Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie

An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog.     

Infective endocarditis of the aortic valve in a Border collie dog with patent ductus arteriosus

Infective endocarditis (IE) in dogs with cardiac shunts has not been reported previously. However, we encountered a dog with concurrent patent ductus arteriosus (PDA) and IE. The dog was a 1-year-old, 13.9-kg female Border collie and presented with anorexia, weight loss, pyrexia (40.4°C) and lameness. A continuous murmur with maximal intensity over the left heart base (Levine 5/6) was detected on auscultation. Echocardiography revealed a PDA and severe aortic stenosis (AS) caused by aortic-valve vegetative lesions. Corynebacterium spp. and Bacillus subtilis were isolated from blood cultures. The dog responded to aggressive antibiotic therapy, and the PDA was subsequently surgically corrected. After a series of treatments, the dog showed long-term improvement in clinical status.     

Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings

Trapped neutrophil syndrome (TNS) is an autosomal recessive inherited neutropenia known in Border Collies since the 1990's. Recently, the causative mutation has been identified in the canine VPS13B gene and a DNA-based diagnosis has now become available. The present paper describes clinical and clinico-pathologic findings in a Border Collie with TNS that was molecularly diagnosed for the first time in Japan. In a 10-week-old male Border Collie with microgenesis and symptoms related to recurrent infections, a hematological examination revealed severe leukopenia due to neutropenia, suggesting the dog to be affected by inherited neutropenic immunodeficiency. Direct DNA sequencing demonstrated that the dog was homozygous for the causative mutation of TNS and both its parents were heterozygous carriers. In addition, a simple and rapid polymerase chain reaction-based length polymorphism analysis coupled with microchip electrophoresis was developed for the genotyping of TNS. This assay could discriminate clearly all genotypes, suggesting that it was suitable for both individual diagnosis and large-scale surveys for prevention.     

Real-time PCR genotyping assay for canine trapped neutrophil syndrome and high frequency of the mutant allele in Border collies

Trapped neutrophil syndrome is an autosomal recessive inherited neutropenia in Border collies. The causative mutation is a 4 base pair deletion in exon 19 of the canine VPS13B gene. In this study, a real-time PCR assay was developed and a genotyping survey was carried out in Border collies in Japan. The carrier frequency was 11.1%, suggesting that the mutant allele frequency is high enough to warrant measures to control and prevent the disease.     

Plasma granulocyte colony-stimulating factor concentrations in neutropenic, parvoviral enteritis-infected puppies

We evaluated the temporal relationship between neutrophil numbers and plasma granulocyte colony-stimulating factor (G-CSF) concentrations in dogs infected with canine parvovirus, a common infectious cause of neutropenia. G-CSF is produced in response to neutropenia, infection, or inflammation, and results in the production and release of neutrophils from the bone marrow. Adequate numbers of functional neutrophils are necessary for protection from infection, and the timely production of G-CSF is a crucial response to certain diseases. The relationship between peripheral neutrophil numbers and plasma G-CSF concentrations during the course of an infectious disease characterized by neutropenia has not been described previously in dogs. Eight mixed-breed puppies were given an oronasal challenge with canine parvovirus, and peripheral neutrophil numbers as well as plasma G-CSF concentrations were measured daily. G-CSF was not detectable in plasma of any dog before the onset of neutropenia, but G-CSF became detectable just after the onset of neutropenia in the 7 dogs that developed clinical illness. Neutropenia persisted or worsened for at least 2 days after plasma G-CSF became detectable in all 7 dogs. Neutrophil nadir, the highest plasma G-CSF concentrations, and the most severe clinical illness occurred concurrently in most dogs. Although 1 dog died while still neutropenic, plasma G-CSF concentrations declined before resolution of neutropenia in the other 6 dogs, and were again below the limits of detection in 5 of the 6 dogs at the time of resolution.     

