The impact of surgery resident training on the duration of tibial plateau leveling osteotomy surgery.

OBJECTIVE: To investigate the impact of surgery resident training on surgery duration in tibial plateau leveling osteotomy (TPLO) and evaluate whether surgery duration differs with each year of residency training. STUDY DESIGN: Retrospective medical record review. ANIMALS: A total of 256 client-owned dogs underwent TPLO. METHODS: Records of dogs that underwent TPLO between August 2019 and August 2022 were reviewed. The effects of the surgeon (faculty/resident) and the procedure (arthrotomy/arthroscopy) on TPLO surgery duration were examined with an analysis of variance, and geometric least squares means (GLSM) were compared. A linear mixed effects model (LMM) was fitted to quantify fixed and random effects. RESULTS: Four faculty surgeons performed 74 (29%) TPLOs, while 10 residents performed 182 (71%) TPLOs under the direct supervision of a faculty surgeon. All TPLOs were conducted with arthrotomy (109; 43%) or arthroscopy (147; 57%). Overall, residents (GLSM, 153 min) required 54% more surgery duration than faculty surgeons (GLSM, 99 min). Surgery duration among first-year residents (GLSM, 170 min) was 15% longer than second- (GLSM, 148 min) and third-year (GLSM, 147 min) residents, whereas the duration did not differ statistically between second- and third-year residents. Arthroscopy, meniscal tear treatment, surgery on the right stifle, and increasing patient weight were also associated with longer surgery duration. CONCLUSION: The duration of TPLO surgery significantly decreased after the first year of residency, but did not decrease afterward. CLINICAL SIGNIFICANCE: The results will aid with resource allocation, curricula planning, and cost management associated with resident training.

Pharmacokinetics, pharmacodynamics and antinociceptive effects of buprenorphine following transdermal administration to horses.

OBJECTIVE: This study describes the pharmacokinetics and pharmacodynamics, including antinociceptive effects, of a transdermal buprenorphine solution in horses. It was hypothesized that transdermal application would lead to sustained blood concentrations and antinociceptive effects with fewer adverse effects compared with intravenous (IV) injection. STUDY DESIGN: Prospective nonrandomized four-part parallel experimental study. ANIMALS: A group of eight horses (three mares and five geldings) aged 6-12 years. METHODS: Horses were administered incremental doses of 15, 30 and 45 µg kg-1 of buprenorphine transdermal solution and a single IV dose of 5 µg kg-1 of buprenorphine with a 2 week washout period between treatments. Concentrations of buprenorphine were determined in plasma using liquid chromatography-tandem mass spectrometry and modeled using a nonlinear mixed effects population pharmacokinetic model to determine pharmacokinetic parameters. Pharmacodynamic effects, including changes in locomotor activity, heart rate, body temperature, gastrointestinal borborygmi, thermal and mechanical nociceptive thresholds were recorded. Mixed effects analysis of variance and post hoc comparisons were performed using a Bonferroni multiple comparison adjustment to assess differences in pharmacodynamic parameters between baseline and each time point within each dose group and between dose groups at the same time point. RESULTS: Transdermal application of buprenorphine resulted in low systemic concentrations relative to IV injection. Bioavailability after transdermal application was 11%. Thermal nociceptive thresholds were significantly (p < 0.05) increased (4.3-10.7% relative to baseline) for up to 72 hours in the IV dose group, but only sporadically in the transdermal dose groups (2.5-9.9% relative to baseline). Changes in locomotor activity, heart rate and borborygmi varied over time and with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Limited thermal antinociceptive effects were observed at the transdermal doses studied likely owing to limited absorption relative to IV dosing. Future studies may be directed toward investigating antinociceptive effects of higher transdermal doses and different application sites.

Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses.

Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus acetaminophen (1.2 mg/kg codeine and 6-6.4 mg/kg acetaminophen) in a three-way balanced crossover design. Plasma samples were collected, concentrations of drug and metabolites determined via liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed. Pharmacodynamic outcomes, including effect on thermal thresholds, were assessed. Codeine Cmax and AUC were significantly different between the codeine and combination group. There was considerable inter-individual variation in the pharmacokinetic parameters for codeine, acetaminophen, and their metabolites in horses. All treatments were well tolerated with minimal significant adverse effects. An increase in the thermal threshold was noted at 1.5 and 2 h, from 15 min through 6 h and 0.5, 1, 1.5, and 3 h in the codeine, acetaminophen, and combination groups, respectively.

Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses.

The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a four-way balanced crossover design, with a 2-week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (Cmax : 11.6-37.8 ng/mL (0.6 mg/kg); 15.8-42.6 ng/mL (0.8 mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8 mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti-nociceptive effects of morphine following oral administration.

Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses.

BACKGROUND: In humans, codeine is a commonly prescribed analgesic that produces its therapeutic effect largely through metabolism to morphine. In some species, analgesic effects of morphine have also been attributed to the morphine-6-glucuronide (M6G) metabolite. Although an effective analgesic, administration of morphine to horses produces dose-dependent neuroexcitation at therapeutic doses. Oral administration of codeine at a dose of 0.6 mg/kg has been shown to generate morphine and M6G concentrations comparable to that observed following administration of clinically effective doses of morphine, without the concomitant adverse effects observed with morphine administration. Based on these results, it was hypothesized that codeine administration would provide effective analgesia with decreased adverse excitatory effects compared to morphine. Seven horses received a single oral dose of saline or 0.3, 0.6 or 1.2 mg/kg codeine or 0.2 mg/kg morphine IV (positive control) in a randomized balanced 5-way cross-over design. Blood samples were collected up to 72 hours post administration, codeine, codeine 6-glucuronide, norcodeine morphine, morphine 3-glucuronide and M6G concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Pre- and post-drug related behavior, locomotor activity, heart rate and gastrointestinal borborygmi were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency. RESULTS: Morphine concentrations were highest in the morphine dose group at all times post administration, however, M6G concentrations were significantly higher in all the codeine dose groups compared to the morphine group starting at 1 hour post drug administration and up to 72-hours in the 1.2 mg/kg group. With the exception of one horse that exhibited signs of colic following administration of 0.3 and 0.6 mg/kg, codeine administration was well tolerated. Morphine administration, led to signs of agitation, tremors and excitation. There was not a significant effect on thermal nociception in any of the dose groups studied. CONCLUSIONS: The current study describes the metabolic profile and pharmacokinetics of codeine in horses and provides information that can be utilized in the design of future studies to understand the anti-nociceptive and analgesic effects of opioids in this species with the goal of promoting judicious and safe use of this important class of drugs.

Prediction of gestational age based on foetal ultrasonographic biometric measurements in light breed horses.

A table was generated, based on foetal ultrasonographic measurements in light breed mares, for each day of gestation beginning with day 100, to provide the predicted value of four biometric parameters: biparietal diameter (BPD), eye approximated volume (EyV), foetal aortic diameter (AortD) and femur length (FL). Using this table, day of gestation was successfully predicted in 23 Quarter Horses (QH) with known mating or ovulation dates. BPD, EyV and FL were the best foetal age predictors between 100- and 200-days gestation predicting within 2 weeks of the actual day of gestation, while BPD and EyV were best between 200 and 300 days (within 3 weeks), and EyV was best after 300 days (within 3 weeks).

Pharmacokinetics of grapiprant and effects on TNF-alpha concentrations following oral administration to horses.

Grapiprant is a prostaglandin E2 receptor antagonist that has been found to be an effective anti-inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses received a single oral administration of 15 mg/kg. Plasma concentrations were determined for 96 h using liquid chromatography-tandem mass spectrometry. Non-compartmental analysis was used to determine pharmacokinetic parameters. Pharmacodynamic effects were assessed ex vivo by stimulating blood samples with PGE2 and determining TNF-ɑ concentrations. Maximum concentration, time to maximum concentration and area under the curve were 327.5 (188.4-663.0) ng/ml, 1 (0.75-2.0) hour and 831.8 (512.6-1421.6) h*ng/ml, respectively. The terminal half-life was 11.1 (8.27-21.2) hr. Significant stimulation of TNF alpha was noted for 2-4 h post-drug administration. Results of this study suggest a short duration of EP4 receptor engagement when administered at a dose of 15 mg/kg.

