Sean P. McDonough

Clinical, anatomic, and immunopathologic characterization of Babesia gibsoni infection in the domestic dog (Canis familiaris)

The pathology associated with acute, chronic, and recrudescent Babesia gibsoni infections was characterized in a group of 6 naturally or experimentally infected, spleen-intact and splenectomized dogs. All experimentally infected dogs became acutely parasitemic, lethargic, anemic, thrombocytopenic, and hemoglobinuric. Anatomic lesions associated, with the disease included diffuse nonsuppurative periportal and centrilobular hepatitis, multifocal necrotizing arteritis, membranoproliferative glomerulonephritis, reactive lymphadenopathy, diffuse erythrophagocytosis, and extramedullary hematopoiesis. The density of CD3+ lymphocytes within the liver sinusoids was markedly increased. Aggregates of large mononuclear cells with immunohistochemical features of activated macrophages were demonstrated in the central veins of the liver. Kupffer cells throughout the hepatic sinusoids appeared hypertrophic and prominent. The density of sinusoidal T lymphocytes, macrophages in central veins, and the degree of Kupffer cell hypertrophy were greatest in the splenectomized dogs. Multifocal deposits of IgM antibody were immunohistochemically demonstrated within the walls of inflamed arteries and renal glomeruli. The results of this study suggest that intense immunostimulation resulting in activation and expansion of T and B lymphocyte populations, macrophage recruitment and activation, vasculitis, glomerulonephritis and anemia contribute to the pathology associated with B. gibsoni infections.

Canine Pericardial Mesothelioma

Mesothelioma of the canine pericardium has been described infrequently, usually as one manifestation of widespread dissemination of the neopla~m.~~~~~ This report de

Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs

OBJECTIVEnTo determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs.nnnANIMALSn1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever-Greyhound crossbreeds.nnnRESULTSnThe Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage.nnnCONCLUSIONS AND CLINICAL RELEVANCEnThe FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.

Hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis: 72 cases (1980–2010)

OBJECTIVEnTo evaluate differences in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis.nnnDESIGNnetrospective case-control study.nnnSAMPLEnLiver tissue specimens from 36 Labrador Retrievers with chronic hepatitis and 36 age- and sex-matched Labrador Retrievers without chronic hepatitis (control dogs).nnnPROCEDURESnLiver tissue specimens were obtained during 2 study periods (1980 to 1997 and 1998 to 2010). For each tissue specimen, a histologic score was assigned independently by each of 2 interpreters, and the hepatic copper concentration was qualitatively determined via rhodanine staining and quantitatively determined via atomic absorption spectroscopy.nnnRESULTSnMean hepatic copper concentration was significantly higher in dogs with chronic hepatitis (614 μg/g of dry weight [range, 104 to 4,234 μg/g of dry weight]), compared with that in control dogs (299 μg/g of dry weight [range, 93 to 3,810 μg/g of dry weight]), and increased significantly over time. A higher proportion of liver tissue specimens collected during the 1998-2010 study period had hepatic copper concentrations > 400 μg/g of dry weight (the upper limit of the reference range), compared with the proportion of liver tissue specimens collected during the 1980-1997 study period. The qualitative copper score did not accurately predict quantitative hepatic copper concentration in 33% of study dogs.nnnCONCLUSIONS AND CLINICAL RELEVANCEnResults suggested that the increase in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis over time may be the result of increased exposure of dogs to environmental copper, most likely via the diet.

Hepatogenous Photosensitization of Sheep in California Associated with Ingestion of Tribulus Tevrestris (Puncture Vine)

Azuma H, Kurita G, Sasaki H, et al.: 1987, Aortic body tumour in a cow. J Jpn Vet Med Assoc 40:523-525. 12. Beham A, Schmid C, Fletcher CDM, et al.: 1992, Malignant paraganglioma of the uterus. Virchows Arch A Pathol Anat 420: 453-457. 13. Böker DK, Wassmann H, Solymosi L: 1983, Paragangliomas of the spinal canal. Surg Neurol 15:461-468. Glenner GC, Grimley PM: 1974, Tumors of the extra-adrenal paraganglion system. In: Atlas of tumor pathology, 2nd ser., 14. fast. 9, pp. 13-86. Armed Forces Institute of Pathology, Washington, DC. Gould VE: 1988, Neuroendocrine tumors. Introduction. Pathol Res Pract 183:117-118. 15.

