Neurologic Disorders of the Foal.

Neurologic disease of foals is a diagnostic and therapeutic challenge for veterinarians. Disease conditions such as neonatal encephalopathy are seen as well as developmental and congenital defects, bacterial infections, and trauma. Neonatal encephalopathy can be considered a "syndrome" with a variety of causes resulting in a similar clinical presentation. These causes can be categorized as maladaptation, hypoxic/ischemic encephalopathy, and metabolic abnormalities, all leading to signs of cerebral and brainstem disease. Spinal cord signs may occasionally be seen, but these signs are usually overshadowed by cerebral disease. Treatment in most cases involves supportive care and outcome is favorable in most cases.

A decision-tree model of career choice for veterinarians in clinical residency programs.

OBJECTIVE: To identify factors that individuals in clinical residency training programs consider when making a choice for or against a career in academic clinical medicine. SAMPLE: 207 veterinarians in clinical residency programs. PROCEDURES: An online survey was distributed to 1,053 veterinarians participating in clinical residency training programs overseen by organizations recognized by the AVMA American Board of Veterinary Specialties. Results were compiled and decision factors were analyzed by means of principal component analysis to identify latent factors from the set of survey items. These factors were then used to construct a decision tree to predict respondents' choice of whether to enter academic medicine or private clinical practice. RESULTS: 207 (20%) responses were analyzed. Ninety-three of 194 (48%) respondents reported a desire to pursue a career in academic medicine, and 101 (52%) reported a desire to pursue a career in private clinical practice. Principal component analysis identified 14 items clustered on research, clinical teaching, classroom teaching, and clinical practice. A decision tree was constructed that resulted in an overall accuracy of 82% in predicting a resident's career choice of academic medicine versus private clinical practice. The construct of professional benefits had a negative effect on desiring a career in academic medicine, whereas the construct of professional priorities and having had a positive residency training experience had a positive effect on desiring a career in academic medicine. CLINICAL RELEVANCE: Understanding factors that attract and encourage residents who might have an aptitude and interest in academic medicine holds important implications for addressing the shortage of veterinarians entering academic medicine.

Perceptions of training, self-efficacy, and mentoring among veterinary clinical specialty trainees.

OBJECTIVE: To determine the perceptions of training, self-efficacy, and mentoring among veterinary clinical specialty trainees on the basis of their career interest. SAMPLE: 207 veterinarians who were either in a residency training program or had recently (within 2 years) completed one in a specialty recognized by the American Board of Veterinary Specialties. PROCEDURES: An online survey was used to collect data about the respondents' perceived preparedness for an academic career, training emphasis, and mentoring received during training and demographic information. Results were compiled and compared by professional career interest (ie, academic medicine or private practice) and gender. RESULTS: Included respondents represented 20% (207/1,053) of those invited. Preferred career choice was academic medicine for 48% (93/194) of respondents and private clinical practice for 52% (101/194) and did not differ by gender. Respondents perceived their likelihood of success in an academic career as high, and these perceptions did not differ by gender or preferred career choice. Mean self-efficacy scores for teaching were high among all respondents for most but not all listed teaching skills and did not differ by gender or preferred career interest. Mean self-efficacy scores were low for formulating research hypotheses and designing studies. Perceptions of training emphasis indicated strong mentoring in the areas of clinical practice and teaching with less mentoring and training emphasis in multiple areas of research and academic activity. CONCLUSIONS AND CLINICAL RELEVANCE: Lower self-efficacy of veterinary clinical specialty trainees in aspects of academic career appeared to be related to training emphasis and mentoring. Enhancement of emphasis on the identified areas of weakness may improve the interest and success of trainees in an academic career.

Evaluation of factors reported by veterinarians who chose not to enter clinical academic veterinary medicine.

