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Utrecht, Netherlands

Mandigers P.J.J.,University Utrecht | Biourge V.,The Royal Canin Research Center | Van Den Ingh T.S.G.A.M.,TCCI Consultancy BV | Ankringa N.,University Utrecht | German A.J.,University of Liverpool
Journal of Veterinary Internal Medicine | Year: 2010

Background: Hydrolyzed protein diets are commonly used to manage canine chronic enteropathies (CE), but their efficacy has not yet been critically evaluated.Hypothesis: A hydrolyzed protein diet is superior to that of a highly digestible (control) diet in the management of CE in dogs.Animals: Twenty-six dogs (18 test diet, 8 control diet) referred for investigation and management of naturally occurring chronic small intestinal disease.Methods: Randomized, open-label, positively controlled trial. After a full diagnostic investigation, which included endoscopy, dogs were assigned either to the test diet or control diet on a 2-:-1 basis (test-:-control). Cases were re-evaluated 3 times (at approximately 3, 6-12 months, and 3 years). Outcome measures included response of clinical signs (complete, partial, none), change in severity of signs (based upon clinical disease activity index; canine inflammatory bowel disease activity index [CIBDAI]), change in body weight, and need for other therapy.Results: There were no significant differences in baseline characteristics (eg, signalment, body weight, and duration of clinical signs), and histopathologic severity between test and control diet groups. However, despite randomization, CIBDAI was significantly higher in the test diet group (P=.013). Most dogs had responded by first evaluation, with no difference between groups (P=.87). However, significantly more dogs on the test diet remained asymptomatic at both the second (P=.0012) and third (P <.001) re-evaluation, and the decrease in CIBDAI was significantly greater (P=.010).Conclusions and Clinical Importance: A hydrolyzed protein diet can be highly effective for long-term management of canine chronic small bowel enteropathy. © 2010 by the American College of Veterinary Internal Medicine. Source

Fieten H.,University Utrecht | Dirksen K.,University Utrecht | van den Ingh T.S.G.A.M.,TCCI Consultancy BV | Winter E.A.,University Utrecht | And 3 more authors.
Veterinary Journal | Year: 2013

d-penicillamine is effectively used in the lifelong treatment of copper toxicosis in Bedlington terriers and Wilson's disease in humans. A complex form of copper-associated hepatitis has recently been characterized in the Labrador retriever. The aims of this study were to evaluate the effectiveness of d-penicillamine treatment for copper-associated hepatitis in this breed, to study the effects on hepatic copper, iron and zinc concentrations, and to evaluate parameters to predict optimal duration of treatment. Forty-three client owned Labrador retrievers that were diagnosed with increased hepatic copper were treated with d-penicillamine and underwent at least one follow-up examination including a liver biopsy for histopathological scoring of inflammatory lesions. Hepatic copper, iron and zinc concentrations were determined in the initial and follow-up biopsies by instrumental neutron activation analysis. The influence of initial hepatic copper concentration, sex, age, d-penicillamine formulation and the occurrence of side effects were investigated for their influence on hepatic copper concentration after a certain period of treatment by generalized mixed modelling. d-penicillamine proved to be effective in reducing hepatic copper concentration and associated inflammatory lesions. Parameters derived from the model can be used to estimate the necessary duration of d-penicillamine treatment for Labrador retrievers with increased hepatic copper concentration. Continuous, lifelong d-penicillamine treatment is not recommended in this breed, as there may be a risk for hepatic copper and zinc deficiency. © 2012 Elsevier Ltd. Source

Van Sprundel R.G.H.M.,University Utrecht | Van den Ingh T.S.G.A.M.,TCCI Consultancy BV | Guscetti F.,University of Zurich | Kershaw O.,Free University of Berlin | And 5 more authors.
Veterinary Journal | Year: 2013

