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  • Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumors
    Rossmeisl, John H.; King, Jamie N.; Robertson, John L.; Weger-Lucarelli, James; Elankumaran, Subbiah (MDPI, 2024-01-29)
    Neurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood–brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment. Dose-limiting toxicities manifested as fever, hematologic, and neurological adverse events, and the maximum tolerated dose (MTD) of rLAS-uPA was 2 × 107 pfu/mL. Mild adverse events, including transient infusion reactions, diarrhea, and fever were observed in 16/18 of dogs treated at or below MTD. No infectious virus was recoverable from body fluids. Neutralizing antibodies to rLAS-uPA were present in all dogs by 2 weeks post-treatment, and viral genetic material was detected in post-treatment tumors from six dogs. Tumor volumetric reductions occurred in 2/11 dogs receiving the MTD. Systemically administered rLAS-uPA NDV was safe and induced anti-tumor effects in canine brain tumors, although modifications to evade host anti-viral immunity are needed to optimize this novel therapy.
  • Comparison of linear and volumetric criteria for the determination of therapeutic response in dogs with intracranial gliomas
    Garcia Mora, Josefa Karina; Robertson, John L.; Hsu, Fang-Chi; Shinn, Richard Levon; Larson, Martha M.; Rylander, Christopher G.; Whitlow, Christopher T.; Debinski, Waldemar; Davalos, Rafael V.; Daniel, Gregory B.; Rossmeisl, John H. (Wiley, 2022-05)
    Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques. Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method. Therapeutic response at 6-weeks will correlate with overall survival (OS). Animals: Forty-six dogs with intracranial gliomas. Methods: Prospective study. Three raters measured tumors using 1D and 2D linear, TTV, and contrast-enhancing volumetric (CEV) techniques on 143 brain MRI to determine agreement between methods, define therapeutic responses, and assess relations with OS. Results: Raters performed 1D the fastest (2.9 ± 0.57 minutes) and CEV slowest (17.8 ± 6.2 minutes). Inter- and intraobserver agreements were excellent (intraclass correlations ≥.91) across methods. Correlations between linear (1D vs 2D; ρ >.91) and volumetric (TTV vs CEV; ρ >.73) methods were stronger than linear to volumetric comparisons (ρ range,.26-.59). Incorporating clinical and imaging data resulted in fewer discordant therapeutic responses across methods. Dogs having partial tumor responses at 6 weeks had a lower death hazard than dogs with stable or progressive disease when assessed using 2D, CEV, and TTV (hazard ration 2.1; 95% confidence interval, 1.22-3.63; P =.008). Conclusions and Clinical Importance: One-dimensional, 2D, CEV, and TTV are comparable for determining therapeutic response. Given the simplicity, universal applicability, and superior performance of the TTV, we recommend its use to standardize glioma therapeutic response criteria.
  • Non-coagulopathic hemothorax in a dog: A case report
    LaVine, Danielle; Conner, Bobbi; Daniel, Gregory B.; Freeman, Mark D. (Wiley, 2022-09)
    An 8-year-old, female-spayed, Blue Heeler presented with suspected non-coagulopathic spontaneous, hemothorax with neoplasia as the most likely differential as coagulation parameters were normal and no obvious history of trauma was reported. Computed tomography scan was crucial for diagnosis of a traumatic partial vascular avulsion injury that was successfully managed supportively.