OBJECTIVE: To identify factors that may have influenced veterinarians' decisions to not pursue careers in clinical academic veterinary medicine. SAMPLE: 363 board-certified veterinarians. PROCEDURES: An online survey, open from July 7 to July 21, 2015, was used to gather data from board-certified veterinarians who were members of ≥ 1 of the 22 specialty organizations recognized by the American Board of Veterinary Specialties of the AVMA. Responses from those who reported never to have held an academic appointment were included in the study. Results were compiled and analyzed by gender and clinical discipline. RESULTS: Approximately 10,000 board-certified veterinarians were solicited to participate in the survey, and 1,314 (13.1%) responded. Among those, 363 (27.6%) reported never having held an academic position. Females more commonly reported no interest in teaching (44/185 [23.8%]) and disagreement with the statement that compensation in academic medicine was too low (39/164 [23.8%]), compared with responses by males (24/158 [15.2%] and 22/148 [14.9%], respectively). The strongest magnitude of interrater agreement was for the paired survey statements regarding too much bureaucracy and excessive expectation for committee and administrative work (weighted κ, 0.569). CONCLUSIONS: Many factors contribute to veterinarians' decisions about whether to pursue careers in academic medicine, and results indicated that some factors may vary depending on gender or clinical discipline. Recognition of these factors may help guide academic leaders in devising strategies and programs to enhance veterinarians' interest in clinical academic medicine careers.

Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis.

Endocrinopathic laminitis is pathologically similar to the multi-organ dysfunction and peripheral neuropathy found in human patients with metabolic syndrome. Similarly, endocrinopathic laminitis has been shown to partially result from vascular dysfunction. However, despite extensive research, the pathogenesis of this disease is not well elucidated and laminitis remains without an effective treatment. Here, we sought to identify novel proteins and pathways underlying the development of equine endocrinopathic laminitis. Healthy Standardbred horses (n = 4/group) were either given an electrolyte infusion, or a 48-h euglycemic-hyperinsulinemic clamp. Cardiac and lamellar tissues were analyzed by mass spectrometry (FDR = 0.05). All hyperinsulinemic horses developed laminitis despite being previously healthy. We identified 514 and 709 unique proteins in the cardiac and lamellar proteomes, respectively. In the lamellar tissue, we identified 14 proteins for which their abundance was significantly increased and 13 proteins which were significantly decreased in the hyperinsulinemic group as compared to controls. These results were confirmed via real-time reverse-transcriptase PCR. A STRING analysis of protein-protein interactions revealed that these increased proteins were primarily involved in coagulation and complement cascades, platelet activity, and ribosomal function, while decreased proteins were involved in focal adhesions, spliceosomes, and cell-cell matrices. Novel significant differentially expressed proteins associated with hyperinsulinemia-induced laminitis include talin-1, vinculin, cadherin-13, fibrinogen, alpha-2-macroglobulin, and heat shock protein 90. In contrast, no proteins were found to be significantly differentially expressed in the heart of hyperinsulinemic horses compared to controls. Together, these data indicate that while hyperinsulinemia induced, in part, microvascular damage, complement activation, and ribosomal dysfunction in the lamellae, a similar effect was not seen in the heart. In brief, this proteomic investigation of a unique equine model of hyperinsulinemia identified novel proteins and signaling pathways, which may lead to the discovery of molecular biomarkers and/or therapeutic targets for endocrinopathic laminitis.

Effects of small- and large-volume resuscitation on coagulation and electrolytes during experimental endotoxemia in anesthetized horses.

BACKGROUND: Small-volume resuscitation (SVR) has been advocated in place of large-volume isotonic resuscitation for the treatment of endotoxemia in horses. The effects of this type of therapy during experimental endotoxemia on electrolytes and coagulation have not been evaluated in the horse. As part of a larger project, the objective of this study was to determine the effects of SVR (hypertonic saline solution [HSS] plus hetastarch [HES]) on coagulation and serum electrolytes concentration, and to compare SVR with large- and small-volume isotonic resuscitation during experimental endotoxemia in anesthetized horses. HYPOTHESIS: SVR does not affect coagulation parameters or serum electrolyte concentrations when compared with either small- or large-volume isotonic crystalloids. ANIMALS: Horses were randomly assigned to 1 of 3 groups. Under halothane anesthesia, endotoxemia was induced by administering 50 microg/kg Escherichia coli endotoxin i.v. The horses were treated for 30 minutes with 15 mL/kg of balanced polyionic crystalloid solution (control), 60 mL/kg of balanced polyionic crystalloid solution (ISO), or 5 mL/kg of HSS followed by 10 mL/kg HES (HSS-HES). METHODS: Prospective randomized trial. RESULTS: Significant differences in coagulation parameters were not found among the groups. Thrombocytopenia was severe in all 3 groups. Serum ionized calcium concentration significantly decreased from baseline in control and ISO groups but not in the HSS-HES group. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that the HSS-HES combination, at the dosage used in this study had no adverse effects on coagulation beyond those produced by endotoxemia. HSS-HES may have a protective effect against endotoxemia-induced ionized hypocalcemia.

