: Chris Stauthammer, DVM, DACVIM (Cardiology)

A retrospective study of 24 dogs with uncomplicated patent ductus arteriosus that was fully occluded and reevaluated within 24 hours, at 3 months, and 1 year following the procedure.

Results1: Following ductal occlusion, decreases were detected in vertebral heart scale size, left ventricular chamber diameter in diastole and in systole, left atrial dimension, fractional shortening, aortic velocity, and ventricular wall thickness. There were no differences between age groups for postocclusion changes except vertebral heart scale size. Systolic dysfunction was detected in 14 (58%) patients on the final visit. Median survival time for all dogs after ductal occlusion was > 11.5 years.

Conclusions and clinical relevance1:
Complete ductal occlusion resulted in immediate removal of the volume overload state and eventual return of cardiac chamber dimensions to reference range, suggesting regression of eccentric hypertrophy. Systolic dysfunction persisted in some dogs but appeared to be clinically unimportant. Most cardiovascular changes were independent of patient age at the time of the procedure.

1. Stauthammer CD, Tobias AH, Leeder DB, Krüger MU. Structural and functional cardiovascular changes and their consequences following interventional patent ductus arteriosus occlusion in dogs: 24 cases (2000-2006). J Am Vet Med Assoc. 2013 Jun 15;242(12):1722-6. doi: 10.2460/javma.242.12.1722. PubMed PMID: 23725436.

Amplatz Canine Duct Occluder studies

Investigators: Anthony H. Tobias, BVSc, PhD, Dipl. ACVIM (Cardiology), Thaibinh P. Nguyenba, DVM
This research involved the design and development of a novel device specifically to conform to the morphology of patent ductus arteriosus in dogs and a minimally invasive per-catheter procedure for device delivery in this species.

Nguyenba TP, Tobias AH. Minimally invasive per-catheter patent ductus arteriosus occlusion in dogs using a prototype duct occluder. J Vet Intern Med. 2008 Jan-Feb;22(1):129-34
Nguyenba TP, Tobias AH. The Amplatz® Canine Duct Occluder: a novel device for patent ductus arteriosus occlusion.  Journal of Veterinary Cardiology 2007; 9: 109-117.

Body Fluid Volume and Cardiac Effects of Methylprednisolone in Cats
Investigators: Anthony H. Tobias, BVSc, PhD, Dipl. ACVIM (Cardiology), Sheila Torres, DVM, MS, PhD, DACVD
Cats that required corticosteriod therapy for dermatologic disorders were studied pre- and post-injection of methylprednisolone.

Publication: Ployngam T, Tobias AH, Smith SA, Torres SM, Ross SJ. Hemodynamic effects of methylprednisolone acetate administration in cats. Am J Vet Res. 2006 Apr;67(4):583-7.

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Clinical Pathology

Evaluation of Feline Antithrombin and D-dimer Concentrations in Populations of Healthy and Clinically Ill Cats

Clotting disturbances are the end result of many serious feline diseases and frequently the cause of the death. Current clotting tests for cats detect only severe changes in clotting.  This study evaluated two laboratory tests to determine how useful and accurate they are.

The investigators found that the chromogenic antithrombin (AT) assay appeared to measure AT in cats but was not helpful in diagnosing disseminated intravascular coagulation (DIC).  The immunoturbidimetric D-dimer assay was not found to be useful for the diagnosis of DIC in cats.

Publication: Brazzell, JL, Borjesson, DL. Evaluation of plasma antithrombin activity and D-dimer concentration in populations of healthy cats, clinically ill cats, and cats with cardiomyopathy. Vet Clin Pathol. 2007 Mar;36(1):79-84.

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Ceramide composition of the stratum corneum of canine patients with dermatitis. 

Principal Investigators: Sheila M. F. Torres, DVM, MS, PhD, DACVD; Lisa Reiter, DVM

This study looked at the composition of the skin of dogs with allergies.  Decreased amounts of ceramides were found in the non-lesional skin of dogs with atopic dermatitis and may be involved in impaired barrier function of their skin. 

Publication: Reiter LV, Torres SM, Wertz PW. Characterization and quantification of ceramides in the nonlesional skin of canine patients with atopic dermatitis compared with controls. Vet Dermatol. 2009 Aug;20(4):260-6. 

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Emergency and Critical Care 

High Mobility Group B-1 Protein as a Diagnostic and Prognostic Tool in Canine Systemic Inflammatory Response Syndrome and Sepsis

Principal Investigator: Kelly Hall, DVM
Contact: Dr. Kelly Hall, Phone: 612-624-6288 E-mail:

HMGB-1 is known to be involved in inflammatory processes in other mammal species (e.g., humans, mice).  HMGB-1 has been identified as a protein in inflammatory processes, including sepsis, arthritis and cancer. This study evaluated whether HMGB-1 can be detected in normal canine patient serum and if it changes significantly in known inflammatory processes (e.g., sepsis) or other naturally occurring animal diseases.

