Clinical Severity Score System in Dogs with Degenerative Mitral Valve Disease

Background

Several risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE).

Hypothesis/Objectives

Data obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification.

Animals

Client‐owned dogs (n = 244) with DMVD recruited from first opinion practice.

Methods

Prospective longitudinal follow‐up of dogs with DMVD. History and PE data were obtained at 6‐month intervals and analyzed with time‐dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken.

Results

History of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes.

Conclusions and Clinical Importance

Routinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings.     

Vitamin D Status in Different Stages of Disease Severity in Dogs with Chronic Valvular Heart Disease

Background

In humans with heart disease, vitamin D deficiency is associated with disease progression and a poor prognosis. A recent study showed that serum 25‐hydroxyvitamin D [25(OH)D] concentration, the hallmark of vitamin D status, was lower in dogs with heart failure than in normal dogs, and a low concentration was associated with poor outcome in dogs with heart failure.

Objectives

To elucidate the vitamin D status of dogs with chronic valvular heart disease (CVHD) at different stages of disease severity.

Animals

Forty‐three client‐owned dogs with CVHD.

Methods

In this cross‐sectional study, dogs were divided into 3 groups (14 dogs in Stage B1, 17 dogs in Stage B2, and 12 dogs in Stage C/D) according to ACVIM guidelines. Dogs underwent clinical examination including echocardiography. Serum 25(OH)D concentrations were measured in each dog.

Results

Serum 25(OH)D concentration was significantly lower in Stage B2 (median, 33.2 nmol/L; range, 4.9–171.7 nmol/L) and C/D (13.1 nmol/L; 4.9–58.1 nmol/L) than in Stage B1 (52.5 nmol/L; 33.5–178.0 nmol/L) and was not significantly different between Stage B2 and Stage C/D. Among clinical variables, there were significant negative correlations between 25(OH)D concentration and both left atrial‐to‐aortic root ratio and left ventricular end‐diastolic diameter normalized for body weight.

Conclusions and Clinical Importance

These results indicate that vitamin D status is associated with the degree of cardiac remodeling, and the serum 25(OH)D concentration begins to decrease before the onset of heart failure in dogs with CVHD.     

Comparative Analysis of mRNA Expression of Surface Antigens between Histiocytic and Nonhistiocytic Sarcoma in Dogs

Background

Definitive diagnosis of histiocytic sarcoma (HS) in dogs is relatively difficult by conventional histopathological examination because objective features of HS are not well defined.

Hypothesis

Quantitative analysis of mRNA expression of selected cellular surface antigens (SAs) specific to HS in dogs can facilitate objective and rapid diagnosis.

Animals

Dogs with HS (n = 30) and dogs without HS (n = 36), including those with other forms of lymphoma (n = 4), inflammatory diseases (n = 6), and other malignant neoplasias (n = 26).

Methods

Retrospective clinical observational study. Specimens were collected by excisional biopsy, needle core biopsy, or fine needle aspiration. To determine HS detection efficacy, mRNA expression levels of selected SAs specific to HS in dogs, including MHC class IIα, CD11b, CD11c, and CD86, were quantitatively analyzed using real‐time quantitative polymerase chain reaction.

Results

Each SA mRNA expression level was significantly higher in HS dogs than in non‐HS dogs (P = .0082). Cutoff values for discriminating between HS and non‐HS dogs based on these expression levels were calculated on the basis of receiver‐operating characteristic analysis. Accuracy of the cutoff values, including MHC class IIα, CD11b, CD11c, and CD86, was 87.9, 86.4, 86.4, and 84.8%, respectively.

Conclusions and Clinical Importance

Our results suggest that quantitative analysis of mRNA expression of the selected SAs could be an adjunctive diagnostic technique with high diagnostic accuracy for HS in dogs. Substantial investigation is required for exclusion of diseases with similar cell types of origin to lymphoma.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Clinical Features and Outcome of Dogs with Epiglottic Retroversion With or Without Surgical Treatment: 24 Cases

Background

Published information describing the clinical features and outcome for dogs with epiglottic retroversion (ER) is limited.

Hypothesis/Objectives

To describe clinical features, comorbidities, outcome of surgical versus medical treatment and long‐term follow‐up for dogs with ER. We hypothesized that dogs with ER would have upper airway comorbidities and that surgical management (epiglottopexy or subtotal epiglottectomy) would improve long‐term outcome compared to medical management alone.

Animals

Twenty‐four client‐owned dogs.

