OBJECTIVE To use proteomic analysis to determine the protein constituents of synovial fluid samples from the stifle joints of dogs with and without osteoarthritis secondary to cranial cruciate ligament rupture (CCLR). ANIMALS 12 dogs with clinically normal stifle joints (controls) and 16 dogs with osteoarthritis secondary to CCLR. PROCEDURES A synovial fluid sample was obtained from all dogs. Synovial fluid total protein concentration was determined by the Bradford assay. Proteins were separated by use of a 1-D SDS-PAGE to detect protein bands that differed between dogs with and without osteoarthritis. Those protein bands then underwent trypsin digestion and were analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, the results of which were compared with a curated protein sequence database for protein identification. One of the most frequently identified proteins, apoprotein (apo) A-I, was then quantified in all synovial fluid samples by use of a competitive-inhibition ELISA. Results were compared between dogs with and without osteoarthritis. RESULTS Median synovial fluid total protein and apo A-I concentrations for dogs with osteoarthritis were significantly greater than those for control dogs. The most abundant proteins identified in the synovial fluid were albumin and apo A-I. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that quantification of synovial fluid total protein and apo A-I concentrations might facilitate diagnosis of osteoarthritis secondary to CCLR in dogs. Further research and validation of synovial fluid apo A-I concentration as a biomarker for osteoarthritis in dogs are necessary before it can be recommended for clinical use.

This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO2) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO2) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO2 to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO2 and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species.

Objective-To determine the prevalence of activating internal tandem duplications (ITDs) in exons 11 and 12 of c-kit in mast cell tumors (MCTs) of dogs and to correlate these mutations with prognosis. Sample Population-157 formalin-fixed, paraffinembedded MCTs from dogs in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis. Procedure-Genomic DNA was isolated from tumor specimens and a polymerase chain reaction procedure was performed to determine whether there were ITDs in exons 11 and 12. Results-We identified ITDs in 1 of 12 (8%) grade-I, 42 of 119 (35%) grade-II, and 9 of 26 (35%) grade-III tumors (overall prevalence, 52 of 157 [33%]). Logistic regression analysis revealed that the odds of grade-II and -III tumors possessing an ITD were approximately 5 times greater than that for grade-I tumors, although these odds did not differ significantly. Although MCTs possessing an ITD were twice as likely to recur after excision and twice as likely to result in metastasis as those without an ITD, these values also did not differ significantly. Conclusions and Clinical Relevance-These results provide evidence that ITDs in c-kit occur frequently in MCTs of dogs. The high prevalence of c-kit activating mutations in MCTs of dogs combined with the relative abundance of mast cell disease in dogs provide an ideal naturally developing tumor in which to test the safety and efficacy of novel small-molecule kinase inhibitors such as imatinib mesylate.

OBJECTIVE To determine the prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma (BCL). ANIMALS 45 dogs with multicentric BCL and 10 healthy control Beagles. PROCEDURES The medical record database of a veterinary teaching hospital was searched to identify dogs with BCL that were treated between November 2005 and April 2015. Information regarding overall response to chemotherapy, progression-free survival (PFS) time, and overall survival time was extracted from each record. Archived lymph node aspirate specimens from dogs with BCL and lymph node aspirate specimens from the 10 control dogs underwent real-time PCR analysis to determine mRNA expression of CD44 variant isoforms of exons 3, 6, and 7 and the CD44 whole isoform. For each isoform, mRNA expression was compared between dogs with BCL and control dogs. The mean relative expression of each isoform was used to classify dogs with BCL into either a high- or low-expression group, and overall response rate, PFS time, and overall survival time (ie, indices of prognosis) were compared between the 2 groups. RESULTS For all isoforms evaluated, mean relative mRNA expression for dogs with BCL was numerically lower than that for control dogs. Dogs with BCL and high CD44 isoform expression had a lower overall response rate, median PFS time, and median overall survival time, compared with dogs with BCL and low CD44 isoform expression. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for dogs with BCL, high expression of exons 3, 6, and 7 was associated with a poor prognosis.

