RESUMEN
BACKGROUND: Adult horses with proprioceptive ataxia and behavior changes that have histologic lesions consistent with neurodegenerative disease have been increasingly recognized. HYPOTHESIS/OBJECTIVES: Describe the history, clinical findings and histopathologic features of horses presented to a referral institution with neuroaxonal degeneration. ANIMALS: One hundred horses with a necropsy diagnosis of neuroaxonal degeneration compatible with neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM). METHODS: Retrospective study of horses presented to the University of Pennsylvania, New Bolton Center, between 2017 and 2021 with a necropsy diagnosis of eNAD/EDM. RESULTS: Affected horses had a median age of 8 years (range, 1-22), and the majority were Warmbloods (72). Sixty-eight horses had behavioral changes, and all 100 had proprioceptive ataxia (median grade, 2/5). Fifty-seven horses had abnormal findings on cervical vertebral radiographs, and 14 had myelographic findings consistent with compressive myelopathy. No antemortem diagnostic test results were consistently associated with necropsy diagnosis of neurodegenerative disease. All 100 horses had degenerative lesions characteristic of eNAD in the brainstem gray matter, and 24 had concurrent degenerative features of EDM in the spinal cord white matter. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical and histopathologic findings in this large group of horses with neurodegenerative disease were most consistent with eNAD/EDM, but with a different signalment and clinical presentation from earlier descriptions. The increasing occurrence of neurodegenerative disease in horses and the safety risk posed emphasize the importance of focused research in affected horses.
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Enfermedades de los Caballos , Distrofias Neuroaxonales , Enfermedades Neurodegenerativas , Compresión de la Médula Espinal , Caballos , Animales , Enfermedades Neurodegenerativas/veterinaria , Estudios Retrospectivos , Distrofias Neuroaxonales/veterinaria , Compresión de la Médula Espinal/veterinaria , Ataxia/veterinaria , Enfermedades de los Caballos/diagnósticoRESUMEN
A 5-year-old imported Zangersheide gelding was evaluated for SC swellings over both forelimbs and lameness localized to the distal metacarpus. Ultrasound examination of the SC masses was compatible with verminous granulomas. Linear hyperechoic foci were present within the suspensory ligament branches of both forelimbs, suggestive of ligamentous parasitic infiltrates. A diagnosis of onchocerciasis was confirmed on biopsy of a SC mass. The gelding was treated with ivermectin and a tapering course of PO dexamethasone but was eventually euthanized. Necropsy confirmed the presence of SC eosinophilic granulomas and degenerative suspensory ligament desmitis, both with intralesional nematodes. Given the location and appearance of the nematode, a diagnosis of Onchocerca sp., most likely O. reticulata, was made. Onchocerciasis should be included as a differential diagnosis for multifocal suspensory ligament desmitis with these sonographic characteristics when paired with SC masses in imported European Warmbloods.
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Artritis , Enfermedades de los Caballos , Enfermedades Musculares , Oncocercosis , Animales , Caballos , Masculino , Onchocerca , Oncocercosis/diagnóstico , Oncocercosis/parasitología , Oncocercosis/patología , Oncocercosis/veterinaria , Ligamentos/patología , Artritis/veterinaria , Enfermedades Musculares/patología , Enfermedades Musculares/veterinaria , Enfermedades de los Caballos/diagnóstico por imagen , Enfermedades de los Caballos/tratamiento farmacológicoRESUMEN
OBJECTIVE: To describe the use and outcome of sclerotherapy with intralesional doxycycline foam in a horse with a mandibular aneurysmal bone cyst. STUDY DESIGN: Case report. ANIMALS: Client-owned 1 year old Standardbred filly. METHODS: The horse presented for progressive mandibular swelling. A 10 mg/mL doxycycline foam was prepared for intralesional injection. Three doses were injected into the lesion under computed tomographic guidance at 6 and 15 weeks after initial treatment. Volume reduction was monitored after each treatment with 3D volumetric rendering and region of interest segmentation using commercially available software. RESULTS: The volume of the lesion decreased from 458.7455 cm3 before treatment, to 363.3101 cm3 at 6 weeks, 273.5855 cm3 at 15 weeks, and 247.2316 cm3 6 months later, resulting in a total reduction of 54% of the initial volume. Bone formation was noted in the lesion. No adverse effects related to doxycycline foam injections were noted. The mandibular swelling was resolved after treatment. CONCLUSION: Intralesional doxycycline sclerotherapy was shown to be efficacious in reducing the volume of the aneurysmal bone cyst in the horse presented in this report. There was complete resolution of mandibular swelling with no side effects related to the intralesional injections.
