Objective—To determine values for total body water (TBW), extracellular fluid volume (ECFV), intracellular fluid volume (ICFV), and plasma volume (PV) in healthy neonatal (< 24 hours old) foals and to create a multifrequency bioelectrical impedance analysis (MF-BIA) model for use in neonatal foals. Animals—7 healthy neonatal foals. Procedures—Deuterium oxide (0.4 g/kg, IV), sodium bromide (30 mg/kg, IV), and Evans blue dye (1 mg/kg, IV) were administered to each foal. Plasma samples were obtained following an equilibration period, and the TBW, ECFV, ICFV, and PV were calculated for each foal. An MF-BIA model was created by use of morphometric measurements from each foal. Results—Mean ± SD values were obtained for TBW (0.744 ± 0.024 L/kg), ICFV (0.381 ± 0.018 L/kg), ECFV (0.363 ± 0.014 L/kg), and PV (0.096 ± 0.015 L/kg). The 95% limits of agreement between the MF-BIA and indicator dilution techniques were within ± 2 L for TBW and ECFV. Conclusions and Clinical Relevance—Fluid volumes in neonatal foals were found to be substantially larger than fluid volumes in adult horses. Multifrequency bioelectrical impedance analysis may be a useful technique for predicting TBW, ICFV, and ECFV in neonatal foals.

Objective—To assess whether the Pfirrmann system for grading lumbar intervertebral disk (IVD) degeneration in humans can also be used in dogs. Animals—202 dogs. Procedures—Magnetic resonance imaging was used to obtain images of vertebral segments from dogs, which were reviewed separately by 3 observers who graded the extent of degeneration in each visible IVD by use of the Pfirrmann classification system used for grading lumbar IVD degeneration in humans. Grading was validated against 2 factors associated with the extent of disk degeneration: type of dog (chondrodystrophic or nonchondrodystrophic breeds) and age. Results—Interobserver and intraobserver agreement for Pfirrmann grading of IVD degeneration were good (κ scores, 0.81 to 0.93). An increase in the extent of disk degeneration was positively correlated with increases in age and with chondrodystrophic breed. Conclusions and Clinical Relevance—The Pfirrmann system was reliably used to grade IVD degeneration in dogs of various breeds and ages. An increase in the extent of IVD degeneration was positively correlated with increases in age and with chondrodystrophic-type dogs.

Escherichia coli O157:H7 remains a threat to humans via cattle-derived fecal contamination of food and water. Preharvest intervention strategies represent a means of reducing the pathogen burden before harvest. In this study, the efficacy of a commercially produced type III secreted protein (TTSP) vaccine was evaluated with the use of a commingled experimental calf infection model (30 placebo-treated animals and 30 vaccinates). The calves were vaccinated on days 0, 21, and 42 and infected with 109 colony-forming units (CFU) of E. coli O157 by oral–gastric intubation on day 56. Fecal shedding was monitored daily for 14 d. Serologic assessment revealed a robust immune response to vaccination; the serum titers of antibodies against EspA, Tir, and total TTSPs were significantly higher in the vaccinates than in the placebo-treated animals on days 21, 42, 56, and 70. Significantly less (P = 0.011) of the challenge organism was shed by the vaccinates than by the placebo-treated animals on days 3 to 10. Peak shedding occurred in both groups on days 3 to 6; during this period the vaccinates showed a mean log reduction of 1.4 (P = 0.002) and a mitigated fraction of 51%. The number of animals shedding was significantly lower among the vaccinates compared with the placebo group on days 3 to 6 (P ≤ 0.05), with a mean prevented fraction of 21%. No differences in the duration of shedding were observed. Owing to the low challenge shedding in both groups on days 11 to 14 (mean CFU/g < 10; median = 0), no significant differences were observed. These data indicate that TTSP vaccination had protective effects through significant reductions in the number of animals shedding and the number of challenge organisms shed per animal and provides evidence that TTSP vaccination is an effective preharvest intervention strategy against E. coli O157.

A useful approach for evaluating antitussive drugs in humans is to determine the sensitivity of the cough reflex to a standard challenge. The purpose of this study was to determine if methods used to induce coughing in humans would be effective when used on awake, untrained, healthy dogs for future application in therapeutic trials involving dogs with spontaneous disease. Methods tested were: mechanically stimulating the trachea by digital compression as well as by vibration from an electric shaver, neck massager, and palm sander (11 dogs), and administering nebulized irritant (3000 micromolar capsaicin), acidic (1 M citric acid), and hypotonic (deionized water) solutions using face masks (4 dogs). The threshold for success was defined as induction of at least 2 moderate or strong coughs in at least 75% of the dogs. None of the methods tested was successful. Digital compression induced soft (n = 2) or moderate (n = 1) coughing in 3 of 11 dogs tested. Nebulization of citric acid induced 1 soft cough in 1 of 4 dogs. It was concluded that coughing cannot be successfully induced in awake, healthy dogs using methods that are successful in humans. Other strategies must be developed so that cough sensitivity can be objectively and non-invasively measured in dogs for clinical research purposes.