OBJECTIVE To develop a novel method for use of diagnostic imaging, finite element analysis (FEA), and simulated biomechanical response behavior of brain tissue in noninvasive assessment and estimation of intracranial pressure (ICP) of dogs. SAMPLE MRI data for 5 dogs. PROCEDURES MRI data for 5 dogs (1 with a geometrically normal brain that had no detectable signs of injury or disease and 4 with various degrees of geometric abnormalities) were obtained from a digital imaging archiving and communication system database. Patient-specific 3-D models composed of exact brain geometries were constructed from MRI images. Finite element analysis was used to simulate and observe patterns of nonlinear biphasic biomechanical response behavior of geometrically normal and abnormal canine brains at various levels of decreasing cerebral perfusion pressure and increasing ICP. RESULTS Changes in biomechanical response behavior were detected with FEA for decreasing cerebral perfusion pressure and increasing ICP. Abnormalities in brain geometry led to observable changes in deformation and biomechanical response behavior for increased ICP, compared with results for geometrically normal brains. CONCLUSIONS AND CLINICAL RELEVANCE In this study, patient-specific critical ICP was identified, which could be useful as a method to predict the onset of brain herniation. Results indicated that it was feasible to apply FEA to brain geometry obtained from MRI data of clinical patients and to use biomechanical response behavior resulting from increased ICP as a diagnostic and prognostic method to noninvasively assess or classify levels of brain injury in clinical veterinary settings.

This study quantified the effect of peripartum reproductive disorders and parity on repeat breeder status and involuntary culling of dairy cows. Reproductive data of 418 383 lactations were taken from a computerized databank of health records for dairy cows. A logistic regression model was used with dystocia, retained placenta (RP), metritis complex, and parity as fixed effect risk factors and herd entered as the random effect. Of the peripartum problems studied, dystocia had the greatest effect on future fertility. Dystocia increased the odds of a cow being a repeat breeder by 44% [odds ratio (OR): 1.44; confidence interval (CI): 1.37 to 1.51]. Compared to first-parity cows, cows in second, third, and fourth parities had significantly higher odds of being a repeat breeder: 18% (OR: 1.18; CI: 1.16 to 1.20); 24% (OR: 1.24; CI: 1.21 to 1.26); and 42% (OR: 1.42; CI: 1.39 to 1.45), respectively. The odds for second-, third-, or fourth-parity repeat breeders being culled were 24% (OR: 1.24; CI: 1.20 to 1.28); 39% (OR: 1.39; CI: 1.35 to 1.43); and 67% (OR: 1.67; CI: 1.62 to 1.71) respectively, while peripartum reproductive problems had less of an effect.

Objective-To explore whether early analysis of spatial data may result in identification of variables associated with epidemic spread of foot and mouth disease. Sample Population-37 farms with infected cattle (ie, case farms) reported within the first 6 days of the 2001 Uruguayan foot-and-mouth disease epidemic. Procedure-A georeferenced database was created and retrospective analysis was performed on case farm location in relation to farm density, cattle density, farm type (ie, beef vs dairy cattle production), road density, case farm distance to the nearest road, farm size, farm ownership, and day of infection. Mean or median results of 1 to 3 day versus 4 to 6 day spatial data were compared. Spatial-temporal associations were investigated by correlation analysis. Results-Comparison of mean or median values between the first 3 days and days 4 to 6 of the epidemic and results of correlation analysis indicated a significant increase in road density, cattle density, and dairy cattle production and a significant decrease in farm size and case farm distance to the nearest road that developed over time. A route that linked most case farms by the shortest possible distance and also considered significantly associated variables was created. It included 86.1% of all case farms reported by 60 days into the epidemic. Conclusions and Clinical Relevance-Epidemic direction can be assessed on the basis of road density and other spatial variables as early as 6 days into an epidemic. Epidemic control areas may be more effectively identified if local and regional georeferenced data are considered.