Characterization of the pharmacokinetics, behavioral effects and effects on thermal nociception of morphine 6-glucuronide and morphine 3-glucuronide in horses.

OBJECTIVE: To describe the pharmacokinetics, behavioral and physiologic effects and effects on thermal thresholds of morphine, morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) following administration to horses. STUDY DESIGN: Randomized balanced crossover study. ANIMALS: A total of seven University-owned horses, five mares and two geldings, aged 3-6 years. METHODS: Horses were treated with a single intravenous dosage of saline, morphine (0.2 mg kg-1), M6G (0.01 mg kg-1) and M3G (0.03 mg kg-1). Blood was collected prior to (baseline) and at several times post administration. Drug and metabolite concentrations were determined by liquid chromatography-mass spectrometry, and plasma pharmacokinetics were calculated. Behavioral observations and physiologic variables (heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were determined at baseline and for up to 6 hours. The effects on thermal nociception were determined and thermal excursion was calculated. RESULTS: The volumes of distribution were 4.75-10.5, 0.244-0.295 and 0.215-0.356 L kg-1 for morphine, M6G and M3G, respectively. Systemic clearances were 26.8-39.6, 3.16-3.88 and 1.46-2.13 mL minute-1 kg-1 for morphine, M6G and M3G, respectively. Morphine administration resulted in signs of excitation as evidenced by an increase in step counts and subjective behavioral observations, whereas M6G and M3G, based on the same criteria, appeared to cause sedative-like effects. Significant effects on thermal nociception were observed until 4 hours post morphine administration, 1 hour post M6G administration and at various times post M3G administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study provide additional information regarding the use of morphine in horses. Less locomotor excitation and gastrointestinal adverse effects, compared with morphine, coupled with favorable effects on thermal nociception are encouraging for further study of the pharmacodynamics of both M6G and M3G in horses.

Health and nutrition of loggerhead sea turtles (Caretta caretta) in the southeastern United States.

Loggerhead sea turtles (Caretta caretta) are opportunistic carnivores that feed primarily on benthic invertebrates and fish. Sea turtle rehabilitation requires provision of a species-specific, balanced diet that supplies nutrition similar to that of a wild diet; this can be challenging because free-ranging loggerheads' diets vary depending on their life stage and geographic location, with predominant prey species dictated by local availability. The goal of this study was to better understand the nutritional needs of subadult and adult loggerheads in rehabilitation. This was accomplished by conducting a retrospective survey of stomach contents identified during gross necropsy of 153 deceased loggerheads that stranded in coastal Georgia, USA. A total of 288 different forage items were identified; the most frequently observed prey items belong to the subphylum Crustacea (N = 131), followed by bony fish (Osteichthyes; N = 45), gastropod mollusks (N = 40), bivalve mollusks (N = 23), and Atlantic horseshoe crabs (Limulus polyphemus; N = 15). The proportions of certain prey items differed significantly with turtle size; adult turtles ate proportionately more gastropods (p = 0.001), and subadults ate proportionately more fish (p = 0.01). Stomach contents information was used to determine common local prey items (blue crab, cannonball jellyfish, horseshoe crab, whelk), which were evaluated for nutritional content. Additionally, we compared hematology and plasma biochemistry profiles (including proteins, trace minerals, and vitamins) between four cohorts of loggerhead turtles, including free-ranging subadults and adults, nesting females, and loggerheads undergoing rehabilitation. This information was applied to inform a regionally specific, formulated diet for tube feeding, and a supplement containing vitamins and minerals for captive loggerheads, to more closely approximate the nutritional content of their natural diet. Assessing the regional and temporal variability in loggerhead diets is an important component in their effective conservation because resultant data can be used to help understand the impacts of environmental perturbations on benthic food webs.

