Upper Airway Obstruction Due to Primary Laryngeal Blastomycosis in a Dog.

A 9 yr old female spayed Labrador retriever presented for progressive dyspnea. Inspiratory stridor and inspiratory and expiratory dyspnea were present, consistent with an upper airway obstruction. A laryngeal exam revealed severe thickening of the arytenoid cartilages and masses associated with the arytenoids. A tracheostomy tube was placed, and the masses were biopsied. Histopathology showed pyogranulomatous inflammation secondary to Blastomyces dermatitidis. The dog was initially treated with amphotericin B and terbinafine in the hospital until the airway obstruction resolved and the tracheostomy tube could be removed. The dog experienced complete recovery after long-term treatment with itraconazole and terbinafine. This is the first report of laryngeal obstruction secondary to primary laryngeal blastomycosis in a dog. Blastomycosis should be considered for cases of obstructive laryngeal disease, and a good outcome can be achieved with antifungal treatment.

Bioavailability and biochemical effects of diclofenac sodium 0.1% ophthalmic solution in the domestic chicken (Gallus gallus domesticus).

OBJECTIVE: To determine if topical ophthalmic diclofenac sodium 0.1% solution alters renal parameters in the domestic chicken, and to determine if the drug is detectable in plasma after topical ophthalmic administration. ANIMALS: Thirty healthy domestic chickens. PROCEDURES: Over 7 days, six birds were treated unilaterally with one drop of artificial tear solution (group 1), 12 birds were treated unilaterally (group 2) and 12 bilaterally (group 3) with diclofenac sodium 0.1% ophthalmic solution. Treatments were provided every 12 h in all groups. Pre- and post-treatment plasma samples from all birds were evaluated for changes in albumin, total protein, and uric acid. Post-treatment samples of all birds, collected 15 min post-administration, were analyzed by high-performance liquid chromatography with mass spectrometry for diclofenac sodium detection. A randomly selected renal sample from each group was submitted for histopathologic review. RESULTS: Changes in pre- and post-treatment plasma albumin were significant (P < 0.05) in groups 2 and 3, but not for group 1. Pre- and post-treatment changes in total protein and uric acid were not significant for any group. Diclofenac sodium was not detectable (limit of detection = 0.10 ng/mL) in plasma samples from birds in group 1. Post-treatment concentration of diclofenac in group 3 was statistically greater than group 2 (P = 0.0008). Histopathologic changes did not identify diclofenac-induced acute renal tubular necrosis. CONCLUSIONS: Ophthalmic diclofenac sodium 0.1% administered topically every 12 h in one or both eyes for 7 days is detectable in systemic circulation in the domestic chicken, but does not cause overt significant changes in plasma uric acid or total protein.

Activation of autophagy and nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain-containing 3 inflammasome during Leishmania infantum-associated glomerulonephritis.

Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum-infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions. An ultrastructural evaluation of glomeruli from animals with VL identified mesangial cell proliferation and interposition. Immunohistochemistry demonstrated significant Leishmania antigen, IgG, and C3b deposition in VL dog glomeruli. Asymptomatic and symptomatic dogs had increased glomerular nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain containing 3 and autophagosome-associated microtubule-associated protein 1 light chain 3 associated with glomerular lesion severity. Transcriptional analyses from symptomatic dogs confirmed induction of autophagy and inflammasome genes within glomeruli and tubules. On the basis of temporal VL staging, glomerulonephritis was initiated by IgG and complement deposition. This deposition preceded presence of nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain containing 3-associated inflammasomes and increased light chain 3 puncta indicative of autophagosomes in glomeruli from dogs with clinical VL and renal failure. These findings indicate potential roles for inflammasome complexes in glomerular damage during VL and autophagy in ensuing cellular responses.

Targeted delivery of vitamin D to the colon using ß-glucuronides of vitamin D: therapeutic effects in a murine model of inflammatory bowel disease.

