Effective Prophylactic Therapy for Exposure to Monkey B Virus (Macacine alphaherpesvirus 1).

Zoonotic monkey B virus (Macacine alphaherpesvirus 1; BV) infections are extremely serious and usually fatal. Drugs currently used for treatment were developed for the treatment of herpes simplex virus but are less effective against BV. Effective suppression of viral replication in the skin could prevent the virus from invading the nervous system. To test this hypothesis, the efficacy of topical administration of several drugs against lethal BV infection was evaluated in female BALB/c mice that were infected by scarification. Drugs were then applied to the site of inoculation. As 3% preparations, most drugs were only minimally effective or ineffective. In contrast, ganciclovir and cidofovir were very effective. The ED50 for cidofovir was 0.007%, compared with 1.1% for ganciclovir. At 0.5%, cidofovir protected against both death and neurologic signs, whereas 5% ganciclovir only protected against death but not neurologic involvement. All genotypes of BV were equally susceptible to cidofovir and ganciclovir. For maximal effectiveness, treatment with both cidofovir and ganciclovir had to be initiated within 8 h of infection. Cidofovir was completely protective when administered only on the day of infection, whereas a minimum of 5 d of treatment was required for maximal ganciclovir efficacy. These studies showed that topical cidofovir treatment started soon after BV exposure was very effective in preventing BV from invading the nervous system, whereas ganciclovir treatment was only partially effective. In addition, cidofovir was protective against a ganciclovir-resistant BV mutant, whereas ganciclovir was not. These studies showed that topical cidofovir treatment started soon after BV exposure is more effective than ganciclovir in preventing BV from invading the CNS.

Metastatic disease in a dog with a well-differentiated perianal gland tumor.

Fine-needle aspirates from a perianal mass on an 8-year-old, intact male, Miniature Poodle presenting for tenesmus showed a uniform population of well-differentiated hepatoid cells with no notable criteria of malignancy. The cytologic diagnosis was a perianal gland tumor, with adenoma likely given the cytomorphology. The abdominal ultrasound revealed multiple, markedly enlarged, intra-abdominal lymph nodes. LN aspirates also showed well-differentiated polygonal, hepatoid cells displaying no notable cellular atypia. The presence of the metastasis led to the interpretation of a well-differentiated, malignant perianal gland tumor despite the benign cellular appearance. Histopathology of the surgically excised perianal mass and one enlarged abdominal lymph node revealed lobules of uniform polygonal hepatoid cells arranged in organized islands and trabeculae surrounded by a single layer of uniform reserve cells. Few mitotic figures were present. The only histopathologic indication of malignancy within the primary mass was the presence of small islands of well-differentiated hepatoid cells infiltrating into adjacent tissue and possible lymphatic invasion. The histopathologic diagnosis was perianal gland adenocarcinoma. Most textbooks describe perianal gland adenocarcinomas as showing increased cellular atypia including pleomorphism, disorganization of hepatoid cells, and increased numbers of pleomorphic reserve cells with mitotic figures. This case is an example of the occurrence of a well-differentiated perianal gland tumor with metastasis and highlights the importance of realizing that with these tumors, a benign cytologic and histologic appearance may not correlate with biologic behavior. To the authors' knowledge, this is the first case reporting both the cytologic and histologic appearance of a well-differentiated metastatic hepatoid gland tumor.

Congenital amelanotic melanoma in a crossbred heifer calf.

A large, pedunculated cutaneous mass protruding from the left flank fold and an enlarged left prefemoral lymph node were found on examination of a 3-d-old crossbred Aberdeen Angus heifer. The calf was asymptomatic aside from peripheral lymphadenopathy, and the mass, along with the left prefemoral lymph node, was surgically excised. Histologic examination of the mass and the lymph node revealed a homogeneous population of neoplastic cells that stained positively with immunohistochemical stains S100 and melan A, supporting a diagnosis of congenital amelanotic melanoma with nodal metastasis. Two months later, the calf became acutely recumbent and was euthanized after clinical examination revealed widespread metastasis. Gross autopsy revealed widely disseminated metastases that involved vertebral bodies, spinal cord, heart, kidneys, lungs, oral mucosa, multiple lymph nodes, and the marrow cavity of several long bones. Our case serves as a reminder that, although rare, congenital neoplasms occur in bovids and have the potential for aggressive, metastatic behavior.

