Autosomal recessive hyposegmentation of granulocytes in Australian Shepherd Dogs indicates a role for LMBR1L in myeloid leukocytes.

Pelger-Huët anomaly (PHA) in humans is an autosomal dominant hematological phenotype without major clinical consequences. PHA involves a characteristic hyposegmentation of granulocytes (HG). Human PHA is caused by heterozygous loss of function variants in the LBR gene encoding lamin receptor B. Bi-allelic variants and complete deficiency of LBR cause the much more severe Greenberg skeletal dysplasia which is lethal in utero and characterized by massive skeletal malformation and gross fetal hydrops. HG phenotypes have also been described in domestic animals and homology to human PHA has been claimed in the literature. We studied a litter of Australian Shepherd Dogs with four stillborn puppies in which both parents had an HG phenotype. Linkage analysis excluded LBR as responsible gene for the stillborn puppies. We then investigated the HG phenotype in Australian Shepherd Dogs independently of the prenatal lethality. Genome-wide association mapped the HG locus to chromosome 27 and established an autosomal recessive mode of inheritance. Whole genome sequencing identified a splice site variant in LMBR1L, c.191+1G>A, as most likely causal variant for the HG phenotype. The mutant allele abrogates the expression of the longer X2 isoform but does not affect transcripts encoding the shorter X1 isoform of the LMBR1L protein. The homozygous mutant LMBR1L genotype associated with HG is common in Australian Shepherd Dogs and was found in 39 of 300 genotyped dogs (13%). Our results point to a previously unsuspected function of LMBR1L in the myeloid lineage of leukocytes.

Association of results of the glutaraldehyde coagulation test with plasma acute phase protein concentrations and hematologic findings in hospitalized cows.

Introduction: The glutaraldehyde test (GAT) allows for animal-side semi-quantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. Methods: For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. Results: Shortened GAT coagulation times were more closely correlated to serum globulin (rs = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = -0.64) and the Clauss method (rs = -0.70). Cows with a markedly (≤3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of ≤14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. Discussion: In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative.

Development and validation of an ELISA to measure regenerating island-derived protein 3E in canine blood.

BACKGROUND: Regenerating island-derived proteins (REG) are upregulated in people with sepsis, pancreatitis, and gastrointestinal diseases. One member of the REG family, namely REG3E, was recently identified in pancreatic tissue and plasma of dogs, with high expression in pancreatitis and sepsis. OBJECTIVES: We aimed to develop and validate an ELISA to measure REG3E concentrations in canine blood. METHODS: An indirect sandwich ELISA was developed using recombinant canine REG3E protein and polyclonal anti-canine REG3E antibodies raised in guinea pigs and rabbits. Antibody specificity was assessed using western blot and mass spectrometric analysis of protein purified from canine plasma. Assay validation included evaluation of dilutional linearity, parallelism, spiking recovery, repeatability and reproducibility, stability, interferences, and comparison of serum and heparinized plasma. RESULTS: Antibodies bound specifically to REG3E with no evidence of cross-reactivity with other proteins. The limit of detection of the ELISA was 15 ng/mL, and the lower limit of quantification was 30 ng/mL. The assay demonstrated good to excellent linearity, dilutional and mixing parallelism, and recovery, with mean observed-to-expected ratios of 104%, 107%, 102%, and 92%, respectively, and no evidence of a hook effect. Coefficients of variation were ≤8.5% for repeatability and ≤14.3% for reproducibility at three different levels. Measurements of REG3E in plasma were not significantly influenced by different storage conditions, freeze-thawing cycles, hemolysis, lipemia, or icterus. There was no significant difference between REG3E concentrations in heparinized plasma and serum samples. CONCLUSIONS: The canine REG3E ELISA has acceptable precision, accuracy, linearity, and reproducibility for the measurement of REG3E in canine plasma and serum.

Hyperlipasemia in dogs with acute kidney injury treated with and without hemodialysis.

