X-linked myotubular myopathy associated with an MTM1 variant in a Maine coon cat.

OBJECTIVE: Describe the clinical course and diagnostic and genetic findings in a cat with X-linked myotubular myopathy. CASE SUMMARY: A 7-month-old male Maine coon was evaluated for progressively worsening gait abnormalities and generalized weakness. Neurolocalization was to the neuromuscular system. Genetic testing for spinal muscular atrophy (LIX1) was negative. Given the progressive nature and suspected poor long-term prognosis, the owners elected euthanasia. Histopathology of skeletal muscle obtained post-mortem disclosed numerous rounded atrophic or hypotrophic fibers with internal nuclei or central basophilic staining. Using oxidative reactions mediated by cytochrome C oxidase and succinic dehydrogenase, scattered myofibers were observed to have central dark staining structures and a "ring-like" appearance. Given the cat's age and clinical history, a congenital myopathy was considered most likely, with the central nuclei and "ring-like" changes consistent with either centronuclear or myotubular myopathy. Whole genome sequencing identified an underlying missense variant in myotubularin 1 (MTM1), a known candidate gene for X-linked myotubular myopathy. NEW OR UNIQUE INFORMATION PROVIDED: This case is the first report of X-linked myotubular myopathy in a cat with an MTM1 missense mutation. Maine coon cat breeders may consider screening for this variant to prevent production of affected cats and to eradicate the variant from the breeding population.

Evidence for the Continued Occurrence of Chorioretinopathy in Working Sheep Dogs in New Zealand in 2010.

A study in conducted 1987 by Hughes et al., found that 39% of working sheep dogs had multifocal retinitis. One of the identified causes was ocular larval migrans, which were a result of migrating ascarid larvae. Since that paper was published, anthelmintic use in farm dogs has been highly recommended. There has been no follow-up study to determine if fundic lesions are still present. The current study aimed to investigate the prevalence of chorioretinopathy in working sheep dogs in the South-West, Waikato, New Zealand. This was a cross-sectional study of 184 working sheep dogs and 51 owners, undertaken in 2010 with owners sampled from New Zealand's South-West Waikato and Tux North Island Dog Trial Championship. Two-way tables were used to explore the relationship between variables. Significance of association was assessed using a Chi-squared or Fisher exact test as appropriate, with a p-value of <0.05 considered significant. Overall prevalence of chorioretinopathy in the working sheep dogs was 44/184 (24%). A significantly higher prevalence of chorioretinopathy was shown in dogs with increasing age, from 2 years to >8 years (p = 0.0007) and in males (p < 0.0001). This study concluded that lesions of chorioretinopathy are still present in working sheep dogs in New Zealand.

Parasitic Nematode and Protozoa Status of Working Sheepdogs on the North Island of New Zealand.

Working farm dogs in New Zealand may have a high parasitic challenge because of access to raw meat and close contact with other dogs. This cross-sectional study aimed to estimate the percentage of dogs with gastrointestinal nematode and protozoan parasite lifecycle stages present in their feces and to identify factors associated with the presence of parasites. A single researcher collected information about the dogs and their management via a questionnaire, body condition scored (BCS) the dogs, and collected fecal samples to determine the parasite burden. Fecal samples were collected from 171 dogs and 40% (95% CI 33.0% to 47.7%) contained parasite ova or (oo)cysts. There was no association between BCS and the presence of nematodes and parasites (p = 0.74) in the feces. The percentage of dogs with parasites present in their feces was not associated with BCS or the frequency with which anthelmintic drugs were reportedly administered (p = 0.61). The high percentage of dogs with parasites are of concern for the health of the dogs and their owners, given the zoonotic potential of some parasites. Further, research should also focus on understanding why reporting giving anthelmintic drugs at least every three months did not eliminate the infection.

Medium-Term Outcome and CT Assessment of Lateral Foraminotomy at the Lumbosacral Junction in Dogs with Degenerative Lumbosacral Stenosis.