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Large Animal Medicine and Surgery

The efficacy of imiquimod 5% cream (Aldara®) in the treatment of aural plaque in horses: a pilot open label-clinical trial.

Investigators: Sheila Torres, DVM, MS, PhD, DACVD; Erin Malone
This clinical trial of 16 horses (21 enrolled, 16 completed) found that topical application of imiquimod 5% cream was effective in treating aural plaques, a condition which affects 22% or more of horses. Cases were followed for up to 22 months and only two horses had recurrence of their lesions.

Publication: Torres SM, Malone ED, White SD, Koch SN, Watson JL. The efficacy of imiquimod 5% cream (Aldara® in the treatment of aural plaque in horses: a pilot open-label clinical trial. Vet Dermatol. 2010 Oct;21(5):503-9.

Efficacy of imiquimod 5% cream in the treatment of equine sarcoids: a pilot study. 

Principal Investigator: Sandra (Nogueira) Koch, DVM, DACVD
This pilot study enrolled 15 horses with sarcoid tumors of mixed type and location. Results showed 12/15 lesions reduced in size by >75%, and 9 resolved completely.

Publication: Nogueira SA, Torres SM, Malone ED, Diaz SF, Jessen C, Gilbert S. Efficacy of imiquimod 5% cream in the treatment of equine sarcoids: a pilot study. Vet Dermatol. 2006 Aug;17(4):259-65.

Aldara® use in Equines.   See this page for FAQs and Veterinarian Instructions for use of Aldara® (imiquimod).

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Feasibility study of a caregiver seizure alert system in canine epilepsy

Abstract (see publication below)
A device capable of detecting seizures and alerting caregivers would be a major advance for epilepsy management, and could be used to guide early intervention and prevent seizure-related injuries. The objective of this work was to evaluate a seizure advisory system (SAS) that alerts caregivers of seizures in canines with naturally occurring epilepsy. Four dogs with epilepsy were implanted with a SAS that wirelessly transmits continuous intracranial EEG (iEEG) to an external device embedded with a seizure detection algorithm and the capability to alert caregivers. In this study a veterinarian was alerted by automated text message if prolonged or repetitive seizures occurred, and a rescue therapy protocol was implemented. The performance of the SAS caregiver alert was evaluated over the course of 8 weeks. Following discontinuation of antiepileptic drugs, the dogs experienced spontaneous unprovoked partial seizures that secondarily generalized. Three prolonged or repetitive seizure episodes occurred in 2 of the dogs. On each occasion, the SAS caregiver alert successfully alerted an on call veterinarian who confirmed the seizure activity via remote video-monitoring. A rescue medication was then administered and the seizures were aborted. This study demonstrates the feasibility of a SAS to alert caregivers to the occurrence of prolonged or repetitive seizures and enables rescue medications to be delivered in a timely manner. The SAS may improve the management of human epilepsy by alerting caregivers of seizures, enabling early interventions, and potentially improving outcomes and quality of life of patients and caregivers.

Publication: Coles LD, Patterson EE, Sheffield WD, Mavoori J, Higgins J, Michael B, Leyde K, Cloyd JC, Litt B, Vite C, et al. Feasibility study of a caregiver seizure alert system in canine epilepsy. Epilepsy Res. 2013 Oct;106(3):456-60. doi: 10.1016/j.eplepsyres.2013.06.007. Epub 2013 Aug 18. PubMed PMID: 23962794.

Clinical characteristics and inheritance of idiopathic epilepsy in Vizslas.

Publication: Patterson EE, Da Y, Mickelson JR, Roberts MC, McVey A, O Brien D, Johnson GS, Armstrong PJ. (2003) Clinical characteristics and inheritance of idiopathic epilepsy in Vizslas. Journal of Veterinary Internal Medicine, 17(3): 319-325.

For more information, please see the Canine Epilepsy Network website.

Neuropathic pain in Cavalier King Charles Spaniels

Principal Investigator: Ned Patterson, DVM, PhD, DACVIM
Contact: Dr. Patterson, 612-625-5799, e-mail:

The Clinical Investigation Center completed a clinical study evaluating the efficacy of a novel treatment for the control of pain associated with syringomyelia in Cavalier King Charles Spaniels. The study was part of a collaborative effort between a Pharmaceutical Company, and the Schools of Veterinary Medicine at the University of Minnesota, the University of Pennsylvania and the Royal Veterinary College in the United Kingdom.   The study actively recruited patients from November 2007 to October 2008 and after screening 119 dogs, a total of fifty two patients participated in the trial. 

