- Illuminating Dark Cases: Veterinary Forensic Pathology Emerges 24 dicembre 2014
McDonough, S. P., Gerdin, J., Wuenschmann, A., McEwen, B. J., Brooks, J. W.
- Postanesthetic Death in a Cat With Myopathy 24 dicembre 2014
Remmers, G., Hayden, D. W., Jaeger, M. A., Ervasti, J. M., Valberg, S. J.
There are few reports of naturally occurring muscular dystrophy in domestic animals. Herein, we describe a case of muscular dystrophy in a 4-year-old neutered male American domestic shorthair cat that died unexpectedly following anesthesia for an elective surgical procedure. Macroscopic muscular hypertrophy and histologic evidence of myofiber size variation, mineralization, myofiber degeneration, and necrosis were compatible with a diagnosis of muscular dystrophy. Extensive endomysial fibrosis was noted histologically in the diaphragm. A complete absence of dystrophin protein in Western blot confirmed the diagnosis of Duchenne muscular dystrophy. Immunofluorescence microscopy revealed reduced levels of dystrophin-associated proteins and an upregulation of utrophin at the sarcolemma. Anesthetic deaths can occur in dystrophin-deficient cats, and therefore muscular dystrophy and the associated cardiomyopathy should be considered in the differential diagnoses for perianesthetic death in cats.
- Commentary: The Role of the Toxicologic Pathologist in Academia 24 dicembre 2014
Turner, P. V., Haschek, W. M., Bolon, B., Diegel, K., Hayes, M. A., McEwen, B., Sargeant, A. M., Scudamore, C. L., Stalker, M., von Beust, B., Wancket, L. M.
Veterinary pathologists working as toxicologic pathologists in academic settings fill many vital roles, such as diagnosticians, educators, and/or researchers. These individuals have spent years investigating pathology problems that mainly or exclusively focus on the reactions of cells, organs, or systems to toxic materials. Thus, academic toxicologic pathologists are uniquely suited both to help trainees understand toxicity as a cause of pathology responses and also to provide expert consultation on toxicologic pathology. Most toxicologic pathologists in academia are employed at colleges of medicine or veterinary medicine, even though specific toxicologic pathology faculty appointments are uncommon in Europe and North America. Academic toxicologic pathologists typically receive lower financial compensation than do toxicologic pathologists in industry, but academic positions generally provide alternative rewards, such as higher workplace autonomy and scheduling flexibility, professional enrichment through student interactions, and enhanced opportunities for collaborative research and advanced diagnostic investigations. Regular participation by academic toxicologic pathologists in professional training opportunities (eg, as pathology and toxicology instructors in medical and veterinary medical courses, graduate programs, and residencies) offers an important means of engendering interest and inspiring veterinarians to select toxicologic pathology and toxicology as their own areas of future expertise.
- Pathological and Biochemical Studies of Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B) in Juvenile Emus (Dromaius novaehollandiae) 24 dicembre 2014
Palmieri, C., Giger, U., Wang, P., Pizarro, M., Shivaprasad, H. L.
Mucopolysaccharidosis (MPS) type IIIB was diagnosed in 14 juvenile emus (Dromaius novaehollandiae), ages 3 weeks to 6 months, based on pathological and biochemical analyses. The animals had a history of neurological signs or sudden death; one of the birds with neurological signs and 3 others experienced acute hemoabdomen. Histopathologically, neuronal swelling and vacuolation in the cerebrum, cerebellum, brainstem, and spinal cord (80%–92%); retina (100%); autonomic ganglia of the intestine (71%); gizzard (50%); adrenal gland (27%); and ear (50%) were noted in affected but not healthy emus. Cytoplasmic vacuoles were also observed in the pancreas, liver, intestine, adrenal glands, and kidneys. The intracytoplasmic inclusions were periodic acid–Schiff and Luxol Fast Blue positive, consistent with a storage disease. Foamy macrophages infiltrated the liver, intestine, tunica media of the aorta, and spleen. By transmission electron microscopy, typical lamellated cytoplasmic bodies were detected in neurons of the brain and retina, while electron-dense bodies consistent with glycosaminoglycan inclusions were observed in hepatocytes and/or hepatic macrophages. The livers of the 2 affected emus studied contained large amounts of heparan sulfate, which is suggestive of MPS type III. Compared with normal controls, hepatic and serum α-N-acetylglucosaminidase activity was very low (
- Mission Critical: Mobilization of Essential Animal Models for Ebola, Nipah, and Machupo Virus Infections 24 dicembre 2014
Zumbrun, E. E.
The reports for Ebola virus Zaire (EBOV), Nipah virus, and Machupo virus (MACV) pathogenesis, in this issue of Veterinary Pathology, are timely considering recent events, both nationally and internationally. EBOV, Nipah virus, and MACV cause highly lethal infections for which no Food and Drug Administration (FDA) licensed vaccines or therapies exist. Not only are there concerns that these agents could be used by those with malicious intent, but shifts in ecological distribution of viral reservoirs due to climate change or globalization could lead to more frequent infections within remote regions than previously seen as well as outbreaks in more populous areas. The current EBOV epidemic shows no sign of abating across 3 West African nations (as of October 2014), including densely populated areas, far outpacing infection rates of previous outbreaks. A limited number of cases have also arisen in the United States and Europe. With few treatment options for these deadly viruses, development of animal models reflective of human disease is paramount to combat these diseases. As an example of this potential, a new treatment compound, ZMapp, that had demonstrated efficacy against EBOV infection in nonhuman primates (NHPs) received an emergency compassionate use exception from the FDA for the treatment of 2 American medical workers infected with EBOV, and they are currently virus free and recovering.