Methods

Retrospective review of medical records to identify dogs with ER that underwent surgical or medical management of ER.

Results

Dogs with ER commonly were middle‐aged to older, small breed, spayed females with body condition score (BCS) ≥6/9. Stridor and dyspnea were the most common presenting signs. Concurrent or historical upper airway disorders were documented in 79.1% of cases. At last evaluation, 52.6% of dogs that underwent surgical management, and 60% of dogs that received medical management alone, had decreased severity of presenting clinical signs. In dogs that underwent surgical management for ER, the incidence of respiratory crisis decreased from 62.5% before surgery to 25% after surgical treatment. The overall calculated Kaplan–Meier median survival time was 875 days.

Conclusion and clinical importance

Our study indicated that a long‐term survival of at least 2 years can be expected in dogs diagnosed with epiglottic retroversion. The necessity of surgical management cannot be determined based on this data, but dogs with no concurrent upper airway disorders may benefit from a permanent epiglottopexy to alleviate negative inspiratory pressures.     

Autologous Peripheral Blood Hematopoietic Cell Transplantation in Dogs with T‐Cell Lymphoma

Background

Peripheral blood hematopoietic cell transplantation (PBHCT) is a feasible treatment option for dogs with B‐cell lymphoma.

Objective

To examine apheresis and PBHCT outcomes in dogs diagnosed with T‐cell lymphoma (TCL).

Animals

Fifteen client‐owned dogs diagnosed with high‐grade TCL.

Methods

After high‐dose cyclophosphamide and rhG‐colony‐stimulating (rhG‐CSF) factor treatment, peripheral blood mononuclear cells were collected using cell separators. The harvested cells then were infused after varying doses of total body irradiation (TBI). Postirradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of hematopoietic engraftment.

Results

More than 2 × 10⁶ CD34+ cells/kg were harvested from 15/15 dogs. Thirteen of 15 (87%) dogs engrafted appropriately, whereas 2 (13%) of the dogs died in the hospital. One dog developed cutaneous B‐cell lymphoma 120 days post‐PBHCT. The median disease‐free interval and overall survival (OS) of the 13 dogs transplanted in first remission from the time of PBHCT were 184 and 240 days, respectively. Stage and substage of disease at diagnosis had no effect on OS. Two of 13 (15%) dogs were alive 741 and 772 days post‐PBHCT.

Conclusions and Clinical Importance

PBHCT may be considered as a treatment option for dogs with TCL.     

Sudden Death Associated with QT Interval Prolongation and KCNQ1 Gene Mutation in a Family of English Springer Spaniels

Background

A 5‐year‐old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam''s death, 3 offspring also died suddenly.

Hypothesis

Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family.

Animals

Four remaining dogs from the affected litter and 11 related dogs.

Methods

Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs.

Results

Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T‐wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure.

Conclusions and Clinical Importance

This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current I _Ks, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.     

Pulmonary Vein‐to‐Pulmonary Artery Ratio is an Echocardiographic Index of Congestive Heart Failure in Dogs with Degenerative Mitral Valve Disease

Background

Early recognition of left‐sided congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD) is important because it influences medical therapy, timing of follow‐up, and outcome.

Hypothesis

Pulmonary vein diameter‐to‐pulmonary artery diameter ratio (PV/PA) measured by echocardiography can predict CHF.

Animals

Ninety‐eight client‐owned dogs, 37 controls, and 61 dogs with DMVD.

Methods

Prospective clinical cohort study. History, physical examination and Doppler‐echocardiography were performed. Dogs were classified as International Small Animal Cardiac Health Council class I, II or III. Congestive heart failure was identified in a subset of 56 dogs based on radiographic findings. The PV/PA was measured in bidimensional (2D) and M‐mode by 2 investigators blinded to the radiologists’ conclusions.

Results

Interobserver coefficients of variation for PV/PA acquisition and measurement were <10%. The PV/PA in control dogs was approximately 1 and increased with class of heart failure. The presence of CHF could be best predicted by measuring PV/PA in 2D echocardiography (cut‐off, 1.7; area under the curve, 0.98; CI, 0.97–0.98; P < .001) with a sensitivity of 96% and a specificity of 91%.

Conclusion and clinical importance

The PV/PA is a simple and reproducible echocardiographic variable that increases with class of heart failure and may help discriminate dogs in CHF from asymptomatic dogs with DMVD. Additional studies are required to determine whether PV/PA might provide additional information in the integrated interpretation of Doppler‐echocardiographic indices of left ventricular filling pressures and could be used for rapid assessment of CHF in dogs in a critical care setting.     