  • Ablative and Immunostimulatory Effects of Histotripsy Ablation in a Murine Osteosarcoma Model
    Hay, Alayna N.; Imran, Khan Mohammad; Hendricks-Wenger, Alissa; Gannon, Jessica M.; Sereno, Jacqueline; Simon, Alex; Lopez, Victor A.; Coutermarsh-Ott, Sheryl; Vlaisavljevich, Eli; Allen, Irving C.; Tuohy, Joanne L. (MDPI, 2023-10-09)
    Background: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in humans, primarily affecting children and adolescents. Significant advancements in treatment options for OS have not occurred in the last several decades, and the prognosis remains grim with only a 70% rate of 5-year survival. The objective of this study was to investigate the focused ultrasound technique of histotripsy as a novel, noninvasive treatment option for OS. Methods: We utilized a heterotopic OS murine model to establish the feasibility of ablating OS tumors with histotripsy in a preclinical setting. We investigated the local immune response within the tumor microenvironment (TME) via immune cell phenotyping and gene expression analysis. Findings: We established the feasibility of ablating heterotopic OS tumors with ablation characterized microscopically by loss of cellular architecture in targeted regions of tumors. We observed greater populations of macrophages and dendritic cells within treated tumors and the upregulation of immune activating genes 72 h after histotripsy ablation. Interpretation: This study was the first to investigate histotripsy ablation for OS in a preclinical murine model, with results suggesting local immunomodulation within the TME. Our results support the continued investigation of histotripsy as a novel noninvasive treatment option for OS patients to improve clinical outcomes and patient prognosis.
  • Differences in Sleep Quality and Sleepiness among Veterinary Medical Students at Multiple Institutions before and after the Pandemic Induced Transition to Online Learning
    Nappier, Michael T.; Alvarez, Elizabeth E.; Bartl-Wilson, Lara; Boynton, Elizabeth P.; Hanlon, Alexandra L.; Lozano, Alicia J.; Ng, Zenithson; Ogunmayowa, Oluwatosin; Shoop, Tiffany; Welborn, Nancy D.; Wuerz, Julia (University of Toronto Press)
    Poor sleep health has been previously documented in veterinary medical students. However, it is not known how universal or widespread this problem is. This study evaluated Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) scores to measure sleep health among students at seven colleges of veterinary medicine in the United States (US). Inadvertently, the transition to online only learning due to the global COVID-19 pandemic was also captured. Veterinary students were found to have universally poor sleep quality and high daytime sleepiness. The transition to online only learning appeared to have little impact on sleep quality, but improved daytime sleepiness scores were observed. The findings suggest poor sleep health is common among veterinary medical students at multiple institutions in the US and that further investigation is necessary.
  • Association between Phenotypes of Antimicrobial Resistance, ESBL Resistance Genes, and Virulence Genes of Salmonella Isolated from Chickens in Sichuan, China
    Shu, Gang; Qiu, Jianyu; Zheng, Yilei; Chang, Lijen; Li, Haohuan; Xu, Funeng; Zhang, Wei; Yin, Lizi; Fu, Hualin; Yan, Qigui; Gan, Ting; Lin, Juchun (MDPI, 2023-08-31)
    The aim of this study was to explore the association between antimicrobial resistance, ESBL genes, and virulence genes of Salmonella isolates. From 2019 to 2021, a total of 117 Salmonella isolates were obtained from symptomatic chickens in Sichuan Province, China. The strains were tested for antimicrobial resistance and the presence of ESBL according to the Clinical and Laboratory Standards Institute (CLSI) instructions. The presence of ESBL genes and genes for virulence was determined using Polymerase Chain Reaction (PCR). In addition, Multilocus Sequence Typing (MLST) was applied to confirm the molecular genotyping. Moreover, the mechanism of ESBL and virulence gene transfer and the relationships between the resistance phenotype, ESBL genes, and virulence genes were explored. The isolates exhibited different frequencies of resistance to antibiotics (resistance rates ranged from 21.37% to 97.44%), whereas 68.38% and 41.03% of isolates were multi-drug resistance (MDR) and ESBL-producers, respectively. In the PCR analysis, blaCTX-M was the most prevalent ESBL genotype (73.42%, 58/79), and blaCTX-M-55 showed the most significant effect on the resistance to cephalosporins as tested by logistic regression analysis. Isolates showed a high carriage rate of invA, avrA, sopB, sopE, ssaQ, spvR, spvB, spvC, stn, and bcfC (ranged from 51.28% to 100%). MLST analysis revealed that the 117 isolates were divided into 11 types, mainly ST92, ST11, and ST3717. Of 48 ESBL-producers, 21 transconjugants were successfully obtained by conjugation. Furthermore, ESBL and spv virulence genes were obtained simultaneously in 15 transconjugants. These results highlighted that Salmonella isolates were common carriers of ESBLs and multiple virulence genes. Horizontal transfer played a key role in disseminating antimicrobial resistance and pathogenesis. Therefore, it is necessary to continuously monitor the use of antimicrobials and the prevalence of AMR and virulence in Salmonella from food animals and to improve the antibiotic stewardship for salmonellosis.