Concurrent multiple myeloma and mast cell neoplasia in a 13-year-old castrated male Maine Coon cat.

A 13-year-old, castrated male Maine Coon cat was presented to Oklahoma State University Boren Veterinary Medical Teaching Hospital for yearly echocardiographic examination monitoring hypertrophic cardiomyopathy (HCM) diagnosed in 2003. Physical examination revealed a heart murmur and premature beats, likely related to HCM, but was otherwise unremarkable. A biochemistry profile revealed a hyperglobulinemia (6.3 g/dL). Cytologic examination of fine-needle aspirates from liver and spleen revealed increased numbers of plasma cells and mast cells, confirmed with subsequent histologic examination. Immunohistochemistry (IHC) for c-kit in the spleen and liver showed mast cells predominantly exhibiting type I staining pattern, with moderate numbers exhibiting type II pattern in spleen, and scattered cells exhibiting type II and III patterns in liver. Bone marrow cytology and core biopsy documented approximately 22% plasma cells. Cutaneous masses on the cat's left shoulder and right carpus were cytologically confirmed mast cell tumors. Serum protein electrophoresis with immunofixation confirmed an IgG monoclonal gammopathy. This is an example of 2 hematologic neoplasms occurring simultaneously in a cat. Concurrent pathologies may be overlooked if a single disease is diagnosed and suspected of causing all clinical signs. Both neoplasms were well differentiated, and neoplastic cells could have easily been interpreted as a reactive population had a full workup not been performed. Missing either diagnosis could result in a potentially lethal outcome. Eleven months after diagnoses, the cat was clinically doing well following a splenectomy and oral prednisolone and chlorambucil chemotherapy. Globulins decreased to 4.9 g/dL.

Efficacy of Bdellovibrio bacteriovorus 109J for the treatment of dairy calves with experimentally induced infectious bovine keratoconjunctivitis.

OBJECTIVE To determine the efficacy of Bdellovibrio bacteriovorus 109J for the treatment of calves with experimentally induced infectious bovine keratoconjunctivitis (IBK). ANIMALS 12 healthy dairy calves. PROCEDURES For each calf, a grid keratotomy was performed on both eyes immediately before inoculation with Moraxella bovis hemolytic strain Epp63-300 (n = 11 calves) or nonhemolytic strain 12040577 (1 calf). For each calf inoculated with M bovis Epp63-300, the eyes were randomly assigned to receive an artificial tear solution with (treatment group) or without (control group) lyophilized B bacteriovorus 109J. Six doses of the assigned treatment (0.2 mL/eye, topically, q 48 h) were administered to each eye. On nontreatment days, eyes were assessed and corneal swab specimens and tear samples were collected for bacterial culture. Calves were euthanized 12 days after M bovis inoculation. The eyes were harvested for gross and histologic evaluation and bacterial culture. RESULTS The calf inoculated with M bovis 12040577 did not develop corneal ulcers. Of the 22 eyes inoculated with M bovis Epp63-300, 18 developed corneal ulcers consistent with IBK within 48 hours after inoculation; 4 of those eyes developed secondary corneal ulcers that were not consistent with IBK. Corneal ulcer size and severity and the time required for ulcer healing did not differ between the treatment and control groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that B bacteriovorus 109J was not effective for the treatment of IBK; however, the experimental model used produced lesions that did not completely mimic naturally occurring IBK.

Thyroglossal Duct Carcinoma in a Cat.

