Chronic hepatitis in Doberman pinschers. A review

Chronic hepatitis in Doberman pinschers is predominantly seen in female dogs, usually between 4 and 7 years of age and was first recognized in the early eighties. The histopathological characteristics of Doberman hepatitis are those of micronodular cirrhosis with histological features of fibrosis, piece meal necrosis and progressive lymphocyte and plasma cell infiltration of the portal triads. Currently there are two hypotheses on the pathogenesis although neither of them has been elucidated. The first hypothesis is that of a copper toxicosis. The second is that of autoimmunity. Similarities and differences with other breeds and studies on both hypotheses are reviewed, as well as results of recent research of our group. Based on recent findings chronic hepatitis in Doberman pinschers is most likely to be a form of copper toxicosis. Although there are several indications that suggest autoimmunity as well, this still remains unclear.     

Prospective clinical trial evaluating spironolactone in Doberman pinschers with congestive heart failure due to dilated cardiomyopathy

Introduction/objectivesWhether the aldosterone antagonist spironolactone has beneficial survival effects in dogs with dilated cardiomyopathy (DCM) is not known. The primary objective of the study was to evaluate the effect of spironolactone, when added to conventional therapy, on survival time in Doberman pinschers with congestive heart failure (CHF) due to DCM.AnimalsSixty-seven client-owned Doberman pinschers with CHF due to DCM.Materials and methodsThe trial design was prospective, randomized, blinded, and placebo controlled. Dogs were randomized to receive 50–75 mg of spironolactone twice daily (n = 34) or a placebo (n = 33), in addition to standard CHF therapy. Follow-up visits were targeted every one–six weeks until endpoint. Quality-of-life questionnaire and physical examination were performed at every visit, while renal biochemistry, ECG, echocardiography, and thoracic radiography were reassessed as needed. The primary endpoint was time to cardiac death, defined as death or euthanasia from CHF or sudden death.ResultsMedian time to primary endpoint in the spironolactone group (183 days) was not statistically significantly different than that for the placebo group (124 days) (P = 0.254). The development of atrial fibrillation (AF) was significantly less frequent in the spironolactone group (n = 7) than the placebo group (n = 15, P = 0.037).ConclusionsWhile median time to cardiac death in the spironolactone group was not statistically significantly different than that in the placebo group, adding spironolactone to conventional therapy resulted in reduced occurrence of AF.     

MENSURATION OF CERVICAL VERTEBRAL RATIOS IN DOBERMAN PINSCHERS AND GREAT DANES

Canine cervical vertebral instability is a complex syndrome involving cervical spinal cord compressive lesions. Doberman pinschers and Great Danes are the most commonly affected breeds. Measurements of vertebral canal diameter (VCD), vertebral body height (H), and vertebral body length (L) were made from C3-C7 in 24 Doberman pinschers and 8 Great Danes by using digital and analog techniques. Significant differences between affected and unaffected sites were noted for Doberman pinschers at C6 (P = 0.039) and C7 (P = 0.027) using analog measurements of VCD/H, and Great Danes at C6 using analog (P = 0.041) and digital (P = 0.004) measurements of VCD/L. Cervical vertebral ratios have potential as a breed-specific screening tool for cervical vertebral instability and warrant longitudinal studies.     

Canine idiopathic dilated cardiomyopathy. Part I: Aetiology, clinical characteristics, epidemiology and pathology

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The aetiology of the myocardial hypokineis is seldom known in the individual case of DCM, although several theories concerning genetic, nutritional, metabolic, inflammatory, infectious, or drug- or toxin-induced myocardial disease have been discussed. DCM is often referred to as being breed-specific for Boxers, Doberman Pinschers, English Cocker Spaniels and other breeds. Review of reports on histopathologic findings in canine DCM reveals two histologically distinct forms of DCM; (1) cardiomyopathy of boxers and of Doberman pinschers, corresponding to the "fatty infiltration-degenerative" type, and (2) the form seen in many giant, large- and medium-sized breeds, including some boxers and Doberman pinschers, which can be classified as the "attenuated wavy fiber" type of DCM. The classification of canine idiopathic DCM according to histologic findigns seems superior to classification suggesting breed-specific syndromes, as some breeds (i.e. boxers and Doberman pinschers) may be affected by both diseases. However, ante mortem aetiological diagnosis of DCM is difficult. DCM carries a poor prognosis in dogs, and few prognostic indicators have been identified.     