  • A Comparison of Dobutamine, Norepinephrine, Vasopressin, and Hetastarch for the Treatment of Isoflurane-Induced Hypotension in Healthy, Normovolemic Dogs
    Henao-Guerrero, Natalia; Ricco-Pereira, Carolina H.; Paranjape, Vaidehi V. (MDPI, 2023-08-19)
    Isoflurane is a commonly used inhalation anesthetic in species undergoing veterinary care that induces hypotension, impacting organ perfusion, making it imperative to minimize its occurrence or identify effective strategies for treating it. This study evaluated and compared the hemodynamic effects of DOB, NEP, VAS, and HES in twelve isoflurane-anesthetized Beagle dogs. The order of the first three treatments was randomized. HES was administered last. Data were collected before treatments (baseline) and after 10 min of a sustained MAP of <45 mmHg induced by a high end-tidal isoflurane concentration (T0). Once treatment was initiated and the target MAP was achieved (65 to 80 mmHg) or the maximum dose reached, data were collected after 15 min of stabilization (T1) and 15 min after (T2). A 15 min washout period with a MAP of ≥65 mmHg was allowed between treatments. The intravenous dosage regimens started and were increased by 50% every five minutes until the target MAP or maximum dose was reached. The dosages were as follows: DOB, 5–15 μg/kg/min; NEP, 0.1–2 μg/kg/min; VAS, 0.5–5 mU/kg/min; and HET, 6% 1–20 mL/kg/min. DOB improved CO, DO2, and VO2, but reduced SVR. VAS elevated SVR, but decreased CO, DO2, and VO2. HES minimally changed BP and mildly augmented CO, DO2, and VO2. These treatments failed to reach the target MAP. NEP increased the arterial BP, CO, MPAP, and PAWP, but reduced HR. Norepinephrine infusion at 0.44 ± 0.19 μg/kg/min was the most efficient therapy for correcting isoflurane-induced hypotension.
  • Bead size has a greater effect on in vitro elution from antimicrobial-impregnated calcium sulfate beads than drug concentration
    Olsen, Ronald S.; Sawyere, Dominique M.; Davis, Jennifer L.; Lanz, Otto I.; Werre, Stephen R. (American Veterinary Medical Association, 2023-05)
    OBJECTIVE To compare the elution characteristics of amikacin-impregnated calcium sulfate (CaSO4) beads based on different drug concentrations and bead size configurations. SAMPLE Six groups of amikacin-impregnated CaSO4 beads and one negative control group. PROCEDURES Amikacin-impregnated CaSO4 beads were formed with either 500 mg (low-concentration) or 1 g (high-concentration) of amikacin per 15 g CaSO4 hemihydrate powder. The number of beads necessary to approximate 150 mg of amikacin for each of the 3 bead sizes (3 mm, 5 mm, and 7 mm) at both low and high concentrations were placed in 6 mL of phosphate-buffered saline. The saline was sampled at 14 time points over 28 days. Amikacin concentrations were determined using liquid chromatography-mass spectrometry. RESULTS Smaller beads reached higher mean peak concentrations than larger beads (P < .0006). Peak concentrations for the low-and high-concentration groups were 20.5 mg/mL and 27.4 mg/mL, 13.1 mg/mL and 14.0 mg/mL, and 8.85 mg/mL and 6.75 mg/mL for the 3 mm, 5 mm, and 7 mm beads, respectively. Bead size also affected the length of therapeutic duration, lasting 6 days for the 3 mm and 5 mm beads and 9 days for the 7 mm beads. However, this was only statistically evident among the high-concentration beads (P < .044). Antimicrobial concentration within the same bead sizes did not affect elution. CLINICAL RELEVANCE Amikacin-impregnated CaSO4 beads achieved extreme supratherapeutic eluent concentrations. While additional studies are needed, bead size significantly affected elution with smaller beads reaching higher peak concentrations and 7 mm, high-concentration beads demonstrating a longer therapeutic duration than smaller beads.
