Objective-To determine kinematic changes to the hoof of horses at a walk after induction of unilateral, weight-bearing forelimb lameness and to determine whether hoof kinematics return to prelameness (baseline) values after perineural anesthesia. Animals-6 clinically normal Quarter Horses. Procedures-For each horse, a sole-pressure model was used to induce 3 grades of lameness in the right forelimb, after which perineural anesthesia was administered to eliminate lameness. Optical kinematics were obtained for both forelimbs with the horse walking before (baseline) and after induction of each grade of lameness and after perineural anesthesia. Linear acceleration profiles were used to identify hoof events, and each stride was divided into hoof-contact, break-over, initial-swing, terminal-swing, and total-swing segments. Kinematic variables were compared within and between limbs for each segment by use of mixed repeated-measures ANOVA. Results-During the hoof-contact and terminal-swing segments, the hoof of the left (nonlame) forelimb had greater sagittal-plane orientation than did the hoof of the right (lame) forelimb. For the lame limb following lameness induction, the break-over duration and maximum cranial acceleration were increased from baseline. After perineural anesthesia, break-over duration for the lame limb returned to a value similar to that at baseline, and orientation of the hoof during the terminal-swing segment did not differ between the lame and nonlame limbs. Conclusions and Clinical Relevance-Subclinical unilateral forelimb lameness resulted in significant alterations to hoof kinematics in horses that are walking, and the use of hoof kinematics may be beneficial for the detection of subclinical lameness in horses.

Objective: To develop an in vitro model of cartilage injury in full-thickness equine cartilage specimens that can be used to simulate in vivo disease and evaluate treatment efficacy. Sample: 15 full-thickness cartilage explants from the trochlear ridges of the distal aspect of the femur from each of 6 adult horses that had died from reasons unrelated to the musculoskeletal system. Procedures: To simulate injury, cartilage explants were subjected to single-impact uniaxial compression to 50%, 60%, 70%, or 80% strain at a rate of 100% strain/s. Other explants were left uninjured (control specimens). All specimens underwent a culture process for 28 days and were subsequently evaluated histologically for characteristics of injury and early stages of osteoarthritis, including articular surface damage, chondrocyte cell death, focal cell loss, chondrocyte cluster formation, and loss of the extracellular matrix molecules aggrecan and types I and II collagen. Results: Compression to all degrees of strain induced some amount of pathological change typical of clinical osteoarthritis in horses; however, only compression to 60% strain induced significant changes morphologically and biochemically in the extracellular matrix. Conclusions and Clinical Relevance: The threshold strain necessary to model injury in full-thickness cartilage specimens from the trochlear ridges of the distal femur of adult horses was 60% strain at a rate of 100% strain/s. This in vitro model should facilitate study of pathophysiologic changes and therapeutic interventions for osteoarthritis.

Objective-To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses. Animals-8 healthy horses. Procedures-A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography-tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen). Results-Zoledronic acid was safely administered IV during a 30-minute period, and no adverse effects were observed. Plasma concentrations of zoledronic acid were consistent with a 2-compartment mammillary model. Plasma concentrations of zoledronic acid were detected for up to 8 hours after administration. Mean total calcium concentrations in plasma were less than the reference range 7 days after zoledronic acid administration. A marker for bone remodeling decreased in concentration after zoledronic acid administration and remained low for the 1-year duration of the study. No changes in BUN and creatinine concentrations were observed after zoledronic acid administration. Conclusions and Clinical Relevance-Zoledronic acid was safely administered in healthy horses. Zoledronic acid is reported as the strongest bisphosphonate presently available, and studies evaluating potential benefits of zoledronic acid in horses with orthopedic conditions are warranted.

Objective—To assess biometric tools for gait analysis in healthy calves by use of pressure mat sensors, a handheld algometer, and serial circumferential measurements of selected joints. Animals—20 six- to eight-week-old healthy male Holstein calves. Procedures—Calves were evaluated over a 4-day period. Gait analysis was performed by training calves to walk over a pressure-sensitive mat, which recorded quantitative measurements. An algometer was applied perpendicular to each joint until an aversion response was observed or a preset limit of 50 N/cm2 was obtained. Circumference measurements of the carpal and tarsal joints were obtained by the application of a flexible measuring tape to defined areas of each limb. Variability between joint circumference measurements and pressure mat variables were analyzed with a standard least squares means model. Algometer measurements were dichotomized, and logistic regression was used to assess the probability that a calf reacted to algometer-applied pressure. Results—1 calf was removed from the study because of lameness. Mean carpal and tarsal joint circumference measurements were reliable and consistent among calves. Algometry results suggested that healthy calves were more sensitive to pressure applied to the elbow and stifle joints, compared with pressure applied to the carpal, tarsal, and metacarpophalangeal or metatarsophalangeal joints. Pressure mat variables of stance time and stride velocity varied greatly among calves, whereas impulse and maximum forces varied little. Conclusions and Clinical Relevance—Findings can serve as reference points for other studies and be used for comparison with results for calves with lameness or altered gaits.

