Arachidonic acid pathway alterations in cerebrospinal fluid of dogs with naturally occurring spinal cord injury.

BACKGROUND: Canine intervertebral disc πherniation causes a naturally-occurring spinal cord injury (SCI) that bears critical similarities to human SCI with respect to both injury pathomechanisms and treatment. As such, it has tremendous potential to enhance our understanding of injury biology and the preclinical evaluation of novel therapies. Currently, there is limited understanding of the role of arachidonic acid metabolites in canine SCI. RESULTS: The CSF concentrations of PLA2 and PGE2 were higher in SCI dogs compared to control dogs (p = 0.0370 and 0.0273, respectively), but CSF LCT4 concentration in SCI dogs was significantly lower than that in control dogs (p < 0.0001). Prostaglandin E2 concentration in the CSF was significantly and positively associated with increased severity of SCI at the time of sampling (p = 0.041) and recovery 42 days post-injury (p = 0.006), as measured by ordinal behavioral scores. CONCLUSION: Arachidonic acid metabolism is altered in dogs with SCI, and these data suggest that these AA metabolites reflect injury severity and recovery, paralleling data from other model systems.

Electrolyte and acid/base changes in dogs undergoing autologous blood transfusion via a cell salvage device.

This study reports electrolyte and acid/base disturbances observed in clinical cases receiving autologous transfusion of blood processed by a cell salvage device. The records of 12 client-owned dogs that received an autologous transfusion via a cell salvage device with pre- and post-autologous transfusion blood work available were reviewed. Blood work from the 12 case dogs was compared to blood work from 12 control dogs with similar diseases. Control dogs received similar surgical treatment and were administered a similar volume per kg of packed red blood cells as case dogs, but did not undergo autologous transfusion. Case dogs that received autologous transfusion via a cell salvage device were significantly more likely to experience a decrease in ionized calcium and magnesium levels post-transfusion than were control dogs. Calcium and magnesium levels should be closely monitored during and after autologous transfusion. Calcium and/or magnesium supplementation may be required.

Changements électrolytiques et acido-basiques chez les chiens subissant une transfusion sanguine autologue à l'aide d'un dispositif de récupération des cellules. Cette étude signale les perturbations électrolytiques et acido-basiques observées dans des cas cliniques recevant une transfusion de sang autologue traitée à l'aide d'un dispositif de récupération des cellules. On a évalué les dossiers de 12 chiens, appartenant à des propriétaires, qui avaient reçu une transfusion autologue à l'aide d'un dispositif de récupération des cellules et avaient subi des analyses sanguines avant et après la transfusion autologue. Les analyses sanguines des 12 chiens ont été comparées aux analyses de 12 chiens témoins atteints de maladies semblables. Les chiens témoins ont reçu des traitements chirurgicaux semblables et un volume semblable par kg de concentré de globules rouges que les chiens du cas, mais n'ont pas subi la transfusion autologue. Il était significativement plus probable que les chiens du cas qui avaient reçu une transfusion autologue à l'aide d'un dispositif de récupération des cellules subissent une baisse du niveau de calcium ionisé et de magnésium après la transfusion que les chiens témoins. Le niveau de calcium et de magnésium devrait être étroitement surveillé durant et après la transfusion autologue. Des suppléments de calcium et/ou de magnésium pourront être requis.(Traduit par Isabelle Vallières).

Screening for Viral Nucleic Acids in the Cerebrospinal Fluid of Dogs With Central Nervous System Inflammation.