A 14 yr old castrated domestic shorthair cat presented for a fluid-filled structure in the ventral cervical region that had been present for 1 yr and had not resolved after repeated aspiration and drainage. Cervical computed tomography showed an approximately 10 cm, fluid-filled, multilobulated mass located on the ventrolateral right side of the cervical region extending into the thoracic inlet. Cytologic examination of the fluid revealed cystic fluid with evidence of chronic hemorrhage. The mass was surgically removed, and histopathologic examination revealed a thyroglossal duct carcinoma. Thyroid and parathyroid gland origin were ruled out by negative immunohistochemical staining for thyroglobulin, parathyroid hormone, calcitonin, and synaptophysin. No adjunctive treatment was performed and no recurrence was noted at 14 mo. Thyroglossal duct carcinoma has not been previously reported in a cat. There are two previous reports of squamous cell carcinoma of the thyroglossal duct in dogs. In humans, with complete removal and no evidence of metastasis, carcinoma of the thyroglossal duct has a good prognosis for recovery.

Studies of Anaplasma phagocytophilum in sheep experimentally infected with the human NY-18 isolate: characterization of tick feeding sites.

Anaplasma phagocytophilum, transmitted by ticks of the genus Ixodes, was first described in Scotland as the agent of tick-borne fever in sheep and more recently as the cause of human granulocytic anaplasmosis in the U.S. and Europe. We previously reported sheep as an experimental host for the human NY-18 isolate of A. phagocytophilum. While clinical signs were not observed and infected granulocytes were not seen in stained blood smears, these sheep served as a good host for infection of ticks. In this research we characterized tick feeding sites to better understand tick/host/pathogen interactions. Ixodes scapularis adults were allowed to feed for 2 and 4 days on experimentally infected sheep, after which biopsies were taken beneath tick feeding sites for histopathology, PCR and immunohistochemistry (IHC) studies. In addition, the expression of selected immune response genes was studied in blood and feeding site biopsies. While necrosis was too advanced in 4-day biopsies for accurate cell counts, higher numbers of eosinophils and neutrophils were found in 2-day biopsies from infected sheep as compared with the uninfected controls. An unexpected result was the documentation of higher dermal inflammation in infected sheep at sites without ticks. A. phagocytophilum infected granulocytes were localized by immunohistochemistry (IHC) in skin biopsies using rabbit antibodies against the recombinant A. phagocytophilum major surface protein 4 as the primary antibody for indirect peroxidase-anti-peroxidase and fluorescent antibody IHC. These infected cells are likely to be the source of infection for ticks. Sheep therefore served as good hosts for studying host/pathogen/tick interactions of this human strain of A. phagocytophilum, and provided a means of producing infected ticks for future studies on tick/pathogen developmental and transmission cycles.

Percutaneous single-fiber reflectance spectroscopy of canine intervertebral disc: is there a potential for in situ probing of mineral degeneration?

BACKGROUND AND OBJECTIVES: Intervertebral disc herniation is a common disease in chondrodystrophic dogs, and a similar neurologic condition also occurs in humans. Percutaneous laser disc ablation (PLDA) is a minimally invasive procedure used increasingly for prevention of disc herniation. Currently, PLDA is performed on thoracolumbar discs with the same laser energy applied regardless of the differing extent of degeneration among mineralized discs. In a previous study performed on 15 normal and 6 degenerated intervertebral discs in chondrodystrophoid canine species, it was demonstrated that percutaneous single-fiber reflectance spectroscopy (SfRS) detected increased light scattering from mineralized intervertebral discs when comparing to normal discs. The objective of this study is to evaluate how SfRS evaluation of mineralized discs in situ fairs with X-ray radiography and computed tomography (CT) diagnoses and if SfRS sensing of the scattering changes correlates with the level of mineral degeneration in nucleus pulposus. MATERIALS AND METHODS: Percutaneous SfRS was performed on a total of 28 intervertebral discs of three dogs post-mortem, through a 20 gauge spinal needle standard to PLDA. The raw SfRS measurement was normalized to extract a dimension-less spectral intensity profile, from which the average over 600-900 nm was used as the SfRS intensity index to compare among the measured discs. The discs were imaged prior to percutaneous SfRS by radiography and CT, and harvested after percutaneous SfRS for histopathologic examinations. RESULTS: Five among 10 discs of dog #1, six among 9 discs of dog #2, and nine out of 9 discs of dog #3 were determined by histopathology to have central focal or multi-focal areas of mineralization occupying 5-75% of the examined area of nucleus pulposus. The overall numbers of discs with detectable and undetectable central mineralization were 20 and 8, respectively. CT resulted in one false positive (FP) and four false negative (FN) diagnoses for dog #1, three FP and zero FN diagnoses for dog #2, and zero FP and one FN diagnosis for dog #3. Of the total 28 discs the CT had an overall positive predictive value (PPV) of 78.8% and an overall negative predictive value (NPV) of 44.4%. X-ray radiography gave five FN diagnoses for dog #1, two FN diagnoses for dog #2, and eight FN diagnoses for dog #3. Of the total 28 discs the radiography had an overall PPV of 100% and an overall NPV of 30.4%. The receiver-operating-characteristic analysis of the SfRS measurement was performed on 24 discs that had a central mineralization not greater than 50%. An area-under-curve of 0.6758 infers that the SfRS intensity weakly indicates the level of mineralization. CONCLUSIONS: Percutaneous SfRS may be useful as an in situ sensing tool for assessing the level of mineral degeneration in intervertebral discs for the prospect of disc-specific dosage adjustment in PLDA.