Hematologic Reference Intervals and Comparison of Natt-Herrick Technique and Smear-Based Leukocyte Estimation in Cockatiels (Nymphicus hollandicus).

Although cockatiels are among the most common avian species maintained as companion animals in the United States, information on standard hematologic reference values for this species is limited. The objectives of this study were to establish hematologic reference intervals (RI) for cockatiels, compare methods using both the Natt-Herrick technique (NHT) and the smear-based estimation technique (SBT), explore age and sex differences in the hematologic findings for this species, and produce the first cockatiel RI for fibrinogen concentration and thrombocyte estimate. Healthy cockatiels (60 males and 60 females, 2-11 years old) from a research colony were included in this study. Blood samples were placed in dipotassium ethylenediaminetetraacetic acid tubes, and erythrocyte counts and thrombocyte estimates were determined via automated analyzer (ADVIA 120) and SBT, respectively. Moreover, leukocyte concentrations were determined using both NHT and SBT to compare these common methods for measuring a complete blood count in cockatiels. Data were analyzed for outliers, distributions, descriptive statistics, and RI via Reference Value Adviser, a set of macroinstructions for Microsoft Excel (Microsoft, Redmond, WA, USA). Lymphocytes were the predominant leukocyte across both methods. According to the NHT, females had significantly higher concentrations of total leukocytes, heterophils, bands, lymphocytes, basophils, and total plasma protein compared with males. Significant inverse polynomial relationships were noted between total leukocyte count and age and lymphocyte counts and age for NHT. Total leukocyte count produced via NHT and SBT were compared using Passing-Bablok and Bland-Altman plots, and no significant constant or proportional biases were found. However, these methods showed wide limits of agreement. While the RI were interchangeable between methods from a clinical standpoint, the same method should be used to assess changes in an individual. The reported RI are uniquely robust given the sample size, balanced sex and age distributions, inclusion criteria, and control over sample collection.

Armed and prohibited: characteristics of unlawful owners of legally purchased firearms.

BACKGROUND: A substantial proportion of individuals who lawfully purchase firearms later become unlawful owners ('prohibited firearm owners'), usually following events associated with an increased risk for future violence. This high-risk population has not previously been described. We aimed to characterise all individuals in California's Armed and Prohibited Persons System (APPS), a statewide programme for recovering firearms from individuals who legally purchased them and later became prohibited from ownership. METHODS: We used univariate and bivariate statistics to describe and compare prohibited firearm owners in APPS with a random sample of non-prohibited firearm owners in relation to age, sex, race/ethnicity and type of firearms owned as of 1 February 2015. We also characterised the geographical distribution of prohibited firearm owners and described their prohibitions. RESULTS: Of the 18 976 prohibited firearm owners, most were men (93%), half were white (53%) and the mean age was 47 years. Prohibited firearm owners were more likely to be male and to be black or Hispanic people than non-prohibited owners. Both prohibited and non-prohibited firearm owners had an average of 2.6 firearms, mostly handguns. Nearly half (48%) of prohibited firearm owners had a felony conviction. Extrapolating from our findings, we estimated that there are approximately 100 000 persons in the USA who unlawfully maintained ownership of their firearms following a felony conviction. CONCLUSIONS: Retention of firearms among persons who become lawfully prohibited from possessing them is common in California. Given the nationwide dearth of a programme to recover such weapons, this is likely true in other states as well.

Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses.

Flunixin meglumine is a highly efficacious nonsteroidal anti-inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post-administration. Serum for determination of thromboxane concentrations and whole blood samples was collected at various time and challenged with lipopolysaccharide, calcium ionophore, or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flunixin, 5-OH flunixin, and eicosanoids were measured using LC-MS/MS and non-compartmental pharmacokinetic analysis performed on concentration data. Serum concentrations of flunixin and 5-OH flunixin were above the limit of quantitation at 96 h post-administration in both serum and urine. The mean (range) for Cmax , Tmax and the terminal half-life were 515.6 (369.7-714.0) ng/ml, 8.67 (8.0 12.0) h, and 22.4 (18.3-42.5) h, respectively. Following transdermal administration, based on effects on eicosanoid synthesis, flunixin meglumine inhibited cyclooxygenase 1 and 2 and 15-lipooxygenase activity, with anti-inflammatory effects lasting for 24-72 h.

