Characterization of clinical presentation, histological features, ultrasonographic findings, and survival in 29 dogs with granulomatous hepatitis.

BACKGROUND: Granulomatous hepatitis (GH) is a form of chronic hepatitis (CH) in dogs for which limited information is published. HYPOTHESIS: Describe the clinical presentation, clinical pathology, ultrasound, and hepatic histopathology findings and to report survival times in dogs with GH. ANIMALS: Twenty-nine client-owned dogs with GH. METHODS: Retrospective observational study. Pathology records were searched. Inclusion criteria included a histopathologic diagnosis of GH, absence of an identified etiology or evidence of extrahepatic granulomatous disease, and a medical record available for review. Clinical presentation, clinical pathologic findings, treatment protocols, and survival times were recorded. Available hepatic biopsy material was graded and scored, and ultrasound evaluations reviewed. RESULTS: The median age was 7 years (range, 0.66-12 years). Nineteen breeds were represented. Decreased appetite (19/29), lethargy (16/29), and fever (13/29) were seen most commonly. All dogs had increased serum transaminase activities, whereas 21/29 and 12/24 had hyperbilirubinemia and neutrophilia, respectively. Ultrasonographic findings included hepatomegaly (12/22), nodular parenchymal lesions (9/22), and hyperechoic parenchymal bands (8/22). Histopathologic necroinflammatory scores were moderate to severe in 16/19 dogs, and fibrosis scores were mild in 14/19 dogs. Treatments varied and included antibiotics, immunosuppressive drugs, and hepatoprotectants. Overall median survival was 635 days (range, 1-2482 days). CONCLUSION AND CLINICAL IMPORTANCE: Granulomatous hepatitis in dogs is associated with high histopathologic grade, fever, neutrophilia, and a high incidence of hepatomegaly and focal parenchymal lesions on ultrasound examination. Despite disease severity on presentation, dogs with GH can have a good outcome with prolonged survival.

Systemic histiocytic disorder in a jaguar (Panthera onca).

A 7-year-old captive female jaguar (Panthera onca) was presented with a 7-day history of dyspnoea and weight loss. Clinical examination revealed hepatomegaly and elevated serum alanine aminotransferase activity. Pulmonary ultrasonography revealed comet-tail images and an alveolar pattern was detected on thoracic radiography. Due to the poor prognosis, the jaguar was euthanized after 10 days. At necropsy, the main gross findings were hepatomegaly, splenomegaly and multifocal to coalescent, slightly elevated grey areas in the lungs. Histological examination revealed neoplastic proliferation of pleomorphic histiocytes arranged in cohesive sheets in the lungs, liver, spleen, kidneys and lymph nodes. Neoplastic cells had intense immunolabelling for vimentin and ionized calcium-binding adaptor molecule 1, and were immunonegative for pancytokeratin, E-cadherin, CD20, CD3 and CD79α. These findings were compatible with a systemic histiocytic disorder, distinct from any well-defined histiocytic proliferative disease in domestic animals.

Diagnostic imaging findings in a referral population of dogs diagnosed with immune-mediated haemolytic anaemia: 50 cases (2015-2018).

OBJECTIVES: To describe and characterise changes documented on thoracic and abdominal imaging of dogs with confirmed immune-mediated haemolytic anaemia. MATERIALS AND METHODS: Medical records from a referral hospital were searched from 2015 to 2018 for all dogs diagnosed with immune-mediated haemolytic anaemia that underwent thoracic and abdominal imaging by radiography, ultrasound or computed tomography. RESULTS: Fifty dogs were included. Thoracic imaging revealed abnormalities in 10 dogs (20%) of which lymphadenopathy and cardiomegaly were documented in four dogs (8%) each, and pleural effusion and pleural thickening in one dog (2%) each. Abdominal imaging revealed abnormalities in 43 dogs (86%), in which hepatomegaly and peritoneal effusion were documented in 20 (40%) and 19 dogs (38%), gallbladder wall thickening and sludge in 16 (32%) and 14 dogs (28%) and splenic nodules and splenomegaly in 13 (26%) and seven dogs (14%), respectively. Hepatic and splenic abnormalities were further investigated via fine needle aspirates in 18 dogs and revealed extramedullary haematopoiesis in 12 hepatic (66.7%) and 14 splenic (77.8%) fine needle aspirate samples. Cholecystocentesis was performed in nine dogs with gallbladder abnormalities and revealed bactibilia in three samples (33.3%). CLINICAL SIGNIFICANCE: In this population of dogs with immune-mediated haemolytic anaemia, thoracic imaging abnormalities were uncommon. Hepatomegaly, peritoneal effusion and gallbladder wall thickening were the most common abdominal imaging findings with bactibilia confirmed in one third of collected bile samples. Hepatosplenomegaly and abdominal lymphadenopathy were not associated with neoplasia in any of the dogs included in this study.

