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Chapman S.E.,IDEXX Laboratories | Hostutler R.A.,MedVet Medical and Cancer Centers for Pets
Clinics in Laboratory Medicine | Year: 2015

Routine biochemical tests generally include serum enzymes, proteins, and other markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining results outside the reference intervals can occur with direct hepatocellular injury, enzyme induction by hepatocytes or biliary epithelium, or decreased hepatic function. However, detection of biochemical abnormalities does not necessarily indicate clinically significant disease. For a comprehensive approach to detection and treatment of hepatobiliary disease, the laboratory results must be correlated with the history and physical examination findings, diagnostic imaging results, and other assays. © 2015 Elsevier Inc.

Schmidt A.F.,University College London | Groenwold R.H.H.,University Utrecht | Amsellem P.,University of Prince Edward Island | Bacon N.,University of Florida | And 7 more authors.
Preventive Veterinary Medicine | Year: 2015

Osteosarcoma (OS) is a malignant tumor of mesenchymal origin that produces osteoid. Given that the prognosis can vary considerably between dogs, we aimed to explore whether treatment could be tailored towards patient subgroups, characterized by their predicted risk of mortality. For the current study, a subset of five nonrandomized studies (400 subjects of whom 88 were dead at 5 months follow-up) was used from a previously published 20 study individual patient data meta-analysis. Missing data was dependent on observed variables and was imputed to correct for this dependency. Based on a previously published multivariable prognostic model, the 5-month mortality risk was predicted. Subsequently, in surgically treated dogs, using a logistic regression model with a random intercept for a study indicator, we explored whether chemotherapy effectiveness depended on predicted 5-month mortality risk. After adjustment for potential confounders the main effect of any chemotherapy was 0.48 (odds ratio) (95%CI 0.30; 0.78). Testing for chemotherapy by predicted 5-month mortality risk interaction revealed that the effects of any chemotherapy decreased with increasing predicted risk; interaction OR 3.41 (1.07; 10.84). Results from individually comparing carboplatin, cisplatin, doxorubicin and doxorubicin combination therapy to no chemotherapy, were similar in magnitude and direction. These results indicate that the main treatment effects of chemotherapy do not necessarily apply to all patients. © 2015 Elsevier B.V.

Nucci D.J.,Alta Vista Animal Hospital | Liptak J.M.,Alta Vista Animal Hospital | Selmic L.E.,Urbana University | Culp W.T.N.,University of California at Davis | And 9 more authors.
Journal of the American Veterinary Medical Association | Year: 2014

Objective—To evaluate the incidence of and factors associated with complications following rectal pull-through (RPT) surgery and the outcome for dogs with rectal tumors.Design—Retrospective case series.Animals—74 dogs with rectal masses.Procedures—Information regarding signalment, history, diagnostic testing, type of rectal disease, surgical details, and postoperative complications, treatments, and outcomes was obtained from medical records and follow-up communications. Survival times were calculated. Descriptive statistics were generated. Regression analyses were used to evaluate the effect of various variables on the development of postsurgical complications and survival time.Results—58 (78.4%) dogs developed postsurgical complications, the most common of which was fecal incontinence with 42 (56.8%) dogs affected, of which 23 (54.8%) developed permanent incontinence. Other complications included diarrhea (n = 32), tenesmus (23), stricture formation (16), rectal bleeding (8), constipation (7), dehiscence (6), and infection (4). The rectal tumor recurred in 10 dogs. The median survival time was 1,150 days for all dogs and 726 days for dogs with malignant tumors. The 2 most common rectal masses were rectal carcinoma and rectal carcinoma in situ, and the dogs with these tumors had median survival times of 696 and 1,006 days, respectively.Conclusions and Clinical Relevance—Dogs with rectal diseases that underwent RPT surgery had a high incidence of complications; however, those dogs had good local tumor control and survival times. The risk and impact of postsurgical complications on the quality of life and oncological outcomes should be discussed with owners before RPT surgery is performed in dogs with rectal masses. © 2014 American Veterinary Medical Association.

Stern J.A.,North Carolina State University | Stern J.A.,Washington State University | Stern J.A.,University of California at Davis | White S.N.,U.S. Department of Agriculture | And 7 more authors.
Human Genetics | Year: 2014

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species. © 2014, The Author(s).

Reynolds C.A.,University of Pennsylvania | Brown D.C.,University of Pennsylvania | Rush J.E.,Tufts University | Fox P.R.,Animal Medical Center | And 8 more authors.
Journal of Veterinary Cardiology | Year: 2012

Objective: To identify risk factors for first-onset congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD). Animals: Eighty-two dogs with and without CHF secondary to DMVD were retrospectively assigned to a derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a prospective validation cohort. Methods: Variables associated with risk of CHF in dogs were identified in a derivation cohort and used to construct a predictive model, which was then prospectively tested through longitudinal examination of a validation cohort. Results: Logistic regression analysis of the derivation cohort yielded a predictive model that included the left atrial to aortic root dimension ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When this model was prospectively applied to the validation cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of the validation cohort revealed that plasma NT-proBNP concentration and indexed left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors for development of first-onset CHF in dogs with DMVD (NT-proBNP ≥1500 pmol/L, odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37-24.28, P = 0.017; LVIDd:Ao ≥3, OR, 6.11, 95% CI, 1.09-34.05, P = 0.039). Conclusions: Measures of left heart size and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with DMVD. These parameters can contribute to the management of dogs with DMVD. © 2012 Elsevier B.V. All rights reserved.

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