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D] has been shown to inhibit development of dextran sodium sulfate (DSS)-induced colitis in mice but can also cause hypercalcemia. The aim of this study was to evaluate whether ß-glucuronides of vitamin D could deliver 1,25(OH)(2)D to the colon to ameliorate colitis while reducing the risk of hypercalcemia. Initial studies demonstrated that bacteria residing in the lower intestinal tract were capable of liberating 1,25(OH)(2)D from 1,25-dihydroxyvitamin D(3)-25-ß-glucuronide [ß-gluc-1,25(OH)(2)D]. We also determined that a much greater upregulation of the vitamin D-dependent 24-hydroxylase gene (Cyp24) was induced in the colon by treatment of mice with an oral dose of ß-gluc-1,25(OH)(2)D than 1,25(OH)(2)D, demonstrating targeted delivery of 1,25(OH)(2)D to the colon. We then tested ß-glucuronides of vitamin D in the mouse DSS colitis model in two studies. In mice receiving DSS dissolved in distilled water and treated with 1,25(OH)(2)D or ß-gluc-1,25(OH)(2)D, severity of colitis was reduced. Combination of ß-gluc-1,25(OH)(2)D with 25-hydroxyvitamin D(3)-25-ß-glucuronide [ß-gluc-25(OH)D] resulted in the greatest reduction of colitis lesions and symptoms in DSS-treated mice. Plasma calcium concentrations were lower in mice treated with ß-gluc-1,25(OH)(2)D alone or in combination with ß-gluc-25(OH)D than in mice treated with 1,25(OH)(2)D, which were hypercalcemic at the time of death. ß-Glucuronides of vitamin D compounds can deliver 1,25(OH)(2)D to the lower intestine and can reduce symptoms and lesions of acute colitis in this model.

Use of terbinafine in the treatment protocol of intestinal Cryptococcus neoformans in a dog.

A 2.5 yr old sexually intact male vizsla was admitted to the Iowa State University Veterinary Teaching Hospital for persistent diarrhea, weight loss, and panhypoproteinemia. Examination revealed an emaciated condition and melena. Two masses were palpated in the cranial abdomen. Hematology and serum biochemistry exhibited a regenerative anemia and confirmed the presence of panhypoproteinemia, suggestive of a protein-losing eneteropathy. Distinct areas of thickened intestinal wall and enlarged mesenteric lymph nodes were found on abdominal ultrasound. Cytology from those nodes showed the presence of suspected Cryptococcus spp., and infection was confirmed utilizing a cryptococcal antigen titer. Medical therapy with lipid-complexed amphotericin B and fluconazole was unsuccessful. Two surgical procedures were performed to remove the affected areas of intestine and lymph nodes, but the disease persisted as evidenced by a persistently elevated cryptococcal antigen titer. Terbinafine was prescribed, which resulted in complete resolution of clinical signs and a steadily decreasing cryptococcal antigen titer. Very few cases of intestinal cryptococcosis have been reported. In this case, infection resulted in a protein-losing enteropathy. In addition, this article describes the use of terbinafine in the treatment of intestinal cryptococcal infection in the dog, which has not been previously reported.

Systemic calcinosis in a Quarter Horse gelding homozygous for a myosin heavy chain 1 mutation.

CASE DESCRIPTION: A 9-year-old Quarter Horse gelding was presented for lethargy, decreased appetite, polyuria and polydipsia (PU/PD), and severe muscle wasting suggestive of immune-mediated myositis. CLINICAL FINDINGS: The horse displayed lethargy, fever, tachyarrhythmia, inappetence, PU/PD, and severe epaxial and gluteal muscle wasting. Clinicopathologic findings were consistent with previously reported cases of systemic calcinosis in horses, including increased muscle enzyme activity, hyperphosphatemia, increased calcium-phosphorus product, hypoproteinemia, and an inflammatory leukogram. A diagnosis of systemic calcinosis was established by histopathologic evaluation of biopsy specimens from skeletal muscle, lung, and kidney. TREATMENT AND OUTCOME: Symptomatic treatment was complemented by IV treatment with sodium thiosulfate to reverse calcium-phosphate precipitation in soft tissue and PO aluminum hydroxide to decrease intestinal phosphorus absorption and serum phosphorus concentration. CLINICAL RELEVANCE: This is the first report in the veterinary literature of an antemortem diagnosis of systemic calcinosis in the horse that was successfully treated and had favorable long-term outcome.

Idiopathic eosinophilic meningoencephalomyelitis in a Rottweiler dog.

