Hydrocephalus secondary to obstruction of the lateral apertures in two dogs.

BACKGROUND: Traditionally, hydrocephalus is divided into communicating or non-communicating (obstructive) based on the identification of a blockage of cerebrospinal fluid (CSF) flow through the ventricular system. Hydrocephalus ex vacuo refers to ventricular enlargement as a consequence of neuroparenchymal loss. Hydrocephalus related to obstruction of the lateral apertures of the fourth ventricles has rarely been described. CASE REPORT: The clinicopathologic findings in two dogs with hydrocephalus secondary to obstruction of the lateral apertures of the fourth ventricle are reported. Signs were associated with a caudal cervical spinal cord lesion in one dog and a caudal brain stem lesion in the other dog. Magnetic resonance imaging (MRI) disclosed dilation of the ventricular system, including the lateral recesses of the fourth ventricle. In one dog, postmortem ventriculography confirmed obstruction of the lateral apertures. Microscopic changes were identified in the choroid plexus in both dogs, yet a definitive cause of the obstructions was not identified. The MRI findings in both dogs are similar to membranous occlusion of the lateral and median apertures in human patients. CONCLUSION: MRI detection of dilation of the entire ventricular system in the absence of an identifiable cause should prompt consideration of an obstruction of the lateral apertures. In future cases, therapeutic interventions aimed at re-establishing CSF flow or ventriculoperitoneal catheterisation should be considered.

Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.

The role of mast cells (MCs) in allergic reactions and parasitic infections is well established. Their involvement in host immune response against bacterial and viral infections is reported. In this study, investigation is made to determine if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting ECA positive for CPV-2 and negative for Canine distemper virus and Canine coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The average total MCC per high-power field in ECA (40.8 ± 2.2) and IBD (24.7 ± 2.1) was significantly higher (P < .05) than in the control (3.4 ± 0.6). Although not significant (P > .05), MCC was also higher in ECA than in IBD. The present study for the first time has documented significantly increased MCs in CPV-2-associated ECA as was previously reported for IBD, showing that MCs may also play an important role in CPV-2-associated ECA. Further studies involving more CPV-infected dogs are recommended to substantiate the findings.

Well-differentiated hepatocellular carcinoma in a ring-tailed lemur (Lemur catta).

A 16-year-old male ring-tailed lemur (Lemur catta) was presented with severe cachexia and an abdominal mass. The encapsulated, multilobular mass replaced the right medial lobe of the liver and compressed the adjacent gall bladder. Multiple haemorrhages and necrotic foci were found within the mass. Microscopically, neoplastic cells formed cords of moderately pleomorphic, polygonal cells with mild to moderate anaplasia. Immunohistochemical markers used for diagnosis of hepatocellular carcinomas in man were used to characterize the neoplastic cells, which expressed hepatocyte-specific antigen, but not glypican-3 or polyclonal carcinoembryonic antigen. Gross, microscopical and immunohistochemical features of the tumour were most consistent with a well-differentiated hepatocellular carcinoma. Although this tumour is common among prosimians, to the authors' knowledge this is the first documented case in a ring-tailed lemur. Hepatocellular carcinomas have been associated with hepatitis virus infections and excessive hepatic iron in man; however, no association was established between this tumour and viral infection or hepatic iron storage disease in the present case.

Granulomatous typhlocolitis, lymphangitis, and lymphadenitis in a horse infected with Listeria monocytogenes, Salmonella Typhimurium, and cyathostomes.

A 15-year-old American Quarter horse mare was euthanized because of poor response to therapy for severe diarrhea. Significant gross findings were limited to the large intestines. The walls of the cecum and colon were thickened with widely scattered nodules in the mucosa and submucosa that extended into the enlarged colic lymph nodes. Microscopically, there was severe granulomatous typhlocolitis, lymphangitis, and lymphadenitis, with many intralesional Gram-positive, non-acid-fast coccobacilli and few cyathostomes. Intralesional bacteria were immunohistochemically and polymerase chain reaction (PCR) assay positive for Listeria monocytogenes. Concurrent infection with Salmonella enterica serovar Typhimurium was detected by PCR and culture. Infection with L. monocytogenes in horses is rare, and coinfection with Salmonella and small strongyles probably contributed to the development of granulomatous typhlocolitis.

Fatal cetacean morbillivirus infection in an Australian offshore bottlenose dolphin (Tursiops truncatus).