Following statistical analysis, the results are promising. There is potential for further development of this new medication to help alleviate the pain associated with syringomyelia. 

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Studies in canine lymphoma

Ito D, Frantz AM, Modiano JF. Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet Immunol Immunopathol. 2014 June; 159(3-4):192-201.


Inflammation, apoptosis, and necrosis induced by neoadjuvant Fas ligand gene therapy improves survival of dogs with spontaneous bone cancer

Principal Investigator: Jaime F Modiano, VMD, PhD, DACVP

A multi-site clinical trial used intratumoral FasL gene therapy delivered in an adenovirus vector (Ad-FasL) in addition to standard of care in 56 dogs with osteosarcoma. 

Tumors from treated dogs had greater inflammation, necrosis, apoptosis, and fibrosis at day 10 (amputation) compared to pretreatment biopsies or to tumors from dogs that did not receive Ad-FasL. Survival improvement was apparent in dogs with inflammation or lymphocyte-infiltration scores >1 (in a 3-point scale), as well as in dogs that had apoptosis scores in the top 50th percentile (determined by cleaved caspase-3). Survival was no different than that expected from standard of care alone in dogs with inflammation scores ≤1 or apoptosis scores in the bottom 50th percentile. Reduced Fas expression by tumor cells was associated with prognostically advantageous inflammation, and this was seen only in dogs that received Ad-FasL. Together, the data suggest that Ad-FasL gene therapy improves survival in a subset of large animals with naturally occurring tumors, and that at least in some tumor types like osteosarcoma, it is most effective when tumor cells fail to express Fas.1 

1. Modiano JF, Bellgrau D, Cutter GR, Lana SE, Ehrhart NP, Ehrhart E, Wilke VL, Charles JB, Munson S, Scott MC, et al. Inflammation, apoptosis, and necrosis induced by neoadjuvant fas ligand gene therapy improves survival of dogs with spontaneous bone cancer. Mol Ther. 2012 Dec;20(12):2234-43. doi: 10.1038/mt.2012.149. Epub 2012 Jul 31. PubMed PMID: 22850679; PubMed Central PMCID: PMC3519983.

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Small Animal Medicine

A multi-institutional study evaluation the diagnostic utility of the spec cPLTM and SNAP® CPLTM in clinical acute pancreatitis in 84 dogs.

Principal Investigator (this site): Jane Armstrong DVM, MS, MBA, DACVIM
This multi-site study examined the diagnostic usefulness (sensitivity and specificity) of the pancreatic lipase blood test and found that these tests have a higher sensitivity than serum amylase or lipase activity in diagnosing clinical acute pancreatitis in dogs.

Publication: McCord K, Morley PS, Armstrong J, Simpson K, Rishniw M, Forman MA, Biller D, Parnell N, Arnell K, Hill S, Avgeris S, Gittelman H, Moore M, Hitt M, Oswald G, Marks S, Burney D, Twedt D. J Vet Intern Med. 2012 Jul-Aug;26(4):888-96.

Treatment of Immune-Mediated Hemolytic Anemia with Individually Adjusted Heparin Dosing in Dogs

Investigators: Sarah Helmond, DVM, David Polzin, DVM, PhD, DACVIM, Jane Armstrong, DVM, MS, MBA, DACVIM

Drs. Sarah Helmond and Maureen Finke (former residents in Internal Medicine) along with Dr. David Polzin, Dr. Jane Armstrong, and Dr. Stephanie Smith (University of Illinois) completed a prospective clinical trial comparing treating dogs with IMHA with individually adjusted doses of heparin to standard of care, fixed low heparin dosing.  Plasma levels were measured using an anti-XA factor assay at Fairview Labs.  The study of 15 dogs found a greater survival rate in the adjusted heparin dosing group than in the group with standard care.

Publication:Helmond SE, Polzin DJ, Armstrong PJ, Finke M, Smith SA.Treatment of Immune-Mediated Hemolytic Anemia with Individually Adjusted Heparin Dosing in Dogs. J Vet Intern Med. 2010 April 6.

Efficacy and safety of lithotripsy

Dr. Jody Lulich evaluated lithotripsy as a method of removing stones from the urinary bladder of dogs as an alternative to surgery.  The laser lithotripter breaks up stones into tiny fragments using thermal energy. These stones are then eliminated through urination. The procedure is done under anesthesia using a cystoscope to visualize stones and to accurately aim the laser. 