A 6-month-old, female, intact Rottweiler dog was presented to the Iowa State University Veterinary Teaching Hospital for a progressive history of abnormal behavior and generalized ataxia. At necropsy, there was eosinophilic infiltration of the brain and spinal cord, most severe in the medulla oblongata, cerebellum, and cervical spinal cord. Infiltrates of eosinophils were also present in the liver and small intestines. The dog was diagnosed with idiopathic eosinophilic meningoencephalomyelitis based on cerebrospinal fluid analysis, histopathology, and special stains to exclude etiologic agents.

A vascular hamartoma arising from the cervical spine of a cat.

A 15-month-old cat presented for evaluation of worsening generalized proprioceptive ataxia. Computed tomography of the cervical spine revealed the presence of a compressive extradural bony mass involving the dorsal aspect of C1. Surgical exploration and debulking of the mass was performed. Histological evaluation of the mass revealed fibrovascular tissue consistent with a vascular hamartoma. This mass was deemed to be originating from the soft tissue associated with the C1 vertebra with subsequent bony proliferation. Surgical debulking of the mass resulted in complete resolution of clinical signs with no evidence of recurrence 2 years after surgery.

Respiratory herpesvirus infection in two Indian Ringneck parakeets.

A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was imported to the United States from Australia. Soon after, 1 parakeet suddenly died, and a second parakeet died after a 2-day course of illness, which consisted of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds had diffuse consolidation and red discoloration of the lungs, as well as thickened, congested air sacs. The microscopic examination revealed multifocal, necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of the affected airways contained numerous, large syncytial cells with up to 15 nuclei. The nuclei of these syncytial cells often contained large, eosinophilic inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and air sacs was hypertrophied and contained syncytial cells with intranuclear inclusion bodies similar to the bronchi. In addition, a few intranuclear inclusion bodies were also present in the epithelial cells that line the air capillaries. On ultrastructural examination, the nuclei of degenerating epithelial cells contained clusters of viral nucleocapsid proteins and unenveloped, icosahedral, viral particles that were approximately 90 nm in diameter. In addition, some epithelial cells contained clusters of enveloped viral particles approximately 105 nm in diameter, within the cytocavitary network. These lesions are characteristic of those caused by respiratory herpesvirus of parakeets.

Unilateral uveitis in a dog with uveodermatologic syndrome.

CASE DESCRIPTION: A 7-year-old Siberian Husky-type dog with heterochromia irides was evaluated because of signs of pain associated with the right eye. CLINICAL FINDINGS: Unilateral panuveitis, iris bombé, and secondary glaucoma were detected in the right eye. Tear production was low bilaterally. Facial and truncal poliosis and vitiligo were also evident; skin biopsy specimens were obtained from the nasal planum. Uveodermatologic syndrome was diagnosed on the basis of histopathologic findings of a lichenoid interface dermatitis and pigmentary incontinence within the dermis. Immunohistochemical analysis was performed on skin samples retrospectively, and findings were inconclusive. TREATMENT AND OUTCOME: Treatment involved topical (ocular) and oral administration of corticosteroids, oral administration of azathioprine, and topical (ocular) administration of a carbonic anhydrase inhibitor and a lacrimostimulant. The secondary glaucoma was refractory to treatment, and the right eye was enucleated. Uveodermatologic syndrome was confirmed via histologic examination of ocular tissues. The left eye remained free of inflammation 16 months after the initial diagnosis. The periocular skin and skin of the nose partially regained pigment, but the hair did not. CLINICAL RELEVANCE: Some breeds in which uveodermatologic syndrome has been reported (eg, Siberian Huskies, Old English Sheepdogs, Australian Shepherds, and Shetland Sheepdogs) often have heterochromia irides. This case highlights the fact that dogs with asymmetric uveal pigmentation may have unilateral ocular changes; therefore, uveodermatologic syndrome should not be excluded as a differential diagnosis on the basis of unilateral clinical signs.

Actinobacillus capsulatus septicemia in a domestic rabbit (Oryctolagus cuniculus).