A juvenile offshore bottlenose dolphin (Tursiops truncatus) was found stranded with neurological signs and unable to swim or float unassisted. It subsequently died, succumbing to a combination of severe pneumonia and encephalitis. Morbillivirus serum neutralisation test serology was positive (titre 1:16) for cetacean morbillivirus and negative for both phocine distemper virus and canine distemper virus. There was concurrent thymic and lymph node lymphoid depletion and necrosis, together with intranuclear and intracytoplasmic acidophilic viral inclusion bodies and multinucleate syncytia within multiple organs. Paramyxovirus capsids were identified in lung sections via electron microscopy and morbillivirus antigen was demonstrated within sections of lung, thymus and brain by immunohistochemistry. Reverse transcription-polymerase chain reaction for morbillivirus nucleoprotein (N) and phosphoprotein (P) genes were positive and phylogenetic gene product sequence analysis revealed 98% and 94% sequence identity to dolphin morbillivirus, respectively. To the authors' knowledge, this is the first report of a cetacean mortality due to morbillivirus infection occurring in the southern hemisphere. Morbillivirus infection should be included in the differential diagnosis of stranded live or dead cetaceans in Australian waters, particularly if animals display neurological signs.

Pathogenesis of a bovine enterovirus-1 isolate in experimentally infected calves.

The pathogenesis and virulence of Bovine enterovirus-1 (BEV-1) in cattle is largely unknown. Reports concerning its virulence suggest that there might be an association between BEV-1 infections and a range of diseases in cattle that vary from respiratory to enteric to reproductive disease and infertility. In the current study, the pathogenesis associated with acute infection of BEV-1 in calves experimentally inoculated with the Oklahoma isolate of BEV-1 was described. Although interpretation of the study was limited by lack of an effective control group, results suggest that an association between inoculation of BEV-1, virus localization, and the potential development of lesions in the brain and heart probably exists. In the experiment, BEV-1 virus localized to the terminal ileum, ileocecal and cecocolonic junctions, spiral colon, and ileocecal lymph nodes; BEV-1 virus was detected in the cytoplasm of enterocytes, lamina propria macrophages, endothelium, neurons of the submucosal and myenteric plexi, and lymphocytes of the submucosal lymphoid tissue. Although no clinical signs were noted following acute infection, BEV-1 was localized in the cerebellar white matter of a calf with encephalitis and in the heart of another calf with coronary arteritis. The current study suggests that the BEV-1 isolate is infectious to young calves and that BEV-1 potentially can have a similar pathogenesis to that observed in natural or experimental enterovirus infections in other species.

Reversible fibroadenomatous mammary hyperplasia in male and female New Zealand white rabbits associated with cyclosporine A administration.

All male and female New Zealand white rabbits in a limbal cell graft study developed marked generalized mammary gland hypertrophy. Postprocedural medications included ophthalmic 0.1% dexamethasone, ophthalmic 0.5% cyclosporine, and subcutaneous cyclosporine A. Cytologic examination revealed epithelial clusters with minimal malignant criteria. On histologic evaluation, there was diffuse glandular hyperplasia with mild cellular atypia and ductal ectasia separated by abundant hypercellular fibrous stroma, consistent with fibroadenomatous mammary gland hyperplasia. The hyperplasia resolved within 2 weeks of cessation of cyclosporine, and at necropsy identifiable mammary masses were not found. Very little has been reported about the use of cyclosporine in laboratory rabbits and its association with development of mammary gland hyperplasia. This is the first report in which administration of cyclosporine to male and female rabbits at a dose as low as 5 mg/kg/day induced benign fibroadenomatous mammary gland hyperplasia. This change regressed after cessation of the drug.

Comparison of CO(2) laser and 4.0 MHz radiosurgery for making incisions in the skin and muscles of green iguanas (Iguana iguana).

Four green iguanas scheduled for euthanasia were used to compare the extent of collateral tissue damage associated with CO(2) laser and 4.0 MHz radiosurgery. The iguanas were anaesthetised and a series of three skin and three muscle incisions was made by 4.0 MHz radiosurgery (0.18 mm wire electrode, 25 W, cut mode) and CO(2) laser (0.3 mm ceramic tip, 15 W focused beam super-pulse mode), and three incisions were made with a scalpel blade as controls. Following euthanasia, a total of 60 skin and 36 muscle sections were evaluated histologically. Radiosurgery and the laser both produced bloodless incisions, but radiosurgery caused significantly less collateral tissue damage in the skin (307 [97] v 386 [108] microm) and the muscle (18 [7] v 91 [15] microm).

Immunohistochemical application of an antibody specific for human CD1a to the diagnosis of canine mast cell tumour.

