Improvement in liver pathology after 4 months of D-penicillamine in 5 doberman pinschers with subclinical hepatitis

Five female Doberman Pinschers with increased hepatic copper concentrations and persistent (3-4 years) subclinical hepatitis were treated with D-penicillamine for 4 months. Before and after treatment, the dogs underwent clinical, hematologic (red blood cell, white blood cell, and differential and thrombocyte counts), and clinical chemistry (creatinine, alkaline phosphatase, alanine aminotransferase, and total bile acid concentrations) examinations, and liver biopsies were examined histologically and their copper content measured quantitatively. No adverse effects were observed during treatment, and CBC and serum chemistry test results did not change. The mean liver copper concentration was 1,036 mg/kg dry matter before treatment and decreased to 407 mg/kg after treatment (P = .03). The copper concentrations had decreased (by between 134 and 1,135 mg/kg dry matter) in all of the dogs. The histopathologic appearance had improved or returned to normal in all 5 dogs. We conclude that D-penicillamine effectively reduced copper retention in these dogs and improved the histopathologic appearance of the lesions. However, because D-penicillamine has both copper-chelating and anti-inflammatory properties, it is not possible to draw conclusions on the etiology of this disease.     

Chronic active hepatitis with cirrhosis in the Doberman pinscher

Chronic active hepatitis with cirrhosis and increased liver copper levels in 8 female (3 spayed) Doberman Pinschers is described. The response to immunosuppressive therapy in two dogs was poor. Laboratory results were not specific for the disease in the Doberman Pinscher and may occur in other liver diseases. The increased copper levels are most probably secondary to hepatocellular cholestasis. Although the pathogenesis is unknown, the disease in the Doberman Pinscher may be regarded as a separate entity.     

Copper-associated chronic hepatitis in Labrador Retrievers

This study summarizes the clinical and pathologic findings in 15 Labrador Retrievers with copper-associated chronic hepatitis (CACH). Our hypothesis was that this form of hepatitis is caused by a defect in hepatic copper metabolism, which most likely originates from a genetic defect. Affected Labradors consisted of 11 female and 4 male Labrador Retrievers. Eight family members of 2 of these patients were examined prospectively, as were 6 unrelated healthy Labrador Retrievers. All dogs were registered at the breed club. The average age at clinical presentation was 7 years (range, 2.5-10.5 years). All dogs were presented for anorexia, which was associated with vomiting in 8 patients. The diagnosis of CACH was based on histologic examination of liver biopsy specimens in all dogs, including semiquantitation of copper. A disproportionate increase in alanine aminotransferase (ALT) activity relative to alkaline phosphatase (ALP) activity, as well as the centrolobular localization of copper and the association of copper accumulation with hepatic lesions, suggested a primary copper storage disease rather than primary cholestatic liver disease causing copper accumulation. Mean hepatic copper concentration measured in related Labradors was 1,317 microg/g dry weight liver (range, 402-2,576 microg/g). Mean hepatic copper concentration of unrelated normal Labradors was 233 microg/g dry weight liver (range, 120-304 microg/g). Our findings support the hypothesis that a hereditary form of hepatitis occurs in Labrador retrievers and is caused by a defect in hepatic copper metabolism.     

Effect of desmopressin acetate administration on primary hemostasis in Doberman Pinschers with type-1 von Willebrand disease as assessed by a point-of-care instrument