- Streptococcus iniae in Gilthead Seabream (Sparus aurata, L.) and Red Porgy (Pagrus pagrus, L.): Ultrastructural Analysis 24 dicembre 2014
Aamri, F. E., Caballero, M. J., Real, F., Acosta, F., Deniz, S., Roman, L., Padilla, D.
Streptococcosis caused by Streptococcus iniae has become one of the most serious marine and freshwater aquatic diseases in the past decade, causing large losses in farmed and wild fish worldwide. In this study, we performed an ultrastructural study of major lesions in gilthead seabream Sparus aurata and red porgy Pagrus pagrus experimentally infected with the S. iniae IUSA-1 strain, isolated in a natural outbreak in Spain in the mentioned species. The transmission electron micrographs revealed the resistance of this pathogen inside the phagosome, indicating that the macrophage may provide a significant bacterial reservoir for continuing infection, disease dissemination, and tissue injury by crossing the blood-brain barrier.
- Experimental Aerosolized Guinea Pig-Adapted Zaire Ebolavirus (Variant: Mayinga) Causes Lethal Pneumonia in Guinea Pigs 24 dicembre 2014
Twenhafel, N. A., Shaia, C. I., Bunton, T. E., Shamblin, J. D., Wollen, S. E., Pitt, L. M., Sizemore, D. R., Ogg, M. M., Johnston, S. C.
Eight guinea pigs were aerosolized with guinea pig–adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig–adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig–adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.
- Comparative Pathology of Neurovirulent Lineage 1 (NY99/385) and Lineage 2 (SPU93/01) West Nile Virus Infections in BALBc Mice 24 dicembre 2014
Williams, J. H., Mentoor, J. D. L., Van Wilpe, E., Venter, M.
The pathology in mice infected with neurovirulent South African lineage 2 West Nile virus (WNV) strains has not previously been described. Three- to 4-month-old male BALBc mice were infected with South African neurovirulent lineage 2 (SPU93/01) or lineage 1 (NY385/99) WNV strains and the gross and microscopic central nervous system (CNS) and extra-CNS pathology of both investigated and compared. Mice infected with both lineages showed similar illness, paralysis, and death from days 7 to 11 postinfection (PI). Two survivors of each lineage were euthanized on day 21 PI. WNV infection was confirmed by nested real-time reverse transcription polymerase chain reaction of tissues, mostly brain, in the majority of mice euthanized sick or that died and in 1 healthy lineage 2 survivor. Gross lesions caused by both lineages were identical and included marked gastric and proximal small intestinal fluid distension as described in a previous mouse study, but intestinal microscopic lesions differed. CNS lesions were subtle. Immunohistochemical (IHC)–positive labeling for WNV E protein was found in neurons multifocally in the brain of 3 lineage 1–infected and 3 lineage 2–infected mice from days 9 to 11 PI, 4 of these including brainstem neurons, and of cecal myenteric ganglion neurons in 1 lineage 2–infected day 8 PI mouse. Findings supported hypotheses in hamsters that gastrointestinal lesions are likely of brainstem origin. Ultrastructurally, virus-associated cytoplasmic vesicular or crystalline structures, or amorphous structures, were found to label IHC positive in control-positive avian cardiomyocytes and mouse thalamic neurons, respectively, and WNV-like 50-nm particles, which were scarce, did not label.
- Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure 24 dicembre 2014
Bell, T. M., Shaia, C. I., Bunton, T. E., Robinson, C. G., Wilkinson, E. R., Hensley, L. E., Cashman, K. A.
Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration–approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection.
- Pleomorphic Xanthoastrocytoma Within the Medulla Oblongata of a Young Dog 24 dicembre 2014
Hostnik, E. T., Kube, S. A., Jortner, B., Hager, D., Garman, R. H.
A 13-week-old male intact Poodle mix dog developed an acute onset of vestibular ataxia, tetraparesis, and vomiting. The patient presented ambulatory, tetraparetic, and ataxic with a head tilt to the left and a disconjugate nystagmus (rotary nystagmus with fast phase to the right in right eye and vertical nystagmus in left eye). There were absent postural reactions in the left pelvic and left thoracic limbs and decreased right-sided postural reactions. Magnetic resonance imaging demonstrated an intra-axial mass within the left midcaudal medulla oblongata. On gross dissection, there was a left-sided neoplasm in the medulla oblongata with surrounding hemorrhage. The histologic findings indicated that the mass was a pleomorphic xanthoastrocytoma. This tumor, an uncommon variant of an astrocytoma most often seen in children and young adult humans, has yet to be described in dogs.