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.     

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.     

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.     

Development of a collagen-binding activity assay as a screening test for type II von Willebrand disease in dogs

OBJECTIVE: To develop an assay to measure canine von Willebrand factor (vWF):collagen-binding activity (CBA) to screen for type 2 von Willebrand disease (vWD) in dogs. SAMPLE POPULATION: 293 plasma samples submitted for analysis of canine vWF antigen (vWF:Ag) and 12 control plasma samples from dogs with inherited type 2 or 3 vWD. PROCEDURE: Bovine collagens were evaluated for suitability as binding substrate for vWF. Assay sensitivity to depletion, proteolytic degradation, or a genetic deficiency of high-molecular-weight vWF were determined. Amounts of vWF:Ag and vWF:CBA were measured. The ratio of vWF:Ag to vWF:CBA was used to discriminate between type 1 and type 2 vWD. RESULTS: An assay for canine vWF activity was developed by use of mixed collagen (types I and III). When vWF:Ag was used to subtype vWD, 48% of the dogs were classified as clinically normal, 9% as indeterminate, and 43% as type 1 vWD. Inclusion of vWF activity resulted in reclassification of 5% of those identified as type 1 to type 2 vWD. However, vWF:CBA of the reclassified dogs was not persistently abnormal, a finding compatible with acquired type 2 vWD. Some Doberman Pinschers had lower antigen-to-activity ratios than other breeds with type 1 vWD, suggesting that Doberman Pinschers have more functional circulating vWF. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of canine vWF activity should be included among the vWF-specific assays used to confirm type 2 vWD. The prevalence of inherited forms of type 2 vWD in screened dogs is lower than acquired forms that can result secondary to underlying disease.     

Hemorrhage from the cosmetic otoplasty of Doberman Pinschers with von Willebrand's disease

The hemorrhagic tendencies of 23 Doberman Pinscher pups were observed during cosmetic otoplasty and were ranked by a +1 to +4 grading system (+1 = least hemorrhage, and +4 = most hemorrhage). A second estimate of the hemostatic competencies of these dogs was made by counting the gauze sponges used in the otoplasties. Factor VIII-related antigen concentrations and coagglutinin cofactor concentrations were measured in plasma samples from blood drawn not more than 30 hours before the surgical procedures were done. The factor VIII-related antigen concentrations were between 9% and 147% of the concentration in a normal plasma pool, and the coagglutinin cofactor concentrations were between 1% and 165%, indicating that some of these dogs had von Willebrand's disease. The hemorrhagic tendencies of 12 pups were graded +1. This group had a mean antigen concentration of 75% (min-max, 38% to 147%) and a mean coagglutinin cofactor concentration of 89% (min-max, 42% to 165%). These were significantly greater than the antigen and cofactor concentrations of the grades +2 (n = 5), +3 (n = 3), or +4 (n = 3) dogs. Significant differences were not found when antigen concentrations of the grade +2 dogs (mean, 16%; min-max, 11% to 22%), grade +3 dogs (mean, 13%; 12% to 16%), and grade +4 dogs (mean, 11%; 9% to 12%) were compared with each other, nor were significant differences seen among the coagglutinin cofactor concentrations of the grade +2 dogs (mean, 7%; min-max, 1% to 11%), grade +3 dogs (mean, 6%, 4% to 8%), and grade +4 dogs (mean, 5%; 2% to 9%).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The effects of desmopressin on hemostatic parameters in the normal dog.

Seven normal unanesthetized dogs were infused with desmopressin in saline (doses 0.2, 0.4 and 0.6 micrograms/kg i.v.) or saline alone, on separate occasions in order to determine the effects of desmopressin on circulating factor VIII coagulant and factor VIII-related antigen activities, on partial thromboplastin times and prothrombin times, on blood platelet count and packed cell volume, and on serum osmolarity. Desmopressin caused a rapid dose-dependent elevation in both factor VIII activities peaking at 30-60 minutes postinfusion. At a dosage of 0.6 microgram/kg desmopressin induced rises in factor VIII coagulant activity and factor VIII-related antigen of 150% and 198% of the preinfusion levels respectively, while the half disappearance times were approximately five and six hours respectively. The other parameters were not significantly affected by even the highest dose of desmopressin used. These results indicate that normal dogs respond to desmopressin in a manner similar to man. The major differences are in the dosage required to produce comparable effects (higher in dogs), and in the fact that the factor VIII-related antigen activity consistently responds to a greater degree than the coagulant activity. It is concluded that desmopressin may have particular value in stimulating elevations in plasma factor VIII-related antigen in dogs deficient in this plasma protein. Six dogs were pretreated with the endorphin inhibitor, naloxone, (0.04 mg/kg I.V.) or sterile saline, three minutes prior to infusion with desmopressin at a dose of 0.6 microgram/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effect of Desmopressin Acetate on Bleeding Times and Plasma von Willebrand Factor in Doberman Pinscher Dogs with von Willebrand''s Disease

Effects of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) on plasma von Willebrand factor (vWf) were studied in 12 purebred Doberman pinschers confirmed to have von Willebrand's disease (vWd) (plasma vWf antigen [vWf:Ag] concentrations, less than 30 U/dl). Twelve dogs had subnormal plasma botrocetin cofactor (BCf) activity and 11 dogs had prolonged buccal mucosa bleeding times. Tranquilization of three dogs with lenperone and three dogs with xylazine did not induce significant changes in mean plasma vWf:Ag concentrations or mean BCf activities. Thirty and 120 minutes after administration of DDAVP (1 micrograms/kg subcutaneously), there was significant shortening of the mean buccal mucosa bleeding time. Ten dogs responded to DDAVP with increases in BCf activity which exceeded 10 U/dl at 30 or 120 minutes, or both, after the drug was administered. At the same time, increases in plasma vWf:Ag concentrations were smaller than the increases in BCf activity. It was shown by multimeric analysis that primarily the higher molecular weight forms of vWf increased in plasma in response to DDAVP.     