BACKGROUND: Hyperlipasemia has been reported in dogs with acute kidney injury (AKI) but associations with AKI severity, hemodialysis (HD) treatment, and outcome have not been extensively evaluated. OBJECTIVES: Investigate the prevalence and clinical relevance of hyperlipasemia in dogs with AKI, treated with and without HD. ANIMALS: Client-owned dogs (n = 125) with AKI. METHODS: Retrospective data extraction from medical records, including signalment, cause of AKI, duration of hospitalization, survival, plasma creatinine concentration, and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methyresorufin) ester (DGGR) lipase activity at admission and throughout hospitalization. RESULTS: A DGGR-lipase activity >3× the upper reference limit (URL) was found in 28.8% and 55.4% of dogs at admission and during hospitalization, respectively, but only 8.8% and 14.9% of dogs, respectively, were diagnosed with acute pancreatitis. Hyperlipasemia >10 × URL was observed in 32.7% of dogs during hospitalization. The DGGR-lipase activity was higher in dogs with International Renal Interest Society (IRIS) Grades 4-5 than Grades 1-3, but correlation between DGGR-lipase activity and creatinine concentration was poor (rs = .22; 95% confidence intervals [CI], 0.04-0.38). Treatment with HD was not associated with DGGR-lipase activity independent of IRIS grade. Survival to discharge and 30 days after admission was 65.6% and 59.6%, respectively. High IRIS grades (P = .03) and high DGGR-lipase activity at admission (P = .02) and during hospitalization (P = .003) were associated with nonsurvival. CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperlipasemia is frequent and often marked in dogs with AKI despite only a minority being diagnosed with pancreatitis. Hyperlipasemia is associated with AKI severity but not independently with HD treatment. High IRIS grade and hyperlipasemia were associated with nonsurvival.

Concentrations and kinetics of renal biomarkers in dogs with gastric dilatation-volvulus with and without 24-h intravenous lidocaine.

Background: Gastric dilatation volvulus (GDV) can lead to organ failure including acute kidney injury (AKI). Due to its cytoprotective, antioxidant and anti-inflammatory effects, lidocaine has a potential to prevent AKI in dogs with GDV. Design and setting: Prospective, observational cohort study in client-owned dogs with GDV. Objective: To determine concentrations of renal biomarkers for AKI in dogs with GDV with and without intravenous (IV) lidocaine therapy. Methods: Thirty-two dogs were randomized to receive either IV lidocaine (2 mg/kg, followed by a lidocaine constant rate infusion at a dose of 50 µg/kg/min over 24 h; n = 17) or no lidocaine (n = 15). Blood and urine samples were taken at admission (T 0) (only blood), during or immediately after surgery (T 1), and 24 (T 24) and 48 (T 48) h after surgery. Plasma creatinine (pCr), plasma neutrophil gelatinase-associated lipocalin (pNGAL), urinary NGAL (uNGAL), uNGAL to creatinine ratio (UNCR), and urinary gamma-glutamyl transferase to creatinine ratio (uGGT/uCr) were evaluated. Biomarker concentrations were compared between dogs with and without IV lidocaine and the course of each marker was determined in comparison to its admission value. Results: In the entire population, a significantly higher pCr at T 0 (median, 95 µmol/L, interquartile range, 82-105) compared with T 1 (69 µmol/L, 60-78), T 24 (63 µmol/L, 52-78), and T 48 (78 µmol/L, 65-87) (P < 0.001) was found. Plasma NGAL increased significantly between T 0 (5.66 ng/mL, 3.58-7.43) and T 24 (7.50 ng/mL, 4.01-11.89) (P = 0.006) and T 48 (9.86 ng/mL, 5.52-13.92) (P < 0.001), respectively. Urinary NGAL increased significantly between T 1 (0.61 ng/mL, 0.30-2.59) and T 24 (2.62 ng/mL, 1.86-10.92) (P = 0.001) and T 48 (4.79 ng/mL, 1.96-34.97 (P < 0.001), respectively. UNCR increased significantly between T 1 (0.15 µg/mmol, 0.09-0.54) and T 24 (1.14 µg/mmol, 0.41-3.58) (P = 0.0015) and T 48 (1.34 µg/mmol, 0.30-7.42) (P < 0.001), respectively. Concentrations of uGGT/uCr increased significantly from T 0 highest at T 24 (6.20 U/mmol, 3.90-9.90) and significantly decreased at T 48 (3.76 U/mmol, 2.84-6.22) (P < 0.001). No significant differences in any renal biomarker concentration were found between dogs with and without IV lidocaine therapy. Conclusion and clinical relevance: Plasma NGAL, uNGAL and UNCR remained increased up to 48 h post-surgery. No evidence of lidocaine-associated renoprotection was found.

Inflammatory biomarker concentrations in dogs with gastric dilatation volvulus with and without 24-h intravenous lidocaine.