  • Evaluation of Electrical Cardiometry for Measuring Cardiac Output and Derived Hemodynamic Variables in Comparison with Lithium Dilution in Anesthetized Dogs
    Paranjape, Vaidehi V.; Garcia-Pereira, Fernando L.; Menciotti, Giulio; Saksena, Siddharth; Henao-Guerrero, Natalia; Ricco-Pereira, Carolina H. (MDPI, 2023-07-20)
    Numerous cardiac output (CO) technologies were developed to replace the ‘gold standard’ pulmonary artery thermodilution due to its invasiveness and the risks associated with it. Minimally invasive lithium dilution (LiD) shows excellent agreement with thermodilution and can be used as a reference standard in animals. This study evaluated CO via noninvasive electrical cardiometry (EC) and acquired hemodynamic variables against CO measured using LiD in six healthy, anesthetized dogs administered different treatments (dobutamine, esmolol, phenylephrine, and high-dose isoflurane) impacting CO values. These treatments were chosen to cause drastic variations in CO, so that fair comparisons between EC and LiD across a wide range of CO values (low, intermediate, and high) could be made. Statistical analysis included linear regression, Bland–Altman plots, Lin’s concordance correlation coefficient (ρc), and polar plots. Values of p < 0.05 represented significance. Good agreement was observed between EC and LiD, but consistent underestimation was noted when the CO values were high. The good trending ability, ρc of 0.88, and low percentage error of ±31% signified EC’s favorable performance. Other EC-acquired variables successfully tracked changes in CO measured using LiD. EC may be a pivotal hemodynamic tool for continuously monitoring circulatory changes, as well as guiding and treating cardiovascular anesthetic complications in clinical settings.
  • Evaluation of gallbladder motility assessed by ultrasonography in dogs with hyperlipidemia
    Villm, Jessica A.; DeMonaco, Stefanie M.; Panciera, David L.; Larson, Martha M.; Bolton, Timothy A. (Wiley, 2023-05)
    Background: The pathogenesis of gallbladder (GB) mucoceles in dogs is unknown. It has been proposed that hyperlipidemia could impair GB motility and contribute to GB mucocele formation. Hypothesis/Objectives: The objective of this study was to compare GB motility in dogs with hyperlipidemia to control dogs using ultrasonography. We hypothesized that hyperlipidemic dogs will have decreased GB motility compared with controls. Animals: Twenty-six hyperlipidemic and 28 healthy, age-matched control dogs were prospectively enrolled. Methods: Cholesterol and triglyceride concentrations were measured in all dogs. Hyperlipidemia was defined as hypercholesterolemia (>332 mg/dL) and/or hypertriglyceridemia (>143 mg/dL) using a biochemical analyzer. Ultrasound was performed before feeding, and 60 and 120 minutes after ingestion of a high fat diet. Gallbladder volumes (GBV) and ejection fractions (EF) were calculated. Results: Hyperlipidemic dogs had significantly larger GBVs (ml/kg) before feeding and 60 minutes after feeding of 1.2 (0.4-7.5; P = .008) and 0.6 (0.1-7.2; P = .04) compared with controls 0.6 (0.2-2.6) and 0.4 (0.1-1.9), respectively. Severely hyperlipidemic dogs had significantly larger GBV at baseline, 60 minutes, and 120 minutes of 1.7 (0.6-7.5; P = .03), 1.3 (0.4-7.2; P = .02), and 1.3 (0.2-8.2; P = .04), respectively compared with mildly hyperlipidemic dogs. EFs at 60 and 120 minutes between controls, hyperlipidemic, and severely hyperlipidemic were all 0.3 at 60 minutes and 0.5, 0.3, and 0.3 at 120 minutes, respectively which were not statistically different. Conclusions and Clinical Importance: Hyperlipidemia leads to GB distention in dogs which could lead to retention of bile and gallbladder disease.
