Department of Small Animal Clinical Sciences

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A case of congenital ureteral atresia causing rare upper and lower urinary tract manifestations in a puppy: a case report
Zalek, Megan; Shah, Rohan; Bolton, Timothy (2021-02-09)
Background Ureteral atresia is the congenital absence of a ureteral opening, resulting in a blind-ended ureter that fails to terminate at the urinary bladder. Consequently, severe hydroureter and hydronephrosis occur ipsilateral to the atresic ureter. However, hydronephrosis contralateral to severe hydroureter, although reported in humans, is not documented in the dog. Additionally, ureteral atresia has not been reported as a cause for lower urinary tract signs directly related to extramural urinary bladder compression. This report aims to describe these unique manifestations of this congenital urinary tract disease, as well as follow-up findings after successful treatment. Case presentation A 4-month-old male Husky puppy was evaluated for pollakiuria, stranguria, and urine dribbling of 1-month duration. During the physical examination, a mass was palpated in the mid-abdomen. Diagnostic imaging and cystoscopy findings were diagnostic for right-sided ureteral atresia with secondary hydroureter and hydronephrosis. The severe right hydroureter caused lower urinary tract signs and contralateral hydronephrosis secondary to regional compression of the left distal ureter and urinary bladder. A right-sided ureteronephrectomy was performed, resolving the stranguria and pollakiuria. Significant reduction in the contralateral (left) hydronephrosis also occurred. Clinical Relevance Ureteral atresia should be considered as a differential diagnosis for lower urinary tract signs and/or bilateral hydronephrosis in a young dog. Reporting this case expands our knowledge of congenital lower urinary tract disease and the etiology of their manifestations in dogs. Surgical resolution of the congenital ureteral abnormality can result in preservation of renal function in the contralaterally obstructed kidney.
Clinical outcomes in dogs with localized splenic histiocytic sarcoma treated with splenectomy with or without adjuvant chemotherapy
Latifi, Max; Tuohy, Joanne L.; Coutermarsh-Ott, Sheryl; Klahn, Shawna L.; Leeper, Haley; Dervisis, Nikolaos G. (Wiley, 2020-09-28)
Background: Localized splenic histiocytic sarcoma (HS) in dogs is a poorly understood disease, and could have longer survival times than disseminated or hemophagocytic HS. Understanding the clinical behavior of localized splenic HS can refine treatment recommendations. Objective: To describe the clinical characteristics and outcomes of dogs with localized splenic HS. Animals: Fourteen client-owned dogs with histologically confirmed splenic HS that received splenectomy. Methods: Multi-institutional retrospective case series—medical records of dogs with splenic HS were reviewed. Dog signalment, clinicopathologic data, primary and adjuvant treatments, and outcomes were obtained. Survival data were calculated using Kaplan-Meier analysis. Dog variables such as age, weight, platelet counts were reported using descriptive statistics. The Cox proportional hazards regression method was used to determine whether potential risk factors (weight, age, albumin level, hematocrit, and platelet count) were associated with PFI. Results: Median survival time for the dogs in this study was 427 days. Twelve dogs received adjuvant lomustine-based chemotherapy. Five dogs (35.7%) were suspected or confirmed to have developed metastatic disease. Eleven dogs died of disease, 1 dog died of unrelated cause, and 2 dogs were alive at final follow-up. Conclusions and Clinical Significance: Histiocytic sarcoma in dogs can manifest as a localized form in the spleen. Dogs with localized splenic HS treated with surgery ± chemotherapy can experience survival times over a year.