Background: Canine gastric dilatation volvulus (GDV) is characterized by tissue ischemia, reperfusion, and systemic inflammation. Evidence exists that lidocaine exerts anti-inflammatory properties and potentially improves outcome. Design and setting: Prospective, randomized observational cohort study in client-owned dogs with GDV. Objective: The primary objective of the study was the determination of pro- and anti-inflammatory biomarker concentrations in dogs with GDV with and without intravenous (IV) lidocaine therapy. The second objective was the evaluation of side effects of lidocaine. Methods: Of 35 dogs included in the study, 20 dogs were assigned to receive lidocaine (LIDO) (2 mg/kg initially, followed by a continuous infusion at a rate of 50 µg/kg/min over 24 h) and 15 dogs not to receive lidocaine (NO-LIDO). Plasma concentrations of cytokines interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma, keratinocyte chemotactic-like, monocyte chemotactic protein, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, T0), immediately after surgery (T1), at 24 h (T24), and at 48 h (T48) post-surgery. Results: No significant differences in concentrations of any cytokines were found between the LIDO- and the NO-LIDO group. Significant lower CRP concentrations (median [range]) were found in dogs with lidocaine compared to dogs without at T24 (97.5 pg/mL [46.3-161.7] vs. 127.9 pg/mL [26.9-182.0]; p = 0.046) and T48 (73.7 pg/mL [18.4-169.4] vs. 116.3 pg/mL [71.4-176.8]; p = 0.002). Dogs receiving lidocaine exhibited significantly impaired mentation, a prolonged period of anorexia, and longer hospitalization compared to dogs without lidocaine. Conclusion: Lidocaine administration had no impact on the plasma levels of cytokines during the 48-h study period, but significantly lower CRP concentrations were found at T24 and T48. Lidocaine's potential side effects require careful decision making regarding its use.

MOCOS-associated renal syndrome in a Brown Swiss cattle.

BACKGROUND: A recessive form of MOCOS-associated xanthinuria type II is described in Tyrolean grey cattle. A similar case was identified in a 5-month-old Brown Swiss calf with hoof overgrowth, rough coat, urine sediment, and pneumonia. HYPOTHESIS/OBJECTIVES: To characterize the disease phenotype, to evaluate its genetic etiology, and to determine the prevalence of the deleterious allele in the Brown Swiss population. ANIMALS: An affected calf, its parents, and 65 441 Swiss dairy cattle. METHODS: The affected animal was clinically examined and necropsied. Microarray genotyping was used to determine the genotypes and to assess the frequency of the MOCOS allele in a Brown Swiss control cohort. RESULTS: Ultrasonography revealed hyperechoic renal pyramids with multifocal distal shadowing and echogenic sediment in the urinary bladder. Necropsy revealed suppurative bronchopneumonia and urolithiasis. Histology revealed numerous nephroliths with multifocal chronic lymphohistiocytic interstitial infiltrates, fibrosis, tubular degeneration, chronic multifocal glomerulonephritis with sclerosis, and bilateral hydronephrosis. Dysplastic changes were observed in the corium of the claw and the cornea. Genetic testing identified the homozygous presence of a known MOCOS frameshift variant in the case. Both parents were heterozygous and the prevalence of carriers in genotyped Brown Swiss cattle was 1.4% (342/24337). CONCLUSIONS AND CLINICAL IMPORTANCE: The findings were consistent with the diagnosis of a recessive renal syndrome similar to xanthinuria type II described in Tyrolean grey cattle. The prevalence of the deleterious MOCOS allele is low in the Brown Swiss breed. However, mating of carriers should be avoided to prevent further losses.

Accuracy of 1,2-o-Dilauryl-rac-glycero-3-glutaric Acid-(6'-methylresorufin) Ester (DGGR)-Lipase to Predict Canine Pancreas-Specific Lipase (cPL) and Diagnostic Accuracy of Both Tests for Canine Acute Pancreatitis.