  • The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy
    Zhang, Shuai; Zheng, Yilei; Du, Hong; Zhang, Wei; Li, Haohuan; Ou, Yangping; Xu, Funeng; Lin, Juchun; Fu, Hualin; Ni, Xueqing; Chang, Li-Jen; Shu, Gang (MDPI, 2023-06-19)
    The excessive intake of fluoride, one of the trace elements required to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with a good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male ICR mice were selected. All mice were randomly divided into five groups: a control (K) group, a model (F) group, a low-dose (LT) group, a medium-dose (MT) group, and a high-dose (HT) group. The control and model groups were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT), or 160 mg/kg (HT) of TMP was fed by gavage for two weeks, with a maximum gavage volume for the mice of 0.2 mL/10 g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study showed that, compared with the model group, TMP alleviated the pathological changes in the liver induced by the fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST, and MDA (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px, and SOD in the liver compared with the model group (p < 0.05). In conclusion, TMP can inhibit oxidative stress by activating the Nrf2 pathway and alleviate the liver injury induced by fluoride.
  • Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study
    Imran, Khan Mohammad; Tintera, Benjamin; Morrison, Holly A.; Tupik, Juselyn D.; Nagai-Singer, Margaret A.; Ivester, Hannah; Council-Troche, McAlister; Edwards, Michael; Coutermarsh-Ott, Sheryl; Byron, Christopher; Clark-Deener, Sherrie; Uh, Kyungjun; Lee, Kiho; Boulos, Paul; Rowe, Cliff; Coviello, Christian; Allen, Irving C. (MDPI, 2023-05-24)
    Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.
  • The T2-FLAIR mismatch sign as an imaging biomarker for oligodendrogliomas in dogs
    Garcia-Mora, Josefa; Parker, Rell L.; Cecere, Thomas; Robertson, John L.; Rossmeisl, John H. (Wiley, 2023-05)
    BackgroundIn humans, the T2-weighted (T2W)-fluid-attenuated inversion recovery (FLAIR) mismatch sign (T2FMM) is a specific imaging biomarker for the isocitrate dehydrogenase 1 (IDH1)-mutated, 1p/19q non-codeleted low-grade astrocytomas (LGA). The T2FMM is characterized by a homogeneous hyperintense T2W signal and a hypointense signal with a hyperintense peripheral rim on FLAIR sequences. In gliomas in dogs, the T2FMM has not been described. Hypotheses/ObjectivesIn dogs with focal intra-axial brain lesions, T2FMM will discriminate gliomas from other lesions. The T2FMM will be associated with the LGA phenotype and presence of microcysts on histopathology. Interobserver agreement for T2FMM magnetic resonance imaging (MRI) features will be high. AnimalsOne hundred eighty-six dogs with histopathologically diagnosed focal intra-axial lesions on brain MRI including oligodendrogliomas (n = 90), astrocytomas (n = 47), undefined gliomas (n = 9), cerebrovascular accidents (n = 33), and inflammatory lesions (n = 7). MethodsTwo blinded raters evaluated the 186 MRI studies and identified cases with the T2FMM. Histopathologic and immunohistochemical slides of T2FMM cases were evaluated for morphologic features and IDH1-mutations and compared to cases without the T2FMM. Gene expression analyses were performed on a subset of oligodendrogliomas (n = 10) with and without T2FMM. ResultsThe T2FMM was identified in 14/186 (8%) of MRI studies, and all dogs with T2FMM had oligodendrogliomas (n = 12 low-grade [LGO], n = 2 high-grade [HGO]; P < .001). Microcystic change was significantly associated with the T2FMM (P < .00001). In oligodendrogliomas with T2FMM, IDH1-mutations or specific differentially expressed genes were not identified. Conclusion and Clinical ImportanceThe T2FMM can be readily identified on routinely obtained MRI sequences. It is a specific biomarker for oligodendroglioma in dogs, and was significantly associated with non-enhancing LGO.