Acute bronchointerstitial pneumonia in two indoor cats exposed to the H1N1 influenza virus.

OBJECTIVE: To describe 2 cases of acute bronchointerstitial pneumonia in indoor domestic cats infected by anthroponotic transmission of pandemic 2009 influenza A H1N1 virus from their owners. CASE SERIES SUMMARY: Two indoor domestic shorthair cats from the same household were evaluated for acute onset of respiratory distress. The owners had been recovering from flu-like illness at the time of presentation. Venous blood gas showed increased pvCO2 while thoracic radiographs revealed severe bronchointerstitial to alveolar patterns in both cats. The cats were treated with oxygen supplementation, antimicrobials, analgesics, diuretics, corticosteroids, bronchodilators, mechanical ventilation (1 cat), and supportive care. Despite initial improvement in the clinical condition of each cat, respiratory function deteriorated and ultimately both cats were euthanized. Gross and histopathologic examination confirmed diffuse, severe bronchointerstitial pneumonia. Pandemic 2009 influenza A H1N1 viral testing by real time PCR was positive in 1 cat. NEW OR UNIQUE INFORMATION PROVIDED: These cases provide further evidence that domestic felids are susceptible to pandemic 2009 influenza A H1N1 virus, and the literature is briefly reviewed for treatment recommendations. H1N1 should be considered in the differential diagnosis for domestic cats presenting with peracute to acute onset of respiratory distress in the right context. While human-to-cat transmission of H1N1 seems probable in several reported cases, cat-to-human transmission has not been identified.

Sheep experimentally infected with a human isolate of Anaplasma phagocytophilum serve as a host for infection of Ixodes scapularis ticks.

Anaplasma phagocytophilum, first identified as a pathogen of ruminants in Europe, has more recently been recognized as an emerging tick-borne pathogen of humans in the U.S. and Europe. A. phagocytophilum is transmitted by Ixodes spp., but the tick developmental cycle and pathogen/vector interactions have not been fully described. In this research, we report on the experimental infection of sheep with the human NY-18 isolate of A. phagocytophilum which then served as a host for infection of I. scapularis nymphs and adults. A. phagocytophilum was propagated in the human promyelocytic cell line, HL-60, and the infected cell cultures were then used to infect sheep by intravenous inoculation. Infections in sheep were confirmed by PCR and an Anaplasma-competitive ELISA. Clinical signs were not apparent in any of the infected sheep, and only limited hematologic and mild serum biochemical abnormalities were identified. While A. phagocytophilum morulae were rarely seen in neutrophils, blood film evaluation revealed prominent large granular lymphocytes, occasional plasma cells, and rare macrophages. Upon necropsy, gross lesions were restricted to the lymphoid system. Mild splenomegaly and lymphadenomegaly with microscopic evidence of lymphoid hyperplasia was observed in all infected sheep. Female I. scapularis that were allowed to feed and acquire infection on each of the 3 experimentally infected sheep became infected with A. phagocytophilum as determined by PCR of guts (80-87%) and salivary glands (67-100%). Female I. scapularis that acquired infection as nymphs on an experimentally infected sheep transmitted A. phagocytophilum to a susceptible sheep, thus confirming transstadial transmission. Sheep proved to be a good host for the production of I. scapularis infected with this human isolate of A. phagocytophilum, which can be used as a model for future studies of the tick/pathogen interface.