Different lipase assays have variable reported diagnostic accuracies for acute pancreatitis (AP) in dogs. The aims of this retrospective study were to evaluate optimal cutoffs for 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR)-lipase to predict diagnostic cutoffs of canine pancreas-specific lipase (cPL; IDEXX). DGGR-lipase activity and cPL from the same blood draw in 301 dogs with a variety of diseases were compared using Spearman's rank correlation, Cohen's kappa agreement, and receiver operating characteristic (ROC) curves. Activity of DGGR-lipase (10−15,616 U/L) and cPL concentrations (8.1−≥2000 µg/L) were highly correlated (rs = 0.91). Areas under the ROC curves (AUCs) to predict cPL >200 and ≥400 µg/L with DGGR-lipase were 0.97 and 0.99, with optimal cutoffs of 143 U/L (sensitivity (Se) 91.7%; specificity (Sp) 95.3%) and 205 U/L (Se 97.5%; Sp 96.4%), and Cohen's kappa agreements of 0.87 and 0.92, respectively. AUCs for a clinical diagnosis of AP, assigned to 87/301 dogs, with DGGR-lipase (0.75) and cPL (0.76) did not differ significantly (p = 0.48); optimal cutoffs were 161 U/L for DGGR (Se 67%; Sp 81%) and 235 µg/L for cPL (Se 68%; Sp 84%). To conclude, DGGR-lipase is a highly accurate predictor of cPL with a comparable performance when used to diagnose AP in dogs.

Single-cell gene expression analysis of cryopreserved equine bronchoalveolar cells.

The transcriptomic profile of a cell population can now be studied at the cellular level using single-cell mRNA sequencing (scRNA-seq). This novel technique provides the unprecedented opportunity to explore the cellular composition of the bronchoalveolar lavage fluid (BALF) of the horse, a species for which cell type markers are poorly described. Here, scRNA-seq technology was applied to cryopreserved equine BALF cells. Analysis of 4,631 cells isolated from three asthmatic horses in remission identified 16 cell clusters belonging to six major cell types: monocytes/macrophages, T cells, B/plasma cells, dendritic cells, neutrophils and mast cells. Higher resolution analysis of the constituents of the major immune cell populations allowed deep annotation of monocytes/macrophages, T cells and B/plasma cells. A significantly higher lymphocyte/macrophage ratio was detected with scRNA-seq compared to conventional cytological differential cell count. For the first time in horses, we detected a transcriptomic signature consistent with monocyte-lymphocyte complexes. Our findings indicate that scRNA-seq technology is applicable to cryopreserved equine BALF cells, allowing the identification of its major (cytologically differentiated) populations as well as previously unexplored T cell and macrophage subpopulations. Single-cell gene expression analysis has the potential to facilitate understanding of the immunological mechanisms at play in respiratory disorders of the horse, such as equine asthma.

Identification of regenerating island-derived protein 3E in dogs.

Regenerating islet-derived protein (REG) 1A (aka pancreatic stone protein) and REG3A (aka pancreatitis-associated protein) are upregulated in humans with sepsis, pancreatitis, and gastrointestinal diseases, but little is known about this protein family in dogs. Our aim was to identify REG1 and REG3 family members in dogs. REG-family genes were computationally annotated in the canine genome and proteome, with verification of gene expression using publicly available RNA-seq data. The presence of the protein in canine pancreatic tissue and plasma was investigated with Western blot and immunohistochemistry, using anti-human REG1A and REG3A antibodies. Protein identity was confirmed with mass spectrometry. Two members of the REG3 subfamily were found in the canine genome, REG3E1 and REG3E2, both encoding for the same 176 AA protein, subsequently named REG3E. Anti-human REG3A antibodies demonstrated cross-reactivity with the canine REG3E protein in pancreas homogenates. In canine plasma, a protein band of approximately 17 kDa was apparent. Mass spectrometry confirmed this protein to be the product of the two annotated REG3E genes. Strong immunoreactivity to anti-human REG3A antibodies was found in sections of canine pancreas affected with acute pancreatitis, but it was weak in healthy pancreatic tissue. Recombinant canine REG3E protein underwent a selective trypsin digestion as described in other species. No evidence for the presence of a homolog of REG1A in dogs was found in any of the investigations. In conclusion, dogs express REG3E in the pancreas, whose role as biomarker merits further investigations. Homologs to human REG1A are not likely to exist in dogs.

Kinetics of Plasma Cytokines, Angiopoietin-2, and C-Reactive Protein in Dogs With Gastric Dilatation Volvulus.