Computed Tomographic Angiography under Sedation in the Diagnosis of Suspected Canine Pancreatitis: A Pilot Study

Background

Computed tomography (CT) is highly accurate for diagnosing pancreatitis in humans. The diagnosis of pancreatitis in dogs is based on clinical signs, laboratory findings, and ultrasonographic (US) changes. There are, however, inherent limitations in relying on laboratory and ultrasound findings for the clinical diagnosis of pancreatitis in dogs.

Hypothesis/Objectives

We hypothesized that CT angiography would be a rapid and reliable method to confirm pancreatitis in dogs compared to ultrasonography. The aim was to describe the CT characteristics and compare them to ultrasound findings and correlate the CT appearance to the severity of the patients'' clinical course.

Animals

A prospective pilot case series; 10 dogs with pancreatitis were enrolled if the history, clinical signs, laboratory, and ultrasonographic findings were indicative of pancreatitis.

Methods

A 3‐phase angiographic CT was performed under sedation. Afterward, each dog had US‐guided aspirates of the pancreas collected and blood drawn for cPLi assay. Images were evaluated for portion of visible pancreas, pancreatic size and margin, pancreatic parenchyma, presence of peripancreatic changes and contrast enhancement pattern. The results were compared with outcome.

Results

An enlarged, homogeneously to heterogeneously attenuating and contrast‐enhancing pancreas with ill‐defined borders was identified in all dogs. CT identified more features characterizing pancreatic abnormalities compared to US. Thrombi were found in 3/10 dogs. Three dogs with heterogeneous contrast enhancement had an overall poorer outcome than those with homogenous enhancement.

Conclusions and Clinical Importance

CT angiography under sedation was used in dogs to confirm clinically suspected pancreatitis and identified clinically relevant and potentially prognostic features of pancreatitis in dogs.     

Prevalence of Chiari‐like Malformations in Clinically Unaffected Dogs

Background

The importance of Chiari‐like malformation (CM) in the generation of clinical signs or the formation of syringomyelia in dogs is incompletely understood, partly because the prevalence of various CM definitions in unaffected dogs is unknown.

Hypothesis/Objectives

The aims were: to estimate the prevalence of CM in dogs asymptomatic for CM or syringomyelia, according to 3 currently used definitions; and, to investigate the effect of brachycephaly and head position during magnetic resonance (MR) imaging on estimates of the prevalence of CM.

Animals

One ninety‐nine client‐owned dogs without apparent signs of CM or syringomyelia.

Methods

Blinded, retrospective analysis. Archived MR images were analyzed for evidence of cerebellar indentation and impaction into or herniation through the foramen magnum. Logistic regression analysis was used to investigate the relationship of CM diagnosis with head position and the cranial index (a measure of brachycephaly).

Results

In 185 non‐Cavalier King Charles Spaniel (CKCS) dogs, indentation was identified in 44% (95% CI, 47–51%) and impaction in 22% (95% CI, 16–28%). No asymptomatic, non‐CKCS dogs showed herniation. Regression analysis showed a significant increase in the odds of indentation and impaction in an extended head position and as the cranial index increased (became more brachycephalic).

Conclusions and Clinical Importance

The high prevalence of cerebellar indentation and impaction suggests that they may be normal anatomical variations and therefore unsuitable as definitions of CM. We suggest that future research into CM in dogs should define cases and controls more strictly so that overlap between normal and abnormal animals is minimized.     

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Background

Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.

Hypothesis/Objectives

The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse‐administered toceranib phosphate (TOC) combined with lomustine.

Animals

Forty‐seven client‐owned dogs with measurable MCT.

Methods

Toceranib phosphate was given PO on days 1, 3 and 5 of a 21‐day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m². All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.

Results

The MTD of lomustine was established at 50 mg/m² when combined with pulse‐administered TOC; the dose‐limiting toxicity was neutropenia. Forty‐one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression‐free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.

Conclusions and clinical importance

Combined treatment with pulse‐administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.     

Clinical Findings and Prevalence of the Mutation Associated with Primary Ciliary Dyskinesia in Old English Sheepdogs

Background

Primary ciliary dyskinesia (PCD) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene (CCDC39) has been identified in the Old English Sheepdog (OES).

Objectives

To describe the clinical findings and the molecular changes of affected dogs and estimate the worldwide prevalence of the mutation in a large cohort of OES.