Gastric and enteric phytobezoars caused by ingestion of persimmon in equids.

CASE DESCRIPTION-13 equids (10 horses, 2 donkeys, and 1 pony) were examined for signs of colic (n = 7), weight loss (6), anorexia (3), and diarrhea (2). Ten equids were evaluated in the fall (September to November). Seven equids had a history of persimmon ingestion. CLINICAL FINDINGS-A diagnosis of phytobezoar caused by persimmon ingestion was made for all equids. Eight equids had gastric persimmon phytobezoars; 5 had enteric persimmon phytobezoars. Gastroscopy or gastroduodenoscopy revealed evidence of persimmon ingestion in 8 of 10 equids in which these procedures were performed. TREATMENT AND OUTCOME-2 of 13 equids were euthanatized prior to treatment. Supportive care was instituted in 11 of 13 equids, including IV administration of fluids (n = 8) and treatment with antimicrobials (5), NSAIDs (5), and gastric acid suppressants (4). Persimmon phytobezoar-specific treatments included dietary modification to a pelleted feed (n = 8); oral or nasogastric administration of cola or diet cola (4), cellulase (2), or mineral oil (2); surgery (4); and intrapersimmon phytobezoar injections with acetylcysteine (1). Medical treatment in 5 of 7 equids resulted in resolution of gastric persimmon phytobezoars. Seven of 8 equids with gastric persimmon phytobezoars and 1 of 5 equids with enteric persimmon phytobezoars survived > 1 year after hospital discharge. CLINICAL RELEVANCE-Historical knowledge of persimmon ingestion in equids with gastrointestinal disease warrants gastroduodenoscopy for evaluation of the presence of persimmon phytobezoars. In equids with gastric persimmon phytobezoars, medical management (including administration of cola or diet cola and dietary modification to a pelleted feed) may allow for persimmon phytobezoar dissolution.

Presence of hyperplastic pectoral mammary glands in a white-footed mouse (Peromyscus leucopus) from a Superfund Site in Oklahoma, USA.

Laboratory experiments have documented the effects of hormones and endocrine-disrupting compounds on mammary development in mammals. However, few observations of mammary hyperplasia have been presented for wild rodents. We describe hyperplastic mammary glands in a wild-caught white-footed mouse (Peromyscus leucopus) from an area contaminated with heavy metals.

Light and transmission electron microscopic characteristics of a novel Hepatozoon spp. in naturally infected cotton rats (Sigmodon hispidus).

A novel species of Hepatozoon was recently reported in cotton rats (Sigmodon hispidus) collected from an area of Oklahoma where American canine hepatozoonosis is endemic. In this study, the various stages of merogony of the parasite were characterized by light and electron microscopy. Meronts occurred within parasitophorous vacuoles in hepatocytes and ranged from mononucleated spherical forms to large, mature forms in vacuoles that contained approximately 50 peripherally arranged merozoites. Developing merozoites had characteristic apicomplexan organelles, including anterior and posterior polar rings, a conoid, microtubules, rhoptries, micronemes, and a trilaminar membrane. As the meronts matured, numerous curvilinear merozoites budded from a residual body. This morphologic characterization extends our understanding of this novel Hepatozoon and adds information about the hepatozoa, apicomplexan parasites that infect numerous species.

Clinical observations, biochemical data, and postmortem and histopathologic findings in young dairy calves fed zeolite clinoptilolite binder combined with milk replacer.

