@article{hepworth-warren_nelson_dembek_young_2023, title={General anesthesia does not induce ultrasonographic changes in the pleura of healthy adult horses anesthetized for elective magnetic resonance imaging}, volume={261}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.12.0550suggested.}, number={4}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Hepworth-Warren, Kate L. and Nelson, Nathan C. and Dembek, Katarzyna A. and Young, Kimberly A. S.}, year={2023}, month={Apr}, pages={500–504} }
 @article{linn-peirano_hepworth-warren_kinsella_diaz-campos_brenseke_cianciolo_schroeder_schreeg_2023, title={Ingesta-associated choledocholithiasis in horses: 2 cases and literature review}, volume={5}, ISSN={["1943-4936"]}, DOI={10.1177/10406387231177251}, abstractNote={Equine ingesta-associated choledocholithiasis is a rare cause of morbidity and mortality. We describe here the clinical, gross, histologic, and microbiologic features of this condition in 2 horses and compare the features to 2 previous cases. Case 1 was a 4-y-old Thoroughbred mare with colic. Case 2 was an 18-y-old American Paint Horse mare with colic, chronic weight loss, and inappropriate mentation. Both had elevated biochemical markers of hepatocellular injury and cholestasis and were euthanized given a poor prognosis. Case 1 had a well-formed 5-cm choledocholith surrounding a piece of hay, and had chronic neutrophilic cholangiohepatitis, bridging fibrosis, and extrahepatic obstruction. Case 2 had an ill-formed choledocholith with occasional hay fragments, wood stick, and twigs, and had regionally extensive hepatocellular necrosis with mild neutrophilic cholangiohepatitis and bridging fibrosis. Enterococcus casseliflavus and Escherichia coli were isolated in both cases; Clostridium spp. were also isolated from case 2. All 4 reported cases had increased activity of cholestatic enzymes, hyperbilirubinemia, portal inflammation, and bridging fibrosis. Colic, pyrexia, leukocytosis with neutrophilia, and elevated hepatocellular enzyme activity were documented in 3 cases. Foreign material in all 4 cases was plant origin (choledochophytolithiasis), including hay ( n = 2), sticks/twigs ( n = 2), and grass awns ( n = 1). Ingesta-associated choledocholithiasis may be considered as a cause of colic, pyrexia, and elevated cholestatic biomarkers in horses.}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Linn-Peirano, Sarah C. C. and Hepworth-Warren, Kate and Kinsella, Hannah and Diaz-Campos, Dubraska and Brenseke, Bonnie M. M. and Cianciolo, Rachel E. E. and Schroeder, Eric and Schreeg, Megan E. E.}, year={2023}, month={May} }
 @article{hepworth-warren_erwin_moore_talbot_young_neault_haugland_robertson_blikslager_2023, title={Risk factors associated with an outbreak of equine coronavirus at a large farm in North Carolina}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1060759}, abstractNote={Equine coronavirus (ECoV) leads to outbreaks with variable morbidity and mortality. Few previous reports of risk factors for infection are available in the literature.To describe unique clinical findings and risk factors for infection and development of clinical disease.135 horses on a farm affected by ECoV outbreak.Retrospective cohort study. Data obtained included age, breed, gender, activity level, housing, and feed at the onset of the outbreak. Factors were evaluated for assessment of risk of infection using simple logistic regression or Fisher's exact test. Significance was set at p ≤ 0.05.Forty-three of 54 (79.6%) horses tested on the farm were positive on fecal PCR for ECoV, and 17 horses (12.6%) developed clinical signs consistent with ECoV. Out of 17 horses in which the presence or absence of signs of colic was noted, 6 of 17 (35.3%) showed signs of colic. Three of these horses had small colon impactions, 2 of which required surgical intervention. Significant risk factors for having positive PCR results included being primarily stalled (OR 167.1, 95% CI 26.4-1719), housing next to a positive horse (OR 7.5, 95% CI 3.1-19.0), being in work (OR 26.9, 95% CI 4.6-281.9), being fed rationed hay vs. ad libitum (OR 1,558, 95% CI 130.8-15,593), and being fed alfalfa hay (OR 1,558, 95% CI 130.8-15,593).This report describes risk factors for ECoV infection many of which were associated with intensive management of show horses. Clinicians should be aware that clinical signs vary and can include severe colic.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Hepworth-Warren, Kate L. and Erwin, Sara J. and Moore, Caroline B. and Talbot, James R. and Young, Kimberly A. S. and Neault, Michael J. and Haugland, Jennifer C. and Robertson, James B. and Blikslager, Anthony T.}, year={2023}, month={Mar} }