Factors associated with outcome following treatment of horses with septic tenosynovitis: 51 cases (1986-2003).

OBJECTIVE: To identify factors associated with outcome (ie, survival and return to function) following treatment of horses with septic tenosynovitis. DESIGN: Retrospective case series. ANIMALS: 51 horses with septic tenosynovitis. PROCEDURES: Information was obtained from medical records and through follow-up conversations with owners. Factors analyzed for an association with outcome included affected limb, etiology, duration of clinical signs prior to examination, presence of complications, primary treatment, secondary treatments, number of surgical procedures, and hospitalization time. RESULTS: Concurrent complications were identified in 41 (80%) horses. The primary treatment consisted of through-and-through lavage in 26 (51%) horses, tenoscopy in 20 (39%), and tenosynoviotomy combined with lavage in 5 (10%). Forty (78%) horses were discharged, and 37 (73%) survived at least 1 year after surgery; 21 of the 37 (57%) returned to their previous or a higher level of performance. Percentages of horses that survived 1 year after discharge and percentages that returned to their intended use did not vary significantly among treatments. Horses with tendon rupture or sepsis of an adjacent joint were significantly less likely to survive. Horses with tendon injury or pannus were significantly less likely to return to their intended use. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that various factors were associated with outcome in horses with septic tenosynovitis. However, surgical technique was not found to be associated with survival rate or rate of return to intended use.

A multicenter case-control study of risk factors for equine protozoal myeloencephalitis.

OBJECTIVE: To identify risk factors for equine protozoal myeloencephalitis (EPM) among horses examined at 11 equine referral hospitals. DESIGN: Case-control study. ANIMALS: 183 horses with EPM, 297 horses with neurologic disease other than EPM (neurologic controls), and 168 horses with non-neurologic diseases (non-neurologic controls) examined at 11 equine referral hospitals in the United States. PROCEDURES: A study data form was completed for all horses. Data were compared between the case group and each of the control groups by means of bivariate and multivariate polytomous logistic regression. RESULTS: Relative to neurologic control horses, case horses were more likely to be > or = 2 years old and to have a history of cats residing on the premises. Relative to non-neurologic control horses, case horses were more likely to be used for racing or Western performance. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that cats may play a role in the natural epidemiology of EPM, that the disease is less common among horses < 2 years of age relative to other neurologic diseases, and that horses used for particular types of competition may have an increased risk of developing EPM.

Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline solutions during experimental endotoxemia in anesthetized horses.

BACKGROUND: Small volume resuscitation has been advocated as a beneficial therapy for endotoxemia in horses but this therapy has not been investigated in a prospective manner. The objective of this study was to determine the cardiopulmonary effects of small-volume resuscitation using hypertonic saline solution (HSS) plus Hetastarch (HES) during experimental endotoxemia in anesthetized horses. HYPOTHESIS: Treatment of horses with induced endotoxemia using HES-HSS does not alter the response of various cardiopulmonary indices when compared to treatment with either small- or large-volume isotonic crystalloid solutions. ANIMALS: Eighteen healthy horses were randomly assigned to 1 of 3 groups. Anesthesia was maintained with halothane. Endotoxemia was induced by administering 50 microg/kg of Escherichia coli endotoxin IV. The horses were treated over 30 minutes with 15 mL/kg of balanced polyionic crystalloid solution (control), 60 mL/kg of balanced polyionic crystalloid solution (ISO), or 5 mL/kg of HSS followed by 10 mL/kg of HES (HSS-HES). METHODS: Prospective randomized trial. RESULTS: Cardiac output (CO) after endotoxin infusion increased significantly (P < .05) from baseline in all groups, whereas mean central venous pressure increased significantly (P < .05) in the ISO group only. Mean pulmonary artery pressure increased from baseline (P < .05) in horses treated with isotonic fluids and HSS-HES. There was no effect of treatment with HSS-HES on CO, systemic vascular resistance (SVR), mean arterial pressure, blood lactate concentrations, or arterial oxygenation. CONCLUSIONS AND CLINICAL IMPORTANCE: The use of HSS-HES failed to ameliorate the deleterious hemodynamic responses associated with endotoxemia in horses. The clinical value of this treatment in horses with endotoxemia remains unconfirmed.

