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OBJECTIVES: To evaluate the prevalence and risk factors for overweight status in dogs under primary veterinary care in the UK. MATERIALS AND METHODS: A retrospective study design was used to estimate the 1-year (2016) period prevalence of overweight status. The clinical records were randomly ordered and manually validated for dogs with overweight status during 2016. Univariable and multivariable logistic regression modelling were used to evaluate associations between risk factors (breed, brachycephalic status, adult bodyweight, bodyweight relative to breed-sex mean, age, sex-neuter and insurance) and overweight status. RESULTS: There were 1580 of 22,333 dogs identified as overweight during 2016. The estimated 1-year period prevalence for overweight status recorded in dogs under veterinary care was 7.1% (95% confidence interval 6.7-7.4). After accounting for confounding factors, eight breeds showed increased odds of overweight status compared with crossbred dogs. The breeds with the highest odds included the Pug (OR 3.12, 95% confidence interval 2.31 to 4.20), Beagle (OR 2.67, 1.75 to 4.08), Golden Retriever (OR 2.58, 1.79 to 3.74) and English Springer Spaniel (OR 1.98, 1.31 to 2.98). Being neutered, middle-aged and insured were additionally associated with overweight status. CLINICAL SIGNIFICANCE: Targeted overweight prevention strategies should be prioritised for predisposed breeds, such as Pugs and Beagles. The findings additionally raise questions about further preventative efforts following neutering. The prevalence estimate suggests veterinary professionals are underreporting overweight status and therefore could be missing key welfare opportunities.
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Enfermedades de los Perros , Animales , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/genética , Perros , Sobrepeso/epidemiología , Sobrepeso/veterinaria , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
Loss-of-function mutations in AGPAT2, encoding 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2), produce congenital generalised lipodystrophy (CGL). We screened the AGPAT2 gene in two siblings who presented with pseudoacromegaly, diabetes and severe dyslipidaemia and identified a novel mutation in AGPAT2 causing a single amino acid substitution, p.Cys48Arg. We subsequently investigated the molecular pathogenic mechanism linking both this mutation and the previously reported p.Leu228Pro mutation to clinical disease. Wild-type and mutant AGPAT2 were expressed in control and AGPAT2-deficient preadipocyte cell lines. mRNA and protein expression was determined, and the ability of each AGPAT2 species to rescue adipocyte differentiation in AGPAT2-deficient cells was assessed. Protein levels of both p.Cys48Arg and p.Leu228Pro AGPAT2 were significantly reduced compared with that of wild-type AGPAT2 despite equivalent mRNA levels. Stable expression of wild-type AGPAT2 partially rescued adipogenesis in AGPAT2 deficient preadipocytes, whereas stable expression of p.Cys48Arg or p.Leu228Pro AGPAT2 did not. In conclusion, unusually severe dyslipidaemia and pseudoacromegaloid overgrowth in patients with diabetes should alert physicians to the possibility of lipodystrophy. Both the previously unreported pathogenic p.Cys48Arg mutation in AGPAT2, and the known p.Leu228Pro mutation result in decreased AGPAT2 protein expression in developing adipocytes. It is most likely that the CGL seen in homozygous carriers of these mutations is largely accounted for by loss of protein expression.
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AIMS/HYPOTHESIS: Genetic insulin receptoropathies are a rare cause of severe insulin resistance. We identified the Ile119Met missense mutation in the insulin receptor INSR gene, previously reported in a Yemeni kindred, in four unrelated patients with Somali ancestry. We aimed to investigate a possible genetic founder effect, and to study the mechanism of loss of function of the mutant receptor. METHODS: Biochemical profiling and DNA haplotype analysis of affected patients were performed. Insulin receptor expression in lymphoblastoid cells from a homozygous p.Ile119Met INSR patient, and in cells heterologously expressing the mutant receptor, was examined. Insulin binding, insulin-stimulated receptor autophosphorylation, and cooperativity and pH dependency of insulin dissociation were also assessed. RESULTS: All patients had biochemical profiles pathognomonic of insulin receptoropathy, while haplotype analysis revealed the putative shared region around the INSR mutant to be no larger than 28 kb. An increased insulin proreceptor to ß subunit ratio was seen in patient-derived cells. Steady state insulin binding and insulin-stimulated autophosphorylation of the mutant receptor was normal; however it exhibited decreased insulin dissociation rates with preserved cooperativity, a difference accentuated at low pH. CONCLUSIONS/INTERPRETATION: The p.Ile119Met INSR appears to have arisen around the Horn of Africa, and should be sought first in severely insulin resistant patients with ancestry from this region. Despite collectively compelling genetic, clinical and biochemical evidence for its pathogenicity, loss of function in conventional in vitro assays is subtle, suggesting mildly impaired receptor recycling only.