Factors affecting successful ultrasound-guided injection into the podotrochlear bursa using a palmarolateral approach.

OBJECTIVE: To evaluate potential factors affecting ultrasonographic visibility of the suprasesamoidean region and the success rate of ultrasound-guided injection (USGI) into the podotrochlear bursa (PB). STUDY DESIGN: Ex vivo, experimental study. ANIMALS: 24 cadaveric forelimbs. METHODS: The PB was distended with 0, 1, or 2 ml of iodinated contrast material and saline under radiographic guidance. Ultrasonographic visibility of the suprasesamoidean region and PB was graded before and after distention with the limb loaded in three positions (vertical, cranial and caudal). Two operators with different experience levels performed an USGI into the PB with methylene blue (12 limbs each [four limbs with each of three volumes of PB distension]) using a palmarolateral approach and caudal foot placement. Limbs were frozen and sectioned to assess accuracy. RESULTS: Ultrasonographic visibility scores of the suprasesamoidean region (p = .0081) and PB (p < .0001) were improved using a caudal foot placement. Higher visibility grades of the suprasesamoidean region were associated with higher injection success rate (p = .047). The injection success was 75% (9/12) for the experienced versus 41.6% (5/12) for the less experienced operator (p = .14). PB distension improved visibility during caudal foot placement (p = .013) but not injection success rates (p = .78). CONCLUSION: Caudal foot placement enhances visibility of the PB and suprasesamoidean region. Limbs with poor visibility of the suprasesamoidean region are more likely to undergo a failed USGI. CLINICAL SIGNIFICANCE: The lateral USGI approach should be performed only in cases of optimal visibility. The reported success rates support the technical challenge of PB injections.

Evaluation of a laparoscopic abdominal simulator assessment to test readiness for laparoscopic ovariectomy in live dogs.

OBJECTIVE: To predict readiness for laparoscopic ovariectomy of live dogs on the basis of performance on a high-fidelity laparoscopic abdominal simulator and to determine interrater reliability of the assessment. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Seventeen fourth-year veterinary students. METHODS: After a standardized laparoscopic training course, each participant performed a laparoscopic ovariectomy with a simulator. This performance was scored in real time by two evaluators using a rubric. Participants achieving a score of 112 of 160 performed a laparoscopic ovariectomy in a live dog, supervised by an instructor in the room. Two evaluators scored video recordings of each procedure using the rubric. Participants' opinions about the simulator were collected with a survey. RESULTS: All participants scored above the threshold (range, 126-151) and successfully completed laparoscopic ovariectomy in a live dog, with an average of 10 of 17 participants requiring verbal guidance and 5 of 17 participants requiring intervention from the instructor. Interrater concordance was excellent for the rubrics used to score performance on the simulator (R = 0.91) and in vivo (R = 0.81). All participants agreed that the simulator should be used to assess trainee readiness prior to surgery in a live dog. CONCLUSION: Participants achieving a score of at least 126 of 160 on the simulator were able to perform a laparoscopic ovariectomy in a live dog under supervision. The scoring system for the simulator had excellent interrater concordance. CLINICAL SIGNIFICANCE: This simulator and scoring system can be used in laparoscopic training programs to assess readiness for progression to the operative setting.

Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses.