Animals

578 OES, including 28 affected and 550 clinically healthy dogs.

Methods

This retrospective study reviewed the data of OES diagnosed with PCD and OES tested for the mutation. Clinical data including results of physical examination and further investigations were obtained on 11/28 dogs. CCDC39 expression was assessed by qRT‐PCR and Western blot analysis in affected dogs and healthy dogs. DNA was extracted on 561/578 dogs and a genetic test by Taqman technology was developed to genotype the CCDC39 mutation in these dogs.

Results

Clinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia. Ultrastructural defects were characterized by central microtubular abnormalities and decreased number of inner dynein arms (IDAs). Molecular analysis revealed a reduced expression of CCDC39 RNA and an absence of CCDC39 protein in affected dogs compared to healthy dogs. The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non‐European dogs (7%).

Conclusion and Clinical Importance

CCDC39 mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.     

The Association of Endothelin‐1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma

Background

Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs with OS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin‐1‐mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression.

Hypothesis

The endothelin‐1 signaling axis is active in canine OS cells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities.

Animals

45 dogs with appendicular OS.

Methods

The expressions of endothelin‐1 and endothelin A receptor were studied in OS cell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin‐1 signaling were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with OS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity.

Results

Canine OS cells express endothelin‐1 and endothelin A receptor, and this signaling axis mediates OS migration, survival, proliferation, and bone alkaline phosphatase activities. In OS‐bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities.

Conclusions and Clinical Importance

Canine OS cells express endothelin‐1 and functional endothelin A receptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin‐1 signaling or excessive osteoproduction within the localized bone microenvironment.     

Serum Lipoprotein Changes in Dogs with Renal Disease

Background

People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated.

Hypothesis

Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high‐density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration.

Animals

Prospective study of client‐owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students.

Methods

Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low‐density lipoproteins (LDL), very low‐density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein‐to‐creatinine ratio were measured by standard methods.

Results

Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD.

Conclusion and Clinical Importance

Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study.     

Vaginal Microbiota of Spayed Dogs with or without Recurrent Urinary Tract Infections

Background

Limited information is available regarding the vaginal microbiota of normal spayed dogs and spayed dogs with recurrent UTIs. Vaginal lactic acid‐producing bacteria (LAB) have been associated with decreased frequency of recurrent urinary tract infection in women and may have a protective role within the urinary tract of female dogs.

Hypothesis/Objectives

Spayed dogs with historical recurrent UTI will have decreased prevalence of LAB and increased prevalence of uropathogenic bacterial populations in the vaginal microbiota when compared with the vaginal microbiota of healthy, spayed dogs.

Animals

Twenty‐one client‐owned adult spayed female dogs with historical recurrent UTI and 23 healthy, spayed female dogs without a history of recurrent UTI.

Methods

Dogs were placed into a recurrent UTI group or control group in this prospective study. Bacterial populations were isolated and characterized from vaginal swabs obtained from each dog.

Results

The most common bacterial isolates obtained from the vaginal tract of all dogs were Escherichia coli (11/44) and S. pseudintermedius (13/44). E. coli was isolated from the vaginal tract of 8 of 21 (38%) dogs in the rUTI group and 3 of 23 (13%) dogs in the control group (P = .08). LAB were isolated from 7 of the 44 dogs. Two of these 7 dogs were in the rUTI group and 5 of the 7 dogs were in the control group.

Conclusions and Clinical Importance

The vaginal microbiota of spayed female dogs with recurrent UTI was similar to the control population of normal, spayed female dogs.     

Incidence,Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

Background

The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and Objectives

To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals

Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods

Retrospective medical record review, from January 2009 through December 2013.

Results

Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016).

Conclusions and Clinical Importance

These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.     

Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Background

Thyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease.

Hypothesis/Objectives

To investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors.

Animals

74 dogs with thyroid neoplasia.

Methods

Immunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase‐2 (cox‐2), and P‐glycoprotein (P‐gp).

Results

Fifty‐four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76–100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox‐2. Seven percent of FTCs and 70% of MTCs expressed P‐gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox‐2 (P = .013), and P‐gp (P < .001) was significantly higher in MTCs compared to FTCs.

Conclusions and Clinical Importance

VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox‐2 and P‐gp may be useful molecular targets in canine MTC.     

Co‐infections with Respiratory Viruses in Dogs with Bacterial Pneumonia

Background

Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis of BP in dogs is complex and the role of canine respiratory viruses has not been fully evaluated.