Pathogenic Idiopathic Extramedullary Hematopoiesis in a Yellow-Collared Macaw (Primolius auricollis).

1.5-year-old yellow-collared macaw (Primolius auricollis) was presented as a referral case for chronic breathing difficulties and coelomic distension. The bird was in poor body condition, and coelomic distension and green-colored urates were noted during the physical examination. Radiographic images revealed a large coelomic space-occupying soft-tissue lesion that was ultrasonographically confirmed to be hepatomegaly; the liver had a heterogeneous echogenic pattern. An ultrasound-guided fine needle aspirate of the liver was performed. The cytological results revealed immature hematopoietic cells with signs of dyserythropoiesis and were consistent with extramedullary hematopoiesis (EMH). The plasma biochemistry panel revealed a marked increase in aspartate aminotransferase and bile acids, consistent with severe hepatic disease. Following the results of the diagnostic tests, chemotherapy was initiated using hydroxyurea. Two weeks after the initial presentation and treatment, the bird died and a full postmortem examination was performed. Macroscopic examination confirmed severe hepatomegaly and severe splenomegaly. Histopathological examination of tissue samples confirmed severe EMH in the liver and spleen, splenic and renal hemosiderosis, and acute pulmonary congestion. The bone marrow was normal. The final diagnosis was pathogenic idiopathic EMH, and this case was unusual in both its presentation and severity. Extramedullary hematopoiesis is usually related to myeloid proliferative disorder, chronic blood loss, hemolytic disease, or chronic inflammatory disease. Mycobacteriosis and parasitic infection have been reported to be associated with EMH in birds; however, the inflammatory patterns seen in those cases were lacking in this case. Myeloproliferative neoplasia also appears an unlikely disease condition in this case considering that histopathology found normal architecture in the studied bone marrow; however, bone marrow abnormalities in locations other than the one sampled could not be excluded. A short review of homeostatic and pathogenic hematopoiesis in birds is provided to support the likely diagnosis of idiopathic EMH.

Chicken hepatomegaly and splenomegaly associated with novel subgroup J avian leukosis virus infection.

BACKGROUND: Subgroup J avian leukosis virus (ALV-J) is an oncovirus which can induce multiple types of tumors in chicken. In this report, we found novel ALV-J infection is closely associated with serious hepatomegaly and splenomegaly in chicken. CASE PRESENTATION: The layer chickens from six flocks in Jiangsu province, China, showed serious hemoperitoneum, hepatomegaly and splenomegaly. Histopathological results indicated focal lymphocytic infiltration, cell edema and congestion in the liver, atrophy and depletion of lymphocyte in the spleen. Tumor cells were not detected in all the organs. avian hepatitis E virus (aHEV), which is thought to be the cause of a very similar disease, big liver and spleen disease (BLS), was not detected. Other viruses causing tumors or liver damage including Marek's disease virus (MDV), reticuloendotheliosis virus (REV), fowl adenovirus (FAdV) and chicken infectious anemia virus (CIAV) were also proved negative by either PCR or RT-PCR. However, we did detect ALV-J in those chickens using PCR. Only novel ALV-J strains were efficiently isolated from these chicken livers. CONCLUSIONS: This is the first report that chicken hepatomegaly and splenomegaly disease was closely associated with novel ALV-J, highlighting the importance of ALV-J eradication program in China.