 @article{hepworth-warren_estell_cowles_amodie_crisman_2023, title={Utility of serum amyloid A in monitoring clinical response to antimicrobial treatment in horses with bacterial pneumonia}, volume={7}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16818}, abstractNote={Abstract Background Serum amyloid A (SAA) is a major acute phase protein in horses which could be a useful tool for assessing clinical response to treatment of bacterial pneumonia in adult horses. Objectives To monitor SAA concentration in response to treatment and identify associations among SAA concentration, WBC and neutrophil counts, and fibrinogen in bacterial pneumonia in adult horses. Animals Eighteen adult horses with bacterial pneumonia. Methods Prospective clinical study. Horses hospitalized with bacterial pneumonia were enrolled and SAA concentration and vital signs were assessed daily. SAA concentration was measured by a handheld meter. CBC and plasma fibrinogen were assessed on days 0, 1, and 2, then every 3 days until discharge. Data were not normally distributed and therefore were log transformed. Log‐transformed data were analyzed and comparisons were performed on LSMeans by the 2‐sided Student's t ‐test at the 5% level of significance. Results Geometric mean SAA concentration on day 0 was 537 μg/mL (SE 383 μg/mL). Geometric mean SAA concentration decreased significantly over time ( P = .0001), peaking at day 2 (geomean 1038 μg/mL, SE 261.7 μg/mL) and decreasing until discharge. Plasma concentration of fibrinogen ( P = .06), neutrophil count ( P = .48), and WBC count ( P = .07) did not change significantly over time. Conclusions and Clinical Importance SAA concentration decreased significantly over the course of treatment and correlated with clinical improvement of pneumonia whereas fibrinogen, neutrophil, and WBC counts did not.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Hepworth-Warren, Kate L. and Estell, Krista and Cowles, Bobby and Amodie, Deborah and Crisman, Mark}, year={2023}, month={Jul} }
 @article{young_hepworth-warren_dembek_2022, title={Comparison of Fluid Analysis and Cytologic Findings of Cerebrospinal Fluid Between Three Collection Sites in Adult Equids With Neurological Disease}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.821815}, abstractNote={Cerebrospinal fluid (CSF) is routinely collected from three sites in the horse, the atlanto-occipital (AO), atlantoaxial (AA), and lumbosacral (LS) space. A comparison between fluid analysis parameters [total protein, total nucleated cell count (TNCC), red blood cell (RBC) count, and morphologic analysis] from samples obtained at each of the three sites has not previously been performed. A retrospective analysis was performed to evaluate the differences in fluid analysis of CSF between the AO, AA, and LS sites in equids presented to a referral service for evaluation of suspected neurological disease. A total of 113 equids aged ≥1 year that underwent CSF collection between 2008 and 2020 were included. Total nucleated cell count, RBC concentration, total protein (TP), and morphologic evaluation between CSF samples obtained from the three sites were compared. When comparing all samples, LS centesis was associated with higher RBC compared to other sites ( p < 0.05); TP was lower in the AA group than in the LS group ( p < 0.05). Within a subset of cytologically unremarkable samples, RBC concentration was highest in LS samples ( p < 0.01); TP was higher in LS samples compared to AA samples ( p < 0.05) and TNCC was higher ( p < 0.01) in AA and LS groups compared to the AO. In cytologically abnormal samples, there were no significant differences between sites in any parameter. Abnormal cytology was correlated with non-survival ( p = 0.0002). Non-survival was associated with higher TNCC ( p < 0.01). The receiver operating characteristic (ROC) curve for TNCC had an area under the curve of 0.67 (95% CI, 0.55–0.79) and indicated that a cutoff value of 24 cells/μL maximized specificity (72%) and sensitivity (54%) to predict non-survival in all horses. Positive predictive value was 45%; negative predictive value was 78%. The concentration of RBC was higher in samples from the LS site. This has clinical implications due to the importance of comparative diagnostics and its potential impact on cytologic evaluation. There were minimal differences in multiple other parameters between sites, which are likely clinically insignificant.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Young, Kimberly A. S. and Hepworth-Warren, Kate L. and Dembek, Katarzyna A.}, year={2022}, month={Apr} }
 @article{hepworth-warren_nelson_dembek_young_2022, title={Comparison of thoracic ultrasonography and thoracic radiography between healthy adult horses and horses with bacterial pneumonia using a novel, objective ultrasonographic scoring system}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.991634}, abstractNote={Thoracic ultrasonography (TUS) is widely used in equine practice but comparison to radiography is limited in horses.To validate a novel, objective scoring system for TUS in adult horses and to compare ultrasonographic and radiographic findings.13 healthy horses and 9 with confirmed bacterial pneumonia.Prospective study in which TUS and radiography were performed on healthy horses and those with bacterial pneumonia confirmed by clinical signs and results of transtracheal wash analysis. Ultrasonography was scored utilizing a novel scoring system evaluating number of comet tail lesions, the presence or absence of pleural effusion and/or pulmonary consolidation in each intercostal space. Eighteen horses had thoracic radiographs taken that were scored by a board-certified radiologist utilizing a previously described system. Total scores were recorded and compared between control and diseased patients.Ultrasonographic scores were significantly higher in the diseased group (median= 126) than in the control group (median = 20, p = 0.01). Receiver operating characteristics (ROC) analysis identified a sensitivity of 66.7% (95% CI 0.417-1) and specificity of 92.3% (95% CI 0.462-1) for the ability of ultrasonography to identify bacterial pneumonia utilizing a TUS score cutoff of 37.TUS had moderate sensitivity and high specificity for identification of bacterial pneumonia in adult horses. TUS appears to be an acceptable stand-alone imaging modality for diagnosis of bacterial pneumonia in horses when radiography is not practical.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Hepworth-Warren, Kate L. L. and Nelson, Nathan and Dembek, Katarzyna A. A. and Young, Kimberly A. S.}, year={2022}, month={Oct} }