Use of a multivariable model to estimate the probability of discharge in hospitalized foals that are 7 days of age or less.

OBJECTIVE: To create a mathematical model to assist in early prediction of the probability of discharge in hospitalized foals < or= 7 days old. STUDY DESIGN: Prospective study. ANIMALS: 1,073 foals. PROCEDURES: Medical records from 910 hospitalized foals < or = 7 days old for which outcome was recorded as died or discharged alive were reviewed. Thirty-four variables including historical information, physical examination findings, and laboratory results were examined for association with survival. Variables associated with being discharged alive were entered into a multivariable logistic regression model. Accuracy of the model was validated prospectively on data from 163 foals. RESULTS: Factors in the final model included age group, ability to stand, presence of a suckle reflex, WBC count, serum creatinine concentration, and anion gap. Sensitivity and specificity of the model to predict live discharge were 92% and 74%, respectively, in the retrospective population and 90% and 46%, respectively, in the prospective population. Accuracy of an equine clinician's initial prediction of the foal being discharged alive was 83%, and accuracy of the model's prediction was 81%. Combining the clinician's prediction of probability of live discharge with that of the model significantly increased (median increase, 12%) the accuracy of the prediction for foals that were discharged and nonsignificantly decreased (median decrease, 9%) the accuracy of the predication for nonsurvivors. CONCLUSIONS AND CLINICAL RELEVANCE: Combining the clinician's initial predication of the probability of a foal being discharged alive with that of the model appeared to provide a more precise early estimate of the probability of live discharge for hospitalized foals.

Effects of injection of botulinum toxin type B into the external anal sphincter on anal pressure of horses.

OBJECTIVE: To determine effects on anal pressure of horses after local injection of the external anal sphincter with Clostridium botulinum toxin type B. ANIMALS: 11 healthy adult horses. PROCEDURE: Peak and resting anal sphincter pressures were measured with a custom-made rectal probe that was connected to a pressure transducer. Pressures were measured before treatment and after injection with botulinum toxin type B (BTB) or saline (0.9% NaCl) solution. Dose titration with 500, 1,000, 1,500, and 2,500 U of BTB was completed. Physical changes, behavior, and anal pressure were recorded for each horse. RESULTS: Injection of 1,000 U of BTB caused a significant reduction in peak anal pressure from days 2 to 84, compared with pressure in control horses. Maximal effect of the toxin was observed within the first 15 days after injection, followed by a slow return to baseline during the 168-day period. Injection of 2,500 U of BTB in the anal sphincter in 1 horse resulted in lethargy, generalized weakness, and dysphagia for 14 days. Adverse clinical effects were not observed in horses after injections with 500, 1,000, or 1,500 U of BTB. CONCLUSIONS AND CLINICAL RELEVANCE: The effect of focal intramuscular injection of BTB in horses is similar to that reported for other species. However, horses appear to be more sensitive to BTB, compared with other species, and clinical signs of botulism may develop at doses exceeding 1,500 U. Injections of BTB in the external anal sphincter of mares may be useful to reduce incisional dehiscence after repair of perineal lacerations.

Diagnoses, clinical pathology findings, and treatment outcome of geriatric horses: 345 cases (2006-2010).

OBJECTIVE: To compare clinical, clinical pathology, and outcome variables between geriatric and nongeriatric horses. DESIGN: Retrospective case-control study. ANIMALS: 690 horses (345 horses ≥ 20 years old and 345 horses > 1 and < 20 years old) examined at a referral hospital. PROCEDURES: Medical records were examined, and data collected included horse description, diagnosis, outcome, and CBC and serum biochemical analysis results. Cases were horses ≥ 20 years old, and controls were horses > 1 and < 20 years old. RESULTS: Mean ± SD age was 23.9 ± 4.6 years for cases and 9.2 ± 3.6 years for controls. Arabian and pony breeds were significantly overrepresented in the geriatric group, compared with the control group. Diagnoses related to the digestive system, musculoskeletal system, and respiratory system were most common in this hospital population overall (cases and controls). Colic was the most common health problem overall. Digestive system disorders were significantly more prevalent among cases. Short-term survival rates for most categories of colic were no different for cases than for controls, with the exception of the category idiopathic colic. Considering all conditions, cases were significantly more likely to be nonsurvivors than were controls. Minor differences in serum biochemical results were found in some disease subcategories. Geriatric horses with colic were not more commonly euthanized than were adult nongeriatric horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that in this population of horses in a referral hospital, age was associated with the prevalence of specific disease conditions. Few differences between cases and controls were found in serum biochemical values.