Background: The degree of systemic inflammation, reperfusion injury and endothelial activation are potentially important determinants of clinical outcomes in dogs with gastric dilatation volvulus (GDV). Objective: To evaluate plasma concentrations and kinetics of inflammatory markers in dogs with GDV over a time frame of 48 h, and to compare to healthy dogs. Design and Setting: Prospective, observational cohort study in client-owned dogs with GDV. Materials and Methods: Fifteen dogs with GDV and 9 healthy control dogs were enrolled. Plasma concentrations of interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma (IFN-γ), keratinocyte chemotactic-like, monocyte chemotactic protein (MCP)-1, Angiopoietin (Ang)-2, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, (T0), immediately after surgery (T1), 24 ± 4 h (T24), and 48 ± 4 h (T48) post-surgery. Cytokines were measured using multiplex magnetic bead assay. Plasma Ang-2 was measured with a commercial human ELISA test kit validated for dogs. Results: Dogs with GDV had significantly higher plasma concentrations of IFN-γ and IL-10 compared to healthy control dogs at all time points. Concentrations of IL-6 were significantly higher at T1 and T24, concentrations of MCP-1 at T24, and concentrations of CRP at T24 and T48. A significant increase between T0 and T1 was found for IL-6, IL-10, and CRP, between T1 and T24 for IL-8, IFN-γ, MCP-1, and CRP, and between T24 and T48 for IL-15, Ang-2, and CRP. A significant decrease between T0 and T1 was found for IL-7, IL-8, IL-15, IL-18, and Ang-2; between T1 and T24 for IL-6 and KC-like; and between T24 and T48 for IL-6. Conclusion: In GDV dogs, a mild pro-inflammatory reaction was present at admission, which peaked immediately after and up to 24 h post-surgery, mainly represented by IL-6, IFN-γ, MCP-1, and CRP, and which decreased at T48. In addition, the anti-inflammatory IL-10 was increased in GDV dogs at all time points.

Hyperlipasemia in critically ill dogs with and without acute pancreatitis: Prevalence, underlying diseases, predictors, and outcome.

BACKGROUND: Hyperlipasemia is frequent in critically ill people without evidence of acute pancreatitis (AP), and has been associated with increased morbidity and mortality. OBJECTIVE: To evaluate the prevalence of hyperlipasemia at admission and development of hyperlipasemia during hospitalization in critically ill dogs, explore factors associated with hyperlipasemia, and evaluate association with outcome. ANIMALS: Critically ill, client owned dogs (n = 1360), presented on emergency and admitted to the intensive care unit, that had 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase activity measured within 24 hours of admission. METHODS: Retrospective cross-sectional study of clinical and laboratory records. RESULTS: The DGGR lipase activity was increased >3× the upper reference limit at admission in 216/1360 (16%) dogs, of which 70/216 (32%) had a clinical diagnosis of AP. Other primary conditions associated with hyperlipasemia were renal, endocrine, and immune-mediated diseases, and upper airway obstruction. Predictors of hyperlipasemia at admission were prior glucocorticoid administration, vomiting and abdominal pain, increased age, plasma bilirubin and creatinine concentrations, and decreased hematocrit. Of dogs with repeat measurements, 78/345 (23%) had significantly increased lipase during hospitalization, of which 13/78 (17%) had a clinical diagnosis of AP. Other primary conditions associated with in-hospital hyperlipasemia were renal and immune-mediated disorders. Predictors of developing hyperlipasemia during hospitalization were hemodialysis events, increased plasma bilirubin and creatinine concentrations, and decreased hematocrit. Hyperlipasemia both at admission and during hospitalization was associated with longer hospitalization and higher mortality. CONCLUSIONS AND CLINICAL IMPORTANCE: Significant DGGR-hyperlipasemia is frequent in critically ill dogs and associated with a variety of nonpancreatic conditions and negative outcome.

Clinicopathological characteristics and prognostic factors for canine multicentric non-indolent T-cell lymphoma: 107 cases.

Canine lymphoma, as the most common haematopoietic malignancy, encompasses a group of heterogeneous diseases and even within the T-cell immunophenotype, differences in clinical presentation and responses to treatment exist. The aim of this retrospective study was to determine outcomes and prognostic factors of 107 dogs with multicentric non-indolent T-cell lymphoma (TCL) receiving lomustine-based (70%) and non-lomustine-based (30%) treatment. The majority were Labradors, Boxers, mixed-breed dogs and Dogue de Bordeaux. Eighty-six percent were substage b, 77% had mediastinal involvement, 15% had suspected bone marrow involvement and 12% had other extra-nodal sites of disease. The overall response rate to induction therapy was 80%; dogs receiving procarbazine in the induction protocol (P = .042), dogs with neutrophil concentration below 8.7 × 10e9 /L (P = .006) and mitotic rate below 10 per 5 high power field (P = .013), had greater response rates. Median progression-free survival (PFS) for the first remission was 105 days; lack of expression of CD3 on flow cytometry (P < .0001) and pretreatment with steroid (P = .012) were significantly associated with shorter PFS. Median overall survival time (OST) was 136 days; co-expression of CD79a (P = .002), lack of CD3 expression on flow cytometry, presence of anaemia (P = .007), and monocytopenia (P = .002) were predictive of shorter OST. Multicentric non-indolent TCL in dogs is an aggressive cancer with new possible prognostic factors.