Publication: Lulich JP, Osborne CA, Albasan H, Monga M, Bevan JM. Efficacy and safety of laser lithotripsy in fragmentation of urocystoliths and urethroliths for removal in dogs. J Am Vet Med Assoc. 2009 May 15;234(10):1279-85.

This procedure is now available as a standard of care in the Veterinary Medical Center

Human Intravenous Immune Globulin in Dogs with Primary Immune-mediated Thrombocytopenia (IMT)

Investigators: Domenico Bianco, DVM, P. Jane Armstrong, DVM, MS, MBA, DACVIM, Robert Washabau, VMD, PhD, DACVIM
This study was designed to compare the effects of human intravenous immunoglobulin plus glucocorticoid versus glucocorticoid alone on platelet count recovery, morbidity, mortality, hospitalization time, and cost in dogs with acute immune-mediated thrombocytopenia.  40 dogs were enrolled with acute immune-mediated thrombocytopenia. 

Publication:Bianco D, Armstrong PJ, Washabau RJ. A prospective, randomized, double-blinded, placebo-controlled study of human intravenous immunoglobulin for the acute management of presumptive primary immune-mediated thrombocytopenia in dogs. J Vet Intern Med. 2009 Sep-Oct;23(5):1071-8. Epub 2009 Aug 5. 

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Small Animal Surgery

Comparison of the analgesic efficacy of perioperative firocoxib and tramadol admininstration in dogs undergoing tibial plateau leveling osteotomy1

Principal Invesigator: Michael Conzemius, DVM, PhD, DACVS

A 30 dog randomized, blinded prospective clinical trial to evaluate the effects of perioperative oral administration of tramadol, firocoxib, and a tramadol-firocoxib combination on signs of pain and limb function after TPLO in dogs. Signs of pain on the short-form Glasgow composite measure pain scale, serum cortisol and limb function on pressure platform gait analysis were measured before and for 3 days after surgery. 

The tramadol group had a significantly greater number of dogs with a pain score > 6 after surgery. There were no significant differences between the firocoxib group and the tramadol-firocoxib group. There were no significant differences in serum cortisol concentrations. Limb function was significantly decreased for dogs in the tramadol group on days 1 and 2 after surgery and in the firocoxib group on day 1 after surgery. Although limb function decreased for dogs in the tramadol-firocoxib group, the change was not significant for any day after surgery.

Conclusions and clinical relevance: Dogs that received firocoxib orally, alone or in combination with tramadol, had lower pain scores, lower rescue opiate administration, and greater limb function than dogs that received only tramadol. When used alone, oral administration of tramadol may not provide sufficient analgesic efficacy to treat dogs with pain after orthopedic surgical procedures.

1. Davila D, Keeshen TP, Evans RB, Conzemius MG. Comparison of the analgesic efficacy of perioperative firocoxib and tramadol administration in dogs undergoing tibial plateau leveling osteotomy. J Am Vet Med Assoc. 2013 Jul 15;243(2):225-31.

Short-term and long-term outcomes for overweight dogs with cranial cruciate ligament rupture treated surgically or nonsurgically2

Principal Investigator: Vicki Wilke, DVM, PhD, DACVS

A prospective, randomized clinical trial of 40 dogs to determine short and long-term rates of successful outcomes of surgical and nonsurgical treatments for overweight dogs with cranial cruciate ligament rupture (CCLR). Dogs received nonsurgical (physical therapy, weight loss and NSAID administration) or surgical (TPLO) treatment groups. Dogs in both groups received the nonsurgical treatments. Dogs were evaluated immediately before and 6, 12, 24 and 52 weeks after initiation of treatments via owner questionnaires, gait analysis, and dual-energy x-ray absorptiometry. 

Results on owner questionnaires indicated dogs in both groups improved in the study, but dogs in the surgical treatment group seemed to have greater improvement. Body fat percentages decreased for dogs in both groups, significantly. Surgical treatment group dogs had a significantly higher peak vertical force for affected limbs vs nonsurgical treatment group dogs at the 24- and 52-week timepoints. Surgical treatment group dogs had a higher probability of a successful outcome vs nonsurgical treatment group dogs.

Conclusions: Overweight dogs with CCLR treated via surgical and nonsurgical methods had better outcomes than dogs treated via nonsurgical methods alone. However, almost two-thirds of the dogs in the nonsurgical treatment group had a successful outcome at the 52-week evaluation time.

2. Wucherer KL, Conzemius MG, Evans R, Wilke VL. Short-term and long-term outcomes for overweight dogs with cranial cruciate ligament rupture treated surgically or nonsurgically. J Am Vet Med Assoc. 2013 May 15;242(10):1364-72. doi: 10.2460/javma.242.10.1364. PubMed PMID: 23634680.


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