Clinical presentation, diagnosis, therapy and outcome of alveolar echinococcosis in dogs.

Alveolar echinococcosis (AE), a parasitic disease primarily of the liver caused by the larval stage of Echinococcus multilocularis, is highly endemic in Switzerland. In contrast to well-established management protocols in people, little is known with regard to optimal treatment strategies in dogs. The objective of this study was to describe the clinical signs and diagnostic procedures in dogs with AE and to evaluate outcome following medical treatment alone or surgery and medical treatment. Of 23 putative AE cases between 2004 and 2014, 20 were classified as confirmed (n=18) or probable (n=2) AE, based on abdominal ultrasound, serology, cytology, histology and/or PCR. Most dogs presented with abdominal distension in an advanced stage of disease. Dogs receiving specific treatment (radical or debulking surgery together with medical treatment, or medical treatment alone) survived longer than dogs left untreated, but no difference was found between treatment types. Survival at one year was associated with absence of free abdominal fluid, absence of abdominal distension and treatment of any type. However, dogs treated with debulking surgery all faced relapse. Findings of this study suggest that in AE-affected dogs for which a therapeutic approach is regarded appropriate by owners and veterinarians, radical surgical resection and medical treatment or, if total resection is not possible, medical treatment alone should be considered. However, studies on larger numbers of dogs are necessary before definitive treatment recommendations can be made.

Combinations of dexmedetomidine and alfaxalone with butorphanol in cats: application of an innovative stepwise optimisation method to identify optimal clinical doses for intramuscular anaesthesia

OBJECTIVES The aim of this study was to optimise dexmedetomidine and alfaxalone dosing, for intramuscular administration with butorphanol, to perform minor surgeries in cats. METHODS Initially, cats were assigned to one of five groups, each composed of six animals and receiving, in addition to 0.3 mg/kg butorphanol intramuscularly, one of the following: (A) 0.005 mg/kg dexmedetomidine, 2 mg/kg alfaxalone; (B) 0.008 mg/kg dexmedetomidine, 1.5 mg/kg alfaxalone; (C) 0.012 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; (D) 0.005 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; and (E) 0.012 mg/kg dexmedetomidine, 2 mg/kg alfaxalone. Thereafter, a modified 'direct search' method, conducted in a stepwise manner, was used to optimise drug dosing. The quality of anaesthesia was evaluated on the basis of composite scores (one for anaesthesia and one for recovery), visual analogue scales and the propofol requirement to suppress spontaneous movements. The medians or means of these variables were used to rank the treatments; 'unsatisfactory' and 'promising' combinations were identified to calculate, through the equation first described by Berenbaum in 1990, new dexmedetomidine and alfaxalone doses to be tested in the next step. At each step, five combinations (one new plus the best previous four) were tested. RESULTS None of the tested combinations resulted in adverse effects. Four steps and 120 animals were necessary to identify the optimal drug combination (0.014 mg/kg dexmedetomidine, 2.5 mg/kg alfaxalone and 0.3 mg/kg butorphanol). CONCLUSIONS AND RELEVANCE The investigated drug mixture, at the doses found with the optimisation method, is suitable for cats undergoing minor clinical procedures.

Novel MesoPorous BioGlass/silk scaffold containing adPDGF-B and adBMP7 for the repair of periodontal defects in beagle dogs

AIM The local delivery of growth factors via gene therapy has gained tremendous awareness in recent years due to their sustained growth factor delivery to target tissues. The aim of this study was to fabricate and investigate a scaffold able to release growth factors via gene therapy for the repair of periodontal tissues. MATERIALS AND METHODS Novel mesoporous bioglass (MBG)/silk fibrin scaffold combined with BMP7 and/or PDGF-B adenovirus was fabricated and tested in vitro for cell migration, proliferation and differentiation. Furthermore, acute-type buccal dehiscence periodontal defects (mesiodistal width × depth: 5 × 5 mm) were created on the buccal portion of the maxillary premolars in five normal male beagle dogs (12 months old, 15.0 ± 2.0 kg) and histologically examined for periodontal regeneration following implantation of the following five groups: (1) no scaffold, (2) MBG/silk scaffold alone, (3) scaffold + adPDGF-B, (4) scaffold + adBMP7, (5) scaffold + adPDGF-b + adBMP7. RESULTS In vitro findings demonstrated that adPDGF-B was able to rapidly recruit periodontal ligament (PDL) cells over sixfold more effectively than adBMP7, whereas adBMP7 was more able to induce osteoblast differentiation of PDL cells. In vivo findings demonstrate that scaffolds loaded with adPDGF-B were able to partially regenerate the periodontal ligament while adBMP7 scaffolds primarily improved new bone formation. The combination of both adPDGF-B and adBMP7 synergistically promoted periodontal regeneration by allowing up to two times greater regeneration of the periodontal ligament, alveolar bone and cementum when compared to each adenovirus used alone. CONCLUSIONS Although both PDGF-B and BMP7 are individually capable of promoting periodontal regeneration to some degree, their combination synergistically promotes wound healing in acute-type buccal dehiscence periodontal defects when delivered simultaneously. This study demonstrates the promise for successful delivery of low-cost, effective growth factor delivery via gene therapy for the treatment of periodontal defects.