Evaluation of clinicopathologic features, response to treatment, and risk factors associated with idiopathic neutropenia in dogs: 11 cases (1990-2002)

OBJECTIVE: To evaluate the clinicopathologic features, response to treatment, and risk factors associated with idiopathic neutropenia in dogs. DESIGN: Retrospective case series. ANIMALS: 11 dogs. PROCEDURES: Medical records of dogs with idiopathic neutropenia were reviewed. Signalment, history, clinical signs, and response to treatment were recorded and compared with that in dogs with neutropenia attributable to known causes and to dogs without neutropenia (controls). RESULTS: Compared with dogs with neutropenia attributable to known causes, dogs with idiopathic neutropenia had lower neutrophil counts and were younger. When compared with control dogs, age < 4 years was identified as a risk factor for developing idiopathic neutropenia. In all dogs with idiopathic neutropenia, remission of neutropenia occurred within 18 days after administration of prednisone (2 to 4 mg/kg [0.9 to 1.8 mg/lb], PO, daily) and no serious complications or infections developed. CONCLUSIONS AND CLINICAL RELEVANCE: An immune-mediated pathogenesis should be considered for dogs with idiopathic neutropenia in which the cause is not known. Severe neutropenia and young age were significantly associated with idiopathic neutropenia in dogs. Prognosis appeared to be excellent with prednisone treatment.     

Centronuclear myopathy in a Border collie dog

A two‐year old, male entire Border collie was presented with a one‐year history of exercise‐induced collapsing on the pelvic limbs. Physical examination revealed generalised muscle atrophy. Neurological examination supported a generalised neuromuscular disorder. Electromyography revealed spontaneous electrical activity in almost all muscles. Unfixed and formaldehyde‐fixed biopsy samples were collected from the triceps brachii, longissimus and vastus lateralis muscles. Histopathological, histochemical and ultrastructural examinations of biopsy specimens were consistent with either centronuclear or myotubular myopathy. The dog clinically improved with supportive treatment with L‐carnitine, co‐enzyme Q10 and vitamin B compound. To the authors’ knowledge, this is the first report of centronuclear/myotubular myopathy in a Border collie.     

Evaluation of a point-of-care hematology analyzer for use in dogs and cats receiving chemotherapeutic treatment

OBJECTIVE: To compare WBC, neutrophil, and platelet counts and Hct values obtained with a point-of-care hematology analyzer with values obtained by a reference method for dogs and cats receiving chemotherapy. DESIGN: Cross-sectional study. ANIMALS:105 dogs and 25 cats undergoing chemotherapy. PROCEDURES:Blood samples were analyzed with a point-of-care hematology analyzer and with an impedance- and laser-based analyzer with manual differential WBC counts. Results for WBC, neutrophil, and platelet counts and Hct were compared. Sensitivity and specificity of the point-of-care analyzer to detect leukopenia, neutropenia, and anemia were calculated. RESULTS: 554 canine and 96 feline blood samples were evaluated. Correlation coefficients for dogs and cats, respectively, were 0.92 and 0.95 for total WBC count, 0.91 and 0.88 for neutrophil count, 0.95 and 0.92 for Hct, and 0.93 and 0.71 for platelet count. Sensitivity and specificity, respectively, of the point-of-care analyzer to detect leukopenia were 100% and 75% for dogs and 100% and 68% for cats; to detect neutropenia were 80% and 97% for dogs and 100% and 80% for cats; to detect anemia were 100% and 80% for dogs and 100% and 66% for cats; and to detect thrombocytopenia were 86% and 95% for dogs and 50% and 87% for cats. CONCLUSIONS AND CLINICAL RELEVANCE:The point-of-care analyzer was reliable for monitoring CBCs of dogs and cats receiving chemotherapy. It had good to excellent correlation for WBC and neutrophil counts and Hct and accurately detected leukopenia, neutropenia, and anemia. Sensitivity of the analyzer for detecting thrombocytopenia was lower but acceptable.     

Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor

Duffy A., Dow S., Ogilvie G., Rao S., Hackett T. Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01153.x. Previously, dogs with canine parvovirus‐induced neutropenia have not responded to treatment with recombinant human granulocyte‐colony stimulating factor (rhG‐CSF). However, recombinant canine G‐CSF (rcG‐CSF) has not been previously evaluated for treatment of parvovirus‐induced neutropenia in dogs. We assessed the effectiveness of rcG‐CSF in dogs with parvovirus‐induced neutropenia with a prospective, open‐label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG‐CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG‐CSF. We found that mean WBC and neutrophil counts were significantly higher (P < 0.05) in the 28 dogs treated with rcG‐CSF compared to disease‐matched dogs not treated with rcG‐CSF. In addition, the mean duration of hospitalization was reduced (P = 0.01) in rcG‐CSF treated dogs compared to untreated dogs. However, survival times were decreased in dogs treated with rcG‐CSF compared to untreated dogs. These results suggest that treatment with rcG‐CSF was effective in stimulating neutrophil recovery and shortening the duration of hospitalization in dogs with parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.     

Evaluation of antineutrophil IgG antibodies in persistently neutropenic dogs

BACKGROUND: Immune-mediated neutropenia (IMN) is one of several causes of persistent neutropenia in dogs. A test to detect IMN in dogs is not available. HYPOTHESIS: A flow cytometric immunofluorescence assay will provide a sensitive method for detection of antineutrophil antibodies in dogs. ANIMALS: The study included 12 neutropenic dogs and 20 healthy dogs. METHODS: An indirect immunofluorescence assay was used to detect immunoglobulin G (IgG) binding to dog neutrophils. Leukoagglutination was evaluated by light microscopy. Neutrophil distribution in scatter plots, neutrophil fluorescence intensity, and the percentage of neutrophils with increased fluorescence intensity was evaluated by use of flow cytometry. RESULTS: Antineutrophil antibodies were detected in the serum of 5 of 6 dogs with a clinical diagnosis of IMN. Leukoagglutination was present in 3 dogs. Four dogs had altered neutrophil distribution in forward-angle versus side-angle light scatter plots. Five of 6 dogs had increased neutrophil fluorescence intensity and 4 of 6 dogs had an increased percentage of neutrophils with increased fluorescence intensity. CONCLUSIONS AND CLINICAL IMPORTANCE: The flow cytometric test for antineutrophil antibodies detects dogs with a clinical diagnosis of IMN. Testing for antineutrophil antibodies should include observation for leukoagglutination, observation of scatter plots for altered distribution of the neutrophil population, observation of the shape of the fluorescence histogram, determination of neutrophil fluorescence intensity, and determination of the percentage of neutrophils with increased fluorescence intensity.     

Analysis of uroliths from cats and dogs in New Zealand, 1993-96

AIMS: Canine and feline uroliths were analysed to determine the prevalence of particular types of urolith and the dog breeds at risk. METHODS: Three hundred and sixty-nine uroliths recovered from 316 dogs and 53 cats between November 1993 and December 1996 were analysed by X-ray diffraction, and by infrared spectrometry where X-ray diffraction alone was non-diagnostic. RESULTS: Bitches of small breeds especially Welsh corgi and Bichon frise, were most frequently affected. Struvite was the most common urolith (204 dogs). Oxalate (60 dogs) was the second most prevalent urolith identified, followed by cystine (24 dogs). The breeds producing cystine calculi were: Dalmatian, Bassett hound, Borzoi, Newfoundland, Shetland sheepdog, Labrador, Chihuahua, Fox terrier, English bulldog, Bichon frise, Doberman pinscher, Border collie. Silica uroliths were identified for the first time in New Zealand. All feline uroliths were struvite. CONCLUSION: The results are useful in determining the prevalence of specific types of urolith in New Zealand and the breeds at risk of forming them.     

Neutropenia in cats with the Chediak-Higashi syndrome.