  • Histotripsy ablation for the treatment of feline injection site sarcomas: a first-in-cat in vivo feasibility study
    Ruger, Lauren N.; Yang, Ester; Coutermarsh-Ott, Sheryl; Vickers, Elliana; Gannon, Jessica; Nightengale, Marlie; Hsueh, Andy; Ciepluch, Brittany; Dervisis, Nikolaos; Vlaisavljevich, Eli; Klahn, Shawna (Taylor & Francis, 2023)
    Purpose Feline soft tissue sarcoma (STS) and injection site sarcoma (fISS) are rapidly growing tumors with low metastatic potential, but locally aggressive behavior. Histotripsy is a non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. In this study, we investigated the in vivo safety and feasibility of histotripsy to treat fISS using a custom 1 MHz transducer. Materials and Methods Three cats with naturally-occurring STS were treated with histotripsy before surgical removal of the tumor 3 to 6 days later. Gross and histological analyses were used to characterize the ablation efficacy of the treatment, and routine immunohistochemistry and batched cytokine analysis were used to investigate the acute immunological effects of histotripsy. Results Results showed that histotripsy ablation was achievable and well-tolerated in all three cats. Precise cavitation bubble clouds were generated in all patients, and hematoxylin & eosin stained tissues revealed ablative damage in targeted regions. Immunohistochemical results identified an increase in IBA-1 positive cells in treated tissues, and no significant changes in cytokine concentrations were identified post-treatment. Conclusions Overall, the results of this study demonstrate the safety and feasibility of histotripsy to target and ablate superficial feline STS and fISS tumors and guide the clinical development of histotripsy devices for this application.
  • Agreement between Electrical Cardiometry and Pulmonary Artery Thermodilution for Measuring Cardiac Output in Isoflurane-Anesthetized Dogs
    Paranjape, Vaidehi V.; Henao-Guerrero, Natalia; Menciotti, Giulio; Saksena, Siddharth; Agostinho, Manuela (MDPI, 2023-04-21)
    In animals, invasive pulmonary artery thermodilution (PATD) is a gold standard for cardiac output (CO) monitoring, but it is impractical in clinical settings. This study evaluates the agreement between PATD and noninvasive electrical cardiometry (EC) for measuring CO and analyzes the other EC-derived hemodynamic variables in six healthy anesthetized dogs subjected to four different hemodynamic events in a sequential order: (1) euvolemia (baseline); (2) hemorrhage (33% blood volume loss); (3) autologous blood transfusion; and (4) 20 mL/kg colloid bolus. The CO measurements obtained using PATD and EC are compared using Bland–Altman analysis, Lin’s concordance correlation (LCC), and polar plot analysis. Values of p < 0.05 are considered significant. The EC measurements consistently underpredict the CO values as compared with PATD, and the LCC is 0.65. The EC’s performance is better during hemorrhage, thus indicating its capability in detecting absolute hypovolemia in clinical settings. Even though the percentage error exhibited by EC is 49.4%, which is higher than the standard (<30%), EC displays a good trending ability. Additionally, the EC-derived variables display a significant correlation with the CO measured using PATD. Noninvasive EC may have a potential in monitoring trends in hemodynamics in clinical settings.