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Quistes Óseos Aneurismáticos , Enfermedades de los Caballos , Caballos , Femenino , Animales , Escleroterapia/veterinaria , Escleroterapia/efectos adversos , Escleroterapia/métodos , Quistes Óseos Aneurismáticos/tratamiento farmacológico , Quistes Óseos Aneurismáticos/etiología , Quistes Óseos Aneurismáticos/veterinaria , Doxiciclina/uso terapéutico , Resultado del Tratamiento , Inyecciones Intralesiones/veterinaria , Enfermedades de los Caballos/etiologíaRESUMEN
In collaboration with the American College of Veterinary Radiology.
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Radiología , Animales , Humanos , Radiografía , Estados UnidosRESUMEN
Phlegmonous gastritis was diagnosed in 2 yearling fillies that were presented with a 1-wk history of fever, lethargy, and hypoproteinemia, associated with a previous diagnosis of equine proliferative enteropathy based on clinical signs and PCR assay detection of Lawsonia intracellularis in fecal samples. Abdominal ultrasound revealed enlargement of the stomach and expansion of its submucosal layer with hypoechoic fluid, as well as thickened hypomotile small intestinal segments. Given the poor prognosis and poor response to treatment, both horses were euthanized, one on the day of presentation and the other after 3 wk of intensive medical management including a combination of antimicrobials, analgesics, and intravenous colloids. At autopsy, acute mural gastritis characterized by severe submucosal edema with suppurative inflammation (i.e., phlegmonous gastritis) and necroulcerative enteritis compatible with the necrotizing form of equine proliferative enteropathy were identified in both horses. The gastric inflammation was associated with thrombosis and mixed bacterial populations, including Clostridium perfringens, that were confined to the submucosa without evidence of mucosal involvement; toxin genes compatible with C. perfringens type C were identified in one case. Human phlegmonous gastritis is an uncommon, often-fatal pyogenic infection that is often associated with mucosal injury, bacteremia, or immunocompromise. Our finding of this unusual gastric lesion in 2 horses with similar signalment, clinical disease, and spectrum of postmortem lesions suggests a similar etiopathogenesis that possibly involves local, regional, or distant hematogenous origin, and should be considered a potential complication of gastrointestinal mucosal compromise in horses.
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Gastritis , Enfermedades de los Caballos , Enfermedades Intestinales , Lawsonia (Bacteria) , Abdomen/patología , Enfermedad Aguda , Animales , Femenino , Gastritis/diagnóstico , Gastritis/patología , Gastritis/veterinaria , Enfermedades de los Caballos/patología , Caballos , Inflamación/veterinaria , Enfermedades Intestinales/veterinariaRESUMEN
OBJECTIVE: To assess the prevalence of tubular genital tract neoplasia in does evaluated at 2 veterinary teaching hospitals; describe the main clinical, surgical, and histopathologic or necropsy findings in affected does; and assess factors potentially associated with short-term prognosis in these animals. ANIMALS: 42 does. PROCEDURES: Medical records of 2 veterinary teaching hospitals were searched to identify does with neoplasia of the tubular genital tract. Signalment; history; physical and diagnostic imaging results; biopsy, surgery, and necropsy findings; and short-term outcome were recorded. Age and breed frequencies for the sample were compared with those of the overall hospital population, and variables of interest were tested for associations with a diagnosis of adenocarcinoma and with short-term outcome by statistical methods. RESULTS: Median age at hospital admission (10 years) was greater for the study sample than for the general hospital population (2 years). Pygmy goats were overrepresented (22/42 [52%]). Common reasons for evaluation were bloody vaginal discharge or hematuria and abdominal straining. Adenocarcinoma (13/42 [31%]), leiomyoma (13 [31%]), and leiomyosarcoma (11 [26%]) were the most common tumors. Does with distant metastasis had greater odds of a diagnosis of adenocarcinoma (OR, 40.5) than does without distant metastasis. In the analysis adjusted for hemorrhagic discharge, odds of euthanasia for does with straining were 13 times those for does without straining. In the analysis adjusted for straining status, does with hemorrhagic discharge had almost 7 times the odds of euthanasia for does without this finding. The survival-to-discharge rate was low (13/42 [31%]). CONCLUSIONS AND CLINICAL RELEVANCE: The frequency of adenocarcinomas in the study sample was unexpectedly high. Further research is needed to confirm the study findings.