OBJECTIVE: To evaluate primary hemostasis following administration of desmopressin acetate (DDAVP) to Doberman Pinschers with type-1 von Willebrand disease (vWD). ANIMALS: 16 nonanemic Doberman Pinschers with type-1 vWD. PROCEDURE: Closure time (CT), defined as time required for occlusion of an aperture by a platelet plug assessed within the point-of-care instrument, plasma von Willebrand factor (vWF) concentration, and buccal mucosal bleeding time (BMBT) were determined before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Baseline closure times measured with adenosine diphosphate ([ADP-CT], 108 to > 300 seconds; reference range, 52 to 86 seconds) and epinephrine ([EPI-CT], 285 to > 300 seconds; 97 to 225 seconds) as platelet agonists were prolonged in all dogs. Following DDAVP administration, ADP-CT (59 to 186 seconds) was significantly shortened from baseline, but there was no decrease in EPI-CT. Although mean plasma vWF concentration increased significantly after DDAVP administration, only 1 dog had an increase of > 35 U/dL. There was no correlation between increase in plasma vWF concentration and shortening of the ADP-CT. Baseline BMBT was prolonged in 12 of 14 dogs, with significant shortening of BMBT after DDAVP administration in 6 of 7 dogs. In vitro replacement of vWF-deficient plasma with plasma from an unaffected dog shortened the ADP-CT whereas in vitro addition of DDAVP had no effect. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of DDAVP to Doberman Pinschers with type-1 vWD resulted in improved hemostatic function, as assessed by the point-of-care instrument and shortening of BMBT, despite minimal increase in plasma vWF concentration.     

Upregulation of major histocompatibility complex class II antigens in hepatocytes in Doberman hepatitis

Major histocompatibility complex (MHC) class II antigen expression in hepatocytes and its correlation with mononuclear cell infiltration into the liver were studied using immunohistochemical techniques in 38 Dobermans with Doberman hepatitis (DH). Liver biopsy samples were obtained from 18 dogs at the subclinical stage. Autopsy samples were taken from 6 DH dogs euthanized for a reason other than DH, from 14 dogs euthanized because of advanced liver failure and from 6 control Dobermans. Upon examination of the control liver samples, no expression of MHC class II antigens was detected in hepatocytes. By contrast, in 15 of the 18 DH biopsies (83%) and in all 20 DH autopsy liver samples, hepatocytes expressed MHC class II molecules. MHC class II expression was either cytoplasmic or membranous and occurred in conjunction with lymphocyte infiltration. A correlation between the inflammatory reaction and the expression of MHC class II in hepatocytes suggests that the aberrant expression of MHC class II in hepatocytes is induced by cytokines. Hepatocytes presenting a putative MHC class II molecule-associated autoantigen could thus become the target of an immune attack mediated by CD4+ T cells. In addition, corticosteroid treatment was observed to significantly decrease MHC class II expression in DH hepatocytes. Inappropriate MHC class II expression in hepatocytes and mononuclear cell infiltration are suggesting an autoimmune nature for chronic hepatitis in Dobermans.     

Evaluation of stability over time for measures of heart-rate variability in overtly healthy Doberman Pinschers

OBJECTIVE: To determine whether results of analysis of heart-rate variability (HRV) in overtly healthy Doberman Pinschers remain stable over time. ANIMALS: 24 overtly healthy client-owned Doberman Pinschers. PROCEDURE: The HRV was analyzed in time- and frequency-domains from 24-hour ambulatory electrocardiographic (Holter) monitor recordings. Activity during paired tests (tests 1 and 2) was similar (17 dogs) or nearly identical (7). Holter recordings and HRV analyses of those 17 dogs were repeated at a mean +/- SD of 65 +/- 50 weeks (median, 51 weeks; range, 10 to 177 weeks), whereas it was repeated for the other 7 dogs at 3 to 9 weeks (mean, 73 +/- 2.1 weeks). RESULTS: Differences between test 1 and test 2 were not significantly different, except for 24-hour means of the normal beat-to-normal beat (NN) intervals in all 5-minute segments. Strongest correlations were for SD of all NN intervals and root mean square successive difference between adjacent NN intervals of the time-domain analyses and total power, very-low frequency power, and high-frequency power of the frequency-domain analyses. When activity during tests 1 and 2 in 7 dogs was stringently controlled, the differences were not significantly different, and correlation factors for the 24-hour HRV analyses exceeded 0.83. CONCLUSIONS AND CLINICAL RELEVANCE: Variables from sequential HRV analyses in overtly healthy Doberman Pinschers with normal echocardiograms are moderately stable when physical activity is not stringently controlled and extremely stable for at least 3 to 9 weeks when physical activity is stringently controlled.     

