Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS‐441524 (5‐10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]‐PCR) and serial ocular imaging using Fourier‐domain optical coherence tomography (FD‐OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS‐441524 shows clinical efficacy and may result in clearance and long‐term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.
Background Glioma-associated microglia/macrophage (GAM) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAM are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment, nor TGF Beta (TGFB) signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis. Spontaneously occurring canine gliomas share many features with human glioma and provide a complementary translational animal model for further study. Given the importance of GAM and TGFB in human glioma, the aims of this study were to further define the GAM-associated molecular profile and the relevance of TGFB signaling in canine glioma that may serve as the basis for future translational studies. Methods GAM morphometry, levels of GAM-associated molecules, and the canonical TGFB signaling axis were compared in archived samples of canine astrocytomas versus normal canine brain. Further, the effect of TGFB on the malignant phenotype of canine astrocytoma cells was evaluated. Results GAMs diffusely infiltrated canine astrocytomas. GAM density was increased in high-grade tumors that correlated with a pro-tumorigenic molecular signature and up-regulation of the canonical TGFB signaling axis. Moreover, TGFB1 enhanced migration of canine astrocytoma cells in vitro. Conclusions Canine astrocytomas share a similar GAM-associated immune landscape with human adult glioma. Our data also support a contributing role for TGFB1 signaling in the malignant phenotype of canine astrocytoma. These data further support naturally occurring canine glioma as a valid model for investigation of GAM-associated therapeutic strategies for human malignant glioma.
OBJECTIVE To evaluate neurological tests and expected results in inland bearded dragons (Pogona vitticeps) and generate recommendations for bearded dragon–specific neurological examination. ANIMALS 26 healthy adult inland bearded dragons. PROCEDURES A complete neurological examination utilizing tests described in both mammals and reptiles was performed on each lizard, and test feasibility and outcome were recorded. RESULTS Tests with poor feasibility included oculocardiac reflex (successfully completed in 62% [16/26] of animals) and voluntary ambulation and swallowing by use of a food item (0% [0/26] of animals). Tests with outcomes considered abnormal in mammals but attributable to normal bearded dragon behavior included head position (head tilt present in 12% [3/26]) and head movement (head bob present in 4% [1/26]). Many tests had absent or inconsistent outcomes, including menace response (present in 19% [5/26]), proprioceptive positioning (present in 4% [1/26] in the thoracic limbs and 0% [0/26] in the pelvic limbs), vent reflex (present in 27% [7/26]), and myotatic reflexes (biceps present in 8% [2/26]; patellar, gastrocnemius, and triceps present in 0% [0/26]). Extensor postural thrust was absent in all successfully tested animals, but a novel reflex termed the caudal thoracic extensor reflex was noted instead in all observed animals (100% [21/21]). CLINICAL RELEVANCE Tests with poor feasibility or inconsistent outcomes should have low priority or be excluded from neurological examinations of inland bearded dragons. Normal behaviors should be considered for head position and movement. A bearded dragon–specific neurological examination protocol derived from these findings is described and recommended in order to decrease stress and improve neurolocalization.
Objective: To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication.
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