Central nervous system (CNS) inflammation is a common cause of neurological dysfunction in dogs. Most dogs with CNS inflammation are diagnosed with presumptive autoimmune disease. A smaller number are diagnosed with an infectious etiology. Additionally, at necropsy, a subset of dogs with CNS inflammation do not fit previously described patterns of autoimmune disease and an infectious cause is not readily identifiable. Because viral infection is a common cause of meningoencephalitis in people, we hypothesize that a subset of dogs presented with CNS inflammation have an occult viral infection either as a direct cause of CNS inflammation or a trigger for autoimmunity. The goal of this research was to screen cerebrospinal fluid from a large number dogs with CNS inflammation for occult viral infection. One hundred seventy-two dogs with neurological dysfunction and cerebrospinal fluid (CSF) pleocytosis were identified. Of these, 42 had meningoencephalitis of unknown origin, six had steroid-responsive meningitis-arteritis, one had eosinophilic meningoencephalitis, five had documented infection, 21 had and undetermined diagnosis, and 97 had a diagnosis not consistent with primary inflammatory disease of the CNS (e.g., neoplasia). CSF samples were subsequently screened with broadly reactive PCR for eight viral groups: adenovirus, bunyavirus, coronavirus, enterovirus, flavivirus, herpesvirus, paramyxovirus, and parechovirus. No viral nucleic acids were detected from 168 cases screened for eight viral groups, which does not support occult viral infection as a cause of CNS inflammation in dogs. La Crosse virus (LACV) nucleic acids were detected from four cases in Georgia. Subclinical infection was supported in two of these cases but LACV could not be ruled-out as a cause of infection in the other two cases, suggesting further research is warranted to determine if LACV is an occult cause of CNS inflammation in dogs.

Circulating neutrophil activation in dogs with naturally occurring spinal cord injury secondary to intervertebral disk herniation.

OBJECTIVE: To investigate the time course of circulating neutrophil priming and activity in dogs with spinal cord injury secondary to intervertebral disk herniation that undergo decompressive surgery. ANIMALS: 9 dogs with spinal cord injury and 9 healthy dogs (controls). PROCEDURES: For dogs with spinal cord injury, blood samples were collected on the day of hospital admission and 3, 7, 30, and 90 days after injury and decompressive surgery. A single blood sample was collected from the control dogs. Flow cytometry analysis was performed on isolated neutrophils incubated with antibody against CD11b and nonfluorescent dihydrorhodamine 123, which was converted to fluorescent rhodamine 123 to measure oxidative burst activity. RESULTS: Expression of CD11b was increased in dogs with spinal cord injury 3 days after injury and decompressive surgery, relative to day 7 expression. Neutrophils expressed high oxidative burst activity both 3 and 7 days after injury and decompressive surgery, compared with activity in healthy dogs. CLINICAL RELEVANCE: For dogs with spinal cord injury, high CD11b expression 3 days after injury and decompressive surgery was consistent with findings for rodents with experimentally induced spinal cord injury. However, the high oxidative burst activity 3 and 7 days after injury and decompressive surgery was not consistent with data from other species, and additional studies on inflammatory events in dogs with naturally occurring spinal cord injury are needed.

Preparation Technique Affects Recipient Immune Targeting of Autologous Mesenchymal Stem Cells.

Fetal bovine serum (FBS) is used for MSC preparation in pre-clinical animal models and veterinary applications, recently in US clinical trials, and for MSC products with current foreign market authorizations. The effect of anti-bovine titers, which are common in animals and humans, has not been investigated. In the equine model, where anti-bovine titers are universally high due to routine vaccination, we evaluated the recipient immune response to autologous MSCs prepared with and without FBS. Preparation of MSCs with FBS resulted in post injection inflammation and antibody mediated cytotoxicity of MSCs when compared to MSCs prepared without FBS. Importantly, synovial MSC concentrations were reduced and LPS induced pain was higher, when FBS was used to prepare MSCs, demonstrating reduced efficacy of FBS prepared MSCs. Fetal bovine serum should no longer be utilized for MSC preparation in pre-clinical study, clinical study, or veterinary applications. The use of FBS in previously reported studies, and in MSC therapeutics with current foreign market authorization, should be considered when interpreting results.

Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting.

Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared with recipients receiving matched allogeneic or autologous MSCs. Importantly, in matched allogeneic and autologous recipients, but not mismatched allogeneic recipients, there was increased stromal derived factor-1 along with increased MSC concentrations in synovial fluid. Until immune recognition of MSCs can be avoided, repeated clinical use of MSCs should be limited to autologous or cross-matched allogeneic MSCs. When non-cross-matched allogeneic MSCs are used in single MSC dose applications, presensitization against donor MHC should be assessed.

Abdominal ultrasound and clinicopathologic findings in 22 cats with exocrine pancreatic insufficiency.