An investigation of the role of soluble CD14 in hospitalized, sick horses.

The objectives of this study were to (1) evaluate the effects of equine soluble CD14 (sCD14) and monoclonal antibodies (mAb) to equine CD14 on lipopolysaccharide-induced tumor necrosis factor α (TNF-α) secretion from equine peripheral blood mononuclear cells (PBMC); and to (2) determine serum concentrations of sCD14 in a population of horses with gastrointestinal diseases or other illnesses likely to result in endotoxemia. Equine PBMC isolated from 10 healthy horses were incubated with Escherichia coli LPS plus CD14 mAb or sCD14 and assayed for TNF-α activity. Pre-incubation with CD14 mAb did not inhibit LPS-induced TNF-α production, whereas use of sCD14 inhibited LPS-induced TNF-α production in a concentration-dependent manner. Additionally, blood samples from 55 ill and 23 healthy horses were used to determine serum concentrations of sCD14. Concentrations of sCD14 were positively correlated to respiratory rate, duration of clinical signs and band neutrophil count. Although serum sCD14 was significantly increased in the ill horses compared to healthy horses, sCD14 did not correlate with outcome. Results of this study indicate that release of sCD14 is increased in ill horses and that TNF-α production by PBMC is decreased when cells are treated with sCD14.

Evaluation of neutrophil apoptosis in horses with acute abdominal disease.

OBJECTIVE: To quantify peripheral blood neutrophil apoptosis in equine patients with acute abdominal disease (ie, colic) caused by strangulating or nonstrangulating intestinal lesions and compare these values with values for horses undergoing elective arthroscopic surgery. ANIMALS: 20 client-owned adult horses. PROCEDURES: Peripheral blood was collected from horses immediately prior to and 24 hours after surgery for treatment of colic (n = 10) or elective arthroscopic surgery (10), and neutrophils were counted. Following isolation by means of a bilayer colloidal silica particle gradient and culture for 24 hours, the proportion of neutrophils in apoptosis was detected by flow cytometric evaluation of cells stained with annexin V and 7-aminoactinomycin D. Values were compared between the colic and arthroscopy groups; among horses with colic, values were further compared between horses with and without strangulating intestinal lesions. RESULTS: Percentage recovery of neutrophils was significantly smaller in preoperative samples (median, 32.5%) and in all samples combined (35.5%) for the colic group, compared with the arthroscopy group (median, 66.5% and 58.0%, respectively). No significant differences in the percentages of apoptotic neutrophils were detected between these groups. Among horses with colic, those with strangulating intestinal lesions had a significantly lower proportion of circulating apoptotic neutrophils in postoperative samples (median, 18.0%) than did those with nonstrangulating lesions (66.3%). CONCLUSIONS AND CLINICAL RELEVANCE: The smaller proportion of apoptotic neutrophils in horses with intestinal strangulation suggested that the inflammatory response could be greater or prolonged, compared with that of horses with nonstrangulating intestinal lesions. Further investigations are needed to better understand the relationship between neutrophil apoptosis and inflammation during intestinal injury.

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro.

Endotoxemia is responsible for severe illness in horses. Individuals can become clinically unresponsive to the endotoxin molecule after an initial exposure; a phenomenon referred to as 'endotoxin tolerance' (ET). ET has been observed clinically in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMC) in vitro, and to describe selected cytokine responses which are associated with ET. ET was induced by culturing cells with three concentrations of endotoxin, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR. ET was induced in all cells exposed to the 2-step endotoxin challenge. The relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge. This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMC. A marked suppression of IL-12 production is associated with ET.