  • Defining an Optimal Range of Centrifugation Parameters for Canine Semen Processing
    Sugai, Nicole; Werre, Stephen; Cecere, Julie; Balogh, Orsolya (MDPI, 2023-04-21)
    Our objective was to determine a clinically relevant range of centrifugation parameters for processing canine semen. We hypothesized that higher gravitational (g) force and longer time of centrifugation would result in improved spermatozoa recovery rate (RR) but poorer semen quality. Cooled storage under standard shipping conditions was used as a stressor to evaluate long-term treatment effects. Individual ejaculates collected from 14 healthy dogs were split into six treatment groups (400 g, 720 g, and 900 g for 5 or 10 min). Sperm RR (%) was calculated post-centrifugation, and plasma membrane integrity (%, Nucleocounter® SP-100™), total and progressive motility (%, subjective and computer-assisted sperm analysis), and morphology (%, eosin-nigrosin staining) were assessed on initial raw semen (T0), post-centrifugation (T1), and 24 h (T2) and 48 h (T3) after cooling. Sperm losses were minimal, and RRs were similar across treatment groups (median >98%, p ≥ 0.062). Spermatozoa membrane integrity was not different between centrifugation groups at any time point (p ≥ 0.38) but declined significantly during cooling (T1 vs. T2/T3, p ≤ 0.001). Similarly, total and progressive motility did not differ across treatments but declined in all groups from T1 to T3 (p ≤ 0.02). In conclusion, our study showed that centrifugation within a range of 400 g–900 g for 5–10 min is appropriate for processing canine semen.
  • A Case of Ovarian Dysplasia and a Vaginal Fibroleiomyoma in a Young Golden Retriever
    McCarter, Samantha; Sponenberg, D. Phillip; Saunders, Geoffrey; Cecere, Julie (Frontiers, 2021-12-24)
    This case demonstrates a unique ovarian congenital anomaly that likely contributed to the development of a rare fibroleiomyoma in the cranial vagina of a young bitch. A 13 month old intact female Golden Retriever presented to the veterinary teaching hospital for urinary incontinence, hematuria, and persistent vaginal discharge. Physical examination revealed a mucopurulent serosanguinous malodorous vulvar discharge, and after further diagnostics was reclassified as persistent estrus. Abdominal palpation and ultrasound revealed uterine thickening and poorly visualized ovaries. The reproductive tract was removed during an ovariohysterectomy, revealing small ovaries and a white anterior vaginal mass. Histopathology revealed dysplastic ovaries with hyperplastic granulosa cells and a benign vaginal fibroleiomyoma. These morphologic changes are consistent with elevated estrogen levels. It was thus concluded that her persistent estrus and the fibroleiomyoma were both secondary to persistent estrogen production by the hyperplastic granulosa cells.
  • Clinical, Diagnostic, and Imaging Findings in Three Juvenile Dogs With Paraspinal Hyperesthesia or Myelopathy as a Consequence of Hemophilia A: A Case Report
    Fowler, Kayla M.; Bolton, Timothy A.; Rossmeisl, John H.; Arendse, Avril U.; Vernau, Karen M.; Li, Ronald H.; Parker, Rell L. (Frontiers, 2022-04-15)
    Three juvenile dogs presented with an acute onset of paraspinal hyperesthesia and/or neurologic deficits. These dogs underwent anesthesia forMRI and additional diagnostics. The thoracolumbar MRI in Dog 1 revealed an accumulation of T2-weighted (T2W) hyperintense, T1-weighted (T1W) iso- to hyperintense, contrast enhancing extradural material. The differential diagnoses were meningitis with secondary hemorrhage or empyema or late subacute hemorrhage. The initial cervical MRI in Dog 2 revealed T1W meningeal contrast enhancement suspected to be secondary to meningitis. A repeat MRI following neurologic decline after CSF sampling revealed a large area of T2W and T1W hyperintensity between fascial planes of the cervical musculature as well as T2W iso- to hyperintense and T1W iso- to hypointense extradural material at the level of C1 consistent with hemorrhage. The cervical MRI in Dog 3 revealed T2W hyperintense and T1W iso- to hypointense extradural compressive material consistent with hemorrhage. Dogs 1 and 2 underwent CSF sampling and developed complications, including subcutaneous hematoma and vertebral canal hemorrhage. Dog 3 underwent surgical decompression, which revealed a compressive extradural hematoma. In each case, a hemophilia panel including factor VIII concentration confirmed the diagnosis of hemophilia A. Dog 1 had a resolution of clinical signs for ~5 months before being euthanized from gastrointestinal hemorrhage. Dog 2 was euthanized due to neurologic decompensation following CSF sampling. Dog 3 did well for 2 weeks after surgery but was then lost to follow-up. This case series provides information on clinical signs, MRI findings, and outcome in 3 juvenile dogs with hemophilia A that developed neurologic deficits or paraspinal hyperesthesia secondary to spontaneous or iatrogenic vertebral canal hemorrhage. Hemophilia A should be considered as a differential in any young dog presenting with an acute onset of hyperesthesia with or without neurologic deficits. This diagnosis should be prioritized in young male dogs that have other evidence of hemorrhage on physical exam.