BACKGROUND: Awareness of exocrine pancreatic insufficiency (EPI) in cats has increased since the development of an assay for feline trypsin-like immunoreactivity (fTLI). Ultrasound findings in cats with EPI have only been reported rarely and described as nonspecific. HYPOTHESIS/OBJECTIVES: To describe the ultrasonographic findings, clinical signs, and concurrent diseases in cats with EPI. ANIMALS: Twenty-two client-owned cats with EPI. METHODS: Multicenter retrospective descriptive study including cats with serum fTLI concentration ≤8 µg/L and an abdominal ultrasound examination performed within 6 weeks of fTLI measurement. Sonographic measurements of maximal pancreatic thickness and maximal pancreatic duct diameter as well as ratios of pancreatic duct diameter to pancreatic thickness were obtained. Additional sonographic findings, concurrent conditions, and clinical signs were recorded. RESULTS: The most common clinical sign was weight loss (15/22 cats). Chronic enteropathy was the most common concurrent disease (13/22 cats). In 39% of cats, the pancreas had minimal or no sonographic alterations. Pancreatic duct dilatation (>2.5 mm), pancreatic duct tortuosity with variable diameter, or both were seen in 6/13 cats. The pancreatic parenchyma was subjectively thin in 6 cats. A significant relationship was found between subjectively thin pancreatic parenchyma and increased pancreatic duct size : pancreatic thickness ratio (P = .004). Diffuse gastrointestinal dilatation with echogenic content was observed in 8/22 cats. CONCLUSION: Exocrine pancreatic insufficiency often causes minimal to no sonographic pancreatic changes. Nonetheless, the findings of thin pancreatic parenchyma, pancreatic duct dilatation, or diffuse small intestinal dilatation with echogenic contents in cats with unexplained weight loss or unformed feces should raise clinical suspicion for EPI.

Multicenter case-control study of signalment, diagnostic features, and outcome associated with cervical vertebral malformation-malarticulation in horses.

OBJECTIVE: To compare signalment of horses with cervical vertebral malformation-malarticulation (CVM) with that of control horses and to describe results of clinical examination, diagnostic imaging and necropsy findings, and reported outcome in horses with CVM. DESIGN: Retrospective case-control study. ANIMALS: 270 horses with CVM and 608 control horses admitted to 6 veterinary hospitals from 1992 through 2007. PROCEDURES: Medical records of participating hospitals were reviewed to identify horses with CVM (ie, case horses) and contemporaneous control (non-CVM-affected) horses that were admitted for treatment. Signalment was compared between case horses and control horses. Results of clinical examination, laboratory and diagnostic imaging findings, necropsy results, and outcome were assessed for horses with CVM. RESULTS: Case horses were younger (median age, 2 years) than were control horses (median age, 7 years). Thoroughbreds, warmbloods, and Tennessee Walking Horses were overrepresented in the CVM group. Gait asymmetry and cervical hyperesthesia were frequently detected in horses with CVM. Vertebral canal stenosis and articular process osteophytosis were commonly observed at necropsy; agreement between the results of radiographic or myelographic analysis and detection of lesions at necropsy was 65% to 71% and 67% to 78%, respectively. Of 263 horses with CVM for which outcome was recorded, 1 died and 172 (65.4%) were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Odds of a diagnosis of CVM were greater in young horses and horses of specific breeds. Detection of gait asymmetry and cervical hyperesthesia were frequently reported in association with CVM. Accurate diagnosis of lesions associated with CVM by use of radiography and myelography can be challenging.

Development of a Canine Rigid Body Musculoskeletal Computer Model to Evaluate Gait.

BACKGROUND: Kinematic and kinetic analysis have been used to gain an understanding of canine movement and joint loading during gait. By non-invasively predicting muscle activation patterns and forces during gait, musculoskeletal models can further our understanding of normal variability and muscle activation patterns and force profiles characteristic of gait. METHODS: Pelvic limb kinematics and kinetics were measured for a 2 year old healthy female Dachshund (5.4 kg) during gait using 3-D motion capture and force platforms. A computed tomography scan was conducted to acquire pelvis and pelvic limb morphology. Using the OpenSim modeling platform, a bilateral pelvic limb subject-specific rigid body musculoskeletal computer model was developed. This model predicted muscle activation patterns, muscle forces, and angular kinematics and joint moments during walking. RESULTS: Gait kinematics determined from motion capture matched those predicted by the model, verifying model accuracy. Primary muscles involved in generating joint moments during stance and swing were predicted by the model: at mid-stance the adductor magnus et brevis (peak activation 53.2%, peak force 64.7 N) extended the hip, and stifle flexor muscles (biceps femoris tibial and calcaneal portions) flexed the stifle. Countering vertical ground reaction forces, the iliopsoas (peak activation 37.9%, peak force 68.7 N) stabilized the hip in mid-stance, while the biceps femoris patellar portion stabilized the stifle in mid-stance and the plantar flexors (gastrocnemius and flexor digitorum muscles) stabilized the tarsal joint during early stance. Transitioning to swing, the iliopsoas, rectus femoris and tensor fascia lata flexed the hip, while in late swing the adductor magnus et brevis impeded further flexion as biceps femoris tibial and calcaneal portions stabilized the stifle for ground contact. CONCLUSION: The musculoskeletal computer model accurately replicated experimental canine angular kinematics associated with gait and was used to predict muscle activation patterns and forces. Thus, musculoskeletal modeling allows for quantification of measures such as muscle forces that are difficult or impossible to measure in vivo.