Chronic active hepatitis in 26 Doberman pinschers

Chronic active hepatitis with increased hepatic copper concentration was diagnosed in 25 female and 1 male Doberman Pinscher dogs. Common clinical signs included polyuria/polydipsia, weight loss, anorexia, icterus, and ascites. Increased liver enzyme activities and abnormal liver function test results were the most consistent clinicopathologic changes. The dogs were assigned to 3 groups on the basis of clinical course of the disease. Group 1 dogs (n = 12) had clinical signs of advanced liver failure and died within one week. Group 2 dogs (n = 7) had less severe clinical signs of liver disease and died within one month. Group 3 dogs (n = 5) did not have clinical signs of illness or had mild clinical signs of liver disease and died 1 to 42 months after initial evaluation. One dog could not be reevaluated and another dog was alive 3 months after initial examination. Treatments consisted of supportive care for dogs in group 1, and dietary manipulations and corticosteroids for dogs in groups 2 and 3. The association of increased liver copper concentration and chronic active hepatitis is not known.     

Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease

OBJECTIVE: To assess the effect of desmopressin (DDAVP) administration in Doberman Pinschers with type 1 von Willebrand disease (vWD) on plasma von Willebrand factor (vWF) multimers through determination of vWF collagen binding activity (vWF:CBA; a functional vWF assay dependent on the presence of high-molecular-weight [HMWI multimers), comparison of vWF antigen concentration (vWF:Ag) to vWF:CBA, and vWF multimer size distribution. ANIMALS: 16 Doberman Pinschers with type 1 vWD and 5 clinically normal control dogs. PROCEDURE: Plasma vWF:Ag and vWF:CBA assays and vWF multimer analysis were performed before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Following DDAVP administration, dogs with type 1 vWD had an increase in mean baseline values of plasma vWF:Ag and vWF:CBA from 10% to 17% for both variables. The mean vWF Ag:CBA ratio at baseline (0.95) was similar after DDAVP administration (0.97), indicating concordant increases in plasma vWF concentration and activity. In control dogs, mean plasma vWF:Ag and vWF:CBA increased from baseline values of 64% to 113% and 58% to 114%, respectively, and the vWF Ag:CBA ratios were unchanged (1.1 vs 1.0) after DDAVP administration. Plasma vWF multimer analysis revealed proportional increases in band intensity for all multimer sizes following DDAVP administration, in comparison to baseline for the control dogs and Doberman Pinschers with vWD, consistent with vWF Ag:CBA ratios of approximately 1. CONCLUSIONS AND CLINICAL RELEVANCE: Beneficial effects of DDAVP on primary hemostasis in Doberman Pinschers with type 1 vWD cannot be explained by preferential increases in HMW vWF multimers.     

Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy

OBJECTIVE: To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation. ANIMALS: 5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs). PROCEDURES: Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure. RESULTS: A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, beta-myosin heavy chain, and troponin T genes. CONCLUSIONS AND CLINICAL RELEVANCE: Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.     

Association between results of ambulatory electrocardiography and development of cardiomyopathy during long-term follow-up of Doberman pinschers

OBJECTIVE: To characterize ambulatory electrocardiographic results of overtly healthy Doberman Pinschers and determine associations between those results and development of dilated cardiomyopathy. DESIGN: Cohort study. ANIMALS: 114 (58 male, 56 female) overtly healthy Doberman Pinschers without echocardiographic evidence of cardiac disease on initial examination. PROCEDURE: Echocardiograms and 24-hour ambulatory electrocardiograms (Holter recordings) were obtained initially and at variable intervals. The status (live vs dead) of all dogs was known at least 2 years and as long as 10 years after initial examination (mean [+/- SD] follow-up time, 4.33 +/- 1.84 years). Associations between development of dilated cardiomyopathy and number of ventricular premature contractions (VPC), age, and sex were determined. RESULTS: 55 dogs (48%) did not have VPC on initial Holter recordings, and only 8 dogs had > 50 VPC/24 hours. The likelihood that a dog would have VPC was associated with increasing age and being male. At least 1 VPC/24 hours, and in particular, > 50 VPC/24 hours or > or = 1 couplet or triplet of VPC/24 hours, were predictive of subsequent development of dilated cardiomyopathy. Fifty-four dogs (47%) developed dilated cardiomyopathy; 12 were still alive at the end of the study, and 42 had died. Twenty-five of these 42 dogs died after the onset of congestive heart failure (CHF), 15 died suddenly before the onset of overt CHF, and 2 died of noncardiac causes. More males developed dilated cardiomyopathy than females, and dogs that died suddenly were approximately 1 year younger than those that developed CHF. CONCLUSIONS AND CLINICAL RELEVANCE: Results of high-quality Holter recordings may be used to identify overtly healthy Doberman Pinschers that are at a high risk for dilated cardiomyopathy.     