 @misc{hepworth-warren_2021, title={Revisiting the use of hydroxyethyl starch solutions in equine fluid therapy}, volume={33}, ISSN={["2042-3292"]}, DOI={10.1111/eve.13340}, abstractNote={Summary The last decade has led to major shifts in opinions on the use of hydroxyethyl starch (HES) solutions in fluid therapy, specifically in human patients with sepsis. The majority of evidence documenting adverse effects of HES solutions on coagulation and renal health come from studies in people. However, these findings have led to investigation into the safety of HES solutions in veterinary species. While there are now studies investigating the effects of HES solutions on coagulation and renal health in dogs, cats and horses, information regarding long‐term follow‐up, clinical significance of these changes and use of these solutions in critically ill animals is still lacking. The information presented here serves to review the physiology of oncotic pressure and the rationale behind colloid use, specifically HES solutions. Additionally, the foundation of arguments against the use of HES and the available literature regarding HES use in animals will be summarised.}, number={8}, journal={EQUINE VETERINARY EDUCATION}, author={Hepworth-Warren, K. L.}, year={2021}, month={Aug}, pages={436–443} }
 @article{wong_hepworth-warren_sponseller_howard_wang_2017, title={Measured and calculated variables of global oxygenation in healthy neonatal foals}, volume={78}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.78.2.230}, DOI={10.2460/ajvr.78.2.230}, abstractNote={Abstract OBJECTIVE To assess multiple central venous and arterial blood variables that alone or in conjunction with one another reflect global oxygenation status in healthy neonatal foals. ANIMALS 11 healthy neonatal foals. PROCEDURES Central venous and arterial blood samples were collected from healthy neonatal foals at 12, 24, 36, 48, 72, and 96 hours after birth. Variables measured from central venous and arterial blood samples included oxygen saturation of hemoglobin, partial pressure of oxygen, lactate concentration, partial pressure of carbon dioxide, and pH. Calculated variables included venous-to-arterial carbon dioxide gap, estimated oxygen extraction ratio, ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen, bicarbonate concentration, base excess, and blood oxygen content. RESULTS Significant differences between arterial and central venous blood obtained from neonatal foals were detected for several variables, particularly partial pressure of oxygen, oxygen saturation of hemoglobin, and oxygen content. In addition, the partial pressure of carbon dioxide in central venous blood samples was significantly higher than the value for corresponding arterial blood samples. Several temporal differences were detected for other variables. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study provided information about several variables that reflect global oxygenation in healthy neonatal foals. Values for these variables in healthy foals can allow for comparison with values for critically ill foals in future studies. Comparison of these variables between healthy and ill foals may aid in treatment decisions and prognosis of clinical outcome for critically ill foals.}, number={2}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wong, David M. and Hepworth-Warren, Kate L. and Sponseller, Beatrice T. and Howard, Joan M. and Wang, Chong}, year={2017}, month={Feb}, pages={230–238} }
 @article{sponseller_clark_gilbertie_wong_hepworth_wiechert_chandramani_sponseller_alcott_bellaire_et al._2016, title={Macrophage effector responses of horses are influenced by expression of CD154}, volume={180}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2016.08.001}, DOI={10.1016/j.vetimm.2016.08.001}, abstractNote={Reactive intermediates contribute to innate immunity by providing phagocytes with a mechanism of defense against bacteria, viruses and parasites. To better characterize the role of CD154 in the production of reactive intermediates, we cloned and expressed recombinant equine CD154 (reqCD154) in Chinese Hamster Ovary (CHO). In co-culture experiments, CHO cells ectopically expressing reqCD154 elicited superoxide production in monocyte-derived macrophages (MDM). Collectively, our results indicate that regulation of CD154 expression plays a role in innate host defenses.}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Sponseller, Brett A. and Clark, Sandra K. and Gilbertie, Jessica and Wong, David M. and Hepworth, Kate and Wiechert, Sarah and Chandramani, Prashanth and Sponseller, Beatrice T. and Alcott, Cody J. and Bellaire, Bryan and et al.}, year={2016}, month={Nov}, pages={40–44} }