Broadly reactive pan-paramyxovirus reverse transcription polymerase chain reaction and sequence analysis for the detection of Canine distemper virus in a case of canine meningoencephalitis of unknown etiology.

Despite the immunologic protection associated with routine vaccination protocols, Canine distemper virus (CDV) remains an important pathogen of dogs. Antemortem diagnosis of systemic CDV infection may be made by reverse transcription polymerase chain reaction (RT-PCR) and/or immunohistochemical testing for CDV antigen; central nervous system infection often requires postmortem confirmation via histopathology and immunohistochemistry. An 8-month-old intact male French Bulldog previously vaccinated for CDV presented with multifocal neurologic signs. Based on clinical and postmortem findings, the dog's disease was categorized as a meningoencephalitis of unknown etiology. Broadly reactive, pan-paramyxovirus RT-PCR using consensus-degenerate hybrid oligonucleotide primers, combined with sequence analysis, identified CDV amplicons in the dog's brain. Immunohistochemistry confirmed the presence of CDV antigens, and a specific CDV RT-PCR based on the phosphoprotein gene identified a wild-type versus vaccinal virus strain. This case illustrates the utility of broadly reactive PCR and sequence analysis for the identification of pathogens in diseases with unknown etiology.

Evaluation of a low-technology system to obtain morphological and mobility trial measurements in dogs and investigation of potential predictors of canine mobility.

OBJECTIVE: To develop a low-technology system that can be used by dog owners to obtain morphological and mobility measurements in companion dogs as candidate components of an eventual canine frailty scale. ANIMALS: 57 adult (≥ 1-year-old) dogs enrolled by 43 owners. PROCEDURES: Morphological measurements of dogs were performed by investigators and dog owners. Dogs participated in timed in-clinic mobility trials across a flat surface (on-leash trial with the owner, on-leash trial with the investigator, and off-leash trial) and on stairs; each trial was repeated 3 times. Owners were asked to conduct a second stair trial at home 2 weeks later. Agreement between owner- and investigator-obtained measurements was assessed with Shrout-Fleiss intraclass correlation coefficients and paired t tests. Age, quartile of projected percentage of mean life span attained (adjusted for body weight), and height were evaluated as predictors of speed and stride length in mobility trials with linear regression and Spearman rank correlation analysis. RESULTS: Agreement between owner- and investigator-obtained morphological measurements was strong. Age was a weak but significant predictor of decreased dog speed in mobility trials (adjusted R2, 0.10 to 0.23). Speed decreased significantly with increasing quartile of projected life span attained. A linear regression model that included height and age predicted dog speed better than models with age or height alone. CONCLUSIONS AND CLINICAL RELEVANCE: Morphological and mobility trial measurements can be obtained by dog owners with minimal training. Low-technology measurements of mobility trial speed offer potential as components in a future scoring scale for canine frailty.

Gastrointestinal pythiosis with concurrent presumptive gastrointestinal basidiobolomycosis in a Boxer dog.