  • Sternohyoideus-sternothyroideus muscle flap to reconstruct oronasal fistulas due to maxillary cancer in four dogs
    Ciepluch, Brittany J.; Seguin, Bernard; Worley, Deanna (Wiley, 2023-02)
    Objective: To describe the repair of oronasal fistulas in dogs treated for maxillary cancer, with a novel sternohyoideus-sternothyroideus muscle flap, and to report the outcome. Animals: Client-owned dogs (n = 4) with oronasal fistulas related to cancer. Study design: Short case series. Methods: Maxillary defects were caused by tissue destruction by the tumor and tumor response to radiation therapy in two cases and a complication of caudal maxillectomy in two cases, one of which had neoadjuvant radiation therapy. All tumors were >4 cm at the level of the maxilla. Flaps were harvested by transecting the ipsilateral sternothyroideus and sternohyoideus muscles from their origin at the manubrium and costal cartilage. The muscles were rotated around the base of the cranial thyroid artery and tunneled subcutaneously in the neck and through an incision in the caudodorsal aspect of the oral cavity. The muscle flap was sutured to the edges of the oronasal fistula. Results: The flap reached as far rostral as the level of the first premolar without tension. All dogs had clinical signs that improved postoperatively. All dogs had partial dehiscence of the flap. Conclusion: This flap was associated with a high rate of complications; however, all flaps were used in challenging cases. Clinical signs related to oronasal fistula were improved in all dogs in this case series.
  • Histotripsy Ablation of Spontaneously Occurring Canine Bone Tumors
    Ruger, Lauren N.; Hay, Alayna N.; Gannon, Jessica M.; Sheppard, Hannah O.; Coutermarsh-Ott, Sheryl L.; Daniel, Gregory B.; Kierski, Katharine R.; Ciepluch, Brittany J.; Vlaisavljevich, Eli; Tuohy, Joanne L. (IEEE, 2023-01)
    Objective: Osteosarcoma (OS) is a devastating primary bone tumor in dogs and humans with limited non-surgical treatment options. As the first completely non-invasive and non-thermal ablation technique, histotripsy has the potential to significantly improve the standard of care for patients with primary bone tumors. Introduction: Standard of care treatment for primary appendicular OS involves surgical resection via either limb amputation or limb-salvage surgery for suitable candidates. Biological similarities between canine and human OS make the dog an informative comparative oncology research model to advance treatment options for primary OS. Evaluating histotripsy for ablating spontaneous canine primary OS will build a foundation upon which histotripsy can be translated clinically into a standard of care therapy for canine and human OS. Methods: Five dogs with suspected spontaneous OS were treated with a 500 kHz histotripsy system guided by real-time ultrasound image guidance. Spherical ablation volumes within each tumor (1.25-3 cm in diameter) were treated with single cycle histotripsy pulses applied at a pulse repetition frequency of 500 Hz and a dose of 500 pulses/point. Results: Tumor ablation was successfully identified grossly and histologically within the targeted treatment regions of all subjects. Histotripsy treatments were well-tolerated amongst all patients with no significant clinical adverse effects. Conclusion & Significance: Histotripsy safely and effectively ablated the targeted treatment volumes in all subjects, demonstrating its potential to serve as a non-invasive treatment modality for primary bone tumors.