 @article{wong_jeffery_hepworth-warren_wiechert_miles_2016, title={Magnetic resonance imaging of presumptive neonatal encephalopathy in a foal}, volume={29}, ISSN={0957-7734}, url={http://dx.doi.org/10.1111/eve.12590}, DOI={10.1111/eve.12590}, abstractNote={A 10-h-old Thoroughbred foal presented with clinical signs consistent with neonatal encephalopathy including absent suckling behaviour, lack of affinity for the mare and seizures. The foal was provided supportive care and treated with broad-spectrum antimicrobials and fed via naso-oesophageal tube. In addition, magnetic resonance imaging (MRI) was performed to investigate for structural changes that might be evident with equine neonatal encephalopathy. Notable findings on MRI included hyperintensity of the basal nuclei and superficial layers of the ventral cerebral hemispheres as well as the ventral thalamic nuclei and rostral aspect of the ventral midbrain. These imaging changes were consistent with the counterpart disease in infants and are the first to document MRI changes in a foal with neonatal encephalopathy. This report serves as an initial description of MRI findings associated with the presumed diagnosis of equine neonatal encephalopathy and also serves to solicit future diagnostic imaging studies that may help elucidate the pathophysiology and prognosis of equine neonatal encephalopathy.}, number={10}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Wong, D. M. and Jeffery, N. and Hepworth-Warren, K. L. and Wiechert, S. A. and Miles, K.}, year={2016}, month={May}, pages={534–538} }
 @article{hepworth-warren_hay kraus_wong_krull_metcalf_2016, title={Septic peritonitis in a Percheron mare associated with Clostridium haemolyticum}, volume={29}, ISSN={0957-7734}, url={http://dx.doi.org/10.1111/eve.12531}, DOI={10.1111/eve.12531}, abstractNote={This report describes an 11-year-old Percheron mare that presented with signs of colic and was ultimately diagnosed with bacterial peritonitis of unknown origin. Bacterial culture of a peritoneal fluid sample isolated 2 Clostridial species, one of which was strongly suspected to be Clostridium haemolyticum. The horse was markedly hypoalbuminaemic at presentation, leading to the development of low oncotic pressure and ventral oedema. The mare was administered a low molecular weight/low molar substitution hydroxyethyl starch solution in conjunction with other therapies that resulted in marked improvement of clinical signs. The purpose of this report is to describe the clinical findings associated with equine peritonitis associated with C. haemolyticum, a rarely identified pathogen in the horse. Secondly, this report serves to describe the beneficial effects of tetrastarch administration in a clinical case with severe hypoalbuminaemia and ventral oedema.}, number={11}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Hepworth-Warren, K. L. and Hay Kraus, B. L. and Wong, D. M. and Krull, A. C. and Metcalf, G. L.}, year={2016}, month={Feb}, pages={603–608} }
 @article{hepworth-warren_wong_fulkerson_wang_sun_2015, title={Bacterial isolates, antimicrobial susceptibility patterns, and factors associated with infection and outcome in foals with septic arthritis: 83 cases (1998–2013)}, volume={246}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.246.7.785}, DOI={10.2460/javma.246.7.785}, abstractNote={Abstract Objective —To determine clinical characteristics, clinicopathologic data, and bacterial culture and antimicrobial susceptibility results associated with septic arthritis in foals ≤ 180 days old. Design —Retrospective case series. Animals —83 foals with septic arthritis. Procedures —Medical records at 2 teaching hospitals between 1998 and 2013 were searched to identify those for foals ≤ 180 days old with confirmed infection of ≥ 1 synovial structure. Data extracted from the records included signalment, clinicopathologic information, bacteriologic culture and antimicrobial susceptibility results, and outcome. Data were analyzed for all foals as a single population and for foals stratified into 3 age groups (≤ 7 days, 8 to 30 days, and 31 to 180 days). Results —Mean ± SD age of all foals was 18.2 ± 25 days (range, 0 to 180 days). The median number of joints affected per foal was 2 (range, 1 to 10 joints). Forty-seven of 83 (56.6%) foals survived to discharge from the hospital. Seventy antemortem synovial fluid samples underwent bacteriologic culture, of which 60 (85.7%) yielded growth. Of the 72 bacterial isolates identified, 45 (62.5%) were gram negative and 27 (375%) were gram positive. Survival rate was positively associated with plasma fibrinogen concentration and negatively associated with number of affected joints. Conclusions and Clinical Relevance —Results indicated the frequency with which certain bacterial agents were isolated from septic joints, which may be beneficial for the empirical treatment of septic arthritis in foals. Also, the positive association between survival rate and plasma fibrinogen concentration may have prognostic value in a clinical setting.}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Hepworth-Warren, Kate L. and Wong, David M. and Fulkerson, Caroline V. and Wang, Chong and Sun, Yaxuan}, year={2015}, month={Apr}, pages={785–793} }
 @article{hepworth-warren_wong_hay-kraus_wang_sun_2015, title={Effects of administration of a synthetic low molecular weight/ low molar substitution hydroxyethyl starch solution in healthy neonatal foals}, volume={56}, journal={Canadian Veterinary Journal}, author={Hepworth-Warren, K.L. and Wong, D.M. and Hay-Kraus, B.L. and Wang, C. and Sun, Y.}, year={2015}, pages={1069–1074} }
 @article{wong_whitley_hepworth_sponseller_2015, title={Pathology in Practice}, volume={247}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.247.1.55}, DOI={10.2460/javma.247.1.55}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Wong, David M. and Whitley, Elizabeth M. and Hepworth, Kate and Sponseller, Brett A.}, year={2015}, month={Jul}, pages={55–57} }
 @article{wong_alcott_davis_hepworth_wulf_coetzee_2015, title={Use of Alprazolam to Facilitate Mare-Foal Bonding in an Aggressive Postparturient Mare}, volume={29}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12510}, DOI={10.1111/jvim.12510}, abstractNote={A healthy 11-year old, 577 kg maiden Quarter Horse mare was examined at the Lloyd Veterinary Medical Center with a 4-day old colt because the mare would bite or kick the foal when the foal attempted to suckle. The owner bottle fed the foal small amounts of mare's milk over the first 4 days of life, but the foal became progressively weaker over time and was recumbent and nonresponsive at presentation. Furthermore, although gestational length and parturition were reportedly normal, the mare had apparently not been producing adequate amounts of milk since the foal was born. Upon presentation (Day 1), the foal weighed 36.8 kg and was severely dehydrated, undernourished, unresponsive, hypothermic (32.2°C; reference range [RR], 37.2–38.6°C), bradycardic (40 beats/min; RR, 96–108 beats/min), hypoglycemic (28 mg/dL; RR, 101–226 mg/dL), hyperlactatemic (4.2 mmol/L; RR, <2.5 mmol/L), and had a low serum immunoglobulin G (IgG: 400–800 mg/dL1 ; RR, >800 mg/dL). A CBC revealed leucopenia (3.41 × 103/μL; RR, 5.1–10.1 × 103/μL) characterized by neutropenia (2.15 × 103/μL; RR, 3.21–8.58 × 103/μL) and relevant serum biochemistry derangements included hypoproteinemia (3.5 g/dL; RR, 5.3–7.9 g/dL), hypoalbuminemia (1.9 g/dL; RR, 2.8–3.7 g/dL), and hyperbilirubinemia (4.61 mg/dL; RR, 0.5–3.9 mg/dL). The foal was treated for failure of transfer of passive immunity and polymicrobial sepsis confirmed via blood culture yielding E. coli and Citrobacter sp. Treatment included administration of 2 L of equine plasma, which increased the serum IgG to >800 mg/dL, fluid resuscitation and treatment, antimicrobial treatment consisting of ceftiofur (Naxel2 ) (5 mg/kg IV q12h) and gentamicin3 (10 mg/kg IV q24h) for 10 days followed by sulfamethoxazole-trimethoprim4 (30 mg/kg PO q12h) for 7 days, nasoesophageal tube feedings and supportive and nursing care. The mare was treated with domperidone5 (1.1 mg/kg PO q24h) to increase milk production. The foal was able to ambulate by Day 4 and by Day 6, was bright and alert and attempted to suckle from the mare frequently. However, the mare consistently demonstrated aggressive behavior toward the foal; therefore the mare's head was tied in a stationary position and periodic sedation (detomidine, Dormosedan,2 0.011 mg/kg IM q6h) was administered while the hindlimbs were hobbled to allow the foal to suckle under strict supervision. Although the foal was able to suckle voluntarily, the mare continued to display violent behavior and attempted to bite and kick the foal, but was constrained by the applied restraints. In an attempt to facilitate mare-foal bonding and provide a means for the foal to suckle unsupervised without maternal sedation or restraint, the mare was administered alprazolam6 (0.035 mg/kg PO q8h) on Day 7. On Day 8, 24 hours after the initial dose of alprazolam, the mare had a quieter demeanor and demonstrated less aggression toward the foal. The next day (Day 9) the mare was not aggressive toward the foal and allowed the foal to suckle regularly. Over the next 2 days, the mare was untied, the hobbles were removed and the foal was allowed to suckle without incident. On Day 11, the mare's physical examination was within acceptable parameters, but the mare appeared mildly sedate; therefore the frequency of alprazolam administration was decreased to twice daily (0.035 mg/kg PO q12h). On Day 14, the foal weighed 44 kg and was suckling regularly without threat from the mare. The mare and foal were subsequently discharged with instructions to administer alprazolam (0.035 mg/kg PO q12h for 3 days, then 0.018 mg/kg PO q12h for 5 days). One week after discharge the owner reported that the mare demonstrated no aggression toward the foal when suckling, and 6 months after presentation the mare and foal were reportedly healthy. Serum alprazolam concentrations from blood samples collected from the mare were subsequently measured at various time points. Specifically, after owner permission was obtained on Day 7 of hospitalization, 12 mL of blood was collected from the mare, just before the first dose of alprazolam administration (Time 0) and at Times 5, 10, 15, 30, 45, and 60 minutes as well as at 2, 4, 6, 8, 12, 24, 36, and 48 hours after the first alprazolam dose and placed in clot tubes; serum was then harvested and frozen at −80°C until further analysis. Alprazolam and its active metabolite, α-hydroxyalprazolam, concentrations in extracted serum samples were measured via liquid chromatography-ion trap mass spectrometry in positive ion mode. Four daughter ions of the parent pseudomolecular ions at a mass-to-charge ratio of 310.2 and 326.2, respectively, were used for quantification. Hydroxyalprazolam-D5 was used as an internal standard. Separation was achieved on a core-shell C18 column7 and guard column with a mobile phase consisting of water and acetonitrile each containing 0.1% formic acid. Retention times were 5.2 minutes for alprazolam and 4.8 minutes for α-hydroxyalprazolam. Using this method, standard curves were linear from 0.2 to 50 ng/mL for both compounds, with a coefficient of determination of >0.99 and a coefficient of variation of 2.25% for alprazolam and 2.41% for α-hydroxyalprazolam. After oral administration, alprazolam was quantifiable in plasma by 10 minutes, and α-hydroxyalprazolam by 30 minutes (Fig 1). The maximum concentrations for alprazolam (16.35 ng/mL) and α-hydroxyalprazolam (1.39 ng/mL) were reached at 4 and 6 hours, respectively. Multiple dose administration every 8 hours led to apparent accumulation of drug at the 24, 36, and 48 hour time points (Fig 1). Normal mare-foal behavior and bonding has been previously described in detail.1-4 Difficulties with mare-foal bonding are relatively rare, and with the exception of a severely physically compromised foal, most problems that occur result from inadequate or abnormal maternal behavior.1 Some aspects of postparturient behavior can appear to be antagonistic or aggressive toward the foal, but can in reality be normal maternal behavior. For example, it is not uncommon for a mare to demonstrate disapproving behavior such as threats to bite or kick or swishing of the tail toward the foal during bumping of the udder and suckling.2 This must be differentiated from inadequate or abnormal maternal behavior, which can be observed in primiparous or multiparous mares, but is more common in the former situation.1, 4 These behavioral abnormalities have been divided into distinct forms: ambivalence, fear of foal, nursing avoidance, extreme protective, and savage attack behavior.1-4 Ambivalence behavior of the mare toward the foal is characterized by lack of attention, bonding and protective behavior whereas fear of the foal behavior is typified by maternal avoidance of the foal whenever the foal approaches.1, 5 Nursing avoidance behavior implies aggressive behavior of the mare toward the foal only during suckling.1, 5 Extreme protective behavior is observed when maternal aggression is directed at humans or other animals and in the process the foal is injured (ie, mare tramples or pushes the foal into an obstacle when trying to intervene between the foal and the perceived threat).1 Finally, savage attack behavior of the mare against the foal is the most violent and severe abnormal behavior and can be life-threatening to the foal.1 Maternal behavior in the mare in this report can be described as a combination of ambivalence and nursing avoidance. In the case described here, the nursing avoidance behavior was aggressive enough toward the foal that the foal could not be left unattended with the dam. When common methods of correcting nursing avoidance (ie, supervised nursing with physical restraint of the mare, repeated sedation) were unsuccessful, alprazolam was administered and facilitated the development of appropriate mare-foal behavior over a 2–3 day time period in this case. Alprazolam is a short-acting anxiolytic of the benzodiazepine class of psychoactive medications and is prescribed to treat anxiety and panic disorders in people as well as dogs and cats.6-8 The exact mechanism of action is unknown, but similar to other benzodiazepines, alprazolam readily crosses the blood brain barrier and interacts with inhibitory neurotransmitter receptors that are directly activated by gamma-amino-butyric acid receptors (GABAA) within the central nervous system (CNS). The net result is general slowing of brain activity producing dose-related CNS depression that can vary from mild cognitive impairment (ie, sedation) to hypnosis.6 In people, alprazolam has a fast onset of action and is readily absorbed after oral administration with plasma concentrations and clinical benefits achieved within the first 1–2 hours of administration.6 The dosage for alprazolam administration in people ranges from 0.25 to 0.5 mg, PO, q8h for anxiety disorders and up to 10 mg daily for panic disorders. A single 1 mg dose of alprazolam in people resulted in a maximum serum concentration (Cmax) between 12 and 22 ng/mL 1–2 hours after administration.6 Similarly, serum alprazolam concentrations were detected in the mare described in this report and reached measurable and comparable plasma concentrations to those in people within 1 hour of administration (serum concentration at 1 hour – 14.1 ng/mL; Cmax of 16.35 ng/mL at 4 hours). In human medicine, optimal reduction in anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20–40 μg/mL.9 After a multiple dose regimen every 8 hours, trough concentrations of alprazolam in the mare of this report were within this target range for the third and sixth dose. Although an exact therapeutic dosage has not been established in horses, the 20 mg (0.035 mg/kg) dose administered to the mare in this report resulted in notable behavioral changes within 24 hours of commencement of alprazolam administration. This coincides with plasma concentrations within the therapeutic range for humans. Adverse effects of alprazolam administration in people include drowsiness, fatigue, weakness, ataxia, and sedation; however, the medication has a wide safety margin evidenced by the very high median lethal dose of alprazolam that will kill 50% of rats (LD50, 331–2171 mg/kg).6, 10 After accidental ingestion of alprazolam in dogs at doses as high as 5.55 mg/kg, clinical signs were similar to those reported in people and included ataxia and disorientation, depression, hyperactivity, gastrointestinal distress, weakness, tremors, vocalization, increased heart and respiratory rate, hypothermia, and increased salivation developing within 10–30 minutes postingestion.11 Despite the high doses ingested, death was not reported in any of those dogs, emphasizing the safety of this drug. Mild sedation was noted 96 hours after the initial oral administration in this mare at which point the frequency of administration was decreased to twice daily. Alprazolam can increase the risk of congenital abnormalities in women when used during the first trimester, thus caution should be used in pregnant mares.12 Furthermore, the pharmacokinetics of alprazolam in breast milk is similar to that in blood of lactating women, suggesting that the medication readily passes into the milk.6 Alprazolam concentrations were not determined from milk samples from the mare, or serum samples from the foal in this report, however, it is likely that drug was present in the mare's milk and therefore could have been absorbed to some extent by the foal. Although no sedation or other behavioral abnormalities were noted in the foal here, it is advisable to use the lowest dosage of alprazolam necessary to achieve the desired maternal behavioral changes, and the duration of administration should be as brief as possible. Preferably, discontinuation of daily alprazolam administration in people involves tapering the dose gradually to zero over several weeks to reduce rebound clinical signs. In the mare in this report, the dose was tapered over a short period of time (days) with no perceived untoward effects. In summary, administration of alprazolam at a dose of 0.035 mg/kg, PO, q8–12 h was an affordable (<$0.50/dose) method to facilitate healthy mare-foal bonding and behavior in an aggressive mare and ultimately allowed the foal to nurse from the mare while reducing the risk of maternally induced injury to the foal. Of note, however, administration of alprazolam to horses is not approved by the Food and Drug Administration and would be classified as extralabel use. Conflict of Interest Declaration: The authors disclose no conflict of interest. Off-label Antimicrobial Declaration: The authors declare no off-label use of antimicrobials.}, number={1}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Wong, D.M. and Alcott, C.J. and Davis, J.L. and Hepworth, K.L. and Wulf, L. and Coetzee, J.H.}, year={2015}, month={Jan}, pages={414–416} }
 @article{hepworth-warren_wilgenbusch_wong_fales-williams_wiechert_sponseller_2014, title={Intrathoracic oesophageal perforation and secondary pleuropneumonia: Five cases}, volume={27}, ISSN={0957-7734}, url={http://dx.doi.org/10.1111/eve.12279}, DOI={10.1111/eve.12279}, abstractNote={Perforation of the oesophagus is an uncommon event that can occur for a variety of reasons. While cervical ruptures of the oesophagus can be managed successfully, intrathoracic lesions warrant a far worse prognosis. Intrathoracic rupture of the oesophagus can occur spontaneously, with no known history of oesophageal obstruction, and may not be identified until a septic pleuropneumonia develops. This report describes the history, clinical presentation, response to therapy and outcome of 5 cases of intrathoracic oesophageal perforation and secondary septic pleuropneumonia.}, number={6}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Hepworth-Warren, K. L. and Wilgenbusch, C. M. and Wong, D. M. and Fales-Williams, A. J. and Wiechert, S. A. and Sponseller, B. A.}, year={2014}, month={Nov}, pages={283–290} }
 @article{hepworth-warren_sponseller_wong_kinyon_2014, title={Isolation of Corynebacterium pseudotuberculosis Biovar equi from a Horse in Central Iowa}, volume={2014}, ISSN={2090-7001 2090-701X}, url={http://dx.doi.org/10.1155/2014/436287}, DOI={10.1155/2014/436287}, abstractNote={Corynebacterium pseudotuberculosis biovar equi is the causative agent of “pigeon fever,” or “dryland distemper” in horses. The agent is typically identified in the Western United States but has recently been identified in Canada; it has not previously been documented as cause of infection in horses in Iowa. This report describes the clinical findings of two horses in Iowa that presented with pectoral abscessation, confirmed in one to be C. pseudotuberculosis biovar equi .}, journal={Case Reports in Veterinary Medicine}, publisher={Hindawi Limited}, author={Hepworth-Warren, Kate L. and Sponseller, Beatrice T. and Wong, David M. and Kinyon, Joann M.}, year={2014}, pages={1–3} }
 @article{hepworth-warren_wong_galow-kersh_williams_2014, title={Metastatic Tumor in Pregnancy: Placental Germ Cell Tumor With Metastasis to the Foal}, volume={34}, ISSN={0737-0806}, url={http://dx.doi.org/10.1016/j.jevs.2014.06.014}, DOI={10.1016/j.jevs.2014.06.014}, abstractNote={Abstract A placental mass was observed in an otherwise-healthy Quarter Horse mare; subsequently, the mare's 52-day-old foal was examined because of hind limb ataxia, urinary incontinence, and raised lesions of the distal limbs. Clinical and biochemical findings were supportive of liver disease and lumbosacral injury. Ultrasonographic evaluation of the abdomen suggested a liver mass, which was confirmed with computed tomography (CT) and determined to be neoplastic via histopathologic evaluation of a liver biopsy sample. Initial histopathology suggested a germ cell tumor. Regions of lysis affecting both femurs and third metacarpal bones and a complete oblique sagittal fracture through the body of the first sacral vertebra were present on CT. Supportive care was provided until CT confirmation of diffuse hepatic neoplasia and vertebral fracture. Necropsy revealed a large multinodular mass within the liver and a pathologic fracture of the first sacral vertebral body. Histopathologic comparison between neoplastic cells examined from the placenta and foal confirmed metastases of a germ cell tumor. Placental tumors are rare in all species; however, when noted in horses, clinicians should be aware of the possibility of metastatic spread to the foal.}, number={9}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Hepworth-Warren, Kate L. and Wong, David M. and Galow-Kersh, Nyomi L. and Williams, Jackie M.}, year={2014}, month={Sep}, pages={1134–1139} }