Effect of severity of myocardial failure on heart rate variability in Doberman pinschers with and without echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVE: To determine whether heart rate variability (HRV) is reduced in Doberman Pinschers with dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 62 overtly healthy Doberman pinschers. PROCEDURE: Heart rate variability was analyzed in time and frequency domains from data obtained during 24-hour ambulatory electrocardiographic Holter recordings in 41 overtly healthy Doberman pinschers with normal echocardiograms and 21 overtly healthy Doberman pinschers with abnormal echocardiograms. RESULTS: Heart rate variability usually was greater during night versus day, and 2 dogs with the most severe myocardial failure had reduced HRV. CONCLUSIONS AND CLINICAL RELEVANCE: Reduced HRV was detected only in Doberman Pinschers with the most severe myocardial failure. Thus, HRV in less severely affected dogs is not reduced, or the normal sinus arrhythmia of dogs renders HRV relatively insensitive. Analysis of HRV did not provide additional information relative to the severity of left ventricular dysfunction or risk of sudden death from that which could be derived from echocardiography, analysis of Holter recordings, and signal-averaged electrocardiography.     

Intervertebral and intravertebral ratios in Doberman pinscher dogs with cervical spondylomyelopathy

No screening method is currently available to differentiate dogs with and without cervical spondylomyelopathy. Intravertebral and intervertebral ratios are used in horses and can predict cervical vertebral malformation. Intervertebral ratios could be a useful screening method for canine cervical spondylomyelopathy. Our purpose was to compare cervical intervertebral and intravertebral ratios in normal vs. affected Doberman pinschers. Forty dogs were studied, 27 affected and 13 normal. Cervical radiographs were obtained in all dogs. The minimum intra- and intervertebral sagittal diameter ratios were established for each cervical vertebrae and disc space from C(2) to C(7) . Comparisons were made between groups and specific vertebral body and disc levels. The effect of gender, age, and method of measurement (analog or digital radiographs) was also studied. There was no difference in either the intervertebral or intravertebral ratio between normal vs. affected dogs. The ratios decreased progressively along the cervical spine, being smallest at C(6) -C(7) and C(7) , respectively. Age, gender, and method of measurement had a significant influence on both inter- and intravertebral ratios, with smaller ratios seen as dogs aged and in male dogs. Based on our results, inter- or intravertebral ratios have no value to distinguish between clinically normal Doberman pinschers and Doberman pinschers with cervical spondylomyelopathy.     

Alterations in the organisation, ultrastructure and biochemistry of the myocardial collagen matrix in doberman pinschers with dilated cardiomyopathy

Remodelling of the collagen matrix of the myocardium has been implicated in the pathogenesis of dilated cardiomyopathy, a major cause of heart failure in Doberman pinschers. The aim of this study was to characterise the myocardial collagen matrix of Dobermans. In clinically normal Dobermans there was evidence of focal fibrosis. Collagen cross-links were altered in both diseased and clinically normal Doberman myocardium as compared with myocardium from control dogs. Extensive remodelling, in the form of a loss of collagen tethers, increased collagen synthesis and alterations in the collagen cross-links, occurs in diseased Doberman myocardium. Changes in the collagenous matrix are also present in apparently normal Dobermans. These changes are likely to be involved in the progression of the disease and may explain the predisposition of this breed to dilated cardiomyopathy.     

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.     

Association between liver copper concentration and subclinical hepatitis in Doberman Pinschers

The prevalence of subclinical hepatitis was investigated in a group of 106 randomly selected 3-year-old Doberman Pinschers. Histopathologic examination of liver samples from 65 dogs (52 dogs with high bile acids, alkaline phosphatase activity, or alanine aminotransferase activity or with copper granules in hepatocytes in a liver aspirate and 13 normal dogs) revealed subclinical hepatitis in 22 dogs (19 females and 3 males). Liver copper concentrations measured by instrumental neutron activation analysis was significantly higher (mean +/- SD; 419 +/- 414 microg/g dry matter) in dogs with hepatitis than those without liver disease (197 +/- 113 microg/g; P = .0008). At 2.6 +/- 0.6 years hepatitis persisted in 5 of 16 dogs available for examination. One dog with a high copper concentration but normal liver subsequently developed subclinical hepatitis after 3 years. During the follow-up period, the average copper concentration of the 6 dogs with persistent subclinical hepatitis was 939 +/- 299 microg/g and had continued to rise significantly (P = .02). The hepatitis in these dogs was associated with apoptotic hepatocytes and copper-laden Kupffer cells in centrolobular regions. The results of this study suggest that there is a relationship among copper storage, hepatocellular damage, and hepatitis in Doberman Pinschers.     