Recombinant human macrophage colony‐stimulating factor‐induced thrombocytopenia in dogs

Summary. To characterize recombinant human macrophage‐colony stimulating factor (rhM‐CSF)‐associated thrombocytopenia (TCP), in vivo studies were performed in dogs, including the biodistributions and recoveries of radiolabelled autologous and allogeneic platelets. rhM‐CSF induced a reversible, dose‐dependent decrease in platelet counts. The number of megakaryocytes in spleen and marrow of rhM‐CSF‐treated dogs was increased two to threefold. Recoveries of allogeneic platelets transfused from rhM‐CSF‐treated donors into tolerized recipients (nu2003=u20033) were not significantly different from allogeneic baseline studies (93u2003±u200310% of baseline values at 24u2003h and 90u2003±u20031% at 40u2003h), whereas autologous platelets infused back into rhM‐CSF‐treated donors had decreased recoveries (45u2003±u20032% of baseline values at 24u2003h, Pu2003=u20030·03 and 20u2003±u20034% at 40u2003h, Pu2003=u20030·001). Platelet biodistribution studies showed increased accumulation of radiolabelled platelets over the spleens and livers of rhM‐CSF‐treated dogs. Histochemistry showed increased levels of platelet‐specific antigen (CD41; glycoprotein IIb) associated with Kupffer cells. The sensitivity of platelets from rhM‐CSF‐treated dogs to activation from thrombin, as measured by expression of P‐selectin (CD62P), was not significantly different when compared with baseline studies (Pu2003= 0·18; nu2003=u20034). These results support the concept that rhM‐CSF induces an activation of the monocyte–macrophage system (MMS), which causes a reversible TCP in a dog model.

Influence of biopsy specimen size, tissue fixation, and assay variation on copper, iron, and zinc concentrations in canine livers

OBJECTIVE-To determine whether metal concentrations in canine liver specimens were influenced by specimen size, assay variability, tissue processing (formalin fixation and deparaffinization), or storage in paraffin blocks. SAMPLE POPULATION-Liver specimens (fresh frozen and deparaffinized) from 2 dogs with chronic hepatitis (high copper but unremarkable iron concentration [liver 1] and unremarkable copper but high iron concentration [liver 2]) as well as fresh and deparaffinized-archived liver specimens from 20 dogs with various hepatopathies. PROCEDURES-Fresh frozen liver specimens (obtained via simulated needle-core and wedge biopsy), fresh hepatic tissue, and deparaffinized-archived specimens (0.5 to 14 years old) were analyzed for concentrations of copper, iron, and zinc by atomic absorption flame spectrometry. Clinical severity scores were assigned on the basis of tissue metal concentrations. RESULTS-Interassay variation of metal standards was < 4%. Measurements of liver tissues on 8 consecutive days yielded high coefficients of variation (3.6% to 50%) reflecting heterogenous histologic metal distribution; variation was highest in liver 1 and deparaffinized-archived tissues. Heterogenous metal distribution was confirmed by histologic evaluation. The largest range of metal concentrations was detected in wedge biopsy specimens. In tissues with high metal concentrations, copper and iron concentrations were significantly lower in needle-core versus wedge biopsy specimens. A higher zinc concentration in deparaffinized-archived specimens masked a low zinc concentration in fresh liver tissue of 10 of 20 (50%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE-Retrospective measurement of copper and iron concentrations but not zinc concentrations in deparaffinized-archived liver specimens provided relevant information. The value of needle-core biopsy specimens for measurement of metal concentrations is questionable.

Pulmonary lymphomatoid granulomatosis in a cat

Pulmonary lymphomatoid granulomatosis was diagnosed in a 9-year-old castrated male domestic shorthair cat with a history of coughing, lethargy, and anorexia. Radiographic examination revealed multiple pulmonary opacities, consolidation of left lung lobes, and enlarged tracheobronchial lymph nodes. Cytologic examination of impression smears of abnormal pulmonary tissue revealed erythrocytes, lymphocytes, and macrophages, with scattered atypical lymphocytes and binucleate cells. Histopathologic evaluation of abnormal lung tissue revealed multiple, coalescing, densely cellular nodules composed of anaplastic and pleomorphic lymphocytes, with scattered binucleate and multinucleate cells. Marked infiltration and effacement of bronchiolar and vascular smooth muscle were present. These features are characteristic of lymphomatoid granulomatosis. To the authors knowledge, this is the first report of pulmonary lymphomatoid granulomatosis in a cat.