Objective-To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). Animals-9 healthy adult Hispaniolan Amazon parrots. Procedures-Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. Results-No changes in the parrots’ behavior were observed. Twelve hours after the first dose was administered, mean +/- SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 +/- 57 ng/mL and 6 +/- 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 +/- 0.78 hours and 2.14 +/- 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. Conclusions and Clinical Relevance-On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

In aerobiology, dose-response studies are used to estimate the risk of infection to a susceptible host presented by exposure to a specific dose of an airborne pathogen. In the research setting, host- and pathogen-specific factors that affect the dose-response continuum can be accounted for by experimental design, but the requirement to precisely determine the dose of infectious pathogen to which the host was exposed is often challenging. By definition, quantification of viable airborne pathogens is based on the culture of micro-organisms, but some airborne pathogens are transmissible at concentrations below the threshold of quantification by culture. In this paper we present an approach to the calculation of exposure dose at microbiologically unquantifiable levels using an application of the “continuous-stirred tank reactor (CSTR) model” and the validation of this approach using rhodamine B dye as a surrogate for aerosolized microbial pathogens in a dynamic aerosol toroid (DAT).

There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx), and interleukin-1 beta (IL-1β) were measured in synovial fluid. Concentrations of NOx and PGE2 in synovial fluid were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.

Although bovine respiratory disease complex (BRDC) is common in post-weaning cattle, BRDC prediction models are seldom analyzed. The objectives of this study were to assess the ability to predict cumulative cohort-level BRDC morbidity using on-arrival risk factors and to evaluate whether or not adding BRDC risk classification and daily BRDC morbidity and mortality data to the models enhanced their predictive ability. Retrospective cohort-level and individual animal health data were used to create mixed negative binomial regression (MNBR) models for predicting cumulative risk of BRDC morbidity. Logistic regression models were used to illustrate that the percentage of correctly (within |5%| of actual) classified cohorts increased across days, but the effect of day was modified by arrival weight, arrival month, and feedlot. Cattle arriving in April had the highest (77%) number of lots correctly classified at arrival and cattle arriving in December had the lowest (28%). Classification accuracy at arrival varied according to initial weight, ranging from 17% (< 182 kg) to 91% (> 409 kg). Predictive accuracy of the models improved from 64% at arrival to 74% at 8 days on feed (DOF) when risk code was known compared to 56% accuracy at arrival and 69% at 8 DOF when risk classification was not known. The results of this study demonstrate how the predictive ability of models can be improved by utilizing more refined data on the prior history of cohorts, thus making these models more useful to operators of commercial feedlots.

Objective: To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration. Animals: 6 healthy cats. Procedures: In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis. Results: Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%. Conclusions and Clinical Relevance: The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.

Objective-To assess the effects of oxygen insufflation rate, respiratory rate, and tidal volume on fraction of inspired oxygen (Fio2) in cadaveric canine heads attached to a lung model. Sample-16 heads of canine cadavers. Procedures-Each cadaver head was instrumented with a nasal insufflation catheter through which oxygen was delivered. The trachea was attached to a sample collection port connected by means of corrugated tubing to a lung model. Eight treatment combinations that varied in respiratory rate (10 or 20 breaths/min), tidal volume (10 or 15 mL/kg), and oxygen insufflation rate (50 or 100 mL/kg/min) were applied to each head in a replicated Latin square design. Gas samples were manually collected, and inspired oxygen concentrations were analyzed. The Fio2 and end-tidal CO2 concentration were determined and compared among sample groups. Results-Estimated least squares mean Fio2 for various treatment combinations ranged from 32.2% to 60.6%. The Fio2 was significantly increased at the higher insufflation rate (estimated marginal least squares mean, 48.7% vs 38.6% for 100 and 50 mL/kg/min, respectively), lower respiratory rate (48.9% vs 38.3% for 10 and 20 breaths/min, respectively), and smaller tidal volume (46.8% vs 40.0% for 10 and 15 mL/kg, respectively). Conclusions and Clinical Relevance-Fio2 in the model was affected by oxygen insufflation rate, respiratory rate, and tidal volume. This information may potentially help clinicians interpret results of blood gas analysis and manage canine patients receiving oxygen insufflation via a nasal catheter.