Clinical features of canine nodal T-cell lymphomas classified as CD8+ or CD4-CD8- by flow cytometry.

Canine T-cell lymphoma (TCL) encompasses a heterogeneous group of diseases with variable clinical presentation, cytomorphology, immunophenotype, and biologic behaviour. The most common types of TCL in dogs involving peripheral lymph nodes include indolent T-zone lymphoma (TZL) and biologically aggressive peripheral T-cell lymphoma (PTCL). TCL phenotypes can be categorized by expression of the surface antigen molecules CD4 and CD8. The majority of TCL cases are CD4+ , with far fewer cases being CD8+ or CD4- CD8- . The clinical features of CD4+ TCLs have been previously described. The less common TCL phenotypes, however, are poorly characterized with little to no information about prognosis. In this retrospective study, we describe and correlate the presenting clinical signs, flow cytometry, and outcomes of 119 dogs diagnosed with nodal, non-TZL, CD8+ or CD4- CD8- TCL by flow cytometry. Skin lesions present at the time of diagnosis were more commonly observed in the CD8+ TCL group. Mediastinal enlargement and/or hypercalcemia were more commonly seen in the CD4- CD8- TCL group. Dogs with either CD8+ or CD4- CD8- TCLs had aggressive clinical disease with median overall survival (OS) times of 198 days and 145 days, respectively. In both groups, neoplastic cell size determined by flow cytometry ranged from small to large, and large cell size was associated with shorter OS times (median OS = 61 days). Cases classified as small cell had a median OS of 257 days. Expression levels of major histocompatibility complex (MHC) class II and CD5 were highly variable among cases but were not prognostically significant in this group of patients.

Canine adrenocorticotropic hormone-producing sinusoidal neuroendocrine tumor associated with Cushing's disease.

An 18-year-old male Yorkshire Terrier was admitted with a history of neurological signs including dullness and progressive tetraparesis. Physical examination revealed bilaterally symmetrical alopecia and pot-bellied abdomen. Computed tomography and necropsy examination showed a mass across the frontal sinus and cerebral frontal lobe, bilateral adrenocortical hyperplasia, and hepatomegaly. Histopathologically, the tumor lesions consisted of sheets, nests, or cords of small- to medium-sized round-to-polyhedral cells. Adrenal cortex showed bilateral diffuse cellular proliferation, and some hepatocytes showed intracytoplasmic glycogen accumulation. Immunohistochemically, the tumor cells were positive for pancytokeratin, chromogranin-A, neuron-specific enolase, S100, synaptophysin, and thyroid transcription factor-1 but negative for microtubule-associated proein-2 and neurofilament, leading to the diagnosis of neuroendocrine tumor. These tumor cells were also positive for adrenocorticotropic hormone.

Prevalence of Trypanosoma cruzi and organ alterations in Virginia opossums (Didelphis virginiana) from western Mexico - short communication.

Small populations of Virginia opossum (Didelphis virginiana) in western Mexico are endangered by hunting and natural predators as well as by different kinds of diseases. After two serological analyses using Serodia® latex particle agglutination and indirect haemagglutination (IHA) tests, 35 (53.03%) of 66 collected opossums in two small towns in western Mexico were positive for the presence of Trypanosoma cruzi. Twenty-eight of the 35 seropositive opossums had pathological lesions: 11 had changes in only one organ, 13 in two organs, and four had pathological changes in three organs. Splenomegaly was the most common finding in the examined opossums, followed by hepatomegaly. These potentially fatal pathological changes could contribute to the scarcity of the opossum population, even leading to the extinction of this species in western Mexico.

Molecular diagnosis of Eimeria stiedae in hepatic tissue of experimentally infected rabbits.