Accuracy of conventional radiography and computed tomography in predicting implant position in relation to the vertebral canal in dogs.

OBJECTIVE To compare the accuracy of radiography and computed tomography (CT) in predicting implant position in relation to the vertebral canal in the cervical and thoracolumbar vertebral column. STUDY DESIGN In vitro imaging and anatomic study. ANIMALS Medium-sized canine cadaver vertebral columns (n=12). METHODS Steinmann pins were inserted into cervical and thoracolumbar vertebrae based on established landmarks but without predetermination of vertebral canal violation. Radiographs and CT images were obtained and evaluated by 6 individuals. A random subset of pins was evaluated for ability to distinguish left from right pins on radiographs. The ability to correctly identify vertebral canal penetration for all pins was assessed both on radiographs and CT. Spines were then anatomically prepared and visual examination of pin penetration into the canal served as the gold standard. RESULTS Left/right accuracy was 93.1%. Overall sensitivity of radiographs and CT to detect vertebral canal penetration by an implant were significantly different and estimated as 50.7% and 93.4%, respectively (P<.0001). Sensitivity was significantly higher for complete versus partial penetration and for radiologists compared with nonradiologists for both imaging modalities. Overall specificity of radiographs and CT to detect vertebral canal penetration was 82.9% and 86.4%, respectively (P=.049). CONCLUSIONS CT was superior to radiographic assessment and is the recommended imaging modality to assess penetration into the vertebral canal. CLINICAL RELEVANCE CT is significantly more accurate in identifying vertebral canal violation by Steinmann pins and should be performed postoperatively to assess implant position.

Description and repeatability of a newly developed spinal cord injury scale for dogs.

The objectives of this study were to describe a new spinal cord injury scale for dogs, evaluate repeatability through determining inter-rater variability of scores, compare these scores to another established system (a modified Frankel scale), and determine if the modified Frankel scale and the newly developed scale were useful as prognostic indicators for return to ambulation. A group of client-owned dogs with spinal cord injury were examined by 2 independent observers who applied the new Texas Spinal Cord Injury Score (TSCIS) and a modified Frankel scale that has been used previously. The newly developed scale was designed to describe gait, postural reactions and nociception in each limb. Weighted kappa statistics were utilized to determine inter-rater variability for the modified Frankel scale and individual components of the TSCIS. Comparisons were made between raters for the overall TSCIS score and between scales using Spearman's rho. An additional group of dogs with surgically treated thoracolumbar disk herniation was enrolled to look at correlation of both scores with spinal cord signal characteristics on magnetic resonance imaging (MRI) and ambulatory outcome at discharge. The actual agreement between raters for the modified Frankel scale was 88%, with a weighted kappa value of 0.93. The TSCIS had weighted kappa scores for gait, proprioceptive positioning and nociception components that ranged from 0.72 to 0.94. Correlation between raters for the overall TSCIS score was Spearman's rho=0.99 (P<0.001). Comparison of the overall TSCIS score to the modified Frankel score resulted in a Spearman's rho value of 0.90 (P<0.001). The modified Frankel score was weakly correlated with the length of hyperintensity of the spinal cord: L2 vertebral body length ratio on mid-sagittal T2-weighted MRI (Spearman's rho=-0.45, P=0.042) as was the overall TSCIS score (Spearman's rho=-0.47, P=0.037). There was also a significant difference in admitting modified Frankel scores (P=0.029) and admitting overall TSCIS scores (P=0.02) between dogs that were ambulatory at discharge and those that were not. Results from this study suggest that the TSCIS is an easy to administer scale for evaluating canine spinal cord injury based on the standard neurological exam and correlates well with a previously described modified Frankel scale.

