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.
PubMed | University Utrecht, University of Florida, MedVet Medical and Cancer Centers for Pets, Utrecht Institute for Pharmaceutical science and 2 more.
Type: | Journal: Preventive veterinary medicine | Year: 2016
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.
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.
Martinez S.A.,MedVet Medical and Cancer Centers for Pets |
Hostutler R.A.,MedVet Medical and Cancer Centers for Pets
Journal of the American Animal Hospital Association | Year: 2014
A 9 yr old spayed female boxer was presented for evaluation of vomiting, lethargy, anorexia, and weight loss. Initial laboratory evaluation revealed a hyperchloremic normal anion gap metabolic acidosis with alkaline urine that was consistent with a diagnosis of distal renal tubular acidosis (RTA). Targeted therapy was initiated with Na bicarbonate (HCO3) and potassium (K) gluconate. Leptospirosis was subsequently diagnosed with paired microagglutination testing (MAT), and doxycycline was added to the other treatments. Clinical signs resolved, and 6 mo after diagnosis, although the dog remained on alkali therapy (i.e., NaHCO3 and K gluconate) and a mild metabolic acidosis persisted, the dog remained otherwise healthy with a good quality of life. To the authors' knowledge, this is the first report to describe the concomitant association of those two disorders. Leptospirosis should be considered for any case of RTA in dogs. © 2014 by American Animal Hospital Association.
Jackson B.L.,MedVet Medical and Cancer Centers for Pets |
Lehmkuhl L.B.,MedVet Medical and Cancer Centers for Pets |
Adin D.B.,MedVet Medical and Cancer Centers for Pets
Journal of Veterinary Cardiology | Year: 2014
Objectives To compare heart rate and arrhythmia frequency and complexity in a normal population of cats to a population of cats with hypertrophic cardiomyopathy (HCM). Animals 17 cats with HCM and 15 cats with normal echocardiograms. Methods Results for echocardiography, electrocardiography, Doppler blood pressure, and 24-h Holter monitoring were compared between groups. Results There was no difference in heart rate between HCM cats and normal cats regardless of modality used. All (17/17) HCM cats had ventricular arrhythmias (geometric mean 124 complexes/24 h) with 82% (14/17) exhibiting complex arrhythmias (couplets, triplets, or ventricular tachycardia). Most (14/15) normal cats had ventricular arrhythmias (geometric mean 4 complexes/24 h), but only 20% (3/15) exhibited complexity. HCM cats had significantly more total ventricular complexes, ventricular premature complexes and accelerated idioventricular rhythm than normal cats (P < 0.0001, P < 0.0001, and P = 0.01, respectively). Eighty eight percent (15/17) of HCM cats had supraventricular arrhythmias (geometric mean 9 complexes/24 h) with 23% (4/17) exhibiting complexity. Sixty percent (9/15) of normal cats had supraventricular arrhythmias (geometric mean 1 complex/24 h) with 13% (2/15) exhibiting complexity. Cats with hypertrophic cardiomyopathy had significantly more supraventricular complexes than normal cats (P = 0.0148). Conclusion Cats with asymptomatic HCM have more frequent and complex ventricular and supraventricular arrhythmias than normal cats but do not have different overall heart rates compared to normal cats. Further studies are needed to determine if these arrhythmias are associated with an increased risk of sudden cardiac death or influence long-term survival. © 2014 Elsevier B.V. All rights reserved.
Jackson B.L.,MedVet Medical and Cancer Centers for Pets |
Adin D.B.,MedVet Medical and Cancer Centers for Pets |
Lehmkuhl L.B.,MedVet Medical and Cancer Centers for Pets
Journal of Veterinary Cardiology | Year: 2015
Objective To investigate the negative chronotropic, antiarrhythmic, and obstruction-relieving effects of atenolol in cats with subclinical hypertrophic cardiomyopathy (HCM). Animals Seventeen cats with HCM. Methods Results for echocardiography, electrocardiography, Doppler blood pressure, and 24 h Holter monitoring were compared in cats before and 2-4 weeks after atenolol therapy (6.25-12.5 mg PO q 12 h). Results The left ventricular outflow tract maximum velocity (LVOT Vmax) decreased after atenolol administration (mean Vmax pre-treatment 3.3 m/s ± 1.8 m/s; post-treatment 1.6 m/s ± 1.0 m/s, p < 0.0001). Heart rate (HR) decreased after atenolol for all HR modalities. The total number of ventricular origin complexes (TotVent) and ventricular premature complexes (VPCs) decreased after atenolol. The VPCs decreased from a geometric mean of 61 complexes/24 h (range, 11-620 complexes/24 h) to 15 complexes/24 h (range, 1-1625 complexes/24 h) (p < 0.0001). Murmur grade decreased after atenolol from a median grade of 3/6 to 2/6 (p < 0.0001). The systolic blood pressure did not change (mean pre-treatment 130 mmHg ± 16 mmHg, mean post-treatment 123 mmHg ± 20 mmHg, p = 0.2). Conclusion Atenolol decreases HR, murmur grade, and LVOT obstruction, and to a lesser degree, frequency of ventricular ectopy, in cats with subclinical HCM. Further studies are needed to determine if sudden cardiac death or long-term outcome is influenced by atenolol administration. © 2015 Elsevier B.V.