Detection of von Willebrand's Disease in Dogs with a Rapid Qualitative Test, Based on Venom-Coagglutinin-Induced Platelet Agglutination

A rapid, qualitative blood test was developed to identify potential bleeders among dogs that are von Willebrand's disease suspects. The test, based on venom coagglutinin-induced agglutination of formalin-fixed washed platelets, was compared to the more lengthy electroimmunoassay for factor VIII-related antigen. The 2 tests were performed on plasma samples from 82 dogs, including 68 Doberman pinschers. The 39 plasma samples that were found to be "clinically normal" by the new test had factor VIII-related antigen concentrations ranging from 32% to 192% of that in a pool of normal canine plasma samples. Plasma samples from the 43 dogs that tested as "potential bleeders" by the new test had factor VIII-related antigen concentrations from 4% to 38%. All 43 "potential bleeders" were Doberman pinschers. Shortly after being evaluated by the new test, 46 of the dogs underwent invasive diagnostic, therapeutic, or cosmetic procedures. Excessive hemorrhage was encountered in 40% of the 25 dogs that tested as "potential bleeders. " In contrast, only 5% of the 21 dogs that tested as "clinically normal" exhibited abnormal bleeding.     

COMPUTED TOMOGRAPHY IN THE EVALUATION OF CAUDAL CERVICAL SPONDYLOMYELOPATHY OF THE DOBERMAN PINSCHER

Caudal cervical spondylomyelopathy is a common neurologic disorder of Doberman pinschers which has a number of striking similarities to cervical spondylotic myelopathy in humans. Diagnosis of this human disease is facilitated considerably by the use of computed tomographic (CT) myelography. Sixteen Doberman pinscher dogs with caudal cervical spondylomyelopathy were studied by conventional myelography followed by CT myelography. A close correlation was noted between the CT myelographic appearance of the cervical spinal cord in these dogs, and that reported for human cervical spondylotic myelopathy. Five dogs had atrophy of the spinal cord, and in another there was an accumulation of contrast medium within the spinal cord. These features are often associated with a poor response to surgical decompression in humans with cervical spondylotic myelopathy. The CT examination provided information that could not be obtained by conventional myelography alone and should be considered as an additional diagnostic procedure in dogs with caudal cervical spondylomyelopathy.     

Von Willebrand's Disease in Two Families of Doberman Pinschers

The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical history as well as the necessity for specific laboratory assays of F VIII including von Willebrand factor activity for the recognition of affected and “carrier” animals.     

Copper Toxicosis in Bedlington Terriers

Copper toxicosis of Bedlington Terriers (Chronic progressive hepatitis) is a genetically transmitted disease. The typical feature of this disease is accumulation of copper in the liver tissue. The changes vary from mild hepatitis to chronic progressive hepatitis and cirrhosis.The material of this study consists of 2 cases of copper toxicosis examined at the Department of Pathology in Helsinki in the years 1980–82. Moreover a re-examination of tissue samples was made of all Bedlington Terriers examined during the years 1969–1982 at the same department. Six of the 14 examined dogs showed a positive reaction for copper in their liver tissues. The possible relationship of the examined dogs is not yet known.     

Influence of antiarrhythmia therapy on survival times of 19 clinically healthy Doberman pinschers with dilated cardiomyopathy that experienced syncope, ventricular tachycardia, and sudden death (1985-1998)

Overtly healthy Doberman pinschers, having moderate to severe myocardial failure secondary to dilated cardiomyopathy, which experienced ventricular tachycardia, syncope or collapse, and sudden death were studied to determine the effect of antiarrhythmic medication on their clinical outcome. Antiarrhythmia drug therapy may have retarded sudden death in 13 treated dogs compared to the six dogs not administered antiarrhythmia drugs.     

Inherited copper toxicosis in the Bedlington terrier: a report of two clinical cases

The clinical signs, laboratory findings and pathological changes are described in two cases of inherited copper toxicosis in the Bedlington terrier. The first case presented with acute signs of depression, vomiting, anorexia, weight loss and jaundice while the second case followed a more chronic course with less severe clinical signs which included weight loss and ascites. Both dogs had elevated circulating levels of alanine aminotransferase (ALT), however other haematological and biochemical parameters, while reflecting liver involvement, varied between the two cases. Chemical analysis of the liver revealed elevated copper levels in both cases (951·7 and 1093·4 μg/g wet weight respectively; normal less than 150 μg/g). These levels, however, are less than some affected but asymptomatic Bedlington terriers. Pathologically the first case had micronodular cirrhosis, while the second had focal hepatitis with fibrosis. Both dogs showed vacuolation of the white matter in the cerebrum, cerebellum, midbrain and medulla. Attention is drawn to the similarities and differences between copper toxicosis in the Bedlington terrier and Wilson's disease in man.     