A 2-year-old female spayed Boxer dog was presented for a 1-month history of progressive hemorrhagic diarrhea with tenesmus and weight loss despite trial courses of antibiotics and diet change. Abdominal ultrasound revealed severe, focal thickening, and loss of normal architecture of the colonic wall with abdominal lymphadenomegaly. Dry-mount fecal cytology, performed on several consecutive days, consistently revealed numerous, round, 16-20 µm structures with basophilic, granular content, and a thin cell wall. Transmission electron microscopy identified these structures as fungi. Culture, polymerase chain reaction (PCR), and sequencing of the internal transcribed spacer, D1/D2 regions, and DNA-directed RNA polymerase II core subunit (RPB2) confirmed the presence of Basidiobolus microsporus in the feces. Biopsies collected via ileocolonoscopy revealed marked, multifocal, chronic, neutrophilic, and eosinophilic ileitis and colitis with ulceration, granulation tissue, and intralesional hyphae (identified with Gomori methenamine silver stain). A Pythium enzyme-linked immunosorbent assay and Pythium-specific PCR performed on the formalin-fixed paraffin-embedded biopsy specimens were positive while Basidiobolus-specific PCR was negative, thus confirming a diagnosis of pythiosis. This report describes a fatal case of colonic and intestinal pythiosis with the presence of fecal Basidiobolus sp. spores, suggestive of concurrent gastrointestinal basidiobolomycosis.

Associations of sex, breed, and age with cervical vertebral compressive myelopathy in horses: 811 cases (1974-2007).

OBJECTIVE: To determine sex, breed, and age distributions in a population of horses with cervical vertebral compressive myelopathy (CVCM), compared with contemporaneous control horses. DESIGN: Retrospective case-control study. ANIMALS: 811 horses with CVCM and 805 control horses. PROCEDURES: The Veterinary Medical Database was searched to identify horses with CVCM and contemporaneous control horses registered between July 1974 and August 2007. Admission date, admitting institution, sex, breed, age at the time of registration in the database, weight, and discharge status (alive, died, or euthanized) were recorded for each case and control horse. RESULTS: On the basis of results of multivariable logistic regression analysis, geldings and sexually intact males had a significantly higher likelihood of having CVCM than females (odds ratio [OR], 2.0 [95% confidence interval, 1.5 to 2.6]; and OR, 2.4 [95% confidence interval, 1.8 to 3.2], respectively). Thoroughbreds, Tennessee Walking Horses, and Warm-bloods were overrepresented in the CVCM group, compared with Quarter Horses. Horses that ranged from < 6 months to < 7 years of age had significantly higher odds of having CVCM, compared with horses > or = 10 years of age. CONCLUSIONS AND CLINICAL RELEVANCE: Sex, breed, and age predilections were detected in horses with CVCM. Improved understanding of these factors will aid clinical recognition of the disease in groups that may have a high prevalence of CVCM or were previously not recognized to be commonly affected. The results may also stimulate future investigations to further delineate etiopathogenesis, such as breed-related genetic causality.

Evaluation of a questionnaire for obtaining owner-perceived, weighted quality-of-life assessments for dogs with spinal cord injuries.

OBJECTIVE: To evaluate a questionnaire for obtaining owner-perceived, weighted quality-oflife assessments for dogs with spinal cord injuries. DESIGN: Evaluation study. Animals-100 dogs with spinal cord injuries and 48 healthy control dogs. PROCEDURES: The questionnaire was adapted from a questionnaire (the schedule for the evaluation of individual quality of life-direct weighting) used for human patients. Specifically, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each of those areas, and provide a weighting for the importance of each area. Results were used to construct a weighted quality-of-life score ranging from 0 to 100 for each dog. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS). RESULTS: A good correlation was found between weighted and VAS quality-of-life scores. Dogs with spinal cord injuries had weighted quality-of-life scores that were significantly lower than scores for control dogs. Quality-of-life areas and activities provided by owners of dogs with spinal cord injuries were similar to areas and activities provided by owners of healthy control dogs and could mostly be encompassed by 5 broader domains: mobility, play or mental stimulation, health, companionship, and other. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the questionnaire could be used to obtain owner-perceived, weighted quality-of-life assessments for dogs with spinal cord injuries. Obtaining owner-perceived quality-of-life assessments for individual dogs should allow veterinarians to better address quality-of-life concerns and expectations of owners.

Owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries.