Effect of tympanic cavity evacuation and flushing on microbial isolates during total ear canal ablation with lateral bulla osteotomy in dogs.

OBJECTIVE To evaluate differences in bacterial numbers, identity, and susceptibility in samples obtained from the tympanic cavity on entry (preflush) and after evacuation and lavage (postflush) and assess perioperative and empiric antimicrobial selection in dogs that underwent total ear canal ablation (TECA) with lateral bulla osteotomy (LBO) or reoperation LBO. DESIGN Prospective clinical study. ANIMALS 34 dogs. PROCEDURE TECA with LBO or reoperation LBO was performed on 47 ears. Pre- and postflush aerobic and anaerobic samples were obtained from the tympanic cavity. Isolates and antimicrobial susceptibility patterns were compared. RESULTS Different isolates (31/44 [70%] ears) and susceptibility patterns of isolate pairs (6/44 [14%] ears) were detected in pre- and postflush samples from 84% of ears. Evacuation and lavage of the tympanic cavity decreased the number of bacterial isolates by 33%. In 26% of ears, bacteria were isolated from post-flush samples but not preflush samples. Only 26% of isolates tested were susceptible to cefazolin. At least 1 isolate from 53% of dogs that received empirically chosen antimicrobials postoperatively was resistant to the selected drugs. Anaerobic bacteria were recovered from 6 ears. CONCLUSIONS AND CLINICAL RELEVANCE Accurate microbiologic assessment of the tympanic cavity should be the basis for selection of antimicrobials in dogs undergoing TECA with LBO. Bacteria remain in the tympanic cavity after evacuation and lavage. Cefazolin was a poor choice for dogs that underwent TECA with LBO, as judged on the basis of culture and susceptibility testing results.

The use of an electronic von Frey device for evaluation of sensory threshold in neurologically normal dogs and those with acute spinal cord injury

The utility and inter-session repeatability of sensory threshold measurements using an electronic von Frey anesthesiometer (VFA) were assessed in a group of six neurologically normal dogs. Sensory threshold values obtained in neurologically normal dogs were compared to those of dogs with acute spinal cord injury (SCI) caused by intervertebral disc extrusion (n=6) and to a group of neurologically normal dogs with cranial cruciate ligament rupture (CCLR; n=6). Sensory threshold values in neurologically normal dogs were 155.8 ± 37.7 g and 154.7 ± 67.2 g for the left and right pelvic limbs, respectively. The difference in mean sensory threshold values obtained for the group when two distinct testing sessions were compared was not statistically significant (P>0.05). Mean sensory threshold values for the group with SCI were significantly higher than those for neurologically normal dogs at 351.1 ± 116.5 g and 420.3 ± 157.7 g for the left and right pelvic limbs, respectively (P=0.01). A comparison of sensory threshold values for the group with CCLR and neurologically normal dogs was not statistically significant (P>0.05). The modified dorsal technique for VFA described here represents a reliable method to assess sensory threshold in neurologically normal dogs and in those with SCI.

Clinical and Breed Characteristics of Idiopathic Head Tremor Syndrome in 291 Dogs: A Retrospective Study.

Objective. To establish signalment and phenomenology of canine idiopathic head tremor syndrome (IHTS), an episodic head movement disorder of undetermined pathogenesis. Design. Retrospective case series. Animals. 291 dogs with IHTS diagnosed between 1999 and 2013. Procedures. Clinical information was obtained from an online community of veterinary information aggregation and exchange (Veterinary Information Network, 777 W Covell Boulevard, Davis, CA 95616) and conducted with their approval. Information on breed, sex, age of onset, tremor description, mentation during the event, effect of distractions and drugs, diagnostics, presence of other problems, and outcome was analyzed. Results. IHTS was found in 24 pure breeds. Bulldogs, Labrador Retrievers, Boxers, and Doberman Pinschers comprised 69%; mixed breeds comprised 17%. Average onset age was 29 months (range: 3 months to 12 years). First episode occurred before 48 months of age in 88%. Vertical (35%), horizontal (50%), and rotational (15%) movements were documented. Possible trigger events were found in 21%. Mentation was normal in 93%. Distractions abated the tremor in 87%. Most dogs did not respond to antiepileptic drugs. Conclusions and Clinical Relevance. This retrospective study documents IHTS in many breeds including Labrador Retrievers, Boxers, and mixed breeds.