PubMed | MedVet Medical and Cancer Centers for Pets
Type: Journal Article | Journal: Veterinary ophthalmology | Year: 2012
To describe the long-term histologic and intraocular pressure (IOP) lowering effects of diode laser transscleral cyclophotocoagulation (TSCP) on the normal equine eye.Eight normal adult horses.TSCP was performed in one randomly assigned eye. Sixty spots were treated at settings of 1500 ms and 1500 mW. Two horses were randomly selected for euthanasia at 2, 4, 12, or 24 weeks post-TSCP. Both eyes were enucleated and histologically evaluated. Intraocular pressure was measured by applanation tonometry prior to TSCP, immediately post-TSCP, twice daily for 7 days post-TSCP and then monthly until study conclusion. A longitudinal model estimated the average IOP values for the treated and untreated eyes at 1 week, 1, 3, and 6 months post-TSCP.All treated eyes at all time periods exhibited four characteristic histologic lesions: scleral collagen hyalinization, ciliary body pigment dispersion and clumping, focal disruption of the ciliary body epithelium, and focal ciliary process atrophy. After TSCP, there were no significant changes in IOP from baseline for the control eyes, while the IOP in treated eyes was significantly decreased from baseline (P < 0.05) at all time periods. The estimated decrease in IOP in the treated eyes compared to baseline IOP at 6 months was -3.76 mmHg for an average decrease in IOP of 20% from baseline.Diode laser TSCP produces histologic lesions in the equine ciliary body that result in a significant and sustained decrease in IOP. TSCP may be an effective management for equine glaucoma.
PubMed | MedVet Medical and Cancer Centers for Pets, University of Georgia and Portland Veterinary Specialists
Type: Case Reports | Journal: Veterinary ophthalmology | Year: 2016
A 14-year-old neutered male Dachshund presented for the evaluation of oculus dexter (OD) third eyelid elevation ongoing for approximately 2months. Complete ophthalmic examination revealed a large, nonpainful, well-demarcated, soft mass at the base of the right third eyelid causing elevation and mild hyperemia. The mass was freely moveable with the third eyelid, and no right globe deviation was noted. No other abnormalities were noted on physical examination, routine blood chemistry, complete blood count, serum T4, urinalysis, or urine cortisol/creatinine ratio. Ocular B-mode ultrasonography showed an anechoic, well-demarcated, homogenous, soft tissue mass at the base of the third eyelid with no orbital extension. A leiomyoma was diagnosed after multiple punch biopsies were obtained from the palpebral surface of the mass. The right third eyelid was excised surgically. Histopathology confirmed a completely excised, nodular, unencapsulated, expansile mass within the third eyelid. Positive smooth muscle actin and negative S-100 immunohistochemistry confirmed a leiomyoma. Bundles of normal smooth muscle were also present adjacent to the mass. The mass was compressing the adjacent lacrimal gland and associated with moderate dacryoadenitis. Twelve months postoperatively, the right globe position and motility remain normal with no evidence of mass regrowth. To the authors knowledge, this is the first reported case of a leiomyoma of the third eyelid in any species. In this case, the mass was completely excised and no regrowth has occurred twelve months after surgery. This case along with independently reviewed canine third eyelids clearly demonstrates the presence of smooth muscle within the canine third eyelid.
PubMed | MedVet Medical and Cancer Centers for Pets and IDEXX Laboratories
Type: Journal Article | Journal: 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.