Canine mast cell tumours (MCTs) may be graded microscopically for prognostic purposes. Grade I (well-differentiated) and grade II (intermediate differentiation) tumours have an abundance of metachromatic granules within the cytoplasm; however, grade III (poorly differentiated) MCTs may be difficult to diagnose as they frequently have fewer discernable granules. Herein we report that a cross-reactive anti-human CD1a monoclonal antibody (clone O10) may be used in immunohistochemistry to identify canine MCTs of all grades. The antibody was applied to tissue sections from 48 canine MCTs of different histological grades. Serial sections from each tumour were stained with toluidine blue and safranin O to compare diagnostic sensitivity. All MCTs were labelled positively by the CD1a antibody, but histochemical staining was often equivocal and identification of mast cells was extremely difficult in some cases. This antibody did not label neoplastic cells in cases of canine histiocytoma, plasmacytoma or amelanotic melanoma; therefore, the reagent may be a valuable marker for the diagnosis of canine MCTs, especially those tumours of histological grade III.

Experimental infection of C3H/HeJ mice with the NY18 isolate of Anaplasma phagocytophilum.

Human granulocytic anaplasmosis (HGA), an emerging disease of public health concern in many areas of the world, is caused by Anaplasma phagocytophilum. Small animal models of A phagocytophilum in laboratory mice have been developed and used to study the pathogenesis of HGA. In this study, we characterized the pathologic changes in acute infection of C3H/HeJ mice experimentally infected with the NY18 isolate of A phagocytophilum. Although no clinical signs were noted, acute infection was associated with gross splenomegaly, microscopic inflammatory lesions in the lung and liver, hyperplastic lesions on the spleen, and clinical pathology abnormalities including neutropenia and monocytosis. This study emphasizes the use of well-defined animal models as a valuable tool for the study of A phagocytophilum infections.

Fatal ulcerative and hemorrhagic typhlocolitis in a pregnant heifer associated with natural bovine enterovirus type-1 infection.

One 2-year-old, 7.5 months pregnant Aberdeen Angus out of a herd of 100 apparently healthy cows, died within 10 hours of hospitalization. At necropsy, multiple foci of mucosal hemorrhage and ulceration were observed in the spiral colon and cecum. Virus isolation from intestinal lesions yielded a cytopathic virus, which was revealed by electron microscopy to be an approximately 27 nm, nonenveloped virus. Further characterization by reverse transcription-polymerase chain reaction (RT-PCR), sequencing of the 5'UTR and partial VP1 coding region, and phylogenetic analysis classified the virus isolate as bovine enterovirus type 1 (BEV-1). No other significant pathogens were detected. This is the first report of BEV-1 isolated in the USA from an animal with fatal enteric disease in more than 20 years. Further investigation is required to determine the prevalence of BEV in North America and to establish the clinical relevance of this understudied virus.

Bovine viral diarrhea virus type 2-induced meningoencephalitis in a heifer.

The brain from a 15-month-old, black female Angus, with a 48-hour history of central nervous system disease, was submitted to the Oklahoma Animal Disease Diagnostic Laboratory. Microscopic findings consisted of acute, multifocal meningoencephalitis, with neuronal degeneration and necrosis and gliosis. Viral isolation yielded noncytopathic bovine viral diarrhea virus (BVDV). Virus genotyping classified the virus as BVDV type 2. Immunohistochemical labeling for BVDV antigens with BVD MAb 3.12F1 clone was prominent in the cytoplasm of neurons, glial cells, ependymal epithelium, perivascular macrophages and spindle cells, smooth muscle cells, and intravascular monocytes of the cerebrum and brain stem. Laboratory results support that tissue alterations occurred as a result of BVDV type 2 infection. In the absence of other clinical signs related to BVDV infection and using the microscopic and laboratory evidence presented, we propose that the BVDV type 2 isolated from this case may represent a neurovirulent strain of the virus. To the best of our knowledge, this is the first report of brain lesions and neuronal viral antigen localization in BVDV genotype 2 viral infection, acquired either congenitally or postnatally.

Effects of an oral contraceptive combination with or without androgen on mammary tissues: a study in rats.

OBJECTIVES: Oral contraceptive (OC) therapy has long been known to produce hypoandrogenemia. However, androgens are not part of any OC therapy available to women. This project was designed to evaluate the effects of low-estradiol containing OC, with or without methyltestosterone (MT), on cell proliferation and progesterone receptor (PgR) expression in mammary gland epithelia of virgin female rats. METHODS: Sixty rats were divided into four groups. One group received OCs, whereas a second group received OC plus MT. A third group of rats was treated with an antiandrogen to mimic the hypoandrogenemic effects caused by OC therapy. All treated groups were compared with age-matched untreated controls. RESULTS: After 15 weeks of treatment, no inflammatory, precancerous, or cancerous lesions were observed in any treatment group. OC plus MT therapy caused significant suppression of epithelial proliferation, a reduction in the number of proliferating cell nuclear antigen-labeled cells, and an increase in the number of PgR-labeled cells. CONCLUSIONS: Our results suggest that a medication containing an estrogen-progestin-androgen combination has antiproliferative effects in mammary glands of experimental animals that could prove to have breast-protective potential in women.

Apoptosis, PCNA, and p53 in Fundulus grandis fish liver after in vivo exposure to N-methyl-N'-nitro-N-nitrosoguanidine and 2-aminofluorene.

Dysfunction in homeostatic mechanisms of cell death and proliferation are considered to be important in the pathogenesis of chemically induced neoplasia. p53 has been implicated in the regulation of cell death and proliferation. To determine whether expression of apoptosis, proliferating cell nuclear antigen (PCNA), and p53 differ between an alkylating agent and a polycyclic aromatic hydrocarbon, host response was measured through sequential immunohistochemical detection of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method), PCNA PC-10, and p53 (PAb 240) in livers of the fish Fundulus grandis. Nine hundred fish were randomly assigned to 3 groups of 300 fish each and kept in separate aquarium tanks. One group of fish was exposed to 6.7 microM N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1 group was exposed to 6.9 mM 2-aminofluorene (2-AF), and the remaining group served as a control. A significant decrease (p = 0.005) in the level of apoptosis and a significant increase (p < 0.0001) in the level of p53 were found on experimental day 180 in the livers of MNNG-exposed fish. PCNA was significantly increased (p < 0.005) by day 9 of the experiment in both MNNG and 2-AF fish when compared with controls, but no significant differences existed between the 2 groups of treated fish. Response of fish liver cells to MNNG-mediated and 2-AF-mediated injury differs, at least initially, in the expression of p53, inhibition of apoptosis, and increased net cell proliferation. Concurrent use of a marker for cell death with a marker of proliferation greatly enhances the assessment of the effect of these compounds on liver cells.

Ultrasound-assisted diagnosis of renal dysplasia in a 3-month-old Quarter Horse colt.

A 3-month-old foal was presented for correction of bilateral angular limb deformities. Azotemia was detected as an incidental finding. Small, misshapened, hyperechoic kidneys with decreased corticomedullary demarcation were noted with ultrasonography. Additionally, the internal renal architecture was abnormal in that the intrarenal vessels and distant collecting system were not clearly seen in either kidney. Ultrasound-guided renal biopsy was suggestive of congenital renal dysplasia, which was later confirmed at necropsy. Clinical, sonographic, and pathologic features of equine renal dysplasia are discussed.

Encephalitis, lymphoid tissue depletion and secondary diseases associated with bovine immunodeficiency virus in a dairy herd.

Encephalitis, lymphoid tissue depletion and secondary infections occurred over a 5-yr-period in Holstein cows infected with bovine immunodeficiency virus (BIV). There were 59 cattle studied, the majority during 1991, when a severe environmental stress occurred, each with one or more primary causes of death, natural or by euthanasia, and most with several secondary diseases. The encephalitis was characterized by meningeal, perivascular and parenchymal infiltration with lymphocytes, occasional plasma cells and macrophages with perivascular edema in some cows. Affected areas included the cerebrum, cerebellum, and spinal cord with no particular distribution pattern recognized. The lymphoid depletion was primarily an absence of follicular development in nodes draining regions with secondary infections such as chronic mastitis and chronic suppurative pododermatitis. Paucity of lymphocytes in thymic-dependent regions of lymph nodes and the spleen suggested a primary depletion of T cells. Secondary infections were often multiple with each cow having several minor conditions, usually considered short-term and treatable. These included mastitis and pododermatitis, with many cows having non-responding abscesses, cellulitis and myositis attributed to injection site infections. A large number of the cattle had parturition difficulties such as dystocia, obturator paralysis, and metritis. Pulmonary, cardiovascular, and intestinal disease were recognized as both primary and secondary disease conditions. There was a high level of infection with bovine leukemia virus with 4 of the 59 cattle having lymphosarcoma. Under practical conditions, the infection with BIV has a different effect on the host than has been observed under experimental conditions. The presence of BIV combined with the stresses associated with parturition and a modern dairy production system were considered causal for the development of untreatable secondary diseases in immunocompromised cattle. The peak incidence in 1991 was attributed to increased environmental stress during renovation of the barn facility. During this time the cattle were kept on open pasture, exposed to an extremely wet winter, and spring weather conditions. The effect of co-infection with bovine leukemia virus, the influence of immunocompromise on the chronicity of mastitis, the relationship with laminitis and pododermatitis, and several questions related to viral transmission, complementarism with bovine leukemia virus, viral reactivation and immunoprophylaxis all remain as viable avenues for future investigations.