OBJECTIVE: This article aims to report the medium-term clinical outcome and assess persistence of enlargement of the lumbosacral lateral intervertebral neurovascular foramen using computed tomography (CT) volumetric analysis in dogs following lateral foraminotomy. MATERIALS: Six dogs that underwent lumbosacral lateral foraminotomy on one or both sides were evaluated with CT prior to, immediately postoperatively (n = 2) and at 12 to 44 months of follow-up. Five out of six dogs had successful clinical outcomes with alleviation of pain and increased levels of activity, according to subjective assessment. Immediate postoperative CT volumetric analysis of the lateral intervertebral neurovascular foramina in two dogs indicated a 650 to 800% increase in volume in extension achieved by foraminotomy (four foramens). At subsequent follow-up, bone regrowth had occurred with reduction in foraminal volume, though in both dogs foraminal volume remained higher than preoperative values. Follow-up CT at a median of 24 months postoperatively indicated a mean 335% increase in volume of the lumbosacral lateral intervertebral neurovascular foramina in extension compared with the preoperative foraminal volume. The follow-up volume was substantially greater than the presurgical volume in four out of six dogs. CLINICAL SIGNIFICANCE: In this limited case series, lateral foraminotomy achieved persistent enlargement of the lumbosacral lateral intervertebral neurovascular foramen in the medium term, but osseous regrowth at the site was demonstrated which may limit the effectiveness of lateral foraminotomy in the longer term. One of two working dogs had recurrent clinical signs that necessitated further surgery.

Effect of dorsal laminectomy and dorsal annulectomy with partial lumbosacral discectomy on the volume of the lateral intervertebral neuroforamina in dogs when the lumbosacral junction is extended.

OBJECTIVE: To determine the effect of dorsal annulectomy and partial discectomy on the volume of the lumbosacral lateral intervertebral neurovascular foramina (intervertebral foramina) in canine cadavers during extension of the lumbosacral junction. STUDY DESIGN: Ex vivo experiment. SAMPLE POPULATION: Lumbosacral specimens from 10 large breed dogs euthanatized for reasons unrelated to lumbosacral disease. METHODS: The lumbosacral specimens were clamped in a wooden jig and scanned using computed tomography (CT) with the lumbosacral junction in a neutral position and loaded in extension using a tensioning device. The 3-dimensional volumes of the lumbosacral intervertebral neurovascular foramina were measured and the extent of any disc degeneration was determined from the CT data. A limited dorsal laminectomy of S1 and a dorsal LS annulectomy and partial discectomy were then performed. The lumbosacral specimens were remounted into the jig and loaded into extension at the same tension and were re-scanned. Measurements of intervertebral foraminal volume were then repeated. RESULTS: The mean volume of the lumbosacral foramina (n = 20) was 381 mm3 in neutral (unloaded) positioning and 137 mm3 when loaded in extension. Following dorsal annulectomy, the mean volume was significantly reduced by a mean of 28% to 98 mm3 (P < .01). The foraminal volume was reduced in 19/20 lumbosacral foramen, with the post-annulectomy volume ranging from 31% to 97% of the pre-annulectomy volume (3%-69% reduction). CONCLUSIONS: This study suggests that a dorsal annulectomy with partial discectomy may induce further dynamic collapse of the lumbosacral articulation in the dog.

Computed tomographic evaluation of dynamic alteration of the canine lumbosacral intervertebral neurovascular foramina.

OBJECTIVE: To develop a computed tomographic (CT) method to measure the volume of the lumbosacral intervertebral neurovascular foramina (IVF) in dogs, and determine the effect of the range of motion of the lumbosacral (LS) junction on this measurement in German shepherd dogs (GSDs) with degenerative lumbosacral stenosis (DLSS) compared to unaffected controls. STUDY DESIGN: In vivo analysis and retrospective case series. SAMPLE POPULATION: Twenty-four working Police GSDs, 12 diagnosed with DLSS and 12 unaffected by DLSS were compared to 10 Greyhounds without DLSS. METHODS: Three-dimensional renderings of CT data were used to measure the lumbosacral foraminal volume of dogs positioned in dorsal recumbency with the LS junction alternately positioned in extension, neutral position, and flexion. RESULTS: Volumetric analysis of the IVF was found repeatable for the extended and neutral positions (interclass correlation coefficient of 0.89 and 0.8, respectively). The mean lumbosacral IVF volume was decreased by 74% between LS flexion and extension in Greyhounds, compared to 79 and 85% reductions in GSDs unaffected and affected by DLSS, respectively. The lumbosacral IVF volume was decreased by 23% when comparing extended to neutral LS positions in Greyhounds, 29% in unaffected GSDs, and 31% in affected GSDs. IVF volumes were smaller in affected GSDs compared to unaffected GSDs (P < .05) and Greyhounds (P < .01). CONCLUSIONS: Positioning the LS junction in full extension decreases the volume of the lumbosacral IVF. This dynamic narrowing was more pronounced in GSDs with signs of DLSS than in GSDs not overtly affected by DLSS.

Trans-pinnal movement of methimazole: an in vitro study showing that methimazole can cross from the inner to outer pinna of cats.