Comparison of direct measurement of intracranial pressures and presumptive clinical and magnetic resonance imaging indicators of intracranial hypertension in dogs with brain tumors
Giannasi, Savannah; Kani, Yukitaka; Hsu, Fang-Chi; Rossmeisl, John H. Jr. (2020-05-16)
Background Intracranial hypertension (ICH) is often presumptively diagnosed based on clinical or imaging findings. Clinical or imaging surrogates of ICH are not usually validated with reference standard direct intracranial pressure (dICP) recordings. Hypotheses Dogs with brain magnetic resonance imaging (MRI) or clinical features of presumed ICH would have higher dICP than dogs lacking those features. Animals Twenty dogs with gliomas and 3 normal controls. Methods Prospective, convenience study. Dogs were presumptively categorized with normal ICP or ICH from scores generated from described clinical and brain MRI indicators of ICH. dICP was recorded in anesthetized dogs using an intraparenchymal microsensor and compared between groups. Results dICP was not different between control (10.4 +/- 2.1 mm Hg) and dogs with glioma (15.6 +/- 8.3 mm Hg), or between dogs in clinically predicted ICP groups. Compared with dogs with MRI-predicted normal ICP, MRI-predicted ICH dogs had higher dICP (10.3 +/- 4.1 versus 19.2 +/- 7.9 mm Hg, P = .004), larger tumors (1.45 +/- 1.2 versus 5.71 +/- 3.03 cm(3), P = .0004), larger optic nerve sheath diameters, and 14/14 (100%) displayed structural anatomical shifts on MRI. At a dICP threshold of 15 mm Hg, the sensitivity of MRI for predicting ICH was 90% and the specificity 69%. Conclusions and Clinical Relevance dICP measurements are feasible in dogs with brain tumors. MRI features including brain herniations, mass effect, and optic nerve size aid in the identification of dogs with ICH. Clinical estimation of ICP did not discriminate between dogs with and without ICH.
Cross-species transcriptional analysis reveals conserved and host-specific neoplastic processes in mammalian glioma
Connolly, Nina P.; Shetty, Amol C.; Stokum, Jesse A.; Hoeschele, Ina; Siegel, Marni B.; Miller, C. Ryan; Kim, Anthony J.; Ho, Cheng-Ying; Davila, Eduardo; Simard, J. Marc; Devine, Scott E.; Rossmeisl, John H. Jr.; Holland, Eric C.; Winkles, Jeffrey A.; Woodworth, Graeme F. (Springer Nature, 2018-01-19)
Glioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity of human glioma, we focused this study on tumors with upregulation of the platelet-derived growth factor signaling axis, a common and early alteration in human gliomagenesis. The results reveal core neoplastic alterations in mammalian glioma, as well as unique contributions of the tumor host to neoplastic processes. Notable differences were observed in gene expression patterns as well as related biological pathways and cell populations known to mediate key elements of glioma biology, including angiogenesis, immune evasion, and brain invasion. These data provide new insights regarding mammalian models of human glioma, and how these insights and models relate to our current understanding of the human disease.
Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review
Tham, Heng L.; Linder, Keith E.; Olivry, Thierry (2020-11-23)
Pemphigus is the term used to describe a group of rare mucocutaneous autoimmune bullous diseases characterized by flaccid blisters and erosions of the mucous membranes and/or skin. When the autoantibodies target desmosomes in the deep layers of the epidermis, deep pemphigus variants such as pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus develop. In this article, we will review the signalment, clinical signs, histopathology and treatment outcome of pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. Canine, feline and equine pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus have many features similar to the human counterpart. These chronic and often relapsing autoimmune dermatoses require aggressive immunosuppressive therapy. In animals, the partial-to-complete remission of pemphigus vulgaris and pemphigus vegetans has been achieved with high dose glucocorticoid therapy, with or without adjunct immunosuppressants; the prognosis is grave for paraneoplastic pemphigus.