A 5-year-old pet rabbit (Oryctolagus cuniculus) died after a 3-day history of anorexia and depression. At necropsy, the stomach was distended with dough-like ingesta and hair consistent with gastric stasis syndrome. The lungs had multifocal, raised red nodules with circumferential hemorrhage. Microscopic examination showed pulmonary hemorrhage with intravascular fibrin thrombi and bacterial colonies, which were present in lesser amounts in the kidney, heart, and liver. Bacterial culture of the lung produced a heavy pure growth of Actinobacillus capsulatus. Acute septicemia is a novel presentation for this pathogen. This is the first documented case of A. capsulatus disease in the contiguous United States and may represent an underdiagnosed to emerging disease of lagomorphs.

Cytokine effects on maturation of the phagosomes containing Mycobacteria avium subspecies paratuberculosis in J774 cells.

Mycobacterium avium subspecies paratuberculosis (M. a. ptb) is an intracellular pathogen of macrophages. Intracellular survival of several species of pathogenic mycobacteria is dependent on inhibition of maturation of the phagosomes containing these pathogens into functional phagolysosomes. In activated macrophages, however, this capacity is reduced, leading to increased bacterial killing. It is the hypothesis of this study that there is increased acidification and maturation of the phagosome containing M. a. ptb in interferon gamma and lipopolysaccharide (IFN-gamma/LPS) activated macrophages. In activated macrophages colocalization of M. a. ptb with either a marker of acidic compartments (Lysotracker Red) or compartments containing a late phagosome maturation marker lysosome-associated membrane protein-1 (Lamp-1) were evaluated by laser confocal microscopy. Intracellular survival of M. a. ptb in activated macrophages was evaluated directly using differential fluorescent live/dead staining. The results of this study demonstrated increased colocalization of both Lysotracker Red and Lamp-1 with FITC labeled M. a. ptb, which correlated with decreased survival of M. a. ptb within activated macrophages.

Disseminated T-cell lymphoma in a bonobo (Pan paniscus).

Disseminated lymphoma was diagnosed in an 8-year-old male bonobo (Pan paniscus). The male bonobo presented with a 4-6 week history of dyspnea and facial swelling around the eyes; thoracic radiographs and computed tomography scan indicated a craniodorsal mediastinal soft tissue mass. Upon gross examination, there was a large, cream to white mass expanding the mediastinum and pericardial sac. The mass extended along the thoracic aorta and cranial vena cava, through the thoracic inlet, along and encircling the trachea, and bilaterally into the thyroid glands. Microscopically, neoplastic lymphocytes were present in the thymus, trachea, lungs, kidney, heart, and numerous other tissues. Immunohistochemical staining of neoplastic lymphocytes revealed diffuse immunoreactivity for cluster of differentiation (CD)3 indicating T-cell lymphoma. Routine viral screening was negative via polymerase chain reaction.

Lymphoid hyperplasia resulting in immune dysregulation is caused by porcine reproductive and respiratory syndrome virus infection in neonatal pigs.

Amid growing evidence that numerous viral infections can produce immunopathology, including nonspecific polyclonal lymphocyte activation, the need to test the direct impact of an infecting virus on the immune system of the host is crucial. This can best be tested in the isolator piglet model in which maternal and other extrinsic influences can be excluded. Therefore, neonatal isolator piglets were colonized with a benign Escherichia coli, or kept germfree, and then inoculated with wild-type porcine reproductive and respiratory syndrome virus (PRRSV) or sham medium. Two weeks after inoculation, serum IgM, IgG, and IgA levels were 30- to 50-, 20- to 80-, and 10- to 20-fold higher, respectively, in animals receiving virus vs sham controls, although <1% was virus specific. PRRSV-infected piglets also had bronchial tree-associated lymph nodes and submandibular lymph nodes that were 5-10 times larger than colonized, sham-inoculated animals. Size-exclusion fast performance liquid chromatography revealed that PRRSV-infected sera contained high-molecular-mass fractions that contained IgG, suggesting the presence of immune complexes. Lesions, inflammatory cell infiltration, glomerular deposits of IgG, IgM, and IgA, and Abs of all three isotypes to basement membrane and vascular endothelium were observed in the kidneys of PRRSV-infected piglets. Furthermore, autoantibodies specific for Golgi Ags and dsDNA could be detected 3-4 wk after viral inoculation. These data demonstrate that PRRSV induces B cell hyperplasia in isolator piglets that leads to immunologic injury and suggests that the isolator piglet model could serve as a useful model to determine the mechanisms of virus-induced immunopathology in this species.