OBJECTIVES: The aim of the study was to determine if methimazole applied in a transdermal formulation to the internal pinna will cross to the external pinna in an in vitro Franz cell model. METHODS: The ears from six cats were harvested soon after death. Whole ears were mounted onto Franz-type diffusion cells with the stratum corneum of the inner pinnae uppermost. A commercial transdermal preparation containing methimazole (0.1 ml/10 mg) was applied to the inner pinnae. At 1, 2, 4, 6, 8, 12, 18, 24 and 30 h, a 200 µl sample of reservoir solution was removed to determine the methimazole concentration by high-performance liquid chromatography. The ears were then dissected, separating the internal pinna from the cartilage and the external pinna, before the methimazole concentration was measured at each site. The thickness of the different regions of the ear was measured on paraffin histology sections. RESULTS: Mean ± SD methimazole concentrations at 30 h for the right and left ear, respectively, were: inner ear, 1.25 ± 0.53 mg/g, 0.39 ± 0.26 mg/g; cartilage, 1.36 ± 0.47 mg/g, 0.33 ± 0.20 mg/g; and outer ear, 1.0 ± 0.32 mg/g, 0.33 ± 0.14 mg/g. There was a difference between the left and right ears (P <0.001). Minimal methimazole concentrations were detected in the receptor fluid. The mean methimazole concentration absorbed by the skin after application of 10 mg was, for the right ear, 3.65 ± 1.27 mg/g and, for the left, 1.08 ± 0.27 mg/g. There was no correlation between methimazole concentrations and thickness of each region of the ear. CONCLUSIONS AND RELEVANCE: Methimazole in a lipophilic vehicle applied to the inner pinna will penetrate to the outer pinna of cats in an in vitro model, which may have safety implications for humans associated with cats treated with transdermal methimazole. Substantial inter-individual variation was found. Further research is required in the area of transdermal penetration of drugs in cats.

A novel mutation in CLCN1 associated with feline myotonia congenita.

Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1:100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a 'swarm of bees'. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine ß-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.

First WNK4-hypokalemia animal model identified by genome-wide association in Burmese cats.

Burmese is an old and popular cat breed, however, several health concerns, such as hypokalemia and a craniofacial defect, are prevalent, endangering the general health of the breed. Hypokalemia, a subnormal serum potassium ion concentration ([K(+)]), most often occurs as a secondary problem but can occur as a primary problem, such as hypokalaemic periodic paralysis in humans, and as feline hypokalaemic periodic polymyopathy primarily in Burmese. The most characteristic clinical sign of hypokalemia in Burmese is a skeletal muscle weakness that is frequently episodic in nature, either generalized, or sometimes localized to the cervical and thoracic limb girdle muscles. Burmese hypokalemia is suspected to be a single locus autosomal recessive trait. A genome wide case-control study using the illumina Infinium Feline 63K iSelect DNA array was performed using 35 cases and 25 controls from the Burmese breed that identified a locus on chromosome E1 associated with hypokalemia. Within approximately 1.2 Mb of the highest associated SNP, two candidate genes were identified, KCNH4 and WNK4. Direct sequencing of the genes revealed a nonsense mutation, producing a premature stop codon within WNK4 (c.2899C>T), leading to a truncated protein that lacks the C-terminal coiled-coil domain and the highly conserved Akt1/SGK phosphorylation site. All cases were homozygous for the mutation. Although the exact mechanism causing hypokalemia has not been determined, extrapolation from the homologous human and mouse genes suggests the mechanism may involve a potassium-losing nephropathy. A genetic test to screen for the genetic defect within the active breeding population has been developed, which should lead to eradication of the mutation and improved general health within the breed. Moreover, the identified mutation may help clarify the role of the protein in K⁺ regulation and the cat represents the first animal model for WNK4-associated hypokalemia.

Specificity and sensitivity of serum canine pancreatic elastase-1 concentration in the diagnosis of pancreatitis.

The aim of the current study was to determine the sensitivity and specificity of serum canine pancreatic elastase-1 (cPE-1) for the diagnosis of pancreatitis in dogs. The study was prospective, assessing dogs presenting with clinical signs similar to pancreatitis. Sixty-one dogs were recruited (49 with pancreatic disease and 12 with non-pancreatic disease). There was no significant difference in serum cPE-1 between dogs with pancreatic disease and non-pancreatic disease. However, there was a significant difference in serum cPE-1 between severe acute pancreatitis and non-pancreatic disease. A cut-off value for serum cPE-1 > 17.24 ng/ml resulted in sensitivity of 61.4% and specificity of 91.7% for diagnosis of all types of pancreatic disease. The sensitivity rose to 65.85% and 78.26% for the diagnosis of all types of acute pancreatitis and severe acute pancreatitis, respectively. Serum cPE-1 is more sensitive at diagnosing severe acute pancreatitis than chronic or mild acute pancreatitis, and has a high positive likelihood ratio. Dogs with chronic pancreatitis tended to have lower serum cPE-1 concentration, suggesting decreased exocrine function.

