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Paul R Wotton

Bio: Paul R Wotton is an academic researcher from University of Bristol. The author has contributed to research in topics: Dilated cardiomyopathy & Cardiomyopathy. The author has an hindex of 3, co-authored 3 publications receiving 237 citations.

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Journal ArticleDOI
TL;DR: The case records of 106 cats with idiopathic cardiomyopathy that presented to the Feline Centre of the University of Bristol between September 1994 and September 2001 were reviewed retrospectively and a greater survival time was observed for cats with UCM when compared with those with HCM, RCM or DCM.
Abstract: The case records of 106 cats with idiopathic cardiomyopathy that presented to the Feline Centre of the University of Bristol between September 1994 and September 2001 were reviewed retrospectively. Hypertrophic cardiomyopathy (HCM) was the most common form seen (57.5%), followed by restrictive cardiomyopathy (RCM) (20.7%), dilated cardiomyopathy (DCM) (10.4%) and unclassified cardiomyopathy (UCM) (10.4%). One cat showed echocardiographic changes compatible with a moderator band cardiomyopathy (MBCM). Most affected cats were domestic short hairs (DSH) (57.5%). The mean (+/-SD, range) age of cats with cardiomyopathy at presentation was 6.8 (4.3, 0.5-16) years, with an equal distribution of males and females. Clinical findings, electrocardiographic changes and radiographic abnormalities were also reviewed. The median survival time for 73 cats for which follow-up data was available was 300 days. A greater survival time was observed for cats with UCM (925 days) when compared with those with HCM (492 days), RCM (132 days) or DCM (11 days).

202 citations

Journal ArticleDOI
TL;DR: The results indicate that promatrix metalloproteinase-9 and neutrophil elastase, both of which are implicated in inflammatory responses, are present in significantly elevated levels in Doberman dilated cardiomyopathy and are raised in clinically normal Dobermans.
Abstract: Objective: Canine dilated cardiomyopathy, commonly affecting Doberman pinschers, results in extracellular matrix remodelling within the myocardium. The aim of this study was to examine the proteolytic activity in myocardium from Doberman pinschers with dilated cardiomyopathy. Methods: Samples of myocardium, obtained rapidly post mortem from the left ventricular free wall of Dobermans with dilated cardiomyopathy, clinically normal Dobermans and control dogs (non-Dobermans), were examined for proteolytic activity using substrate gel zymography. Gels were analysed by scanning densitometry. Results: Promatrix metalloproteinase-9 activity was significantly increased in all Doberman myocardium when compared to controls. A significant increase in an enzyme, identified to be neutrophil elastase by inhibition of its activity by Elastatinal and Western blotting, was also detected in all Dobermans when compared to controls. Conclusions: The results indicate that promatrix metalloproteinase-9 and neutrophil elastase, both of which are implicated in inflammatory responses, are present in significantly elevated levels in Doberman dilated cardiomyopathy and are raised in clinically normal Dobermans. Both proteolytic enzymes degrade a wide variety of connective tissue components and thus the increased levels found may play an important role in the structural remodelling seen in the myocardium and subsequent heart failure. Increased proteolytic enzyme levels in clinically normal Dobermans may be indicative of the predisposition of the breed to dilated cardiomyopathy.

42 citations

Journal ArticleDOI
TL;DR: Characterising the myocardial collagen matrix of Dobermans found changes in the collagenous matrix are likely to be involved in the progression of the disease and may explain the predisposition of this breed to dilated cardiomyopathy.

10 citations


Cited by
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Journal ArticleDOI
TL;DR: The purpose of this review is to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease, and to dispel the historical belief that the myCardial matrix is a passive structure.
Abstract: It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive hear...

1,042 citations

Journal ArticleDOI
TL;DR: Testing the hypothesis that the inflammatory cytokines can regulate fibroblast extracellular matrix metabolism found that IL-1β increased the expression of proMMP... and TNF-α each increased total matrix metalloproteinase (MMP) activity as measured by in-gel zymography.
Abstract: —We tested the hypothesis that the inflammatory cytokines can regulate fibroblast extracellular matrix metabolism. Neonatal and adult rat cardiac fibroblasts cultures in vitro were exposed to interleukin (IL)–1β (4 ng/mL), tumor necrosis factor-α (TNF-α; 100 ng/mL), IL-6 (10 ng/mL), or interferon-γ (IFN-γ; 500 U/mL) for 24 hours. IL-1β, and to a lesser extent TNF-α, decreased collagen synthesis, which was measured as collagenase-sensitive [3H]proline incorporation, but had no effect on cell number or total protein synthesis. IL-1β decreased the expression of procollagen α1(I), α2(I), and α1(III) mRNA, but increased the expression of procollagen α1(IV), α2(IV), and fibronectin mRNA, indicating a selective transcriptional downregulation of fibrillar collagen synthesis. IL-1β and TNF-α each increased total matrix metalloproteinase (MMP) activity as measured by in-gel zymography, causing specific increases in the bands corresponding to MMP-13, MMP-2, and MMP-9. IL-1β increased the expression of proMMP...

467 citations

Journal ArticleDOI
TL;DR: The abundance and activation of matrix metalloproteinases significantly increases in ulcerative colitis and Crohn's mucosa and inhibitors of these proteolytic enzymes may therefore be of therapeutic value in the treatment of inflammatory bowel disease.

315 citations

Journal ArticleDOI
TL;DR: In apparently healthy cats, detection of a heart murmur is not a reliable indicator of cardiomyopathy, which was common in the healthy cats evaluated in this study.
Abstract: Objective—To determine the prevalence of cardiomyopathy and the relationship between cardiomyopathy and heart murmurs in apparently healthy cats. Design—Cross-sectional study. Animals—103 privately owned, apparently healthy domestic cats. Procedures—Cats were physically and echocardiographically examined by 2 investigators independently. Left ventricular wall thickness was determined via 2-dimensional echocardiography in short-axis and long-axis planes. Left ventricular hypertrophy was identified when end-diastolic measurements of the interventricular septum or posterior wall were ≥ 6 mm. Cats with left ventricular hypertrophy but without left ventricular dilatation were considered to have hypertrophic cardiomyopathy (HCM). The associations between heart murmurs and Doppler echocardiographic velocity profiles indicative of dynamic ventricular outflow tract obstruction were evaluated. Results—Heart murmurs were detected in 16 (15.5%; 95% confidence interval, 9.2% to 24.0%) cats; of these, 5 had cardiomyopa...

211 citations

Journal ArticleDOI
TL;DR: It is found thatpertrophic cardiomyopathy is common in apparently healthy cats, in contrast with otherCardiomyopathies, and heart murmurs are also common, and are often functional.

161 citations