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Cabras , Hospitales Veterinarios , Animales , Femenino , Genitales , Pronóstico , Estudios RetrospectivosRESUMEN
A 10-year-old male neutered cavalier King Charles Spaniel with a 1-year history of degenerative mitral valve disease presented for dyspnea and severe weakness. He was diagnosed with congestive heart failure, systolic dysfunction, presumptive myocardial infarction and a left atrial thrombus based on thoracic radiographs, electrocardiogram and echocardiographic findings. Clinical signs also suggested right foreleg embolism. The dog was euthanized due to the grave prognosis and a postmortem evaluation was performed. The postmortem examination confirmed myocardial infarction and was thought to be due to embolic showering from the thrombus attached to a partial thickness left atrial endocardial tear.
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Enfermedades de los Perros/patología , Atrios Cardíacos/patología , Insuficiencia de la Válvula Mitral/veterinaria , Infarto del Miocardio/veterinaria , Animales , Perros , Cardiopatías/complicaciones , Cardiopatías/veterinaria , Masculino , Infarto del Miocardio/patología , Rotura/patología , Rotura/veterinaria , Trombosis/complicaciones , Trombosis/veterinariaAsunto(s)
Neoplasias Óseas/veterinaria , Enfermedades de los Gatos/diagnóstico , Paladar Duro/patología , Animales , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/patología , Gatos , Diagnóstico por Imagen/veterinaria , Resultado Fatal , Masculino , Paladar Duro/diagnóstico por imagen , RadiografíaRESUMEN
Coronavirus infection of the murine central nervous system (CNS) provides a model for studies of viral encephalitis and demyelinating disease. Mouse hepatitis virus (MHV) neurotropism varies by strain: MHV-A59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain JHM.SD (MHV-4) causes fatal encephalitis with extensive neuronal spread of virus. In addition, while neurons are the predominant CNS cell type infected in vivo, the canonical receptor for MHV, the carcinoembryonic antigen family member CEACAM1a, has been demonstrated only on endothelial cells and microglia. In order to investigate whether CEACAM1a is also expressed in other cell types, ceacam1a mRNA expression was quantified in murine tissues and primary cells. As expected, among CNS cell types, microglia expressed the highest levels of ceacam1a, but lower levels were also detected in oligodendrocytes, astrocytes, and neurons. Given the low levels of neuronal expression of ceacam1a, primary neurons from wild-type and ceacam1a knockout mice were inoculated with MHV to determine the extent to which CEACAM1a-independent infection might contribute to CNS infection. While both A59 and JHM.SD infected small numbers of ceacam1a knockout neurons, only JHM.SD spread efficiently to adjacent cells in the absence of CEACAM1a. Quantification of mRNA for the ceacam1a-related genes ceacam2 and psg16 (bCEA), which encode proposed alternative MHV receptors, revealed low ceacam2 expression in microglia and oligodendrocytes and psg16 expression exclusively in neurons; however, only CEACAM2 mediated infection in human 293T cells. Therefore, neither CEACAM2 nor PSG16 is likely to be an MHV receptor on neurons, and the mechanism for CEACAM1a-independent neuronal spread of JHM.SD remains unknown.
