An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs.

Sudden cardiac death in the young (SCDY) is a devastating event that often has an underlying genetic basis. Manchester Terrier dogs offer a naturally occurring model of SCDY, with sudden death of puppies as the manifestation of an inherited dilated cardiomyopathy (DCM). We performed a genome-wide association study for SCDY/DCM in Manchester Terrier dogs and identified a susceptibility locus harboring the cardiac ATP-sensitive potassium channel gene ABCC9. Sanger sequencing revealed an ABCC9 p.R1186Q variant present in a homozygous state in all SCDY/DCM-affected dogs (n = 26). None of the controls genotyped (n = 398) were homozygous for the variant, but 69 were heterozygous carriers, consistent with autosomal recessive inheritance with complete penetrance (p = 4 × 10-42 for the association of homozygosity for ABCC9 p.R1186Q with SCDY/DCM). This variant exists at low frequency in human populations (rs776973456) with clinical significance previously deemed uncertain. The results of this study further the evidence that ABCC9 is a susceptibility gene for SCDY/DCM and highlight the potential application of dog models to predict the clinical significance of human variants.

Lymphomatosis as a Cause of Abdominal Pain and Distension in Two Adult Horses.

Two equine patients presented separately with severe abdominal distention, colic, lethargy, and decreased appetite. An ante-mortem diagnosis of lymphoma was reached in each case based on peritoneal fluid cytology. Due to a poor prognosis, the horses were humanely euthanized. Post-mortem examination with histology and immunohistochemistry confirmed both cases as lymphoma: alimentary B-cell lymphoma of the distal jejunum and cecum in one case, and T-cell lymphoma of the cecum in the second case. Both cases exhibited extensive metastasis with peritoneal and pleural serosae covered in small nodules and plaque like masses consistent with lymphomatosis. These cases document a unique presentation of lymphoma in equine patients presenting as peritoneal lymphomatosis with ascites.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Evaluation of serum MMP-2 and MMP-3, synovial fluid IL-8, MCP-1, and KC concentrations as biomarkers of stifle osteoarthritis associated with naturally occurring cranial cruciate ligament rupture in dogs.

The purpose of this study was to evaluate matrix metalloproteinases (MMP) -2 and MMP-3 in serum, and keratinocyte-derived chemoattractant (KC), interleukin 8 (IL-8) and monocyte chemoattractant 1 (MCP-1) in synovial fluid (SF) as stifle osteoarthritis (OA) biomarkers in dogs. Dogs with naturally occurring cranial cruciate ligament (CrCL) rupture (OA group) and healthy controls were recruited. Stifles with CrCL deficiency were surgically stabilized. Serum, SF, and synovial biopsy samples were collected from the OA group preoperatively, whereas samples were collected once from control dogs. A blinded veterinary pathologist graded synovial biopsies. Serum and SF analyses were performed using xMAP technology. General linear regression was used for statistical comparisons of serum biomarkers, and mixed linear regression for SF biomarkers and temporal concentration changes. The overall discriminative ability was quantified using area under curve (AUC). Spearman's correlation coefficient was used to assess correlations between synovial histology grades and the biomarkers. Samples from 62 dogs in the OA group and 50 controls were included. The MMP-2 and MMP-3 concentrations between the OA and control groups were not significantly different, and both with an AUC indicating a poor discriminative ability. All three SF biomarker concentrations were significantly different between the OA group and controls (P <0.05). The MCP-1 was the only biomarker showing an acceptable discriminative performance with an AUC of 0.91 (95% confidence interval: 0.83-0.98). The sum of the inflammatory infiltrate score was significantly correlated with all three SF biomarkers (P <0.01). Summed synovial stroma, and all scores combined were significantly correlated with IL-8 and MCP-1 concentrations (P <0.003), and the summed synoviocyte scores were significantly correlated with MCP-1 concentrations (P <0.001). Correlations between MCP-1 concentrations and synovial histopathologic grading and its discriminative ability suggest its potential as a synovitis biomarker in canine stifle OA associated with CrCL rupture.

Malignant Mesothelioma of the Vaginal Tunic and Peritoneum in a Young Stallion.