Hepatic (64)Cu excretion in Dobermanns with subclinical hepatitis

To investigate whether Dobermanns have impaired copper excretion an intravenous radioactive copper isotope ((64)Cu) was used as a tracer. Five patients and eight normal dogs (5 normal Dobermanns and 3 Beagles) were studied. The five female Dobermann patients had a subclinical hepatitis and an increased hepatic copper concentration (median 822mg/kg, range 690-1380mg/kg dry matter). The normal dogs, five Dobermanns and three Beagles, had no abnormal liver histopathology and hepatic copper concentrations were considered normal (Dobermanns; median 118mg/kg, range 50-242mg/kg dry matter; Beagles; median 82mg/kg, range 50-88mg/kg dry matter). Cholestasis was excluded in all dogs by means of a (99m)Tc-Bis-IDA hepatobiliary scintigraphy. Plasma clearance of (64)Cu was comparable in all dogs with no statistically significant differences. The excretion of (64)Cu into the bile, although not statistically significant, was less for the Dobermanns with subclinical hepatitis compared to the normal dogs. The findings suggest that impaired copper excretion may play a role in the aetiology of chronic hepatitis in the Dobermann.     

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with echocardiographic abnormalities

OBJECTIVE: To identify, by means of 24-hour ambulatory electrocardiography, electrocardiographic abnormalities in overtly healthy Doberman Pinschers in which results of echocardiography were abnormal. DESIGN: Clinical case series. ANIMALS: 56 (35 male, 21 female) overtly healthy Doberman Pinschers with echocardiographic evidence of cardiomyopathy on initial examination that subsequently died of cardiomyopathy. PROCEDURE: Twenty-four-hour ambulatory electrocardiographic (Holter) recordings obtained at the time of initial examination were reviewed. For all dogs, scan quality was > 90%. RESULTS: Initial Holter recordings of all 56 dogs contained ventricular premature contractions (VPC). Thirty-six (65%) dogs had > 1,000 VPC/24 h, 17 (31%) had > 5,000 VPC/24 h, and 11 (19%) had > 10,000 VPC/24 h. Fifty-four (96%) dogs had couplets of VPC, 37 (66%) had triplets of VPC, and 36 (64%) had episodes of nonsustained (< 30 seconds) ventricular tachycardia. Number of VPC/24 h during the initial Holter recordings was positively correlated with numbers of couplets and triplets of VPC and number of ventricular escape beats and negatively correlated with left ventricular fractional shortening. Twenty-eight dogs died suddenly prior to the putative onset of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that along with echocardiography, 24-hour ambulatory electrocardiography can be used to help identify overtly healthy Doberman Pinschers with cardiomyopathy.     

Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups

Background: Dilated cardiomyopathy (DCM) in Doberman Pinschers is an autosomal dominant inherited disease. The prevalence of DCM in Doberman Pinschers of various age groups in Europe is currently unknown, but this information would be important to develop recommendations for screening programs. Objectives: To evaluate the prevalence of cardiomyopathy in various age groups of Dobermans. Animals: Seven hundred and seventy‐five examinations in 412 Doberman Pinschers. Methods: Dogs were included in a prospective longitudinal cohort study. Each examination included echocardiography and 24‐hour ECG (Holter) examination. A cut‐off value of >100 ventricular premature contractions (VPCs) per 24 hours on Holter examination or abnormal echocardiography was considered diagnostic for cardiomyopathy. The cumulative prevalence included all dogs with DCM and healthy dogs >7 years of age. Results: DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs. Conclusions and Clinical Importance: The prevalence of Doberman cardiomyopathy is very high in Europe. Disease manifestation and progression are different between male and female dogs. Yearly screening for DCM by Holter examination and echocardiography is recommended, starting at 2 years of age.     

Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy

OBJECTIVE: To evaluate the coding region of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy (DCM) for mutations that could be responsible for the development of the condition ANIMALS: 28 dogs (16 Doberman Pinschers with DCM and 12 mixed-breed control dogs). PROCEDURE: Ten milliliters of blood was collected from each dog for DNA extraction. Polymerase chain reaction (PCR) primers were designed to amplify canine exonic regions, using the sequences of exons 2 to 6 of the cardiac actin gene. Single-stranded conformational polymorphism analysis was performed for each exon with all samples. Autoradiographs were analyzed for banding patterns specific to affected dogs. The DNA sequencing was performed on a selected group of affected and control dogs. RESULTS: Molecular analysis of exons 2 to 6 of the cardiac actin gene did not reveal any differences in base pairs between affected dogs and control dogs selected for DNA evaluation. CONCLUSIONS: Mutations in exons 5 and 6 of the cardiac actin gene that have been reported in humans with familial DCM do not appear to be the cause of familial DCM in Doberman Pinschers. Additionally, evaluation of exons 2 to 6 for causative mutations did not reveal a cause for inherited DCM in these Doberman Pinschers. Although there is evidence that DCM in Doberman Pinschers is an inherited problem, a molecular basis for this condition remains unresolved. Evaluation of other genes coding for cytoskeletal proteins is warranted.     

Erythrocytic antioxidant defense, lipid peroxides level and blood iron, zinc and copper concentrations in dogs naturally infected with Babesia gibsoni

Babesiosis is a common tick borne disease of dogs in tropical and subtropical regions of the world caused by different species of Babesia. The present study aimed to examine erythrocyte lipid peroxide and erythrocytic antioxidant levels in dogs with clinical babesiosis, caused by Babesia gibsoni, and impact of the disease on blood iron, zinc and copper levels. The study was conducted on 10 naturally occurring cases of canine babesiosis with the history of tick infestation, erratic pyrexia, and prolonged illness. Microscopic examination of Giemsa stained peripheral blood smears confirmed B. gibsoni infection in the erythrocytes. Six apparently healthy dogs of different age, sex and breeds, brought for either health checkup or vaccination were used for comparison. Levels of erythrocytic antioxidant enzymes were significantly (P<0.01) higher in sick dogs than those of cytologically negative dogs (catalase: 0.192+/-0.024 units/mg Hb vs 0.074+/-0.004 units/mg Hb; superoxide dismutase: 0.014+/-0.0009 units/mg Hb vs 0.006+/-0.0008 units/mg Hb and lipid peroxide: 6.01+/-0.30 nmol MDA/mg Hb vs 1.89+/-0.10 nmol MDA/mg Hb). The levels of blood micronutrients were significantly low in these dogs (iron: 89.87+/-8.12 microg/g vs 126.44+/-14.65 microg/g; zinc: 3.67+/-1.85 microg/g vs 5.62+/-1.83 microg/g and copper: 0.55+/-0.63 microg/g vs 0.65+/-0.04 microg/g). The study demonstrated oxidative damage in dogs naturally infected with B. gibsoni. Low level of blood iron, zinc and copper seems to have an additional role in the genesis of anaemia and oxidative stress.     

Plasma fatty acid concentrations in Boxers and Doberman Pinschers

OBJECTIVE: To compare plasma fatty acid concentrations and the relationships of fatty acids to arrhythmias in Boxers versus Doberman Pinschers. ANIMALS: 38 Boxers and 13 Doberman Pinschers. PROCEDURES: Boxers and Doberman Pinschers evaluated via Holter recording and for which a blood sample was available were included. Echocardiograms were performed in 49 of 51 dogs. The number of ventricular premature complexes (VPCs)/24 h was counted and fatty acids analyzed. Plasma fatty acid concentrations and VPCs/24 h, as well as correlations between the 2 variables, were compared between the 2 breeds. RESULTS: Compared with the Doberman Pinschers, Boxers had significantly higher plasma concentrations of gamma-linolenic acid but lower concentrations of arachidonic acid. Total n-6 fatty acids and total polyunsaturated fatty acid concentrations were higher in Doberman Pinschers. There were significant, but weak, positive correlations between VPCs and oleic acid, total n-3 fatty acids, and total n-9 fatty acids in Boxers but not in Doberman Pinschers. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that plasma fatty acid concentrations may differ between Boxers and Doberman Pinschers and that the relationship between fatty acid concentrations and VPCs may be different between these 2 breeds.     