Genotypic characterisation and cluster analysis of Campylobacter jejuni isolates from domestic pets, human clinical cases and retail food.

The genetic similarity of Campylobacter jejuni isolates from pets, compared to human clinical cases and retail food isolates collected in Ireland over 2001-2006 was investigated by cluster analysis of pulsed-field gel electrophoresis (PFGE) fingerprinting profiles. Comparison of the PFGE profiles of 60 pet isolates and 109 human isolates revealed that seven (4.1%) profiles were grouped in clusters including at least one human and one pet C. jejuni isolate. In total six (1.6%) of 60 pet and 310 food profiles were in clusters with at least one food and one pet C. jejuni isolate. The detection of only a small number of genetically indistinguishable isolates by PFGE profile cluster analysis from pets and from humans with enteritis in this study suggests that pets are unlikely to be an important reservoir for human campylobacteriosis in Ireland. However, genetically indistinguishable isolates were detected and C. jejuni from pets may circulate and may contribute to clinical infections in humans. In addition, contaminated food fed to pets may be a potential source of Campylobacter infection in pets, which may subsequently pose a risk to humans.

Association between skin surface pH, temperature and Staphylococcus pseudintermedius in dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

Secondary bacterial infection is a frequent complication in lesional skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP). However, the influence of skin pH and temperature in determining the composition of the cutaneous microflora at lesional sites has not been investigated. The association between ImR-LPP and pedal skin temperature, pH and Staphylococcus pseudintermedius isolates was thus evaluated. Temperature and pH were measured in 20 dogs with ImR-LPP and in 30 clinically healthy control dogs, and S. pseudintermedius was cultured from interdigital and palmoplantar swabs in both groups and scored semi-quantitatively for bacterial growth. In the ImR-LPP group, mean skin pH was slightly, but significantly, higher at both interdigital and palmoplantar sites. Staphylococcus pseudintermedius was isolated more frequently, and scores for bacterial growth were also significantly higher. However, mean skin temperatures were not significantly different from those in the control group. The isolation of S. pseudintermedius was significantly associated with ImR-LPP, with the single exception of isolates on Columbia blood agar from the palmoplantar region. However, pH and temperature were not significantly associated with the disease, and were not associated with the isolation of S. pseudintermedius at most sites sampled. Staphylococcus pseudintermedius was not isolated from all feet sampled in dogs with ImR-LPP. Taken together, these data would suggest that S. pseudintermedius infection is most likely to be a secondary phenomenon in dogs with ImR-LPP, and that changes in skin pH and temperature are not significant risk factors for this disease.

Composition of uroliths in small domestic animals in the United Kingdom.

The mineral composition of 7819 small animal uroliths in the UK was determined by semi-quantitative X-ray diffraction over a period of 90 months from 2002 to 2010. Canine and feline uroliths constituted 97% of the study population and the mineral phase detected most frequently was struvite (43%), followed by calcium oxalate (41%). Uroliths from crossbreeds, Dalmatians, Yorkshire terriers and Shih Tzus accounted for almost 30% of all canine uroliths, with the highest frequency in Dalmatians, which had a predominance of urate uroliths. The average ages of dogs and cats with uroliths were 7.0 years and 7.4 years, respectively. The ratio of the number of dogs presenting with struvite compared to oxalate phases reached a maximum at 3years of age.