Mesothelioma is a rare malignancy in horses. This report describes a case in which marked hemoperitoneum, moderate anemia, and moderate dependent edema were the presenting clinical signs in a 2-year-old Standardbred stallion with mesothelioma of the vaginal tunic. On necropsy, approximately 40 L of dark red fluid distended the abdomen. A dark red mass infiltrated and effaced the right pampiniform plexus, and red nodular masses were present multifocally on the parietal and visceral peritoneal surfaces. Histopathologically, the masses were composed of malignant spindle cells with a sarcomatoid appearance. Using immunohistochemistry, tumor cells were cytokeratin and vimentin positive and factor VIII-related antigen negative: compatible with a diagnosis of mesothelioma. This is the first report of mesothelioma arising from the vaginal tunic of a horse with subsequent spread to the peritoneum. This case adds additional information regarding the clinical presentation and behavior of mesothelioma originating from the vaginal tunic in horses.

Absolute polycythemia in a bald eagle (Haliaeetus leucocephalus).

An approximately 6-mo-old female bald eagle (Haliaeetus leucocephalus) was presented for an inability to fly and bilateral drooped wings. Pectoral muscle atrophy with a moderate polycythemia was present. Over the course of 3 wk, there were no improvements in flight capacity, although the bird gained substantial weight. Further investigation revealed a prominent cyanosis that was responsive to oxygen therapy, a chronic respiratory acidosis with hypoxia, a cardiac murmur, and a persistent polycythemia. No obvious antemortem etiology for the clinical findings was discovered on computerized tomography, angiography, or echocardiography. The bird was euthanatized as a result of the poor prognosis. Necropsy and histopathology revealed no significant cardiovascular or pulmonary pathology. No myopathy was evident on electron microscopy of formalin-fixed tissues. Based on these diagnostics, a neuromuscular disorder is suspected as the cause for the blood gas abnormalities, with a resulting polycythemia from the hypoxia.

Septic peritonitis and uroperitoneum secondary to subclinical omphalitis and concurrent necrotizing cystitis in a colt.

A 15-day-old American Quarter horse colt was presented for depression and pyrexia. Peritonitis was diagnosed following peritoneal fluid analysis. Exploratory laparotomy revealed an area of focal necrosis over the dorsal wall of the urinary bladder leading to peritonitis and uroperitoneum. The affected area of the urinary bladder was resected and the peritonitis resolved with medical treatment.

Comparison of bacterial culture, histopathology, and immunohistochemistry for the diagnosis of Johne's disease in culled dairy cows.

Paired samples of formalin-fixed, paraffin-embedded ileum and lymph node from 204 culled dairy cows were investigated for evidence of infection by Mycobacterium avium subsp. paratuberculosis. Of the samples, 151 were from animals that were tissue-culture positive for M. avium subsp. paratuberculosis, and 53 were from animals that were tissue and fecal culture negative. From the culture-positive animals, M. avium subsp. paratuberculosis was isolated from 78 samples of ileum and from 107 samples of lymph node. Ziehl-Neelsen acid-fast and immunoperoxidase stained slides were examined for 15 minutes each. Acid-fast organisms were identified in 7 of 78 (8.97%) and 6 of 106 (5.61%) culture-positive ileum and lymph node samples, respectively. Immunohistochemical (IHC) analysis of the same tissues identified infection in the ileum of 9 of 78 (11.54%) and in the lymph node of 5 of 106 (4.67%) culture-positive tissues. All tissues from culture-negative animals tested negative when using acid-fast and IHC staining. The sensitivity of these 2 tests in detecting M. avium subsp. paratuberculosis in culled dairy cows was not significantly different, and the tests exhibited substantial to almost perfect agreement. Both tests were much less sensitive than bacterial culture, detecting less than 6% of tissues positive compared with culture.

Intracranial meningioma causing internal ophthalmoparesis in a dog.

A 10-year-old, spayed female, Irish water spaniel was presented with a 2-week history of anisocoria characterized by mydriasis of the right eye compared to the left eye in ambient light. Ophthalmic and neurological examinations, combined with pharmacological testing, identified a disease process affecting the right parasympathetic nucleus of cranial nerve 3 (CN III) and/or the parasympathetic component of CN III. Magnetic resonance imaging (MRI) identified a mass involving the right midbrain and extending caudally to the rostral border of the medulla oblongata. The dog became comatose within 12 h following MRI and was euthanized. Histopathology identified the intracranial mass as a meningioma.