Development and Evaluation of a Caregiver Reported Quality of Life Assessment Instrument in Dogs With Intracranial Disease
Weiske, Rebecca; Sroufe, Maureen; Quigley, Mindy; Pancotto, Theresa E.; Werre, Stephen R.; Rossmeisl, John H. Jr. (2020-08-18)
In veterinary medicine, quality of life (QOL) assessment instruments, which are important components of the holistic evaluation of treatment success, have largely not included organ-specific concerns that may be broadly relevant to caregivers of dogs with intracranial disease. The objective of this study was to identify core questionnaire items and domains that contribute to health-related QOL (HRQOL) in dogs with intracranial disease. A questionnaire was developed that contained 39 QOL-related items encompassing physical, social/companionship, and brain-specific domains associated with the treatment of dogs with intracranial disease, and administered to caregivers of 56 dogs diagnosed with genetic, inflammatory, neoplastic, traumatic, and vascular brain diseases, 52 healthy dogs, and 20 dogs with non-neurological illnesses. Clinician derived functional measures of each dog's health status including chronic pain, Karnofsky performance, and modified Glasgow coma scale scores were also recorded. Principal component analysis refined the final questionnaire, termed the CanBrainQOL-24, to 24-items within the three domains with a minimum Cronbach's alpha of 0.7, indicative of good internal consistency. The CanBrainQOL-24 discriminated between healthy and diseased dogs. Physical and brain-specific domains were significantly different between dogs with intracranial and non-neurological diseases. Significant correlations were observed between owner reported visual analog scores and CanBrainQOL-24 scores, as well between clinician derived functional status measures and owner reported QOL. The CanBrainQOL-24 contains core questions relevant to caregiver assessment of HRQOL in dogs with a variety of intracranial diseases, and provides information that is complementary to clinician derived functional outcome measures.
Diagnostic accuracy of a point-of-care test using voided urine samples for detection of bacteriuria in dogs with signs of lower urinary tract disease
Grant, David C.; Nappier, Michael T.; Corrigan, Virginia Kiefer (Wiley, 2021-02-01)
Background: Bacterial urine culture is recommended in dogs suspected of having urinary tract infection (UTI), but there is expense and delay in obtaining such results. Hypothesis/Objective: To determine the diagnostic performance of a rapid immunoassay (RIA) dipstick for detection of bacteriuria using voided urine from dogs with clinical signs of lower UTI. Animals: Twenty-four client-owned dogs. Methods: Voided urine was collected and the RIA performed within 30 minutes. Urine collected by cystocentesis was submitted for aerobic urine culture. McNemar's test and kappa coefficient were calculated to determine agreement between the 2 tests. Results: Nine of 21 dogs (43%) had UTI verified by aerobic urine culture. There was 1 false-negative and no false-positive RIA results. Sensitivity, specificity, positive predictive value, and negative predictive value of the RIA were 89%, 100%, 100%, and 92%, respectively. Conclusions and Clinical Importance: This RIA is promising for correctly identifying whether or not voided urine samples from dogs with lower urinary tract clinical signs have true bacteriuria in a rapid, inexpensive manner. Additional patients should be enrolled in a similar study to determine if diagnostic performance is robust in a large population.
Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
Hendricks-Wenger, Alissa; Aycock, Kenneth N.; Nagai-Singer, Margaret A.; Coutermarsh-Ott, Sheryl; Lorenzo, Melvin F.; Gannon, Jessica; Uh, Kyungjun; Farrell, Kayla; Beitel-White, Natalie; Brock, Rebecca M.; Simon, Alexander; Morrison, Holly A.; Tuohy, Joanne L.; Clark-Deener, Sherrie; Vlaisavljevich, Eli; Davalos, Rafael V.; Lee, Kiho; Allen, Irving C. (Nature Research, 2021-04-07)
New therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients’ anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.
