Pharmacokinetics of a FDA-labeled dose of diclazuril administered orally once weekly to adult horses.

Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (ProtazilTM) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five individual diclazuril doses were administered at weekly intervals to 8 adult horses. Blood was collected via venipuncture immediately before (trough concentration) and 10 hours after (peak concentration) each diclazuril administration. Following the fifth dose, additional blood samples were collected every 24 hours after the peak blood collection for 7 days. All plasma samples were analyzed by high-pressure liquid chromatography. The pharmacokinetic analysis was performed using a nonlinear mixed effects model. The mean population-derived peak concentration was 264 ng/mL and the mean terminal half-life was 3.6 days. Thus, the oral administration of an FDA-labeled dose of diclazuril to healthy horses once a week was able to produce steady-state plasma drug concentrations known to inhibit S. neurona in vitro.

A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.

Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection-the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert® I.N. (Flu Avert), which is known to stimulate strong antiviral responses, will enhance antiviral innate immunity, and that these responses would also provide protection from EHV-1 infection. To test our hypothesis, primary equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and innate immunity was evaluated for 10 days following treatment. The timing of Flu Avert treatment was also evaluated for optimal effectiveness to reduce EHV-1 replication by modulating early immune responses to EHV-1. The induction of interferons, cytokine and chemokine mRNA expression, and protein secretion was evaluated by high-throughput qPCR and multiplex protein analysis. Intracellular and extracellular EHV-1 titers were determined by qPCR. Flu Avert treatment resulted in the modulation of IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment. Coinciding with the timing of optimal chemokine induction, our data also suggested the same timing for reduction of EHV-1 replication. In combination, our results suggest that Flu Avert may be effective at counteracting some of the immune-modulatory properties of EHV-1 at the airway epithelium and the peak for this response occurs 5-8 days post-Flu Avert treatment. Future in vivo studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.

Ultrasonographic visualization of colonic mesenteric vasculature as an indicator of large colon right dorsal displacement or 180° volvulus (or both) in horses.

Visualization of colonic mesenteric vasculature during transabdominal ultrasonographic examination of horses with colic can be a predictor of right dorsal displacement of the large colon or 180° large colon volvulus, or both. Medical records of 82 horses having had surgical treatment of colic and having received a transabdominal ultrasonographic examination on admission were reviewed. Colonic mesenteric vessels were sonographically identified coursing laterally on the right side of the abdomen in 24 of the 82 cases. Horses with colonic vessels identified on ultrasound were 32.5 times more likely to be diagnosed at surgery with either large colon right dorsal displacement or 180° large colon volvulus than those in which vessels were not seen (P < 0.001). Visualization of colonic mesenteric vessels on ultrasound provided a sensitivity of 67.7%, specificity of 97.9%, positive predictive value of 95.8%, and negative predictive value of 81% for large colon right dorsal displacement or 180° large colon volvulus, or both.

Case report: squamous cell carcinoma of the urinary bladder in a horse.

A 14-year-old Hanoverian gelding was evaluated after a 10-week history of occasional straining during urination and dark red urine production after exercise. Physical examination findings were within normal limits. After 2 weeks of clinical signs, ultrasonography had found no abnormalities in the kidneys or bladder. A freely voided urine sample revealed an elevated protein concentration (500 mg/dL; reference range: <100 mg/dL) and few red blood cells. Vitamin C supplementation was suggested to acidify the urine, as was provision of a salt block to encourage water intake.

Neonatal encephalopathy in foals.

Neonatal encephalopathy is a common central nervous system disorder of neonatal foals and human infants, resulting in clinical signs such as lethargy, inappropriate behavior, seizures, and other neurologic deficits. Although neonatal encephalopathy is frequently seen in equine practice, a paucity of veterinary clinical and basic science research data is available. Therefore, the pathophysiologic mechanisms of this disorder in equids, such as energy deprivation, excess excitatory amino acids, and free radical injury, have been extrapolated from human medicine. Equine veterinarians have used various diagnostic and therapeutic regimens from human medicine with reasonable success in equine patients. Understanding the potential pathophysiologic mechanisms involved in neonatal encephalopathy can facilitate management of affected foals.

Periparturient hemorrhage in mares: 73 cases (1998-2005).

OBJECTIVE: To determine signalment, physical examination and clinicopathologic abnormalities, outcome, and subsequent fertility of mares with periparturient hemorrhage (PPH) and identify factors associated with outcome (ie, survival vs death). DESIGN: Retrospective case series. ANIMALS: 73 mares. PROCEDURES: Medical records were reviewed for information on age, breed, initial complaint, physical examination and clinicopathologic abnormalities, treatment, outcome, and subsequent fertility. RESULTS: Median age was 14.0 years (range, 5 to 24 years), and median number of foals produced prior to the diagnosis of PPH was 8 (range, 1 to 16). Ten (14%) mares had prepartum hemorrhage and 63 (86%) had postpartum hemorrhage. Treatment was aimed at restoring cardiovascular volume, enhancing coagulation, controlling pain, and reducing the effects of endotoxemia. Sixty-one (84%) mares survived and 12 (16%) died or were euthanized. Common complications included fever, leukopenia, retained fetal membranes, increased digital pulses, thrombophlebitis, and cardiac arrhythmias. Of the 53 surviving mares for which subsequent breeding information was available, 26 (49%) produced 1 or more foals after recovering from PPH. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that PPH can develop in mares of any age and parity. Treatment was associated with a good prognosis for survival and a reasonable prognosis for future fertility.

Halicephalobus gingivalis-associated meningoencephalitis in a Thoroughbred foal.

A 13-week-old Thoroughbred colt from central Kentucky was euthanized after an acute onset of ataxia, blindness, head tremors, leaning to the right, recumbency, and seizures. Microscopically, there was a verminous meningoencephalitis characterized by an eosinophilic and granulomatous inflammatory reaction primarily affecting the cerebellum. Dispersed within regions of inflammation were numerous cross and longitudinal sections of intact and degenerative small nematodes. The nematodes had dorsoflexed ovaries and ventroflexed vulvas, which are distinguishing features of Halicephalobus gingivalis. Intact nematodes, compatible with H. gingivalis, also were recovered and identified from portions of the brain that had been frozen for 5-week post-necropsy examination via tissue maceration and additional laboratory techniques.

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.

Veterinary critical care.

Veterinary species experience similar perturbations of their health to those of human patients. When the long-term prognosis is good and providing suffering can be minimized, animals stand to benefit greatly from recent advances in the field of emergency and critical care. Outcomes in many conditions in small and large animals have improved markedly in the last 15 years, as management has improved, making the financial and emotional investment in critical care worthwhile for many owners.