Objective: To determine whether therapeutic concentrations of levetiracetam can be achieved in cats and to establish reasonable IV and oral dosing intervals that would not be associated with adverse effects in cats. Animals: 10 healthy purpose-bred cats. Procedures: In a randomized crossover study, levetiracetam (20 mg/kg) was administered orally and IV to each cat. Blood samples were collected 0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after administration. Plasma levetiracetam concentrations were determined via high-performance liquid chromatography. Results: Mean ± SD peak concentration was 25.54 ± 7.97 μg/mL. The mean y-intercept for IV administration was 37.52 ± 6.79 μg/mL. Half-life (harmonic mean ± pseudo-SD) was 2.95 ± 0.95 hours and 2.86 ± 0.65 hours for oral and IV administration, respectively. Mean volume of distribution at steady state was 0.52 ± 0.09 L/kg, and mean clearance was 2.0 ± 0.60 mL/kg/min. Mean oral bioavailability was 102 ± 39%. Plasma drug concentrations were maintained in the therapeutic range reported for humans (5 to 45 μg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild, transient hypersalivation was evident in some cats after oral administration. Conclusions and Clinical Relevance: Levetiracetam (20 mg/kg) administered orally or IV to cats every 8 hours should achieve and maintain concentrations within the therapeutic range for humans. Levetiracetam administration has favorable pharmacokinetics for clinical use, was apparently tolerated well, and may be a reasonable alternative antiepileptic drug in cats.

Objective—To evaluate symmetry of the hind limbs in orthopedically normal trotting dogs. Animals—19 orthopedically normal Labrador Retrievers with no history of lameness. Procedures—Retroreflective markers were applied to the hind limb joints, and a 4-camera kinematic system captured positional data at 200 Hz in tandem with force platform data collection while the dogs trotted. Morphometric data were combined with kinematic and force data in an inverse dynamics method to calculate net joint moments and powers at the joints as well as total support moment for each limb. Dogs were identified as right or left dominant when their total support moment was > 10% asymmetric between sides. Results—10 of the 19 dogs were mechanically dominant in the right hind limb as determined by their total support moments. One dog was left dominant, and the remaining 8 were symmetric. Right-dominant dogs had larger net joint moments at the right hip, tarsal, and metatarsophalangeal joints and a smaller moment at the right stifle joint, compared with values for the left hind limb. The 1 left-dominant dog had the exact opposite findings. Hip and stifle joint moments and powers varied between limbs of the right-dominant and left-dominant groups in the timing of their transition from negative to positive, and power amplitudes varied at the hip, tarsal, and metatarsophalangeal joints but not the stifle joint. Conclusions and Clinical Relevance—Sound trotting dogs can have asymmetries in limb and joint mechanics. These natural mechanical asymmetries should be taken into account when considering models to evaluate stresses at joints and when considering surgery for cruciate ligament rupture.

Objective-To evaluate effects of extracorporeal shock wave therapy (ESWT) and polysulfated glycosaminoglycan treatment (PSGAGT) on subchondral bone (SCB), serum biomarkers, and synovial fluid biomarkers in horses with induced osteoarthritis. Animals-24 healthy 2- to 3-year-old horses. Procedures-An osteochondral fragment was created on the distal aspect of the radial carpal bone in 1 middle carpal joint of each horse. Horses were randomly allocated to receive local application of ESWT (days 14 and 28; n = 8), PSGAGT (IM, q 4 d for 28 days; 8), or a sham ESWT probe (placebo; days 14 and 28; 8). Serum biomarkers were measured every 7 days, and synovial fluid biomarkers were measured every 14 days. Bone density was measured by use of computed tomography on days 0 and 70, and microdamage and bone formation variables were compared among groups at the end of the study (day 70). Results-There was no significant effect of ESWT or PSGAGT on any bone variable. Serum osteocalcin concentration was significantly greater in horses that received ESWT, compared with placebo-treated horses, and serum concentration of the C-terminal telopeptide of type I collagen was significantly higher in horses that received ESWT, compared with placebo- and PSGAG-treated horses. Concentrations of the synovial fluid epitope CS846 were significantly higher in joints with osteoarthritis treated with ESWT Conclusions and Clinical Relevance-Treatment of osteoarthritis with ESWT had no effect on SCB but did induce increases in serum biomarkers indicative of bone remodeling. Treatment of osteoarthritis with PSGAG had no effect on SCB or biomarkers.