The early detection of Eimeria stiedae in the hepatic tissue of experimentally infected rabbits was investigated using molecular assay. Forty 6-week-old male New Zealand rabbits were divided into two groups. Group A (30 animals) was infected with 2.5 × 10(4) sporulated oocysts of E. stiedae per animal on Day 0 and Group B (10 animals) was used as the uninfected controls. Three animals from Group A and one from Group B were sacrificed at 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27 days post infection (PI). Gross and microscopic post-mortem findings were recorded. Polymerase chain reaction (PCR) of the E. stiedae internal transcribed spacer 1 genomic region was conducted on blood, liver tissue, and feces from the Group A experimentally infected animals. Macroscopically, the liver showed irregular yellowish white nodules pathognomonic to E. stiedae infection beginning on Day 15 PI. Hepatomegaly and ascites were obvious from Day 21-24 PI. The presence of different E. stiedae schizonts and gametocytes in the histopathological sections of the biliary epithelium were evident on Day 15 PI. The E. stiedae PCR was first positive in liver tissues on Day 12 and in fecal samples on Day 18 PI, but the blood samples were negative. In conclusion, the PCR can be used for early diagnosis and control of E. stiedae schizonts before shedding of the oocysts in feces.

Natural Progression of Canine Glycogen Storage Disease Type IIIa.

Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc4, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc4 might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies.

Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison).

Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with Aroclor 1268 exposure.

Diagnostic exercise: poor performance in a racehorse.

A 9-year-old Thoroughbred gelding presented with a 97-day history of poor performance and intermittent fever. Clinicopathologic changes included increased serum activity of γ-glutamyltransferase and alkaline phosphatase, mild hyperbilirubinemia, and leukocytosis with neutrophilia and lymphopenia. Abdominal ultrasound revealed hepatomegaly with hyperechoic hepatic parenchyma and biliary distention. Pathologic findings included marked hepatomegaly (liver 3.6% of body weight), firm hepatic consistency with a diffuse enhanced reticular pattern, severe portal bridging and sinusoidal fibrosis, oval cell/bile duct hyperplasia, and bile stasis. The differential diagnoses and diagnostic workup to achieve the diagnosis are briefly discussed.

Xylitol.

Xylitol is a prevalent sugar substitute found in a wide variety of foods, particularly those labeled as "low carb." It is found in many medicines and dental products both for its antibacterial activity and to increase palatability. Originally, this toxin was recognized as a problem in dogs following sugarless gum ingestions. Xylitol is generally nontoxic to mammals except for dogs. In the dog, xylitol induces marked increases in insulin production and occasionally hepatopathy. The clinical syndrome is manifested with signs consistent with profound hypoglycemia, hypokalemia, hypophosphatemia, and acute hepatic failure. Treatment relies upon administration of intravenous glucose, hepatic support, and general supportive care.

Investigação do gene p53 de frangos expostos às aflatoxinas / Investigation of p53 gene in poultries exposed to aflatoxins

Identificou-se o efeito das aflatoxinas (AFs) sobre o gene p53 de frangos de corte, de linhagem comercial, separados em: grupo experimental, tratado (GT) com ração comercial contendo 2,8ppm de AFs totais durante 21 dias consecutivos, e grupo-controle (GC), sem exposição às AFs. Macroscopicamente, as alterações caracterizaram-se por hepatomegalia e aspecto pálido-amarelado com alguns focos hemorrágicos e, histologicamente, por desarranjo trabecular, pleomorfismo hepatocítico com cariomegalia, degeneração vacuolar intracitoplasmática, necrose com infiltração linfocítica e hiperplasia de ductos biliares. A PCR com os primers GSPT53c-1 com base no gene candidato a p53 (GenBank XM_424937.2) gerou um produto de aproximadamente 350 pares de base. O amplicon sequenciado a partir do DNA dos frangos do GT não apresentou mutação ou deleção, assim como padrão de bandas do PCR-RFLP não foi distinto entre ambos os grupos experimentais e a sequência depositada no banco de genes. Os resultados sugerem que não ocorreu transversão devido à exposição às AFs no fragmento amplificado. Conclui-se que a PCR-RFLP e o sequenciamento do produto da PCR não são ferramentas apropriadas para diagnóstico da exposição de frangos às AFs nas condições experimentais empregadas.