OBJECTIVE: To identify any adverse effects on health or performance in young dairy calves fed clinoptilolite mixed with milk replacer. ANIMALS: 26 male Holstein calves (1 to 7 days old). PROCEDURES: Twice daily for 28 days, calves were fed milk replacer with no clinoptilolite (control group; n=8), 0.5% clinoptilolite (low-dosage group; 9), or 2% clinoptilolite (high-dosage group; 9); each calf consumed approximately 12% of its body weight (based on the replacer solids in the milk replacer mixture)/d. For each calf, subjective health assessments, weight and rectal temperature measurements, and CBC and serum biochemical analyses were performed at intervals. All calves underwent necropsy. RESULTS: 2 calves were euthanized during the experiment because of bronchopneumonia or enteritis. Body weight and average daily gain did not differ among treatment groups. The percentage of monocytes and serum total protein concentration in the low-dosage group were higher than values in the control and high-dosage groups. Compared with values for either clinoptilolite-treated group, BUN concentration was greater in the control group. Serum globulin concentration differed significantly among groups (2.77, 2.50, and 2.36 g/dL in the low-dosage, control, and high-dosage groups, respectively). At necropsy, gross lesions associated with clinoptilolite treatment were not detected in any of the calves. CONCLUSIONS AND CLINICAL RELEVANCE: Even under stressful conditions, clinoptilolite fed at low or high dosages did not affect the performance of dairy calves and had no negative effect on WBC count and blood metabolite concentrations and enzyme activities. Clinoptilolite ingestion was not associated with treatment-specific gross changes.

Dendritic cell leukemia in a Golden Retriever.

An 8-year-old castrated male Golden Retriever was evaluated for decreased appetite, lethargy, and labored breathing of 1-week duration. Bilateral pulmonary infiltrates, hepatomegaly, and splenomegaly were present. Results of a CBC revealed marked leukocytosis (62,600/microL; reference interval 4000-15,500/microL) and large numbers of atypical cells (30,700/microL) with abundant cytoplasm. There was no concurrent anemia, neutropenia, or thrombocytopenia. Morphology of the atypical cells was most consistent with a histiocytic origin. Similar cells were identified in bone marrow aspirates, and were morphologically suggestive of the macrophage variant of disseminated histiocytic sarcoma. However, flow cytometry of the abnormal circulating cells revealed CD1c, CD11c, and major histocompatibility complex (MHC) Class II expression without expression of CD11d or lymphoid markers, consistent with myeloid dendritic antigen-presenting cells. At necropsy, the splenic architecture was effaced by neoplastic histiocytes that were also infiltrating lung, liver, an abdominal lymph node, myocardium, an bone marrow. Immunohistochemistry of the splenic neoplastic cells confirmed dendritic cell origin (CD1c+, CD11c+, MHC II+, no expression of CD11d and lymphoid markers). To the authors' knowledge, this is the first report of canine dendritic cell leukemia-in this instance accompanied by marked tissue infiltration.

Experimental transmission of Hepatozoon americanum to rodents.

Laboratory-raised cotton rats (Sigmodon hispidus), outbred white mice (Mus musculus), and C57BL/6J-Lystbg-J/J mice (M. musculus) that were administered approximately 50 sporulated oocysts of Hepatozoon americanum (AF176836) by gavage developed inflammatory lesions containing parasitic cystozoites in cardiac and skeletal muscle, kidney, and lung. Sprague-Dawley rats (Rattus norvegicus) similarly exposed showed no evidence of infection. Cystozoites were first detected by histopathologic examination four weeks after exposure to oocysts. Globular, PAS-positive material accumulated around the cystozoites as the duration of infection lengthened. Nested PCR analysis of tissues collected 16 weeks post-exposure was positive for the 18S rRNA Hepatozoon sp. gene and the DNA sequence of the fragment amplified was 99.6% and 99.8% identical to H. americanum sequences previously reported from naturally-infected dogs (AF176836 and AY864676, respectively). Merogonous and gamontogonous stages of the parasite were not detected in any of the cystozoite-infected rodents.