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Resistencia a la Insulina/fisiología , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Adulto , África , Células Cultivadas , Niño , Femenino , Haplotipos , Humanos , Lactante , Resistencia a la Insulina/genética , Masculino , Mutagénesis Sitio-Dirigida , Mutación , Reacción en Cadena de la Polimerasa , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Amino-terminal probrain natriuretic peptide (NT-proBNP) has been proposed as a useful biomarker for heart disease in dogs. In humans, decreased glomerular filtration rate (GFR) increases NT-proBNP. OBJECTIVE: To investigate whether decreased GFR as indicated by plasma creatinine concentration is associated with increased NT-proBNP in dogs without heart disease. ANIMALS: Four groups of dogs: healthy (n= 39), azotemic (n= 36), heart disease (n= 37), and congestive heart failure (CHF) (n= 7) presented to 2 teaching hospitals. METHODS: Prospective observational cohort study. Plasma creatinine concentration and NT-proBNP were measured in every dog. Nonparametric tests were used to compare the differences among groups. The median and actual results for each group were compared with the manufacturer's recommended and previously published suggestions for cut-off values for diagnosis of heart disease. RESULTS: Median (range) plasma creatinine concentration was 1.47 (1.06-1.70), 4.36 (1.74-15.6), 1.22 (0.69-1.91), and 1.45 (0.63-1.64) mg/dL and median (range) NT-proBNP was 118 (2-673), 556 (37-1,819), 929 (212-5,658), and 3,144 (432-5,500) pmol/L for the healthy, azotemic, heart disease, and CHF groups, respectively. Pair-wise comparison indicated a significant difference among all groups for NT-proBNP (P< or = .049). Plasma creatinine concentration was significantly higher in the azotemic group compared with other groups (P < .001) but there was no significant among other groups. Application of 3 recommended cut-off values led to misclassification of dogs with azotemia as having heart disease. CONCLUSIONS: Azotemia results in NT-proBNP being increased to concentrations reported as diagnostic of heart disease or heart failure in dogs. Care should be employed when interpreting the results of NT-proBNP in patients with known or possible increased plasma creatinine concentration.
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Azotemia/veterinaria , Enfermedades de los Perros/metabolismo , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Animales , Azotemia/sangre , Biomarcadores , Estudios de Cohortes , Perros , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismoRESUMEN
BACKGROUND: Chronic hepatitis (CH) in dogs is common but little is known about factors associated with survival. Ascites is a well-recognized negative prognostic indicator in humans. HYPOTHESIS: Ascites is a negative prognostic indicator in CH in dogs. ANIMALS: Thirty-four dogs with histologically confirmed CH presented to 1 institution between 1996 and 2005. METHODS: Retrospective observational study. CH was diagnosed by histopathology of liver tissue according to the WSAVA criteria. Ascites was diagnosed by abdominal ultrasound. The association of ascites with survival from diagnosis or onset of owner-reported clinical signs until death from any cause or from liver disease was analyzed. Ascitic and nonascitic groups were further analyzed for differences in treatment and sex. RESULTS: Fourteen of 34 dogs had ascites. Survival from diagnosis to death from liver disease was 0.4 months (95% confidence interval [CI], 0.2-0.6) for ascitic dogs and 24.3 months (CI 11.4-37.1) for nonascitic dogs (P < .001), and from onset of signs to death from liver disease was 2.0 months (CI 0.0-5.6) for ascitic dogs and 33.0 months (CI 8.6-57.4) for nonascitic dogs (P= .0020). Diet and spironolactone use differed between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Ascites is a significant negative prognostic indicator in dogs with CH. Veterinarians and owners can use this information to aid clinical decision making in affected dogs.
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Ascitis/veterinaria , Enfermedades de los Perros/patología , Hepatitis Animal/patología , Hepatitis Crónica/veterinaria , Animales , Ascitis/patología , Perros , Femenino , Hepatitis Crónica/patología , Masculino , Estudios RetrospectivosRESUMEN
An eight-year-old, neutered male Burmese cat presented with five days vomiting and anorexia. Physical examination, clinical pathology and diagnostic imaging findings suggested a perirenal pseudocyst. After partial resection of the perirenal capsule clinical signs temporarily resolved, but the cat was euthanased 34 days postoperatively as a result of seizures and recurrence of vomiting. Postoperative histopathology showed neoplastic transitional cells within and lining the resected perirenal capsule; a diagnosis of transitional cell carcinoma was confirmed post-mortem. To the authors' knowledge, this is the first report of this presentation of transitional cell carcinoma. Transitional cell carcinoma should be a differential diagnosis for the aetiology of perirenal pseudocyst.