To identify the effects of aflatoxins (AFs), Cobb lineage poultry were separated in an experimental group in which they were treated with commercial ration containing 2.8ppm of total AFs during 21 days (TG) and a control group without AFs exposure (CG). In the liver of poultries exposed to AFs, alterations were microscopically observed, which were characterized by hepatomegaly, a pale yellowish aspect with some hemorrhagic spots, and histologically a trabecullar disarranging pleomorphic hepatocytes with cariomegaly, intracytoplasmatic vacuolar degeneration, necrosis, lymphocytic infiltration and hyperplasia of biliary ducts. The PCR with GSPT53c-1 primers based on p53 candidate gen (GenBank XM_424937.2) generated a product of approximately 350 base pairs. The sequenced amplicon obtained from the DNA of treated poultry did not display any mutation or deletion, and the PCR- RFLP bands patterns were also not distinct in both experimental groups. The results indicated that transversion did not occur in the fragment amplified due to AFs exposure. As a consequence of results obtained with p53 gene (NM_205264.1) we concluded that PCR-RFLP and sequencing of PCR product are not appropriate diagnostic tools for the detection of poultry exposure to AFs, at least in the experimental conditions performed.

Visceral leishmaniasis in a captive crab-eating fox Cerdocyon thous.

Visceral leishmaniasis (VL) is a zoonotic disease with worldwide distribution. The crab-eating fox (Cerdocyon thous) is considered a wild reservoir of many zoonotical diseases, particularly VL. This study reported the presence of Leishmania infantum amastigotes in different organs of one captive C. thous found dead in a zoo. This animal was positive by the indirect fluorescence antibody test and had many clinical signs of VL. Intracellular amastigote forms of L. infantum were seen in neutrophils and macrophages in sample tissues from skin, lymph nodes (popliteal, submandibular, prescapular, and mesenteric), spleen, and liver. The numbers of positive cells and intracellular parasites were higher in macrophages than in neutrophils. In addition, polymerase chain reaction demonstrated extensive distribution of Leishmania DNA in C. thous tissues from multiple organs. The presence of intracellular amastigotes in neutrophils and macrophages as well as DNA of the parasite in tissues, specifically skin demonstrate that this crab-eating fox is an adequate host for L. infantum and reinforce the importance of VL for symptomatic wild canids kept in captivity in endemic areas.

Primary hepatic Mycobacterium tuberculosis complex infection with terminal dissemination in a pig-tailed macaque (Macaca nemestrina).

An adult, female, pig-tailed macaque (Macaca nemestrina) of Indonesian origin presented with profound weight loss, anemia (PCV, 29%; normal, 36% to 45%), hypoalbuminemia (1.0 g/dL; normal, 3.5 to 5.2 g/dL), elevated alkaline phosphatase (1990 U/L; normal, 26 to 98 U/L), and an elevated erythrocyte sedimentation rate (75 mm/h; normal, less than 20 mm/h). Abdominal ultrasonography demonstrated an enlarged liver with hyperechoic areas. Euthanasia was performed. Grossly, the liver had multifocal, effacing, white masses throughout and was enlarged with rounded edges. There were 2, small nodules in the right lung lobes. Histologically, the hepatic masses were densely fibrous-encapsulated granulomas with vast central necrosis. The lung nodules also were maturing granulomas, and one kidney and one atrium had small, early granulomas. Fite acid-fast stains of liver and lung revealed very few acid-fast bacilli. PCR analysis of paraffin-embedded liver identified Mycobacterium tuberculosis complex. Culture of the liver was negative twice. This macaque had 16 negative intradermal tuberculin skin tests over the course of 6 y. We hypothesize that the animal arrived with a latent hepatic or enteric infection that later recrudesced and disseminated. Primary hepatic mycobacteriosis is not a typical presentation of tuberculosis in macaques. Negative tuberculin skin tests can be seen with latent infections and extrapulmonary tuberculosis such as Pott disease. This case underscores the problems associated with current surveillance procedures and the risks associated with latent mycobacterial infections in macaques.