Successful management of Heinz body hemolytic anemia associated with leek (Allium ampeloprasum) ingestion in a South American coati (Nasua nasua).

OBJECTIVE: To describe the diagnosis, management, and outcome of Heinz body hemolytic anemia in a South American coati (Nasua nasua) secondary to suspected leek (Allium ampeloprasum) toxicosis. CASE SUMMARY: A South American coati presented with Heinz body hemolytic anemia following addition of leeks to its diet for 2-5 days prior to initial presentation. Administration of a whole blood transfusion from an animal of the same species (conspecific) and supportive care resulted in immediate improvement in clinical signs. Normal behavior fully returned within 6 days of transfusion. Hematological evidence of anemia resolved by 4 weeks and there were no significant features of oxidative injury present by 8 weeks following initial presentation. NEW INFORMATION PROVIDED: This is the first reported case of Heinz body hemolytic anemia, suspected leek toxicosis, and administration of a blood transfusion in this species.

Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation.

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health.

Aldosterone-producing adrenocortical carcinoma with myxoid differentiation in a cat.

A 10-year-old male neutered Persian cat was presented with an abdominal mass and history of weakness. Blood smear examination found marked elliptocytosis, and serum biochemical analysis revealed hypokalemia, hypochloremia, increased creatine kinase activity, and a high aldosterone concentration. Cytologic examination of the mass revealed neoplastic endocrine cells with moderate criteria of malignancy, favoring adrenocortical neoplasia. The adrenal mass was surgically excised and histologically characterized by lobules of mildly pleomorphic, polygonal neoplastic cells with moderate to abundant, occasionally granular, eosinophilic cytoplasm. Lobules were separated by fine fibrovascular trabeculae, and numerous cystic cavities containing amorphous eosinophilic material that stained positive with Alcian blue and periodic acid-Schiff were seen. Neoplastic cells were multifocally positive for cytochrome P450 aldosterone synthase. Based on clinicopathologic and immunohistochemical findings the present case was diagnosed as an aldosterone-producing adrenocortical carcinoma with myxoid differentiation. While this entity has not been reported in cats, myxoid differentiation of adrenocortical carcinomas has been found in other species and can pose a major diagnostic challenge on microscopic examination.

Successful medical management of a domestic longhair cat with subdural intracranial empyema and multifocal pneumonia.

OBJECTIVE: To describe a case of successful medical management of subdural intracranial empyema and multifocal pneumonia in a domestic longhaired cat. CASE SUMMARY: A 7-year-and-8-month-old male neutered domestic longhair cat presented with tachypnea, respiratory compromise, vestibular ataxia, obtundation, left-sided head tilt, and multiple cranial nerve deficits. Neuroanatomical localization was multifocal with central vestibular involvement. Magnetic resonance imaging of the head indicated diffuse subdural empyema, mainly affecting the middle cranial fossa and the right cerebrum. Analysis of cerebrospinal fluid revealed degenerate neutrophils with a mixed population of intracellular bacilli. Computed tomography (CT) of the thorax was suggestive for multifocal pneumonia. Aggressive medical management with IV fluids, oxygen supplementation, mannitol boluses, dexamethasone, and broad-spectrum antimicrobials was initiated. The cat demonstrated gradual improvement within 24 hours following initiation of treatment. General physical and neurological examinations, 9 weeks after initiating treatment, did not reveal any abnormalities. A CT examination performed at this time revealed resolution of the cat's pulmonary lesions. The cat was still free of clinical signs, 9 months after treatment was started. NEW OR UNIQUE INFORMATION PROVIDED: Subdural empyema is infrequently reported in cats and has high mortality rates even following surgical treatment. To the authors' knowledge, this is the first reported case of successful medical management of a cat with subdural empyema and suggests that aggressive medical management should be attempted in cats that are not considered surgical candidates.

Phenotypic heterogeneity of peripheral monocytes in healthy dogs.

Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14posMHC IIneg, CD14posMHC IIpos and CD14negMHC IIpos. Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14posMHC IIneg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations.