- Equine sinusitis aetiology is linked to sinus microbiome by amplicon sequencingLowman, Megan E.; Tipton, Craig D.; Labordere, Alexandra L.; Brown, James A. (Wiley, 2022-10)Background: Information regarding the microbiome in sinusitis using genetic sequencing is lacking and more-in-depth understanding of the microbiome could improve antimicrobial selection and treatment outcomes for cases of primary sinusitis. Objectives: To describe sinus microbiota in samples from horses with sinusitis and compare microbiota and the presence of antimicrobial resistance genes between primary, dental-related and other secondary causes of sinusitis. Study design: Retrospective case series. Methods Records of equine sinusitis from 2017 to 2021 were reviewed and historical microbial amplicon sequence data were obtained from clinical diagnostic testing of sinus secretions. Following bioinformatic processing of bacterial and fungal sequence data, the sinus microbiota and importance of sinusitis aetiology among other factors were investigated from the perspectives of alpha diversity (e.g., number of operational taxonomic units [OTUs], Hill1 Diversity), beta diversity, and differentially abundant taxa. Quantitative PCR allowed for comparisons of estimated bacterial abundance and detection rate of common antibiotic resistance-associated genes. In a smaller subset, longitudinal analysis was performed to evaluate similarity in samples over time. Results: Of 81 samples analysed from 70 horses, the bacterial microbiome was characterised in 66, and fungal in five. Only sinusitis aetiology was shown to significantly influence microbiome diversity and composition (p < 0.05). Dental-related sinusitis (n = 44) was associated with a significantly higher proportion of obligate anaerobic bacteria, whereas primary sinusitis (n = 12) and other (n = 10) groups were associated with fewer bacteria and higher proportions of facultative anaerobic and aerobic genera. Antimicrobial resistance genes and fungal components were exclusively identified in dental-related sinusitis. Main limitations: Retrospective nature, incomplete prior antimicrobial administration data. Conclusions: Molecular characterisation in sinusitis identifies microbial species which may be difficult to isolate via culture, and microbiome profiling can differentiate sinusitis aetiology, which may inform further treatment, including antimicrobial therapy.
- The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in HorsesMacDonald, Elizabeth S.; Barrett, Jennifer G. (Frontiers Media, 2020-01-21)One hallmark of mesenchymal stem cells (MSCs) is the ability to differentiate into multiple tissue types which assists in tissue regeneration. Another hallmark of MSCs is their potent anti-inflammatory and immunomodulatory properties and the potential to treat inflammatory, immune-mediated, and ischemic conditions. In equine practice, MSCs have shown efficacy in the treatment of musculoskeletal disorders such as tendinopathy, meniscal tears and cartilage injury. However, there are many equine disease processes and conditions that may benefit from the immunomodulatory properties of MSCs. Examples include conditions associated with overwhelming acute inflammatory response such as systemic inflammatory response syndrome to chronic diseases characterized by a prolonged low level of inflammation such as equine asthma and recurrent uveitis. For the acute inflammatory response processes, there is often high morbidity and mortality with no effective immunomodulatory treatment to prevent the overwhelming synthesis of proinflammatory mediators. For chronic inflammatory disease processes, frequently long-term corticosteroid treatment is the therapeutic mainstay, with serious potential complications. Thus, there is an unmet need for alternative anti-inflammatory treatments for both acute and chronic illnesses in horses. While MSCs show promise for such conditions, much research is needed before a clinically safe and effective treatment will be available. Optimal MSC tissue source, patient vs. donor source (autologous vs. allogeneic) and cell growth conditions need to be determined for each problem. For immediate use, allogeneic MSC treatments is preferable, but immune tolerance and adequate safety require further study. MSC collection and cryopreservation from horses before they are injured or ill, whether from umbilical cord tissue, bone marrow or adipose might become more widespread. Once these fundamental approaches to treating specific diseases with MSCs are determined, the route of administration, dose and timing of administration also need to be studied. To provide a framework for development of MSC immunomodulatory treatments, this article reviews the current understanding of equine MSC anti-inflammatory and immunomodulatory properties and proposes how MSC therapy may be further developed to treat acute onset systemic inflammatory processes and chronic inflammatory diseases.
- The Use of Adipose-Derived Progenitor Cells and Platelet-Rich Plasma Combination for the Treatment of Supraspinatus Tendinopathy in 55 Dogs: A Retrospective StudyCanapp, Sherman O., Jr.; Canapp, Debra A.; Ibrahim, Victor; Carr, Brittany Jean; Cox, Catherine; Barrett, Jennifer G. (Frontiers, 2016-09-09)Objective: To report clinical findings and outcomes for 55 dogs with supraspinatus tendinopathy (ST) treated with adipose-derived progenitor cells and platelet-rich plasma (ADPC-PRP) therapy. Methods: Medical records of client-owned dogs diagnosed with ST that were treated with ADPC-PRP combination therapy were reviewed from 2006 to 2013. Data collected included signalment, medical history, limb involvement, prior treatments, physical and orthopedic examination, objective temporospatial gait analysis findings, diagnostic imaging results (radiography, magnetic resonance imaging, musculoskeletal ultrasonography), arthroscopy findings, and outcome. Results: Following ultrasound-guided injection of ADPC-PRP, objective gait analysis was available on 25 of the 55 dogs at 90 days post ADPC-PRP therapy. Following treatment, a significant increase in total pressure index percentage (TPI%) was noted in the injured (treated) forelimb at 90 days post treatment (p = 0.036). At 90 days following treatment, 88% of cases had no significant difference in TPI% of the injured limb to the contralateral limb. The remaining 12% of cases had significantly improved (p = 0.036). Bilateral shoulder diagnostic musculoskeletal ultrasound revealed a significant reduction in tendon size (CSA) in the treated tendon at 90 days following treatment when compared to the initial CSA (p = 0.005). All cases showed significant improvement in fiber pattern of the affected supraspinatus tendon by the ultrasound shoulder pathology rating scale.
- Prospective pre- and post-race evaluation of biochemical, electrophysiologic, and echocardiographic indices in 30 racing thoroughbred horses that received furosemideGunther-Harrington, Catherine T.; Arthur, Rick; Estell, Krista; Martinez Lopez, Beatriz; Sinnott, Alexandra; Ontiveros, Eric; Varga, Anita; Stern, Joshua A. (2018-01-18)Background Exercise induced cardiac fatigue (EICF) and cardiac dysrhythmias are well described conditions identified in high-level human athletes that increase in frequency with intensity and duration of exercise. Identification of these conditions requires an understanding of normal pre- and post-race cardiac assessment values. The objectives of this study were to (1) characterize selected indices of cardiac function, electrophysiologic parameters, and biochemical markers of heart dysfunction prior to and immediately after high level racing in Thoroughbred horses receiving furosemide; and (2) create pre- and post-race reference values in order to make recommendations on possible screening practices for this population in the future. Results Thirty Thoroughbred horses were enrolled in the study with an age range of 3–6 years. All horses received furosemide prior to racing. Physical exams, ECGs, and echocardiograms were performed prior to racing (T0) and within 30–60 min following the race (T1). Blood samples were obtained at T0, T1, 4 h post-race (T4) and 24 h after the race (T24). Electrolytes, hematocrit, cardiac troponin I, and partial pressure CO2 values were obtained at all time points. Heart rate was significantly increased post-race compared to baseline value with a median difference of 49 bpm, 95% CI [31,58],(P < 0.0001). No dysrhythmias were noted during ECG assessment. Following the race, an increase in number of horses demonstrating regurgitation through the aorta and AV valves was noted. Systolic function measured by fractional shortening increased significantly with a mean difference of 7.9%, 95% CI [4.8, 10.9], (P < 0.0001). Cardiac troponin I was not different at pre- and immediately post-race time points, but was significantly increased at T4 (P < 0.001). Troponin returned to baseline value by T24. Conclusions This study utilized a before and after study design where each horse served as its own control, as such the possible effect of regression to the mean cannot be ruled out. The reference intervals generated in this study may be used to identify selected echocardiographic and electrocardiographic abnormalities in racing horses receiving furosemide.
- Comparison of equine tendon-, muscle-, and bone marrow–derived cells cultured on tendon matrixStewart, Allison A.; Barrett, Jennifer G.; Byron, Christopher R.; Yates, Angela C.; Durgam, Sushmitha S.; Evans, Richard B.; Stewart, Matthew C. (AVMA, 2009-06)Objective—To compare viability and biosynthetic capacities of cells isolated from equine tendon, muscle, and bone marrow grown on autogenous tendon matrix.
- Engineering Tendon: Scaffolds, Bioreactors, and Models of RegenerationYoungstrom, Daniel W.; Barrett, Jennifer G. (Hindawi, 2016)Tendons bridge muscle and bone, translating forces to the skeleton and increasing the safety and efficiency of locomotion. When tendons fail or degenerate, there are no effective pharmacological interventions. The lack of available options to treat damaged tendons has created a need to better understand and improve the repair process, particularly when suitable autologous donor tissue is unavailable for transplantation. Cells within tendon dynamically react to loading conditions and undergo phenotypic changes in response to mechanobiological stimuli. Tenocytes respond to ultrastructural topography and mechanical deformation via a complex set of behaviors involving force-sensitive membrane receptor activity, changes in cytoskeletal contractility, and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell-matrix forces with high fidelity. While early bioreactor designs have greatly expanded our knowledge of mechanotransduction, traditional scaffolds do not fully model the topography, composition, and mechanical properties of native tendon. Decellularized tendon is an ideal scaffold for cultivating replacement tissue and modeling tendon regeneration. Decellularized tendon scaffolds (DTS) possess high clinical relevance, faithfully translate forces to the cellular scale, and have bulk material properties that match natural tissue. This review summarizes progress in tendon tissue engineering, with a focus on DTS and bioreactor systems.
- Atrial Fibrillation in Eight New World CamelidsBozorgmanesh, R.; Magdesian, K. G.; Estell, Krista; Stern, J. A.; Swain, E. A.; Griffiths, L. G. (2016-01)BACKGROUND: There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). OBJECTIVE: Describe clinical signs and outcome of AF in NWC. ANIMALS: Eight New World Camelids admitted with AF. METHODS: A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). RESULTS: All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). CONCLUSIONS AND CLINICAL IMPORTANCE: Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions.
- Pneumonia Caused by Klebsiella spp. in 46 HorsesEstell, Krista; Young, A.; Kozikowski, T.; Swain, E. A.; Byrne, B. A.; Reilly, Christopher M.; Kass, P. H.; Aleman, M. (2016-01)BACKGROUND: Klebsiella spp. are implicated as a common cause of bacterial pneumonia in horses, but few reports describe clinical presentation and disease progression. HYPOTHESIS/OBJECTIVES: To describe the signalment, clinicopathologic data, radiographic and ultrasonographic findings, antimicrobial susceptibility, outcome, and pathologic lesions associated with Klebsiella spp. pneumonia in horses. ANIMALS: Forty-six horses from which Klebsiella spp. was isolated from the lower respiratory tract. METHODS: Retrospective study. Medical records from 1993 to 2013 at the William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis were reviewed. Exact logistic regression was performed to determine if any variables were associated with survival to hospital discharge. RESULTS: Survival in horses <1 year old was 73%. Overall survival in adults was 63%. For adults in which Klebsiella pneumoniae was the primary isolate, survival was 52%. Mechanical ventilation preceded development of pneumonia in 11 horses. Complications occurred in 25/46 horses, with thrombophlebitis and laminitis occurring most frequently. Multi-drug resistance was found in 47% of bacterial isolates. Variables that significantly impacted survival included hemorrhagic nasal discharge, laminitis, and thoracic radiographs with a sharp demarcation between marked caudal pulmonary alveolar infiltration and more normal-appearing caudodorsal lung. CONCLUSIONS AND CLINICAL IMPORTANCE: Klebsiella spp. should be considered as a differential diagnosis for horses presenting with hemorrhagic pneumonia and for horses developing pneumonia after mechanical ventilation. Multi-drug resistance is common. Prognosis for survival generally is fair, but is guarded for adult horses in which K. pneumoniae is isolated as the primary organism.
- Blood and Cerebrospinal Fluid α-Tocopherol and Selenium Concentrations in Neonatal Foals with Neuroaxonal DystrophyFinno, C. J.; Estell, Krista; Katzman, S.; Winfield, L.; Rendahl, A.; Textor, J.; Bannasch, D. L.; Puschner, B. (2015-11)BACKGROUND: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on α-tocopherol (α-TP)-deficient diet. OBJECTIVE: Intramuscular α-TP and selenium (Se) administration at 4 days of age would have no significant effect on serum or cerebrospinal fluid (CSF) α-TP in healthy foals. Serum and CSF α-TP, but not Se, would be significantly decreased in NAD/EDM-affected foals during first year of life. ANIMALS: Fourteen Quarter horse foals; 10 healthy foals supplemented with 0.02 mL/kg injectable α-TP and Se (n = 5) or saline (n = 5) at 4 days of age and 4 unsupplemented NAD/EDM-affected foals. METHODS: Complete neurologic examinations were performed, blood and CSF were collected before (4 days of age) and after supplementation at 10, 30, 60, 120, 180, 240, and 360 days of age. Additional blood collections occurred at 90, 150, 210, and 300 days. At 540 days, NAD/EDM-affected foals and 1 unsupplemented healthy foal were euthanized and necropsies performed. RESULTS: Significant decreases in blood, CSF α-TP and Se found in the first year of life in all foals, with most significant changes in serum α-TP from 4-150 days. Dam α-TP and Se significantly influenced blood concentrations in foals. Injection of α-TP and Se did not significantly increase CSF Se, blood or CSF α-TP in healthy foals. NAD/EDM-affected foals had significantly lower CSF α-TP through 120 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Injection of α-TP and Se at 4 days of age does not significantly increase blood or CSF α-TP. Despite all 14 foals remaining deficient in α-TP, only the 4 genetically predisposed foals developed NAD/EDM.