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Antígeno Carcinoembrionario/genética , Sistema Nervioso Central/virología , Infecciones por Coronavirus/etiología , Virus de la Hepatitis Murina , Neuronas/virología , Receptores Virales/genética , Animales , Antígeno Carcinoembrionario/análisis , Línea Celular , Sistema Nervioso Central/patología , Regulación de la Expresión Génica , Humanos , Ratones , Ratones Noqueados , Neuronas/patología , ARN Mensajero/análisis , Receptores de Coronavirus , Receptores Virales/análisis , Especificidad de la Especie , Distribución TisularRESUMEN
Murine coronavirus (mouse hepatitis virus, MHV) is a collection of strains that induce disease in several organ systems of mice. Infection with neurotropic strains JHM and A59 causes acute encephalitis, and in survivors, chronic demyelination, the latter of which serves as an animal model for multiple sclerosis. The MHV receptor is a carcinoembryonic antigen-related cell adhesion molecule, CEACAM1a; paradoxically, CEACAM1a is poorly expressed in the central nervous system (CNS), leading to speculation of an additional receptor. Comparison of highly neurovirulent JHM isolates with less virulent variants and the weakly neurovirulent A59 strain, combined with the use of reverse genetics, has allowed mapping of pathogenic properties to individual viral genes. The spike protein, responsible for viral entry, is a major determinant of tropism and virulence. Other viral proteins, both structural and nonstructural, also contribute to pathogenesis in the CNS. Studies of host responses to MHV indicate that both innate and adaptive responses are crucial to antiviral defense. Type I interferon is essential to prevent very early mortality after infection. CD8 T cells, with the help of CD4 T cells, are crucial for viral clearance during acute disease and persist in the CNS during chronic disease. B cells are necessary to prevent reactivation of virus in the CNS following clearance of acute infection. Despite advances in understanding of coronavirus pathogenesis, questions remain regarding the mechanisms of viral entry and spread in cell types expressing low levels of receptor, as well as the unique interplay between virus and the host immune system during acute and chronic disease.
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Enfermedades Virales del Sistema Nervioso Central/virología , Infecciones por Coronavirus/virología , Virus de la Hepatitis Murina/patogenicidad , Animales , Encéfalo/virología , Antígeno Carcinoembrionario/fisiología , Enfermedades Virales del Sistema Nervioso Central/inmunología , Infecciones por Coronavirus/inmunología , Ratones , Virus de la Hepatitis Murina/genética , Virus de la Hepatitis Murina/inmunología , Virus de la Hepatitis Murina/fisiología , Neuroinmunomodulación/inmunología , Linfocitos T/inmunología , Proteínas Virales/genética , Proteínas Virales/fisiología , Tropismo Viral/fisiologíaRESUMEN
Immunotherapy of established solid tumors is rarely achieved, and the mechanisms leading to success remain to be elucidated. We previously showed that extended control of advanced-stage autochthonous brain tumors is achieved following adoptive transfer of naive C57BL/6 splenocytes into sublethally irradiated line SV11 mice expressing the SV40 T Ag (T Ag) oncoprotein, and was associated with in vivo priming of CD8(+) T cells (T(CD8)) specific for the dominant epitope IV (T Ag residues 404-411). Using donor lymphocytes derived from mice that are tolerant to epitope IV or a newly characterized transgenic mouse line expressing an epitope IV-specific TCR, we show that epitope IV-specific T(CD8) are a necessary component of the donor pool and that purified naive epitope IV-specific T(CD8) are sufficient to promote complete and rapid regression of established tumors. While transfer of naive TCR-IV cells alone induced some initial tumor regression, increased survival of tumor-bearing mice required prior conditioning of the host with a sublethal dose of gamma irradiation and was associated with complete tumor eradication. Regression of established tumors was associated with rapid accumulation of TCR-IV T cells within the brain following initial priming against the endogenous T Ag in the peripheral lymphoid organs. Additionally, persistence of functional TCR-IV cells in both the brain and peripheral lymphoid organs was associated with long-term tumor-free survival. Finally, we show that production of IFN-gamma, but not perforin or TNF-alpha, by the donor lymphocytes is critical for control of autochthonous brain tumors.