Heart rate variability in Doberman Pinschers with and without echocardiographic evidence of dilated cardiomyopathy

OBJECTIVE: To characterize the salient variables of the time-domain analysis of heart rate variability (HRV) in clinically normal Doberman Pinschers and to compare those variables with those of Doberman Pinschers with cardiomyopathy and mild to moderate myocardial failure. ANIMALS: 46 Doberman Pinschers. PROCEDURE: HRV was analyzed in the time-domain from 24-hour Holter recordings obtained from 28 Doberman Pinschers with normal echocardiograms and 18 Doberman Pinschers with echocardiograms consistent with mild to moderate myocardial failure. RESULTS: Significant differences in HRV variables between the 2 groups of dogs were not detected. The HRV was greater during the nighttime (12 AM to 6 AM), compared with the 24-hour day and an 18-hour (6 AM to 12 AM) period. CONCLUSIONS AND CLINICAL RELEVANCE: HRV of dogs with mild to moderate myocardial failure was not different from that of clinically normal dogs, because there were no disturbances of autonomic balance, baroreceptor function, and other factors that influence HRV in the dogs with cardiomyopathy, or the sensitivity of time-domain analysis was overwhelmed by normal sinus arrhythmia. The techniques now used to study HRV have important limitations, especially in dogs, and better noninvasive tests of autonomic function are needed.     

von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers

OBJECTIVE: To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. ANIMALS: 102 client-owned Doberman Pinschers. PROCEDURES: Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. RESULTS: Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. CONCLUSIONS AND CLINICAL RELEVANCE: Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.     

Effect of Desmopresssin in Normal Dogs and Dogs with von Willebrand's Disease

Desmopressin acetate (DDAVP(R)), a synthetic analogue of vasopressin was slowly administered intravenously to 12 healthy dogs of various breeds and 10 Doberman Pinschers with mild-to-moderate type I von Willebrand's disease at a dose of 0.3, 1.0 and 3.0 micro g/kg body weight. Plasma von Willebrand factor:antigen was measured by an electroimmunoassay prior to and 30, 60, 90, 120 and 180 minutes after desmopressin infusion. Desmopressin induced only very modest and statistically insignificant increases in von Willebrand factor in both groups. We conclude that the response to desmopressin as measured by circulating von Willebrand factor is much less pronounced in healthy dogs and in Doberman Pinschers with von Willebrand's disease than in humans.     

The distribution of vitamin A and retinol-binding protein in the blood plasma, urine, liver and kidneys of carnivores

The contents of retinol and retinyl esters as well as retinol-binding protein (RBP) in the plasma, urine, liver and kidneys of dogs, raccoon dogs and silver foxes were investigated. In the plasma and urine of all three species, vitamin A was present as retinol and retinyl esters. Vitamin A levels (1376+/-669 microg x g(-1)) were significantly higher in the livers of dogs than in the kidneys (200+/-217 microg x g(-1), P < 0.001 ). However, vitamin A levels in the kidneys of raccoon dogs (291+/-146 microg x g(-1)) and silver foxes (474+/-200 microg x g(-1)) were significantly higher than in the liver (67+/-58 microg x g(-1) and 4.3+/-2.4 microg x g(-1), respectively, both P < 0.001). RBP was immunologically detected in the blood plasma of all species, but never in the urine. In the liver, immunoreactive RBP was found in hepatocytes. In the kidneys of all species, RBP was observed in the cells of the proximal convoluted tubules. The levels of vitamin A in the livers of raccoon dogs and silver foxes were extremely low, which would be interpreted as a sign of great deficiency in humans. This observation might indicate that the liver status cannot be used as an indicator of vitamin A deficiency in canines. The high levels of vitamin A in the kidneys in all three species may indicate a specific function of the kidney in the vitamin A metabolism of canines.