Many advances have been made in the characterisation of primary liver tumours in humans, in particular relating to the identification and role of hepatic progenitor cells, resulting in a new classification. The aim of the present study was to investigate the presence and relative frequency of morphological types of canine primary hepatic neoplasms and to determine whether a classification similar to the human scheme can be applied to these canine neoplasms. Canine primary liver tumours ( n=. 106) were examined histologically and with the immunohistochemical markers keratin 19, HepPar-1, epithelial membrane antigen/mucin-1, CD10, neuron-specific enolase and chromogranin-A. Eleven nodular hyperplasias and 82 tumours of hepatocellular origin were diagnosed. The latter were subdivided in hepatocellular tumours with 0-5% positivity for K19 ( n=. 62), which were well differentiated and had no evidence of metastasis, tumours with >5% positivity for K19 ( n=. 17), which were poorly differentiated and had intrahepatic and/or distant metastasis, and a scirrhous subgroup ( n=. 3) with an intermediate position with regard to K19 staining and malignancy. Ten cholangiocellular tumours (nine cholangiocellular carcinomas and one cholangiolocarcinoma) were diagnosed and all had intrahepatic and/or distant metastases. Three neuroendocrine carcinomas were also diagnosed. Histopathological and immunohistochemical examination of canine primary hepatic neoplasms can differentiate hepatocellular, cholangiocellular and neuroendocrine tumours, in accordance with the most recent human classification system. © 2013 Elsevier Ltd. Source

Fieten H.,University Utrecht | Hooijer-Nouwens B.D.,University Utrecht | Biourge V.C.,Royal Canin Research Center | Leegwater P.A.J.,University Utrecht | And 3 more authors.
Journal of Veterinary Internal Medicine | Year: 2012

Background: Copper-associated hepatitis is an inherited disease in the Labrador Retriever. Apart from genetic factors, dietary intake of copper and zinc are suspected to play a role in the pathogenesis. Objectives: To investigate whether dietary copper and zinc levels of commercially available dry diets are associated with hepatic copper and zinc concentrations in Labrador Retrievers. Animals: Fifty-five Labrador Retrievers that were fed a single brand and type of commercial dry food for at least 1 year. Of these, 44 dogs were family members of Labrador Retrievers with copper-associated hepatitis. Methods: Liver biopsies, blood samples, and diet samples were obtained. Liver specimens were scored histologically and copper and zinc concentrations were quantified. Dietary concentrations of copper and zinc were measured. The association between dietary intake of copper and zinc and hepatic copper and zinc concentrations was investigated by linear regression analysis. Results: High dietary copper and low dietary zinc levels were significantly associated with high hepatic copper levels. No association between dietary intake and hepatic zinc was present. Conclusions and Clinical Relevance: Dietary copper and zinc at current levels in commercially available dry dog food can influence hepatic copper and can be a risk factor for the development of copper-associated hepatitis in Labrador Retrievers with a genetic susceptibility to copper. © 2012 by the American College of Veterinary Internal Medicine. Source

Fieten H.,University Utrecht | Biourge V.C.,Royal Canin Research Center | Watson A.L.,Royal Canin Research Center | Leegwater P.A.J.,University Utrecht | And 2 more authors.
Veterinary Journal | Year: 2014

Canine hereditary copper-associated hepatitis is characterized by gradual hepatic copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at creating a negative copper balance with metal chelators, of which d-penicillamine is the most commonly used. d-penicillamine often causes gastro-intestinal side effects and life-long continuous therapy may lead to a deficiency of copper and zinc. The aim of the current study was to investigate the effect of a low-copper, high-zinc diet as an alternative to continuous d-penicillamine treatment for the long-term management of canine copper-associated hepatitis.Sixteen affected Labrador retrievers were followed for a median time period of 19.1. months (range, 5.9-39. months) after being effectively treated with d-penicillamine. The dogs were maintained on a diet containing 1.3. ±. 0.3. mg. copper/1000. kcal and 64.3. ±. 5.9. mg. zinc/1000. kcal. Liver biopsies were taken every 6. months for histological evaluation and copper determination. Plasma alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum albumin were determined.Dietary treatment alone was sufficient to maintain hepatic copper concentration below 800. mg/kg dry weight liver in 12 dogs during the study period. Four dogs needed re-treatment with d-penicillamine. ALT activity and albumin concentration were not associated with hepatic copper concentration, but showed a significant association with the stage and grade of hepatitis respectively. In conclusion, a low-copper, high-zinc diet can be a valuable alternative to continuous d-penicillamine administration for long-term management of dogs with copper-associated hepatitis. The copper re-accumulation rate of an individual dog should be considered in the design of a long-term management protocol and in determining re-biopsy intervals. © 2013 Elsevier Ltd. Source

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