Thirteen cats with Chediak-Higashi syndrome and 22 control cats from the same colony, were evaluated for neutropenia. The absolute neutrophil counts of the Chediak-Higashi syndrome cats were significantly less (P less than 0.05) than those of the control cats. It is concluded that Chediak-Higashi syndrome cats, like Chediak-Higashi syndrome humans, have a neutropenia associated with the other manifestations of the syndrome. Lysozyme activity which was undetectable in the serum of both Chediak-Higashi syndrome and control cats was not of use for determining if the neutropenia was the result of neutrophil destruction.     

Evaluation of a manual technique for detection of neutropenia and thrombocytopenia in dogs receiving chemotherapy

OBJECTIVE: To determine accuracy of a manual technique for detection of neutropenia and thrombocytopenia in dogs receiving chemotherapy. DESIGN: Masked prospective study. ANIMALS: 11 dogs treated with chemotherapy for neoplasia. PROCEDURE: 124 blood samples from dogs being treated with chemotherapy for various neoplasms were processed through an automated cell counter, and results were compared with those obtained by use of a rapid manual technique for estimating neutrophil and platelet concentrations to determine whether the manual technique could accurately detect dogs with neutropenia or thrombocytopenia. RESULTS: By use of automated techniques, neutropenia (< 3,000 cells/microl) was detected in 17 of 124 blood samples, and thrombocytopenia (< 100,000 platelets/microl) was detected in 3 of 124 blood samples. The manual technique correctly identified 16 of 17 (94%) blood samples with neutropenia, with a specificity of 92% (98/107). The manual technique correctly identified 3 of 3 (100%) blood samples with thrombocytopenia, with specificity of 94% (114/121). CONCLUSIONS AND CLINICAL RELEVANCE: Manual estimates of neutrophil and platelet counts are sensitive and specific; however, a full differential cell count is still preferable.     

Specific heart muscle disease secondary to lymphosarcoma in a dog

This case report describes the clinical, imaging, clinical pathology and necropsy findings in a five-year-old male Border collie with low output cardiac failure. The heart was enlarged by infiltrative lymphosarcoma.     

Surgical Treatment of a Canine Intranasal Meningoencephalocele

Objective— To report the clinical signs, diagnosis, and surgical treatment of an intranasal meningoencephalocele in a dog.
Study Design— Case report.
Animal— Female Border collie, 5 months old.
Methods— A right intranasal meningoencephalocele was identified by computed tomography and magnetic resonance imaging.
Results— The lesion was approached by a modified transfrontal craniotomy. Surgical closure of the defect at the level of the cribriform plate and removal of extruded brain tissue resulted in regression of lacrimation and coincided with absence of seizuring. Treatment with phenobarbital was gradually reduced and stopped at 7 months after surgery. At 28 months the dog remained free of seizures.
Conclusion— Meningoencephalocele, although rare, can cause seizures in dogs and can be treated surgically.
Clinical Relevance— A transfrontal craniotomy with excision of the meningoencephalocele and closure of the defect can be an effective treatment for an intranasal meningoencephalocele in dogs.     

Ulcerative dermatosis of the Shetland sheepdog and rough collie dog may represent a novel vesicular variant of cutaneous lupus erythematosus

A syndrome of ulcerative dermatitis (UDSSC) previously has been described as unique to the Shetland sheepdog and rough collie dog. The pathogenesis of this disease is poorly understood and it has been suggested that it may be a variant of canine dermatomyositis (DM) which is also seen in these breeds. Information on the clinical presentation and previous medical history was collected from five Shetland sheepdogs and three rough collie dogs previously diagnosed with UDSSC. Characteristic features of the disease were adult onset in the summer months with annular, polycyclic and serpiginous ulcerations distributed over sparsely haired areas of the body. Skin biopsies taken from active lesions were compared in a blinded fashion with histological sections from seven Shetland sheepdogs and one rough collie with DM. Dermatomyositis was characterized histologically as a cell poor interface dermatitis associated with follicular atrophy. In contrast, the lesional pattern of UDSSC is that of a lymphocyte-rich interface dermatitis and folliculitis with vesiculation at the dermal–epidermal junction. The authors conclude that these represent two distinct diseases and that UDSSC may be a vesicular form of cutaneous lupus erythematosus seen in the adult rough collie dog and Shetland sheepdog.     