Objective-To evaluate 2 commercially available transfection reagents for transfection efficiency and distribution of small interfering RNA (siRNA) molecules to chondrocytes in monolayer cultures and full-thickness cartilage explants from guinea pigs and horses. Sample-Cartilage explants from 5 one-month-old and 3 adult guinea pigs and 5 adult clinically normal horses. Procedures-Monolayer chondrocytes and uniform cartilage explants were exposed to 1 of 2 siRNA transfection complexes according to manufacturers' protocols (1micromolar [1×]). Additionally, monolayer chondrocytes were exposed to 2× the suggested amount of a proprietary siRNA molecule. Full-thickness cartilage explants were treated with 1× (1micromolar), 2× (2micromolar), and 4× (4micromolar) or 1× (0.13micromolar), 4× (0.52micromolar), and 8× (1.04micromolar) the recommended concentrations of the proprietary siRNA and the cationic liposome siRNA, respectively, in equivalent media volumes. Use of fluorescent siRNA duplexes allowed quantification of transfected cells via flow cytometry and direct visualization of the depth and distribution of in situ transfection via fluorescent microscopy. Results-With both transfection reagents, > 90% of monolayer chondrocytes were transfected. In explants, only use of the proprietary molecule achieved > 50% transfection efficiency, whereas use of the cationic liposome achieved < 20%. Only the proprietary molecule-treated cartilage consistently contained fluorescent cells throughout all zones; the cationic liposome-transfected chondrocytes were restricted to explant surfaces. Conclusions and Clinical RelevanceRobust transfection of chondrocytes in monolayer was achieved with both reagents, but only use of the proprietary molecule attained effective full-thickness transfection of explants that may allow relevant transcript reduction via RNAi.

Objective—To evaluate cartilage thickness of the talus (especially at sites predisposed to osteochondrosis dissecans [OCD]) in growing and adult dogs not affected with OCD. Sample—Tarsocrural joints from cadavers of 34 juvenile (approx 3 months old) and 10 adult dogs. Procedures—Tarsal cartilage thickness was examined via a stereophotography microscopic system. Articular cartilage thickness was determined at 11 locations on longitudinal slices of the trochlear ridges and the sulcus between the ridges and at 2 locations in the cochlea tibiae. Cartilage thickness was measured at the proximal, proximodorsal, dorsal, and distal aspects of the trochlear ridges; proximodorsal, dorsal, and distal aspects of the trochlear sulcus; and craniolateral and caudomedial aspects of the cochlea tibiae. Differences within a joint and between sexes were evaluated. Results—Mean cartilage thickness decreased from proximal to distal in juvenile (lateral trochlear ridge, 1.52 to 0.41 mm; medial trochlear ridge, 1.10 to 0.40 mm) and from proximal to dorsal in adult (lateral trochlear ridge, 0.41 to 0.34 mm; medial trochlear ridge, 0.33 to 0.23 mm) dogs. Cartilage was thickest at the proximal aspect of the lateral trochlear ridge in both groups. Differences in proximodorsal, dorsal, and distal aspects of the ridges were not evident. Conclusions and Clinical Relevance—Healthy tarsocrural joints did not have thicker cartilage in sites predisposed to development of OCD. Evaluation of affected tarsocrural joints is necessary to exclude influences of cartilage thickness. These data are useful as a reference for distribution of cartilage thickness of the trochlea of the talus in dogs.

Objective—To develop a parsimonious statistical model to predict incidence of lameness in the subsequent lactation by use of data collected at cessation of lactation in dairy cows. Animals—574 cows. Procedures—At cessation of lactation during hoof trimming, body condition score (BCS), visual locomotion score, digital cushion thickness (DCT), and digital lesions were assessed. Results—140 (24%) cows were treated for claw horn disruption lesions (CHDLs) at cessation of lactation (114 with sole ulcers [pododermatitis circumscripta] and 26 with white line disease). The BCS was highly associated with DCT. Cows with CHDLs at cessation of lactation had significantly lower DCT, compared with other cows. All 3 logistic regression models predicted the incidence of CHDLs in the subsequent lactation with good accuracy; the area under the receiver operating characteristic curves was 0.76, 0.76, and 0.77 for the first, second, and third logistic regression models, respectively. Conclusion and Clinical Relevance—Evaluation of 3 logistic regression models indicated that lameness could be predicted with good accuracy by use of all 3. The ability to predict lameness will facilitate the implementation of lameness prevention strategies by targeting specific cows.