Cutaneous infiltrates and peripheral blood immune responses in dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

This study characterizes T- and B-lymphocyte responses in the peripheral blood and lesional skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP), a term previously proposed to denote a subpopulation of dogs with idiopathic pododermatitis. T-cell (CD3+, CD4+ and CD8+ ) and B-cell (CD21+) counts were significantly increased in both the epidermis and dermis of lesional ImR-LPP skin compared with that in pedal skin from healthy controls. CD3+ , CD4+, CD8+ and CD21+ cells were commonly observed in perivascular sites in the superficial dermis, periadnexally, beneath the dermal-epidermal (DE) junction and in the epidermis of lesional ImR-LPP skin. The CD8+ /CD3+ T-cell ratio in peripheral blood was significantly increased in the ImR-LPP group (0.42 versus 0.35 in controls). Serum IgA, IgG and IgM concentrations were all significantly elevated in affected dogs. Lymphocyte stimulation indices in ImR-LPP dogs were comparable with control levels except for a lower response to ionomycin (6.0 versus 11.1). Dogs with ImR-LPP had a higher incidence and mean (semi-quantitative) score for IgA, IgG and IgM deposits in the epidermis, and a significantly increased incidence of dermal IgA+, IgG+ and IgM+ mononuclear inflammatory cells. The results indicate that upregulated T- and B-lymphocyte responses may contribute to the pathogenesis of the skin lesions observed in dogs with ImR-LPP.

Antimicrobial resistance profiles and mechanisms of resistance in Campylobacter jejuni isolates from pets.

The presence of antimicrobial resistance in 51 Campylobacter jejuni isolates obtained from cats and dogs was determined by E-testing. Resistance to nalidixic acid (37.3% of isolates), ciprofloxacin (19.6%), tetracycline (13.7%), ampicillin (13.7%), erythromycin (11.8%), and chloramphenicol (5.9%) was detected. Resistance to two antimicrobials or more was present in 31.4% of isolates, and one isolate was resistant to all six antimicrobials. Of the isolates with ciprofloxacin and/or nalidixic acid resistance, 54.5% had the gyrA substitution Thr-86-Ile on sequencing. The tet o gene was detected in 75.0% isolates with high-level resistance to tetracycline. With the observed antimicrobial resistance in C. jejuni isolates from pets in this study, and the detection of identical mechanisms for quinolone and tetracycline resistance in pets and humans, pets should be considered a potential source of (multi)resistant C. jejuni infections in humans.

Canine pododermatitis and idiopathic disease.

Pododermatitis is a common inflammatory skin disease of dogs. As pedal lesions are reported in many canine dermatoses, a methodical series of diagnostic tests is required to establish the underlying aetiology. However, laboratory/ancillary investigations may prove unrewarding, prompting a diagnosis of idiopathic disease. Various hypotheses have been proposed to explain the pathogenesis of idiopathic pododermatitis including pedal conformation, trauma, immunosuppression, bacterial infection, furunculosis and dermal granuloma formation. Idiopathic pododermatitis accounts for 0.5% of all dermatology referrals to the authors' clinic. A sub-group within this population is characterised histopathologically by epidermal hyperplasia, hyperkeratosis, spongiosis, dermal oedema and perivascular aggregates of lymphocytes and plasma cells. The term lymphocytic-plasmacytic pododermatitis (LPP) has previously been proposed to reflect the histological appearance of such lesions. Affected dogs, although systemically well, characteristically have pruritus, erythema, swelling, pain and alopecia of the feet. Although non-responsive to antimicrobial therapy, antiparasitic agents and elimination diets, these dogs typically respond well to immunomodulatory therapy.

A study of dendritic cell and MHC class II expression in dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

The term immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP) has previously been proposed to denote a sub-population of dogs with idiopathic pododermatitis. The objective of this study was to investigate dendritic cell (DC) and MHC class II antigen expression in lesional skin of dogs with ImR-LPP (n=47). Median epidermal CD1c(+) cell counts were 37.8 and 12.5 mm(-1) in ImR-LPP dogs and healthy controls (n=27), respectively (P<0.01), while the corresponding dermal cell counts were 180.9 and 45.0 mm(-2), respectively (P<0.01). Intra-epidermal clusters of DCs were observed in 18/47 dogs with ImR-LPP. Median epidermal MHC class II(+) cell counts were 32.5 and 10.5 mm(-1) in ImR-LPP dogs and healthy controls, respectively (P<0.01), while the corresponding dermal cell counts were 216.9 and 46.9 mm(-2), respectively (P<0.01). Dermal MHC class II(+) staining was primarily associated with DCs (47/47 dogs), mononuclear inflammatory cells (45/47), fibroblast-like cells (19/47) and vascular endothelium (14/47). The DC hyperplasia and increased MHC class II expression in lesional ImR-LPP skin are consistent with enhanced antigen presentation, and suggest that both parameters may contribute to the pathogenesis of ImR-LPP through the priming and activation of CD4(+) T cells. Equally, it is possible that the enhanced DC numbers observed in this study may contribute to the immunoregulation of steady-state pathology in lesional ImR-LPP skin through additional expanded, although as yet unresolved, mechanisms.

Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis.

Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.