Neutropenia associated with vincristine and L-asparaginase induction chemotherapy for canine lymphoma

Vincristine (VCR) and L-asparaginase (L-ASP) are commonly used to treat canine lymphoma. As single agents, these drugs are not myelosuppressive. However, in combination, VCR and L-ASP cause severe neutropenia in some dogs. It has been recommended that L-ASP be administered 12-24 hours after VCR to minimize toxicity. The purpose of this retrospective study was to determine the prevalence of neutropenia after VCR/L-ASP induction therapy for canine lymphoma and to evaluate risk factors for myelosuppression, especially the interval between VCR and L-ASP administration. Medical records of 147 dogs were reviewed. L-ASP was given 0 (n = 50), 6 (n = 23), 18 (n = 20), or 24 (n = 54) hours after VCR. Forty percent of the dogs were neutropenic 7 days after VCR/L-ASP, and 18% had neutrophil counts of <1,000 cells/microL. The median neutrophil count was 3,712 cells/microL (range 0-30,968 cells/microL). No correlation was found between administration interval and day 7 neutrophil count (P = .84) or development of gastrointestinal signs, including vomiting (P = .80), diarrhea (P = .52), and decreased appetite (P = .30). No significant predictors of neutropenia were identified. Higher clinical stage and substage b were associated with decreased appetite after treatment (P = .04 and .01, respectively). Sixteen percent of the dogs were hospitalized. This study demonstrates that VCR/L-ASP induction for canine lymphoma may result in neutropenia but that separation of VCR and L-ASP administration may not be necessary to avoid toxicity.     

Luxation of the radial carpal bone in four dogs

Four cases of radial carpal bone luxation in dogs seen at Glasgow University Veterinary School in a period of six years are described. Three were border collie types. Two of these were working sheepdogs and the third was an agility triallist. The fourth was a rough collie. All were adult, two were male and two were female. Three cases were of short duration and were managed by open reduction of the luxation and surgical stabilisation of the radial carpal bone. The other was of longer duration and was treated by pancarpal arthrodesis. In all cases the carpus was supported externally for one to two months following surgery. At the time of writing, the progress of only the three working dogs was known. Despite the presence of osteoarthritic changes in the carpi of these dogs, they all became sound and returned to work. A mechanism for the injury based upon the results of cadaver studies is proposed.     

Use of Recombinant Canine Granulocyte Colony-Stimulating Factor to Decrease Myelosuppression Associated with the Administration of Mitoxantrone in the Dog

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.     

An indirect flow cytometric test for detection of anti-neutrophil antibodies in dogs

OBJECTIVE: To develop a clinically applicable assay for detection of serum anti-neutrophil antibodies in dogs. SAMPLE POPULATION: Serum samples of 20 healthy dogs and 20 sick dogs. PROCEDURES: An indirect immunofluorescence assay was developed in which canine serum was incubated with paraformaldehyde-fixed neutrophils and subsequently incubated with fluorescein-conjugated rabbit anti-dog IgG. Neutrophil median fluorescence intensity and the percentage of neutrophils with an increase in fluorescence intensity were determined by use of a flow cytometer. RESULTS: Neutrophils incubated with serum from healthy and sick dogs had a normally distributed curve when displayed as a histogram. Alloantibodies or immune complexes that significantly affected test results were not detected. Hyperglobulinemia did not appear to affect test results. The neutrophil donor did not significantly affect test results. With 1 exception, results for the sick dogs did not differ appreciably from those for healthy dogs. Serum from a dog with steroid-responsive neutropenia had a greater neutrophil fluorescence value and percentage of neutrophils with an increase in fluorescence intensity, compared with either healthy or sick dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The indirect immunofluorescence test gave consistent results for healthy and sick dogs and detected anti-neutrophil antibodies in a dog with steroid-responsive neutropenia. Definitive evaluation of the test will be dependent on evaluation of persistently neutropenic dogs and correlation of test results with a response to immunosuppressive therapy.