Feasibility and accuracy of 3D printed patient-specific skull contoured brain biopsy guides
Shinn, Richard L.; Park, Clair; DeBose, Kyrille; Hsu, Fang-Chi; Cecere, Thomas E.; Rossmeisl, John H. Jr. (2021-07)
Objective Design 3D printed skull contoured brain biopsy guides (3D-SCGs) from computed tomography (CT) or T1-weighted magnetic resonance imaging (T1W MRI). Study Design Feasibility study. Sample Population Five beagle dog cadavers and two client-owned dogs with brain tumors. Methods Helical CT and T1W MRI were performed on cadavers. Planned target point was the head of the caudate nucleus. Three-dimensional-SCGs were created from CT and MRI using commercially available open-source software. Using 3D-SCGs, biopsy needles were placed into the caudate nucleus in cadavers, and CT was performed to assess needle placement accuracy, followed by histopathology. Three-dimensional-SCGs were then created and used to perform in vivo brain tumor biopsies. Results No statistical difference was found between the planned target point and needle placement. Median needle placement error for all planned target points was 2.7 mm (range: 0.86-4.5 mm). No difference in accuracy was detected between MRI and CT-designed 3D-SCGs. Median needle placement error for the CT was 2.8 mm (range: 0.86-4.5 mm), and 2.2 mm (range: 1.7-2.7 mm) for MRI. Biopsy needles were successfully placed into the target in the two dogs with brain tumors and biopsy was successfully acquired in one dog. Conclusion Three-dimensional-SCGs designed from CT or T1W MRI allowed needle placement within 4.5 mm of the intended target in all procedures, resulting in successful biopsy in one of two live dogs. Clinical Significance This feasibility study justifies further evaluation of 3D-SCGs as alternatives in facilities that do not have access to stereotactic brain biopsy.
Frame-Based Stereotactic Biopsy of Canine Brain Masses: Technique and Clinical Results in 26 Cases
Rossmeisl, John H. Jr.; Andriani, Rudy T.; Cecere, Thomas E.; Lahmers, Kevin K.; LeRoith, Tanya; Zimmerman, Kurt L.; Gibo, Denise M.; Debinski, Waldemar (2015)
This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.
High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma
Partridge, Brittanie R.; O'Brien, Timothy J.; Lorenzo, Melvin F.; Coutermarsh-Ott, Sheryl; Barry, Sabrina L.; Stadler, Krystina L.; Muro, Noelle; Meyerhoeffer, Mitchell; Allen, Irving C.; Davalos, Rafael V.; Dervisis, Nikolaos G. (2020-03)
Purpose: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. Materials and Methods: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. Results: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3(+)/CD4(-)/CD8(-) lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm(3) +/- 0.74 and 1.56 cm(3) +/- 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm +/- 28.2 and 957 V/cm +/- 24.4 V/cm (P = .0004). Conclusions: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.
High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity
Ringel-Scaia, Veronica M.; Beitel-White, Natalie; Lorenzo, Melvin F.; Brock, Rebecca M.; Huie, Kathleen E.; Coutermarsh-Ott, Sheryl; Eden, Kristin; McDaniel, Dylan K.; Verbridge, Scott S.; Rossmeisl, John H. Jr.; Oestreich, Kenneth J.; Davalos, Rafael V.; Allen, Irving C. (2019-06)
Background: Despite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However, there is currently a paucity of data pertaining to immune system activation following H-FIRE and other electroporation based tumor ablation techniques. Methods: Here, we utilized the mouse 4T1 mammary tumor model to evaluate H-FIRE treatment parameters on cancer progression and immune system activation in vitro and in vivo. Findings: H-FIRE effectively ablates the primary tumor and induces a pro-inflammatory shift in the tumor microenvironment. We further show that local treatment with H-FIRE significantly reduces 4T1 metastases. H-FIRE kills 4T1 cells through non-thermal mechanisms associated with necrosis and pyroptosis resulting in damage associated molecular pattern signaling in vitro and in vivo. Our data indicate that the level of tumor ablation correlates with increased activation of cellular immunity. Likewise, we show that the decrease in metastatic lesions is dependent on the intact immune system and H-FIRE generates 4T1 neoantigens that engage the adaptive immune system to significantly attenuate tumor progression. Interpretation: Cell death and tumor ablation following H-FIRE treatment activates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory state to a pro-inflammatory state. The non-thermal damage to the cancer cells and increased innate immune system stimulation improves antigen presentation, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immunity. (C) 2019 The Authors. Published by Elsevier B.V.