Copper toxicosis in Bedlington Terriers in the United Kingdom

This paper summarizes the clinical and laboratory data on two adult Bedlington Terriers with liver disease associated with copper toxicosis. The younger dog, at 3 years, had elevated serum levels of alanine aminotransferase and alkaline phosphatase with active parenchymal cell degeneration and hepatitis. The second dog developed chronic hepatic failure at 5 years with advanced cirrhosis. Both dogs had stainable copper granules in the liver and chemical analysis of their livers revealed elevated copper contents (1,027 and 10,728 μg/g dry weight; normal less than 300 μg/g). These are the first published cases of this inherited abnormality of copper metabolism in this breed in this country.     

Comparison of the large muscle group widths of the pelvic limb in seven breeds of dogs

Orthopaedic diseases are common in the pelvic limbs of dogs, and reference values for large muscle groups of the pelvic limb may aid in diagnosis such diseases. As such, the objective of this study was to compare the large muscle groups of the pelvic limb in seven breeds of dogs. A total of 126 dogs from different breeds were included, and the widths of the quadriceps, hamstring and gastrocnemius muscles were measured from images of the lateral radiographies. The width of the quadriceps was not different between the breeds, but the widths of the hamstring and gastrocnemius muscles were significantly different between the breeds. The widest hamstring and gastrocnemius muscles were seen in the Rottweilers and the Boxers, respectively. The narrowest hamstring and gastrocnemius muscles were seen in the Belgian Malinois and the Golden retrievers, respectively. All ratios between the measured muscles differed significantly between the breeds. Doberman pinschers and Belgian Malinois had the highest ratio of gastrocnemius width:hamstring width. Doberman pinschers had also the highest ratio of quadriceps width:hamstring width. German shepherds had the highest ratio of gastrocnemius width:quadriceps width. The lowest ratios of quadriceps width:hamstring width were determined in the German shepherds. The ratios of the muscle widths may be used as reference values to assess muscular atrophy or hypertrophy in cases of bilateral or unilateral orthopaedic diseases of the pelvic limbs. Further studies are required to determine the widths and ratios of the large muscle groups of the pelvic limbs in other dog breeds.     

Use of zinc acetate to treat copper toxicosis in dogs.

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.     

Detection of Bartonella henselae and Bartonella clarridgeiae DNA in hepatic specimens from two dogs with hepatic disease

A 4-year-old Basset Hound and a 6-year-old Doberman Pinscher were referred for diagnostic evaluation following documentation of persistently increased hepatic enzyme activities and hepatic dysfunction. Histologic evaluation of hepatic biopsy specimens from the 2 dogs revealed granulomatous hepatitis in the Basset Hound and lymphocytic hepatitis with fibrosis and copper accumulation in the Doberman Pinscher. No etiologic agents were identified histologically. Bartonella henselae DNA was subsequently amplified from hepatic tissue from the Basset Hound and Bartonella clarridgeiae was amplified from hepatic tissue from the Doberman Pinscher. Amplification was performed with a polymerase chain reaction assay incorporating primers that target a portion of the 16S-23S rRNA intergenic spacer region. Both dogs were treated with azithromycin, in combination with a variety of other medications and herbal treatments, and improved clinically. Identification of Bartonella DNA in these dogs indicates the need for future prospective studies to determine the clinical relevance of Bartonella spp infection in dogs with hepatic disease.     

P‐39 Canine and feline vitiligo in São Paulo (Brazil): clinical and epidemiological features

Melanodermas and leukodermas are conditions involving skin pigment changes. Vitiligo, an acquired leukoderma, is an uncommon canine and feline skin disorder, with a likely autoimmune pathogenesis. It is seen more frequently in young adult purebred animals and has no apparent sex predisposition. In Brazil the first report of vitiligo was in 1986. In a 16‐year period, 12 cases of vitiligo, including 11 dogs (six Rottweilers, two Doberman pinschers, one great dane, one boxer, and one mongrel dog) and one cat (Siamese), were diagnosed at our hospital. Diagnosis was based on history, physical examination, Wood´s lamp examination, and histopathologic evaluation (H&E and Masson‐Fontana stains). Among the dogs, seven were male with a mean age of 34.5 months. The clinical evolution was known in five patients. Skin lesions included leukotrichia (100%) and leukoderma of the nose (100%), buccal mucosa (66.5%), lips (85.7%), and footpads (8.5%). Leukonychia was rarely seen. The only lesion in the cat was depigmented footpads. Funding: Self‐funded.