OBJECTIVE: To evaluate changes over time in owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries and determine whether scores were associated with underlying etiology or with veterinarian-assigned scores for severity of neurologic dysfunction. DESIGN: Cohort study. ANIMALS: 100 dogs with spinal cord injury. PROCEDURES: Duration of dysfunction, modified Frankel neurologic injury score, and etiology were recorded. At initial and recheck (4- to 6-week) evaluations, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each area, and provide a weighting for the importance of each area; results were used to construct a weighted quality-of-life score. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS). RESULTS: At initial and recheck evaluations, weighted quality-of-life scores were higher for ambulatory than for nonambulatory dogs. However, scores did not differ among groups when dogs were grouped on the basis of underlying etiology or duration of injury. Dogs with an increase in Frankel score between the initial and recheck evaluations had a significant increase in weighted quality-of-life score, whereas for dogs that did not have any change in Frankel score, initial and recheck weighted quality-of-life scores were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that owner-assigned, weighted quality-of-life scores for dogs with spinal cord injuries did not vary significantly on the basis of underlying etiology or duration of injury but were higher for ambulatory than for nonambulatory dogs.

Adverse effects and outcome associated with dexamethasone administration in dogs with acute thoracolumbar intervertebral disk herniation: 161 cases (2000-2006).

OBJECTIVE: To determine complications and neurologic outcomes associated with dexamethasone administration to dogs with surgically treated thoracolumbar intervertebral disk herniation, compared with dogs not receiving dexamethasone. DESIGN: Retrospective case series. ANIMALS: 161 dogs with surgically confirmed thoracolumbar disk herniation. PROCEDURES: Medical records from 2 hospitals were used to identify dogs that had received dexamethasone < 48 hours prior to admission (dexamethasone group dogs), dogs that received glucocorticoids other than dexamethasone < 48 hours prior to admission (other-glucocorticoid group dogs), and dogs that received no glucocorticoids (nontreatment group dogs). Signalment, neurologic injury grade, laboratory data, and complications were extracted from medical records. RESULTS: Dexamethasone group dogs were 3.4 times as likely to have a complication, compared with other-glucocorticoid or nontreatment group dogs. Dexamethasone group dogs were 11.4 times as likely to have a urinary tract infection and 3.5 times as likely to have diarrhea, compared with other-glucocorticoid or nontreatment group dogs. No differences in neurologic function at discharge or recheck evaluation were detected among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that treatment with dexamethasone before surgery is associated with more adverse effects, compared with treatment with glucocorticoids other than dexamethasone or no treatment with glucocorticoids, in dogs with thoracolumbar intervertebral disk herniation. In this study population, no difference in outcome was found among groups. These findings suggest that the value of dexamethasone administration before surgery in dogs with thoracolumbar disk herniation should be reconsidered.

Evaluation of the success of medical management for presumptive thoracolumbar intervertebral disk herniation in dogs.

OBJECTIVE: To determine the success of medical management of presumptive thoracolumbar disk herniation in dogs and the variables associated with treatment outcome. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n=223) with presumptive thoracolumbar disk herniation. METHODS: Medical records from 2 clinics were used to identify affected dogs, and owners were mailed a questionnaire about success of therapy, recurrence of clinical signs, and quality of life (QOL) as interpreted by the owner. Signalment, duration and degree of neurologic dysfunction, and medication administration were determined from medical records. RESULTS: Eighty-three percent of dogs (185/223) were ambulatory at initial evaluation. Successful treatment was reported for 54.7% of dogs, with 30.9% having recurrence of clinical signs and 14.4% classified as therapeutic failures. From bivariable logistic regression, glucocorticoid administration was negatively associated with success (P=.008; odds ratio [OR]=.48) and QOL scores (P=.004; OR=.48). The duration of cage rest was not significantly associated with success or QOL. Nonambulatory dogs were more likely to have lower QOL scores (P=.01; OR=2.34). CONCLUSIONS: Medical management can lead to an acceptable outcome in many dogs with presumptive thoracolumbar disk herniation. Cage rest duration does not seem to affect outcome and glucocorticoids may negatively impact success and QOL. The conclusions in this report should be interpreted cautiously because of the retrospective data collection and the use of client self-administered questionnaire follow-up. CLINICAL RELEVANCE: These results provide an insight into the success of medical management for presumptive thoracolumbar disk herniation in dogs and may allow for refinement of treatment protocols.

Evaluation of the success of medical management for presumptive cervical intervertebral disk herniation in dogs.