Invited Review-Neuroimaging Response Assessment Criteria for Brain Tumors in Veterinary Patients
Rossmeisl, John H. Jr.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos G.; Klahn, Shawna L. (Wiley-Blackwell, 2014-03-01)
Magnetization transfer and diffusion tensor imaging in dogs with intervertebral disk herniation
Shinn, Richard L.; Pancotto, Theresa E.; Stadler, Krystina L.; Werre, Stephen R.; Rossmeisl, John H. Jr. (Wiley, 2020-10-02)
Background: Quantitative magnetic resonance imaging (QMRI) techniques of magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) provide microstructural information about the spinal cord. Objective: Compare neurologic grades using the modified Frankel scale with MTR and DTI measurements in dogs with thoracolumbar intervertebral disk herniation (IVDH). Animals: Fifty-one dogs with thoracolumbar IVDH. Methods: Prospective cohort study. Quantitative MRI measurements of the spinal cord were obtained at the region of compression. A linear regression generalized estimating equations model was used to compare QMRI measurements between different neurological grades after adjusting for age, weight, duration of clinical signs, and lesion location. Results: Grade 5 (.79 × 10−3 mm2/s [median],.43−.91 [range]) and axial (1.47 × 10−3 mm2/s,.58−1.8) diffusivity were lower compared to grades 2 (1.003,.68−1.36; P =.02 and 1.81 × 10−3 mm2/s, 1.36−2.12; P <.001, respectively) and 3 (1.07 × 10−3 mm2/s,.77−1.5; P =.04 and 1.92 × 10−3 mm2/s, 1.83−2.37; P <.001, respectively). Compared to dogs with acute myelopathy, chronic myelopathy was associated with higher mean (1.02 × 10−3 mm2/s,.77−1.36 vs.83 × 10−3 mm2/s,.64−1.5; P =.03) and radial diffusivity (.75 × 10−3 mm2/s,.38−1.04 vs.44 × 10−3 mm2/s,.22−1.01; P =.008) and lower MTR (46.76, 31.8−56.43 vs. 54.4, 45.2−62.27; P =.004) and fractional anisotropy (.58,.4−0.75 vs.7,.46−.85; P =.02). Fractional anisotropy was lower in dogs with a T2-weighted intramedullary hyperintensity compared to those without (.7,.45−.85 vs.54,.4−.8; P =.01). Conclusion and Clinical Relevance: Mean diffusivity and AD could serve as surrogates of severity of spinal cord injury and are complementary to the clinical exam in dogs with thoracolumbar IVDH.
NLRX1 suppresses tumorigenesis and attenuates histiocytic sarcoma through the negative regulation of NF-lambda B signaling
Coutermarsh-Ott, Sheryl; Simmons, Alysha; Capria, Vittoria; LeRoith, Tanya; Wilson, Justin E.; Heid, Bettina; Philipson, Casandra W.; Qin, Q.; Hontecillas, Raquel; Bassaganya-Riera, Josep; Ting, Jenny P.-Y.; Dervisis, Nikolaos G.; Allen, Irving C. (Impact Journals, 2016-05-31)
Orthostatic hypotension secondary to a suspected thymoma in a dog: a case report
Hansford, Jeremy; Henao-Guerrero, Natalia (2020-10-13)
Background This is the first case report description, to our knowledge, of a cranial mediastinal mass (suspected thymoma) causing orthostatic hypotension in a dog. Case presentation A Labrador Retriever presented for urethral stent placement during cystoscopy secondary to transitional cell carcinoma diagnosis. During anesthesia, the patient had unexpected severe and poorly-responsive hypotension following a shift in position. Several days later, an intrathoracic mass was discovered, raising concerns that the position of the mass in relation to the great vessels and heart may have been the cause of the hypotension. The patient returned for a second stent placement, and computed tomography of the chest confirmed a cranial mediastinal mass, most suspected to be thymoma based on the results of cytology. The patient was kept in sternal recumbency, but when re-positioning to left lateral recumbency, there was a dramatic blood pressure drop that corrected with a return to sternal positioning. Conclusions To our knowledge, orthostatic hypotension has not been described in relation to thymoma in dogs. Thymomas are rare; however, they may be associated with disease of autonomic dysfunction, such as myasthenia gravis, that may lead to orthostatic hypotension. This has been described within the human literature, and we hypothesize it was present in the currently described case. Concurrently, thymomas may grow to a substantial size and cause direct compression of the intrathoracic vasculature. As such, it should be on the differential list for poorly-responsive hypotension following a shift in body positioning under anesthesia.
Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain
Rossmeisl, John H. Jr.; Garcia, Paulo A.; Robertson, John L.; Ellis, Thomas L.; Davalos, Rafael V. (Korean Society of Veterinary Science, 2013-12-01)
This study describes the neuropathologic features of normal canine brain ablated with non-thermal irreversible electroporation (N-TIRE). The parietal cerebral cortices of four dogs were treated with N-TIRE using a dose-escalation protocol with an additional dog receiving sham treatment. Animals were allowed to recover following N-TIRE ablation and the effects of treatment were monitored with clinical and magnetic resonance imaging examinations. Brains were subjected to histopathologic and ultrastructural assessment along with Bcl-2, caspase-3, and caspase-9 immunohistochemical staining following sacrifice 72 h post-treatment. Adverse clinical effects of N-TIRE were only observed in the dog treated at the upper energy tier. MRI and neuropathologic examinations indicated that N-TIRE ablation resulted in focal regions of severe cytoarchitectural and blood-brain-barrier disruption. Lesion size correlated to the intensity of the applied electrical field. N-TIRE-induced lesions were characterized by parenchymal necrosis and hemorrhage; however, large blood vessels were preserved. A transition zone containing parenchymal edema, perivascular inflammatory cuffs, and reactive gliosis was interspersed between the necrotic focus and normal neuropil. Apoptotic labeling indices were not different between the N-TIRE-treated and control brains. This study identified N-TIRE pulse parameters that can be used to safely create circumscribed foci of brain necrosis while selectively preserving major vascular structures.
Phase I trial of convection-enhanced delivery of IL13RA2 and EPHA2 receptor targeted cytotoxins in dogs with spontaneous intracranial gliomas
Rossmeisl, John H. Jr.; Herpai, Denise; Quigley, Mindy; Cecere, Thomas E.; Robertson, John L.; D'Agostino, Ralph B.; Hinckley, Jonathan; Tatter, Stephen B.; Dickinson, Peter J.; Debinski, Waldemar (2021-03)
Background. The interleukin-13 receptor alpha 2 (IL13RA2) and ephrin type A receptor 2 (EPHA2) are attractive therapeutic targets, being expressed in similar to 90% of canine and human gliomas, and absent in normal brain. Clinical trials using an earlier generation IL-13 based cytotoxin showed encouraging clinical effects in human glioma, but met with technical barriers associated with the convection-enhanced delivery (CED) method. In this study, IL-13 mutant and ephrin A1 (EFNA1)-based bacterial cytotoxins targeted to IL13RA2 and EPHA2 receptors, respectively, were administered locoregionally by CED to dogs with intracranial gliomas to evaluate their safety and preliminary efficacy. Methods. In this phase I, 3 + 3 dose escalation trial, cytotoxins were infused by CED in 17 dogs with gliomas expressing IL13RA2 or EPHA2 receptors. CED was performed using a shape-fitting therapeutic planning algorithm, reflux-preventing catheters, and real-time intraoperative MRI monitoring. The primary endpoint was to determine the maximum tolerated dose of the cytotoxic cocktail in dogs with gliomas. Results. Consistent intratumoral delivery of the cytotoxic cocktail was achieved, with a median target coverage of 70% (range, 40-94%). Cytotoxins were well tolerated over a dose range of 0.012-1.278 mu g/mL delivered to the target volume (median, 0.099 mu g/mL), with no dose limiting toxicities observed. Objective tumor responses, up to 94% tumor volume reduction, were observed in 50% (8/16) of dogs, including at least one dog in each dosing cohort >0.05 mu g/mL. Conclusions. This study provides preclinical data fundamental to the translation of this multireceptor targeted therapeutic approach to the human clinic.