Objectives

The aim of this study was to investigate the occurrence of viral co‐infections in dogs with BP and to assess demographic or clinical variables as well as disease severity associated with viral co‐infections.

Animals

Twenty household dogs with BP caused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused by Bordetella bronchiseptica (BBTB).

Methods

Prospective cross‐sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well as B. bronchiseptica and Mycoplasma spp. were analyzed in respiratory samples using PCR assays.

Results

CPIV was detected in 7/20 and CRCoV in 1/20 dogs with BP. Respiratory viruses were not detected in dogs with BBTB. There were no significant differences in clinical variables between BP dogs with and without a viral co‐infection.

Conclusion and Clinical Importance

Respiratory viruses were found frequently in dogs with BP and may therefore play an important role in the etiology and pathogenesis of BP. Clinical variables and disease severity did not differ between BP dogs with and without viral co‐infection.     

Urinary Corticoid Concentrations Measured by 5 Different Immunoassays and Gas Chromatography‐Mass Spectrometry in Healthy Dogs and Dogs with Hypercortisolism at Home and in the Hospital

Background

Determination of the urinary corticoid‐to‐creatinine ratio (UCCR) is an important screening test in the diagnosis of hypercortisolism (HC). However, urinary cortisol metabolites interfere with cortisol measurement in immunoassays, leading to decreased specificity. Gas chromatography‐mass spectrometry (GC‐MS) is considered the gold standard for steroid hormone analysis, because it provides a high level of selectivity and accuracy.

Objectives

To prospectively compare the UCCR of healthy dogs and dogs with HC determined by 5 different immunoassays and by GC‐MS and to evaluate the influence of veterinary care on UCCR.

Animals

Twenty healthy dogs; 18 dogs with HC.

Methods

Urine was collected in the hospital and again after 6 days at home. Three chemiluminescence immunoassays (Access 2, Beckmann; Immulite 2000, DPC Siemens, with and without trichloromethane extraction) and 2 RIAs (Utrecht in house; Access Beckmann) were used. GC‐MS analyses were performed with Agilent 6890N/5973N. Urinary corticoid concentrations were related to urinary creatinine concentrations.

Results

Immunoassay results were significantly higher compared to GC‐MS results. Evaluation of bias plots and clinical assessment made on the basis of the assay results of each dog indicated substantial disagreement among the assays. Sensitivity varied from 37.5 to 75% and with selected assays was lower in samples from day 6 compared to day 0. GC‐MS was not superior to the immunoassays in discriminating healthy from HC dogs.

Conclusions and Clinical Importance

Considerable variation must be anticipated comparing different urinary cortisol assays. Establishing an assay‐ and laboratory‐specific reference range is critical when using UCCR.     

Neutrophil Gelatinase‐Associated Lipocalin in Dogs With Sepsis Undergoing Emergency Laparotomy: A Prospective Case–Control Study

Background

Neutrophil gelatinase‐associated lipocalin (NGAL) is an early indicator of acute kidney injury (AKI) in dogs and its use has not been evaluated in dogs with sepsis.

Animals

Fifteen dogs with sepsis requiring laparotomy (study dogs) and 10 dogs undergoing surgery for intervertebral disc disease (control dogs).

Objective

To determine whether NGAL increases in dogs with sepsis undergoing emergency laparotomy and whether it is correlated with development of AKI and survival.

Methods

Longitudinal study conducted at a referral teaching hospital. Serum neutrophil gelatinase‐associated lipocalin (sNGAL), urinary NGAL normalized to urinary creatinine concentration (UNCR), and serum creatinine concentration were measured at 4 time points (admission, after anesthesia, and 24 and 48 hours postsurgery). Development of AKI (increase in serum creatinine concentration of 0.3 mg/dL) and in‐hospital mortality were recorded. Linear mixed‐model analysis was employed to assess differences between groups over time. Mann–Whitney U‐test was performed for comparison of continuous variables between groups and Chi square or Fisher''s exact tests were used to assess correlation between discrete data.

Results

Serum NGAL and UNCR were significantly higher in study dogs across all time points (P = .007 and P < .001, respectively) compared with controls. Urinary NGAL normalized to creatinine in the study group was not significantly different between survivors (n = 12) and nonsurvivors (n = 3). Dogs that received hydroxyethyl starch had significantly higher UNCR across all time points (P = .04) than those that did not.

Discussion—Conclusion

Serum neutrophil gelatinase‐associated lipocalin and UNCR are increased in dogs with sepsis requiring emergency laparotomy. Additional studies are needed to evaluate its role as a marker of AKI in this population.