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Antígenos Transformadores de Poliomavirus/inmunología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Citotoxicidad Inmunológica , Epítopos Inmunodominantes/metabolismo , Virus 40 de los Simios/inmunología , Animales , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/virología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/trasplante , Línea Celular Transformada , Células Cultivadas , Neoplasias del Plexo Coroideo/inmunología , Neoplasias del Plexo Coroideo/patología , Neoplasias del Plexo Coroideo/terapia , Neoplasias del Plexo Coroideo/virología , Femenino , Epítopos Inmunodominantes/genética , Epítopos Inmunodominantes/inmunología , Inmunoterapia Adoptiva/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Ratas , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
The coronavirus mouse hepatitis virus (MHV) induces a minimal type I interferon (IFN) response in several cell types in vitro despite the fact that the type I IFN response is important in protecting the mouse from infection in vivo. When infected with MHV, mice deficient in IFN-associated receptor expression (IFNAR(-/-)) became moribund by 48 h postinfection. MHV also replicated to higher titers and exhibited a more broad tissue tropism in these mice, which lack a type I IFN response. Interestingly, MHV induced IFN-beta in the brains and livers, two main targets of MHV replication, of infected wild-type mice. MHV infection of primary cell cultures indicates that hepatocytes are not responsible for the IFN-beta production in the liver during MHV infection. Furthermore, macrophages and microglia, but not neurons or astrocytes, are responsible for IFN-beta production in the brain. To determine the pathway by which MHV is recognized in macrophages, IFN-beta mRNA expression was quantified following MHV infection of a panel of primary bone marrow-derived macrophages generated from mice lacking different pattern recognition receptors (PRRs). Interestingly, MDA5, a PRR thought to recognize primarily picornaviruses, was required for recognition of MHV. Thus, MHV induces type I IFN in macrophages and microglia in the brains of infected animals and is recognized by an MDA5-dependent pathway in macrophages. These findings suggest that secretion of IFN-beta by macrophages and microglia plays a role in protecting the host from MHV infection of the central nervous system.
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Encéfalo , ARN Helicasas DEAD-box/metabolismo , Interferón Tipo I/inmunología , Macrófagos/inmunología , Macrófagos/virología , Microglía/inmunología , Microglía/virología , Virus de la Hepatitis Murina/inmunología , Animales , Astrocitos/citología , Astrocitos/metabolismo , Astrocitos/virología , Células de la Médula Ósea/citología , Células de la Médula Ósea/fisiología , Encéfalo/citología , Encéfalo/fisiología , Encéfalo/virología , Células Cultivadas , ARN Helicasas DEAD-box/genética , Hepatitis Viral Animal/inmunología , Hepatocitos/citología , Hepatocitos/metabolismo , Hepatocitos/virología , Helicasa Inducida por Interferón IFIH1 , Macrófagos/citología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/citología , Virus de la Hepatitis Murina/genética , Neuronas/citología , Neuronas/metabolismo , Neuronas/virología , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/metabolismo , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/metabolismo , Replicación ViralRESUMEN
Virus-specific CD8(+) T cells are critical for protection against neurotropic coronaviruses; however, central nervous system (CNS) infection with the recombinant JHM (RJHM) strain of mouse hepatitis virus (MHV) elicits a weak CD8(+) T-cell response in the brain and causes lethal encephalomyelitis. An adoptive transfer model was used to elucidate the kinetics of CD8(+) T-cell priming during CNS infection with RJHM as well as with two MHV strains that induce a robust CD8(+) T-cell response (RA59 and SJHM/RA59, a recombinant A59 virus expressing the JHM spike). While RA59 and SJHM/RA59 infections resulted in CD8(+) T-cell priming within the first 2 days postinfection, RJHM infection did not lead to proliferation of naïve CD8(+) T cells. While all three viruses replicated efficiently in the brain, only RA59 and SJHM/RA59 replicated to appreciable levels in the cervical lymph nodes (CLN), the site of T-cell priming during acute CNS infection. RJHM was unable to suppress the CD8(+) T-cell response elicited by RA59 in mice simultaneously infected with both strains, suggesting that RJHM does not cause generalized immunosuppression. RJHM was also unable to elicit a secondary CD8(+) T-cell response in the brain following peripheral immunization against a viral epitope. Notably, the weak CD8(+) T-cell response elicited by RJHM was unique to CNS infection, since peripheral inoculation induced a robust CD8(+) T-cell response in the spleen. These findings suggest that the failure of RJHM to prime a robust CD8(+) T-cell response during CNS infection is likely due to its failure to replicate in the CLN.