Serum and fecal canine α1-proteinase inhibitor concentrations reflect the severity of intestinal crypt abscesses and/or lacteal dilation in dogs.

Gastrointestinal (GI) protein loss, due to lymphangiectasia or chronic inflammation, can be challenging to diagnose. This study evaluated the diagnostic accuracy of serum and fecal canine α1-proteinase inhibitor (cα1PI) concentrations to detect crypt abscesses and/or lacteal dilation in dogs. Serum and fecal cα1PI concentrations were measured in 120 dogs undergoing GI tissue biopsies, and were compared between dogs with and without crypt abscesses/lacteal dilation. Sensitivity and specificity were calculated for dichotomous outcomes. Serial serum cα1PI concentrations were also evaluated in 12 healthy corticosteroid-treated dogs. Serum cα1PI and albumin concentrations were significantly lower in dogs with crypt abscesses and/or lacteal dilation than in those without (both P <0.001), and more severe lesions were associated with lower serum cα1PI concentrations, higher 3 days-mean fecal cα1PI concentrations, and lower serum/fecal cα1PI ratios. Serum and fecal cα1PI, and their ratios, distinguished dogs with moderate or severe GI crypt abscesses/lacteal dilation from dogs with only mild or none such lesions with moderate sensitivity (56-92%) and specificity (67-81%). Serum cα1PI concentrations increased during corticosteroid administration. We conclude that serum and fecal α1PI concentrations reflect the severity of intestinal crypt abscesses/lacteal dilation in dogs. Due to its specificity for the GI tract, measurement of fecal cα1PI appears to be superior to serum cα1PI for diagnosing GI protein loss in dogs. In addition, the serum/fecal cα1PI ratio has an improved accuracy in hypoalbuminemic dogs, but serum cα1PI concentrations should be carefully interpreted in corticosteroid-treated dogs.

Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assay based on recombinant TBEV subviral particles

Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with thousands of cases and millions vaccinated against it. The risk of TBE might be assessed through analyses of the samples taken from wildlife or from animals which are in close contact with humans. Dogs have been shown to be a good sentinel species for these studies. Serological assays for diagnosis of TBE in dogs are mainly based on purified and inactivated TBEV antigens. Here we describe novel dog anti-TBEV IgG monoclonal antibody (MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions of Finland. Altogether, 148 dog serum samples were tested by novel assays and results were compared to those obtained with a commercial IgG enzyme immunoassay (EIA), hemagglutination inhibition test and IgG IFA with TBEV infected cells. Compared to reference tests, the sensitivities of the developed assays were 90-100% and the specificities of the two assays were 100%. Analysis of the dog serum samples showed a seroprevalence of 40% on Åland Islands and 6% on Southwestern archipelago of Finland. In conclusion, a specific and sensitive EIA and IFA for the detection of IgG antibodies in canine sera were developed. Based on these assays the seroprevalence of IgG antibodies in dogs from different regions of Finland was assessed and was shown to parallel the known human disease burden as the Southwestern archipelago and Åland Islands in particular had considerable dog TBEV antibody prevalence and represent areas with high risk of TBE for humans.

Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs.

BACKGROUND Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

Evidence of cardiac injury and arrhythmias in dogs with acute kidney injury

OBJECTIVES Cardiac involvement in the course of acute kidney injury is described in humans as cardiorenal syndrome type 3 but has received only limited attention in dogs. This study was designed to evaluate cardiac injury and dysfunction in acute kidney injury in dogs and its association with outcome. METHODS This prospective cohort study enrolled 24 client-owned dogs with acute kidney injury. Cardiac disorders were evaluated with thoracic radiographs, echocardiography, 24-hour Holter monitoring and cardiac troponin I concentrations within 2 days of admission and 7 to 10 days later. RESULTS Most dogs were diagnosed with leptospirosis (n=18, 75%) and presented with moderate-to-severe acute kidney injury, International Renal Interest Society grades III to V. Dogs with ê100 ventricular premature complexes per 24 hour in the first examination (n=8) had significantly higher initial cTnI concentrations (P=0·007) compared to dogs with fewer than 100. In receiver operating characteristic curve analysis, the number of ventricular premature complexes was predictive of outcome (AUC 0·83, P<0·001). CLINICAL SIGNIFICANCE Acute kidney injury seems to be associated with cardiac injury and arrhythmias in dogs. The data do not indicate a cardiac cause of poor outcome in dogs with increased number of ventricular premature complexes but the association may reflect the severity of disease.