OBJECTIVE: To determine the success of medical management of presumptive cervical disk herniation in dogs and variables associated with treatment outcome. DESIGN: Retrospective case series. ANIMALS: Dogs (n=88) with presumptive cervical disk herniation. METHODS: Dogs with presumptive cervical and thoracolumbar disk herniation were identified from medical records at 2 clinics and clients were mailed a questionnaire related to the success of therapy, clinical recurrence of signs, and quality of life (QOL) as interpreted by the owner. Signalment, duration and degree of neurologic dysfunction, and medication administration were determined from medical records. RESULTS: Ninety-seven percent of dogs (84/87) with complete information were described as ambulatory at initial evaluation. Successful treatment was reported for 48.9% of dogs with 33% having recurrence of clinical signs and 18.1% having therapeutic failure. Bivariable logistic regression showed that non-steroidal anti-inflammatory drug (NSAID) administration was associated with success (P=.035; odds ratio [OR]=2.52). Duration of cage rest and glucocorticoid administration were not significantly associated with success or QOL. Dogs with less-severe neurologic dysfunction were more likely to have a successful outcome (OR=2.56), but this association was not significant (P=.051). CONCLUSIONS: Medical management can lead to an acceptable outcome in many dogs with presumptive cervical disk herniation. Based on these data, NSAIDs should be considered as part of the therapeutic regimen. Cage rest duration and glucocorticoid administration do not appear to benefit these dogs, but this should be interpreted cautiously because of the retrospective data collection and use of client self-administered questionnaire follow-up. CLINICAL RELEVANCE: These results provide insight into the success of medical management for presumptive cervical disk herniation in dogs and may allow for refinement of treatment protocols.

Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model.

BACKGROUND: Intra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy. A direct comparison of the response of the synovial joint to intra-articular injection of autologous versus allogeneic MSCs has not been performed. The objective of this study was to assess the clinical response to repeated intra-articular injection of allogeneic versus autologous MSCs prepared in a way to minimize xeno-contaminants in a large animal model. METHODS: Intra-articular injections of bone marrow-derived, culture-expanded MSCs to a forelimb metacarpophalangeal joint were performed at week 0 and week 4 (six autologous; six autologous with xeno-contamination; six allogeneic). In the week following each injection, clinical and synovial cytology evaluations were performed. RESULTS: Following the first intra-articular injection, there were no differences in clinical parameters over time. Following the second intra-articular injection, there was a significant adverse response of the joint to allogeneic MSCs and autologous MSCs with xeno-contamination with elevated synovial total nucleated cell counts. There was also significantly increased pain from joints injected with autologous MSCs with xeno-contamination. CONCLUSIONS: Repeated intra-articular injection of allogeneic MSCs results in an adverse clinical response, suggesting there is immune recognition of allogeneic MSCs upon a second exposure.

Early Blockade of Matrix Metalloproteinases in Spinal-Cord-Injured Dogs Results in a Long-Term Increase in Bladder Compliance.

Spinal cord injury (SCI) is often accompanied by reduced bladder compliance, which contributes to adverse conditions including urinary tract infections and vesicoureteral reflux. Reduced compliance is, in part, attributed to extensive remodeling of the bladder wall, including the extracellular matrix (ECM). Here, we tested the hypothesis that blockade of matrix metalloproteinases (MMPs), known for their ability to remodel the ECM, improves bladder compliance in dogs with SCI. We first evaluated dogs with naturally occurring SCIs resulting from intervertebral disc herniation (IVDH). After characterizing the natural history of urological recovery by cystometry in healthy dogs (n = 10) and dogs with SCIs (n = 20), we conducted a randomized, double-blinded, placebo-controlled clinical trial in dogs with IVDH-associated SCIs to assess the efficacy of the broad-spectrum MMP inhibitor, GM6001, given within 48 h post-injury. The primary outcomes were bladder compliance, as measured by cystometry, and an ordinal gait score (Texas Spinal Cord Injury Score; TSCIS) at day 42 post-SCI. Dogs (n = 93) were randomized to receive either dimethyl sulfoxide (DMSO) or GM6001+DMSO. There were transient, but significantly (p = 0.023) greater, adverse events (31 of 42; 74%) in the GM6001-treated group relative to vehicle controls (22 of 46; 48%). Whereas there were no differences in TSCIS between treatment groups at day 42 (p = 0.9679), bladder compliance was significantly higher in dogs treated with GM6001+DMSO compared to controls (p = 0.0272). Further studies are needed to determine whether this inhibition results from a direct interaction with the bladder wall or indirectly through neural-based mechanisms.