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.     

Chronic hepatitis in Doberman pinschers. A review

Summary

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.     

von Willebrand heterotopic osteochondrofibrosis in Doberman pinschers: five cases (1980-1987)

Five cases involving female Doberman Pinschers, each with a mass composed of osseous, chondrous, or fibrous tissue, or a combination thereof, formed in or around the muscles of the hip, were reviewed. In each dog, the mass severely limited the coxofemoral joint range or motion, especially when the joint was extended. Surgical debulking resulted in a favorable outcome. All dogs tested had plasma concentrations of von Willebrand factor antigen below established normal limits. We believe that the low concentrations of von Willebrand factor antigen commonly found in Doberman Pinschers may predispose them to the development of this condition and its resulting pelvic limb lameness, presumably because of increased risk of microvascular bleeding. This association is presumptive because 2 dogs in our study had a history of excessive bleeding either before or after being treated for the hip condition. Trauma was associated in 2 cases. All 5 dogs, however, bled more than usual during the curative surgery. These 5 cases, plus additional reported cases, confirm this syndrome, which warrants recognition. The name von Willebrand heterotopic osteochondrofibrosis of Doberman Pinschers was selected because it identified the basic features of the syndrome.     

Heart rate variability in the dog: is it too variable?

The purpose of the study was to evaluate resting heart rate variability (HRV) as a simple noninvasive screening test for early autonomic derangement, heralding the development of occult dilated cardiomyopathy (DCM). Time and frequency domain HRV parameters were evaluated in 32 healthy Doberman pinschers, as potential predictors of the development of occult DCM within the following year and correlated with plasma catecholamines, markers of sympathoexcitation. Ten Dobermans with occult DCM and 8 Dobermans with congestive heart failure (CHF) were positive controls. Seven of the 32 "healthy" dogs developed occult DCM over the course of the study. None of the HRV parameters were associated with the development of occcult DCM based on univariate logistic regression. In dogs who developed occult DCM, plasma norepinephrine (NE) was inversely correlated with % fractal power (r = -0.81, P = 0.05). In dogs with occult DCM (positive controls), plasma NE was inversely correlated with fractal power (r = -0.81, r = 0.03), total power (r = -0.08, P = 0.03), high frequency power (r = -0.75, P = 0.05) and the standard deviation of the RR (r = -0.83, P = 0.02). The great inherent variability of the test may have limited our ability to discriminate between physiologic and pathophysiologic data, rendering this methodology inadequate as a screening test for early occult DCM. However, the negative correlations of NE with various forms of spectral power in dogs with occult DCM suggests that early in the natural history of DCM, there is parasympathetic withdrawal. A reduction in the nonharmonic, fractal component may be the first recognizable abnormality in the power spectrum of dogs who will develop DCM.     

Determination of Canine Factor VIII-related Antigen Using Commercial Antihuman F VIII Serum

Factor VIII-related antigen (F VIII:AGN) in 21 canine plasma samples was assayed by immunoelectrophoresis using a rabbit anticanine F VIII serum prepared from a canine F VIII concentrate and a commercial rabbit antihuman F VIII serum. A good correlation existed (r value 0.916) between the antigen levels obtained using the two sera. In normal dogs the plasma F VIII:AGN level was 95 +/- 39% (Mean +/- SD) compared to 175 +/- 40% in dogs with severe hemophilia A and 17 +/- 15% in dogs with von Willebrand's disease. It was concluded that there was sufficient cross reactivity between canine F VIII and commercial rabbit antihuman F VIII serum to make the latter useful in the differential diagnosis of F VIII deficiencies in the dog.     

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.     

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.     

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.     

Immediate intradermal flea antigen reactivity in clinically normal adult dogs from south Florida, USA

Eighty-six clinically normal adult dogs from southern Florida, USA, with no history of dermatitis, were intradermally skin tested with Greer flea antigen 1:1000 w/v to determine the prevalence of positive immediate intradermal reactivity. This study describes the test group of animals and reports the prevalence of sensitivity to the Greer whole-body flea antigen in normal dogs living in a flea-rich environment. Similar to previous research, the highest prevalence of reactivity to flea antigen occurred at 3–4 years of age. The results indicate that 24% of clinically normal dogs from a flea-rich environment exhibited positive immediate skin test reactivity. These dogs had no clinical signs of flea allergic dermatitis (FAD) in spite of ongoing flea exposure. A 2-year follow-up telephone call to the owners of these flea antigen intradermal skin test (IDST)-positive dogs indicated that only two of 21 dogs had developed clinical signs of FAD.     

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.     

Haemophilia A in German shepherd dogs

Haemophilia A was diagnosed in 14 male German shepherd dogs. Factor VIII: coagulant (FVIII:C) activities ranged from 1.13% of a normal canine plasma pool. von Willebrand's factor antigen values were normal or increased in all 9 of these dogs which were tested. Twelve of these dogs had a common maternal grandsire. Five dogs had exhibited no tendency to bleed (when tested between 2 to 23 months of age). They were tested because of pedigree links with clinically affected animals. Common clinical signs in the latter dogs included: bleeding from the mouth, subcutaneous and intramuscular haematomas and lameness. Since these dogs usually had a mild to moderate deficiency of FVIII:C, they may survive to adulthood without exhibiting clinical signs severe enough to necessitate veterinary attention.