Digital image analysis of rhodanine-stained liver biopsy specimens for calculation of hepatic copper concentrations in dogs

OBJECTIVEnTo evaluate the accuracy of digitally scanned rhodanine-stained liver biopsy specimens for determination of hepatic copper concentration and compare results with qualitatively assigned histologic copper scores in dogs.nnnSAMPLEn353 liver biopsy specimens from dogs.nnnPROCEDURESnSpecimens (n = 139) with quantified copper concentration ranging from 93 to 6,900 μg/g were allocated to group 1 (< 400 μg/g [37]), group 2 (401 to 1,000 μg/g [27]), group 3 (1,001 to 2,000 μg/g [34]), and group 4 (> 2,001 μg/g [41]); stained with rhodanine; and digitally scanned and analyzed with a proprietary positive pixel algorithm. Measured versus calculated copper concentrations were compared, and limits of agreement determined. Influence of nodular remodeling, fibrosis, or parenchymal loss on copper concentration was determined by digitally analyzing selected regions in 17 specimens. After method validation, 214 additional liver specimens underwent digital scanning for copper concentration determination. All sections (n = 353) were then independently scored by 2 naive evaluators with a qualitative scoring schema. Agreement between assigned scores and between assigned scores and tissue copper concentrations was determined.nnnRESULTSnLinear regression was used to develop a formula for calculating hepatic copper concentration ≥ 400 μg/g from scanned sections. Copper concentrations in unremodeled specimens were significantly higher than in remodeled specimens. Qualitative scores widely overlapped among quantitative copper concentration groups.nnnCONCLUSIONS AND CLINICAL RELEVANCEnCalculated copper concentrations determined by means of digital scanning of rhodanine-stained liver sections were highly correlated with measured values and more accurate than qualitative copper scores, which should improve diagnostic usefulness of hepatic copper concentrations and assessments in sequential biopsy specimens.

Clinical features of progressive vacuolar hepatopathy in Scottish Terriers with and without hepatocellular carcinoma: 114 cases (1980-2013)

OBJECTIVEnTo characterize signalment, clinical features, clinicopathologic variables, hepatic ultrasonographic characteristics, endocrinologic profiles, treatment response, and age at death of Scottish Terriers with progressive vacuolar hepatopathy (VH) with or without hepatocellular carcinoma (HCC).nnnDESIGNnRetrospective case series.nnnANIMALSn114 Scottish Terriers with progressive VH.nnnPROCEDURESnElectronic databases from 1980 to 2013 were searched for adult (age > 1 year) Scottish Terriers with histopathologic diagnoses of diffuse glycogen-like VH. Available sections of liver specimens were histologically reevaluated to confirm diffuse VH with or without HCC; 8 dogs with HCC only had neoplastic tissue available. Physical examination, clinicopathologic, treatment, and survival data were obtained.nnnRESULTSn39 of 114 (34%) dogs with VH had HCC detected at surgery or necropsy or by abdominal ultrasonography. Histologic findings indicated that HCC was seemingly preceded by dysplastic hepatocellular foci. No significant differences were found in clinicopathologic variables or age at death between VH-affected dogs with or without HCC. Fifteen of 26 (58%) dogs with high hepatic copper concentrations had histologic features consistent with copper-associated hepatopathy. Although signs consistent with hyperadrenocorticism were observed in 40% (46/114) of dogs, definitive diagnosis was inconsistently confirmed. Assessment of adrenal sex hormone concentrations before and after ACTH administration identified high progesterone and androstenedione concentrations in 88% (22/25) and 80% (20/25) of tested dogs, respectively.nnnCONCLUSIONS AND CLINICAL RELEVANCEnResults suggested that VH in Scottish Terriers may be linked to adrenal steroidogenesis and a predisposition to HCC. In dogs with VH, frequent serum biochemical analysis and ultrasonographic surveillance for early tumor detection are recommended.