Presumptive Identification of Smooth Brucella Strain Antibodies in Canines
Helms, Alyssa B.; Balogh, Orsolya; Franklin-Guild, Rebecca; Lahmers, Kevin K.; Caswell, Clayton C. (Frontiers, 2021-07-08)
Brucellosis is a zoonotic disease caused by a Gram-negative coccobacillus. There are four Brucella strains of zoonotic importance in our domestic species, subdivided by their culture phenotypes: Brucella abortus (B. abortus), B. melitensis, B. suis (smooth strains) and B. canis (rough strain). Dogs can serve as hosts for all four of the zoonotic strains; however, routine serologic testing in dogs has been limited to the identification of B. canis antibodies. The aim of our study was to identify smooth Brucella strain antibodies in canines. We hypothesize that the Brucella abortus Fluorescence Polarization Assay would be successful in identifying smooth Brucella strain antibodies in canines. Ninety-five dogs, including forty-five hog hunting dogs were screened for circulating antibodies to any of the four zoonotic strains of the bacteria utilizing a combination of Canine Brucella Slide Agglutination Test (CBSA), Brucella canis Agar Gel Immunodiffusion II test (AGIDII), Brucella abortus Card Agglutination Test (BCA), and the Brucella abortus Fluorescence Polarization Assay (FPA). Test interpretation results yielded a 0% (0/95) smooth Brucella strain seropositivity rate, with 2% (2/95) of dogs yielding inconclusive rough Brucella strain serology results (0–2% rough strain seropositivity rate). Additionally, a retrospective portion of the study was performed to identify sera containing circulating antibodies to any of the smooth strains of Brucella by testing previously banked canine serum samples stored at Cornell’s Veterinary Diagnostic Laboratory from 2018 to 2019 via Brucella abortus FPA. Of the 769 serum samples tested, 13/769 (1.7%) yielded an inconclusive result, 725/769 (94.2%) were negative, 30/769 (4%) yielded a positive FPA test result, and 1/769 (0.1%) had to be excluded due to insufficient sample remaining to perform the diagnostic test. Of the 30 FPA positive canine serum samples, 97% (29/30) also tested positive on the CBSA test. Additionally, there was a statistically significant (p < 0.0001) likelihood of altered (spayed/neutered) and mixed breed dogs to be FPA positive when compared to intact, purebred dogs, respectively.
Risk factors for adverse events occurring after recovery from stereotactic brain biopsy in dogs with primary intracranial neoplasia
Shinn, Richard L.; Kani, Yukitaka; Hsu, Fang-Chi; Rossmeisl, John H. Jr. (2020-09-14)
Background Stereotactic brain biopsy (SBB) allows for histopathologic diagnosis of brain tumors. Adverse events (AE) occur in 5 to 29% of dogs after SBB, but risk factors associated with developing AE are poorly described. Objective Identify clinicopathologic, diagnostic imaging, or procedural variables that are associated with AE in dogs after SBB. Animals Twenty-nine dogs with brain tumors. Methods Retrospective, case-control study. Dogs had laboratory investigations performed before SBB, as well as clinical examinations and diagnostic imaging of the brain before and after SBB. Cases experienced AE after SBB including transient exacerbation of preexisting neurologic deficits, transient new deficits, or permanent neurologic deficits. Controls had SBB performed without AE. Fisher's exact and Student'sttests were used to examine associations between the postulated risk factors and AE. Results Adverse events occurred in 8/29 (27%) dogs, and 7/8 AE (88%) were transient. Cases were significantly more likely to have T2W-heterogenous tumors (88 versus 38%;P= .04) and lower platelet counts (194.75 +/- 108.32 versus 284.29 +/- 68.54 x10(3)/mm(3),P= .006). Dogs with gradient echo signal voids present on baseline imaging were significantly more likely to have hemorrhage present after biopsy, and 7/8 (88%) of cases had hemorrhage on imaging after SBB. Conclusion and Clinical Importance Twenty-seven percent of dogs undergoing SBB experience AE, with the majority of AE resolving with 1 week. Platelet counts should be >= 185 000/mm(3)to minimize risk of SBB-associated AE. Observation of intracranial hemorrhage after biopsy can have important clinical implications, as this was observed in 88% of dogs with AE.

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