Plasma UCHL-1 as a Biomarker of Brain Injury in Hospitalized Foals With Neonatal Encephalopathy.

A plasma biomarker such as ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) to distinguish neonatal encephalopathy (NE) from other disorders and provide prognostic information would be useful for equine practitioners. In this prospective study, plasma UCHL-1 was measured in 331 hospitalized foals ≤4 days of age. Clinical diagnoses of neonatal encephalopathy only (NE group, n = 77), sepsis only (Sepsis group, n = 34), concurrent sepsis and NE (NE+Sepsis group, n = 85), or neither sepsis nor NE (Other group, n = 101) were made by the attending veterinarian. Plasma UCHL-1 concentrations were measured by ELISA. Differences between clinical diagnoses groups were evaluated and receiver operator curve (ROC) analysis was performed to assess diagnostic and prognostic performance. Median admission UCHL-1 concentration was significantly higher for NE (18.22 ng/mL; 7.93-37.43) and NE+Sepsis (17.42 ng/mL; 7.67-36.24) groups than Other foals (7.77 ng/mL; 3.92-22.76). Admission UCHL-1 was significantly higher in nonsurvivors (16.66 ng/mL; 6.89-34.84) than survivors (10.27 ng/mL; 5.82-29.94). Overall diagnostic performance of admission UCHL-1 concentration for NE diagnosis was determined (AUC 0.61; 95% confidence interval [CI] = 0.55-0.68); sensitivity and specificity for predicting NE were 73% and 49% respectively. Overall prognostic performance of time to lowest UCHL-1 concentration for predicting nonsurvival was determined (AUC 0.72; 95% CI = 0.65-0.79); sensitivity and specificity were 86% and 43% respectively. In this foal population, differences in plasma UCHL-1 concentrations were observed between foals with NE or NE with sepsis, and other diagnoses. The diagnostic and prognostic value of admission UCHL-1 concentration was limited.

Lipidomic analysis of surfactant and plasma from horses with asthma and age-matched healthy horses.

OBJECTIVE: To perform lipidomic analysis of surfactant and plasma from asthmatic and healthy horses. ANIMALS: 30 horses with clinical signs of asthma and 30 age-matched control horses. PROCEDURES: Detailed history, physical examination, CBC, and bronchoalveolar lavage fluid (BALF) cytologies were obtained. Asthmatic horses were grouped based on their BALF inflammatory profile: severe equine asthma (SEA), mild equine asthma with neutrophilic airway inflammation (MEA-N), or mild equine asthma with eosinophilic airway inflammation (MEA-E). Each asthma group was assigned its own age-matched control group. Lipidomic analysis was completed on surfactant and plasma. Surfactant protein D (SP-D) concentrations were measured in serum and BALF. RESULTS: SEA surfactant was characterized by a phospholipid deficit and altered composition (increased ceramides, decreased phosphatidylglycerol, and increased cyclic phosphatidic acid [cPA]). In comparison, MEA-N surfactant only had a decrease in select phosphatidylglycerol species and increased cPA levels. The plasma lipidomic profile was significantly different in all asthma groups compared to controls. Specifically, all groups had increased plasma phytoceramide. SEA horses had increased plasma cPA and diacylglycerol whereas MEA-N horses only had increased cPA. MEA-E horses had increases in select ceramides and dihydrocermides. Only SEA horses had significantly increased serum SP-D concentrations. CLINICAL RELEVANCE: The most significant surfactant alterations were present in SEA (altered phospholipid content and composition); only mild changes were observed in MEA-N horses. The plasma lipidomic profile was significantly altered in all groups of asthmatic horses and differed among groups. Data from a larger population of asthmatic horses are needed to assess implications for diagnosis, prognosis, and treatment.

Randomized blinded controlled trial of dipyrone as a treatment for pyrexia in horses.

OBJECTIVE To evaluate the effectiveness and safety of dipyrone to control pyrexia in horses with naturally occurring disease under field conditions. ANIMALS 138 horses with pyrexia and various infections evaluated at 14 veterinary sites in 12 states. PROCEDURES In the first (effectiveness) phase of this 2-phase study, horses were randomly assigned 3:1 to receive 1 dose of dipyrone (30 mg/kg [13.6 mg/lb], IV) or an equivalent amount of placebo. Effectiveness was defined as a decrease in rectal temperature ≥ 1.1°C (2°F), compared with the pretreatment value, or a rectal temperature of ≤ 38.3°C (101.0°F) 6 hours after treatment administration. Horses deemed to have an appropriate reduction in rectal temperature (regardless of treatment group) by 6 hours were immediately entered into the safety phase of the study, in which dipyrone was administered IV at 30 mg/kg between 0 and 8 times up to every 8 hours on an as-needed basis, as determined by the clinical investigators. Horses were monitored throughout for adverse events. RESULTS A significantly greater proportion of dipyrone-treated horses (76/99 [77%]) had an effective treatment response than did placebo-treated horses (6/31 [19%]). Posttreatment adverse events were mild and transient. No differences in types or prevalence of gastrointestinal adverse events were evident between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE Dipyrone was effective in controlling pyrexia by 6 hours after IV administration of a single 30-mg/kg dose in a large proportion of treated horses. Adverse effects were minimal.

Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses.

OBJECTIVES: To measure serum polymyxin B concentration after single and repeated IV infusions in horses. ANIMALS: 5 healthy horses. PROCEDURES: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. RESULTS: In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and 1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. CONCLUSIONS AND CLINICAL RELEVANCE: Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.

Reproductive tract infections in horses.

Diagnosis, treatment, and, ultimately, prevention of reproductive disease are vital components of equine veterinary medicine. A thorough understanding of anatomy and physiology is necessary to reconcile the pathologic findings of disease. Only then can a rational treatment plan be formulated. Many recent advances in knowledge about the reproductive system of multiple species have application to the mare and stallion.

Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease).

Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 microg/kg p.o. q24h (range, 1.7-5.5 microg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg p.o. q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml; range, 4.2-173) were significantly lower (P < .01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml: range, 10-1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P = .04). Significantly (P = .02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7).

Development of a likelihood of survival scoring system for hospitalized equine neonates using generalized boosted regression modeling.

BACKGROUND: Medical management of critically ill equine neonates (foals) can be expensive and labor intensive. Predicting the odds of foal survival using clinical information could facilitate the decision-making process for owners and clinicians. Numerous prognostic indicators and mathematical models to predict outcome in foals have been published; however, a validated scoring method to predict survival in sick foals has not been reported. The goal of this study was to develop and validate a scoring system that can be used by clinicians to predict likelihood of survival of equine neonates based on clinical data obtained on admission. METHODS AND RESULTS: Data from 339 hospitalized foals of less than four days of age admitted to three equine hospitals were included to develop the model. Thirty seven variables including historical information, physical examination and laboratory findings were analyzed by generalized boosted regression modeling (GBM) to determine which ones would be included in the survival score. Of these, six variables were retained in the final model. The weight for each variable was calculated using a generalized linear model and the probability of survival for each total score was determined. The highest (7) and the lowest (0) scores represented 97% and 3% probability of survival, respectively. Accuracy of this survival score was validated in a prospective study on data from 283 hospitalized foals from the same three hospitals. Sensitivity, specificity, positive and negative predictive values for the survival score in the prospective population were 96%, 71%, 91%, and 85%, respectively. CONCLUSIONS: The survival score developed in our study was validated in a large number of foals with a wide range of diseases and can be easily implemented using data available in most equine hospitals. GBM was a useful tool to develop the survival score. Further evaluations of this scoring system in field conditions are needed.