BACKGROUND: Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Horses received a single intravenous dose of saline, 0.25, 0.5 and 1.0 mg/kg meperidine. Blood was collected before administration and at various time points until 96 hours post administration. Plasma and urine samples were analyzed for meperidine and normeperidine by liquid chromatography-mass spectrometry and plasma pharmacokinetics determined. Behavioral and physiologic data (continuous heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were collected at baseline through 6 hours post administration. The effect of meperidine administration on thermal nociception was determined and thermal excursion calculated. RESULTS: Meperidine was rapidly converted to the metabolite normeperidine. The volume of distribution at steady state and systemic clearance (mean ± SD) ranged from 0.829 ± 0.138-1.58 ± 0.280 L/kg and 18.0 ± 1.4-22.8 ± 3.60 mL/min/kg, respectively for 0.5-1.0 mg/kg doses. Adverse effects included increased dose-dependent central nervous excitation, heart rate and cutaneous reactions. Significant effects on thermal nociception were short lived (up to 45 minutes at 0.5 mg/kg and 15 minutes at 1.0 mg/kg). CONCLUSIONS: Results of the current study do not support routine clinical use of IV meperidine at a dose of 1 mg/kg to horses. Administration of 0.5 mg/kg may provide short-term analgesia, however, the associated inconsistent and/or short-term adverse effects suggest that its use as a sole agent at this dose, at best, must be cautiously considered.

Chronic progressive lymphoedema in Friesian horses: suggestive phenotype of affected horses and genome-wide association study.

BACKGROUND: Chronic progressive lymphoedema (CPL) is a disabling condition affecting various draft horse breeds, including Friesian horses. HYPOTHESIS: The high incidence of CPL in Friesian horses suggests a genetic component and a predisposing phenotype. ANIMALS: For the genomic study, 26 affected and 19 control horses were evaluated. Body measurements were taken from 28 affected and nine control Friesian horses. METHODS AND MATERIALS: Axiom® Equine Genotyping Array with a total of 307,474 single nucleotide polymorphism (SNPs) was used for the case/control genome-wide association study (GWAS). Height, weight and leg measurements (seven different body measurements) were obtained and compared between groups. RESULTS: No significant associations were identified with the GWAS. There were significant differences (P < 0.05) in gaskin length measurements between CPL-affected horses and controls. CONCLUSION: The current study suggests that the potential genetic contribution to CPL in Friesian horses is complex and may include other SNP-associated factors. Significantly increased gaskin length of affected horses suggests a phenotype prone to developing CPL.

Physiologic effects of furosemide in combination with water restriction when administered at 4 and 24 hours prior to high-intensity treadmill training.

Although controversial, due to its reported effectiveness in attenuating bleeding associated with exercise-induced pulmonary hemorrhage (EIPH), furosemide is currently a permitted race day medication in most North American racing jurisdictions. The objective of this study was to assess the efficacy of furosemide in reducing the presence and severity of EIPH when administered 24 hr prior to strenuous treadmill exercise. Eight exercised Thoroughbred horses received saline or 250 mg of furosemide either 4 or 24 hr prior to high-speed treadmill exercise in a balanced 3-way cross-over design. Blood samples were collected for determination of furosemide, lactate, hemoglobin, blood gas, and electrolyte concentrations. Heart rate and pulmonary arterial pressure were measured throughout the run and endoscopic examination and bronchoalveolar lavage (BAL) performed. Horses were assigned an EIPH score and the number of red blood cells in BAL fluid determined. Although not significantly different, endoscopic EIPH scores were lower in the 4-hr versus the 24-hr and saline groups. RBC counts were not significantly different between the treatment groups. Pulmonary arterial pressures were significantly increased at higher speeds; however, there were no significant differences between dose groups when controlling for speed. A small sample size and unknown bleeding history warrant a larger-scale study.

Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses.