 @article{wong_davis_alcott_hepworth-warren_galow-kersh_rice_coetzee_2014, title={Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares}, volume={38}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12192}, DOI={10.1111/jvp.12192}, abstractNote={The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0–∞) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1–12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Wong, D. M. and Davis, J. L. and Alcott, C. J. and Hepworth-Warren, K. L. and Galow-Kersh, N. L. and Rice, S. and Coetzee, J. F.}, year={2014}, month={Nov}, pages={301–304} }
 @article{wong_hepworth_yaeger_miles_wilgenbusch_2013, title={Imaging Diagnosis - Hypoglycemia Associated with Cholangiocarcinoma and Peritoneal Carcinomatosis in a Horse}, volume={56}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/vru.12107}, DOI={10.1111/vru.12107}, abstractNote={An 8-year-old Thoroughbred mare presented for decreased appetite, ataxia, and weakness. Abdominal ultrasound revealed a large volume of anechoic fluid along with multiple masses involving the spleen, liver, and diaphragm. Pleural fluid was identified via ultrasonography and thoracic radiography. Thoracic radiographs also identified pulmonary interstitial nodules, an undulant dorsal diaphragmatic margin and enlargement of tracheobronchial lymph nodes. Clinical signs of weakness and mild seizures were concurrent with hypoglycemic episodes. The final diagnosis was cholangiocarcinoma with extensive metastasis. Clinical signs of weakness, ataxia, and seizures were attributed to a paraneoplastic syndrome of tumor-associated hypoglycemia that has been infrequently reported in horses.}, number={1}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Wong, David and Hepworth, Kate and Yaeger, Michael and Miles, Kristina and Wilgenbusch, Conrad}, year={2013}, month={Sep}, pages={E9–E12} }
 @article{wong_witty_alcott_sponseller_wang_hepworth_2013, title={Renal Replacement Therapy in Healthy Adult Horses}, volume={27}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12049}, DOI={10.1111/jvim.12049}, abstractNote={Background Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF. Objective To investigate efficacy and safety of RRT in horses. Animals Five healthy adult horses. Methods A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period. Results Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P ≤ .007). A significant increase in serum phosphorus (P ≤ .001) and decrease in BUN (P < .001) were also noted. A significant prolongation of prothrombin (P < .01) and partial thromboplastin time (P < .0001) were observed along with a decrease in platelet count (P ≤ .04). Conclusions and Clinical Importance Renal replacement therapy can safely and effectively be used in adult horses.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Wong, D.M. and Witty, D. and Alcott, C.J. and Sponseller, B.A. and Wang, C. and Hepworth, K.}, year={2013}, month={Mar}, pages={308–316} }
 @article{hepworth_wong_sponseller_alcott_sponseller_ben-shlomo_whitley_2013, title={Survival of an adult Quarter Horse gelding following bacterial meningitis caused by Escherichia coli}, volume={26}, ISSN={0957-7734}, url={http://dx.doi.org/10.1111/eve.12011}, DOI={10.1111/eve.12011}, abstractNote={Bacterial meningitis in the mature horse is a rare and typically fatal condition. This report describes a 7-year-old Quarter Horse gelding that initially presented following suspected trauma to the left eye but subsequently developed bacterial meningitis, and a nasal and palpebral abscess, all of which cultured the same isolate of Escherichia coli. The entry site of infection in bacterial meningitis is often related to a breach in the calvarium and extension of bacteria residing in the paranasal sinuses. This case is unique as there were multiple pathways through which bacteria may have entered the central nervous system including haematogenous spread from a nasal abscess, local extension of periocular infection or an undetected skull fracture. Aside from persistent blindness in the left eye, the horse made a full recovery.}, number={10}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Hepworth, K. L. and Wong, D. M. and Sponseller, B. A. and Alcott, C. J. and Sponseller, B. T. and Ben-Shlomo, G. and Whitley, R. D.}, year={2013}, month={Jan}, pages={507–512} }
 @article{hepworth‐warren_alcott_2013, title={Treatment and resolution of zilpaterol hydrochloride toxicity in a Quarter Horse gelding}, volume={26}, ISSN={0957-7734 2042-3292}, url={http://dx.doi.org/10.1111/eve.12092}, DOI={10.1111/eve.12092}, abstractNote={Zilpaterol hydrochloride is a β-2 agonist utilised as a repartitioning agent in cattle. In recent years, it has also been used illicitly among human athletes and body builders, and administered to racehorses. While there are numerous anecdotal reports of the effects of zilpaterol in horses, this is the first documented clinical case of equine zilpaterol toxicity. The horse presented with marked tachycardia, profuse sweating and generalised muscle fasciculations. Ultimately, treatment was initiated with propranolol and the horse made a complete recovery.}, number={2}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Hepworth‐Warren, K. L. and Alcott, C. J.}, year={2013}, month={Nov}, pages={81–85} }