OBJECTIVE: To describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of 12 Thoroughbred horses, nine geldings and three mares, aged 4-8 years. METHODS: Horses were administered codeine (0.6 mg kg-1) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography-mass spectrometry, and plasma pharmacokinetics were determined. Heart rate and rhythm, step counts, packed cell volume and total plasma protein were measured before and 4 hours after administration. RESULTS: Codeine was rapidly converted to the metabolites norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Plasma codeine concentrations were best represented using a two-compartment model. The Cmax, tmax and elimination t½ were 270.7 ± 136.0 ng mL-1, 0.438 ± 0.156 hours and 2.00 ± 0.534 hours, respectively. M3G was the main metabolite detected (Cmax 492.7 ± 35.5 ng mL-1), followed by C6G (Cmax 96.1 ± 33.8 ng mL-1) and M6G (Cmax 22.3 ± 4.96 ng mL-1). Morphine and norcodeine were the least abundant metabolites with Cmax of 3.17 ± 0.95 and 1.42 ± 0.79 ng mL-1, respectively. No significant adverse or excitatory effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Following oral administration, codeine is rapidly metabolized to morphine, M3G, M6G, C6G and norcodeine in horses. Plasma concentrations of M6G, a presumed active metabolite of morphine, were comparable to concentrations reported previously following administration of an analgesic dose of morphine to horses. Codeine was well tolerated based on pharmacodynamic variables and behavioral observations.

Effect of topical application of 0.5% proparacaine on corneal culture results from 33 dogs, 12 cats, and 19 horses with spontaneously arising ulcerative keratitis.

OBJECTIVE: To investigate the effect of topically applied proparacaine on bacterial and fungal culture results and to compare cytologic and culture results in patients with ulcerative keratitis. PROCEDURE: Corneal samples were collected from 33 dogs, 19 horses, and 12 cats with spontaneously arising ulcerative keratitis. Samples for bacterial (dogs, cats, horses) and fungal (horses) cultures were collected prior to and following application of 0.5% proparacaine or saline. All patients then received a topical anesthetic, and samples were collected for cytology. Frequency of cultivatable bacteria before (Swab 1) and after (Swab 2) application of proparacaine or saline was compared using Fisher's exact test. Homogeneity of culture and cytology results was assessed using McNemar's test. RESULTS: No difference was detected in number of animals from which bacteria were isolated from Swab 1 or Swab 2 for proparacaine (21/37 and 17/37, respectively) or saline (10/27 and 12/27, respectively). Small numbers prevented analysis of fungal culture results in horses between Swab 1 and Swab 2 for proparacaine (2/12 and 1/12, respectively) or saline (both, 1/8). Bacteria were isolated from 10 of 20 horses and detected cytologically in 3 of these; fungi were isolated from 3 of 20 horses and detected cytologically in 2 of these. Bacteria were detected more frequently using culture (31/64) than cytology (19/64). CONCLUSION: Proparacaine did not significantly alter bacterial or fungal culture results in cats, dogs, or horses; however, clinical significance warrants investigation. Culture and cytology provided complementary data; both should be performed to maximize organism detection in patients with ulcerative keratitis.

Effects of 5% sodium chloride ophthalmic ointment on thickness and morphology of the normal canine cornea.

OBJECTIVE: To determine the effect of 5% sodium chloride ophthalmic ointment (5% NaCl) on thickness and morphology of the normal canine cornea using ultrasonic pachymetry (USP), in vivo confocal microscopy (IVCM), and Fourier-domain optical coherence tomography (FD-OCT). METHODS: Five healthy laboratory Beagles received ophthalmic examinations including USP, IVCM, and FD-OCT prior to and at fixed intervals following treatment. The right and left eyes were treated with 5% NaCl and artificial tears ophthalmic ointment (AT), respectively, every 2 hours for 4 treatments/d (days 2-9), and then hourly for 7 treatments/d (day 10). Treatment groups were statistically compared using mixed-effects linear regression. RESULTS: Treatment with 5% NaCl resulted in a 12 µm decrease in corneal thickness from baseline (P < .001), while there was no significant difference in corneal thickness between values obtained at baseline and following treatment with AT (P = .82). Epithelial cell density significantly increased from baseline (530 ± 52 cells/mm2 ) to 577 ± 43 and 567 ± 15 cells/mm2 with 5% NaCl and AT, respectively (P = .003 and .005, respectively). However, keratocyte cell density in the anterior and posterior stroma and endothelial cell density did not significantly differ following treatment with 5% NaCl or AT ointment (P > .05). CONCLUSIONS: Short-term topical treatment with 5% NaCl decreased corneal thickness in normal dogs with no observable changes in corneal morphology or signs of ocular toxicity.