Evidence of hypercoagulability in dogs with parvoviral enteritis

OBJECTIVE: To determine whether dogs with naturally occurring canine parvoviral (CPV) enteritis have laboratory evidence of hypercoagulability. DESIGN: Case-control study. Animals-9 dogs with naturally occurring CPV enteritis and 9 age-matched control dogs. PROCEDURE: Blood was collected from all dogs within 24 hours of admission for thromboelastography (TEG) and determination of activated partial thromboplastin time (aP-TT), prothrombin time (PT), antithrombin III (AT) activity, and fibrinogen concentration. Fibrin-fibrinogen degradation product (FDP) concentration, D-dimer concentration, and platelet count were obtained in dogs with CPV enteritis only. Records were reviewed for evidence of thrombosis or phlebitis. RESULTS: All 9 dogs with CPV enteritis had evidence of hypercoagulability, determined on the basis of significantly increased TEG maximum amplitude and decreased AT activity. Fibrinogen concentration was significantly higher in dogs with CPV enteritis than in control dogs. The aPTT was moderately prolonged in dogs with CPV enteritis, and FDP concentration was < 5 mg/ml in 7 of 9 dogs. No dogs had a measurable D-dimer concentration. Platelet counts were within reference range. Four of 9 dogs had clinical evidence of venous thrombosis or phlebitis associated with catheters. One dog had multifocal splenic thrombosis identified at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with CPV enteritis have a high prevalence of clinical thrombosis or phlebitis and laboratory evidence of hypercoagulability without disseminated intravascular coagulopathy. Thromboelastography may help identify hypercoagulable states in dogs.     

CONTRAST‐ENHANCED ULTRASONOGRAPHIC CHARACTERISTICS OF ADRENAL GLANDS IN DOGS WITH PITUITARY‐DEPENDENT HYPERADRENOCORTICISM

A noninvasive method for quantifying adrenal gland vascular patterns could be helpful for improving detection of adrenal gland disease in dogs. The purpose of this retrospective study was to compare the contrast‐enhanced ultrasound (CEUS) characteristics of adrenal glands in 18 dogs with pituitary‐dependent hyperadrenocorticism (PDH) vs. four clinically healthy dogs. Each dog received a bolus of the contrast agent (SonoVue®, 0.03 ml/kg of body weight) into the cephalic vein, immediately followed by a 5 ml saline flush. Dynamic contrast enhancement was analyzed using time–intensity curves in two regions of interest drawn manually in the caudal part of the adrenal cortex and medulla, respectively. In healthy dogs, contrast enhancement distribution was homogeneous and exhibited increased intensity from the medulla to the cortex. In the washout phase, there was a gradual and homogeneous decrease of enhancement of the adrenal gland. For all dogs with PDH, there was rapid, chaotic, and simultaneous contrast enhancement in both the medulla and cortex. Three distinct perfusion patterns were observed. Peak perfusion intensity was approximately twice as high (P < 0.05) in dogs with PDH compared with that of healthy dogs (28.90 ± 10.36 vs. 48.47 ± 15.28, respectively). In dogs with PDH, adrenal blood flow and blood volume values were approximately two‐ to fourfold (P < 0.05) greater than those of controls. Findings from the present study support the use of CEUS as a clinical tool for characterizing canine adrenal gland disease based on changes in vascular patterns.     

Reconstruction of chest wall defects after rib tumor resection: a comparison of autogenous, prosthetic, and composite techniques in 44 dogs

Objective— To compare short‐ and long‐term outcome and complications of chest wall reconstruction in dogs using autogenous, prosthetic, and composite autogenous–prosthetic techniques. Study Design— Historical cohort. Animals— Dogs (n=44) with spontaneous tumors arising from or involving the chest wall. Methods— Medical records were reviewed for dogs with rib and/or sternal tumors treated by chest wall resection and reconstruction. Signalment, preoperative clinical features, intraoperative findings and complications, reconstruction technique (autogenous muscle flap, prosthetic mesh, or composite autogenous–prosthetic technique), and short‐ (≤14 days) and long‐term (>14 days) postoperative complications were determined from the medical records and telephone contact with owners and referring veterinarians. Associations between chest wall reconstruction technique and postoperative complications were tested with Cox proportional hazards. Results— Chest wall defects were reconstructed with autogenous muscle flaps (29 dogs), prosthetic mesh (3), and a composite technique of prosthetic mesh and either autogenous muscle or omental pedicle flap (12). Early postoperative complications were recorded in 8 dogs (18.2%) and included seroma (5) and pleural effusion and peripheral edema (3). One dog had a late complication (2.3%) with a mesh‐related infection 767 days postoperatively. Overall, complications occurred in 10.3% of autogenous, 25.0% of composite, and 66.7% of prosthetic reconstructions. Chest wall reconstruction with Marlex mesh alone was associated with a significantly increased risk of postoperative complications compared with autogenous reconstruction (P=.027). Reconstruction of sternal defects (3), 2 of which were performed with Marlex mesh alone, was associated with a significantly increased risk of complications compared with lateral chest wall reconstructions (P=.037). Conclusions— Large chest wall defects can be reconstructed with autogenous and composite techniques, but prosthetic mesh should be covered with well‐vascularized autogenous muscle or omentum to decrease the risk of postoperative complications. Sternal defects should be reconstructed with rigid techniques. Clinical Relevance— Chest wall reconstruction with autogenous muscle flaps or a combination of autogenous techniques with prosthetic mesh is associated with a low rate of infection and other complications.     

Transpalpebral ultrasonographic measurement of the optic nerve sheath diameter in healthy dogs

Objective

To develop a reference range for ultrasonographically measured optic nerve sheath diameter (ONSD‐US) in dogs. We hypothesized that ONSD‐US can be measured reliably and is associated with weight but not age, sex, or body condition score (BCS), and that the relationship between weight and ONSD‐US in dogs is allometric due to canine size variations.

Design

Prospective, observational study.

Setting

University teaching hospital.

Animals

Seventy‐eight healthy adult dogs.

Interventions

The ONSD was measured by a standardized transpalpebral approach.

Measurements and Main Results

Regression analysis showed the relationship between weight and ONSD was better fit with a linear model (R² = 0.8510) than an allometric model (R² = 0.7917). Multiple regression analysis showed ONSD is associated with weight (P < 0.0001), age (P = 0.0021), and BCS (P = 0.0007), but not with sex. Dominance analysis showed 94.6% of the variance explained by the model was due to weight. Intraclass correlation coefficient (ICC) analysis showed excellent interobserver (ICC = 0.9338–0.9608) and intraobserver (ICC = 0.9893) reliability.

Conclusions

These results suggest that ONSD‐US may be reliably measured in dogs using our described transpalpebral approach, and we have calculated prediction intervals based on body weight. Future studies are needed to determine if ONSD‐US measurements are associated with intracranial hypertension as shown in human medicine.     

Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis

Background: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin‐1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. Objective: To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). Animals: Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. Methods: Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. Results: No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05–3.38) than healthy Beagle dogs (1.28, 1.07–1.53; P < .001), healthy WHWT (1.56, 1.25–1.85; P < .001), dogs with EBP (0.94 0.68–1.01; P = .001), and dogs with CB (1.54 0.74–1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut‐off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. Conclusions and Clinical Importance: Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF.     

Principles of peripheral blood mononuclear cell apheresis in a preclinical canine model of hematopoietic cell transplantation

BACKGROUND: Preclinical studies of peripheral blood mononuclear cell (PBMC) transplantation conducted in a well-established canine hematopoietic cell transplantation (HCT) model have been successfully translated to human patients over the past 5 decades. OBJECTIVE: We retrospectively investigated the safety and feasibility of PBMC apheresis in the canine model of HCT by analyzing apheresis parameters, cell yields, and the impacts of donor-related and apheresis-related variables on collection yields and donor stability. ANIMALS: One hundred and twenty dogs that underwent PBMC aphereses were evaluated. METHODS: Aphereses were performed with a COBE Spectra blood separator and a central dual-lumen catheter, with or without recombinant canine granulocyte colony-stimulating factor (rcG-CSF) stem cell mobilization. RESULTS: Aphereses from dogs not given rcG-CSF yielded an average volume of 280 +/- 42 mL containing an average of 15,086 +/- 9,834 leukocytes/mL. Aphereses from dogs given rcG-CSF yielded an average volume of 261 +/- 55 mL containing an average of 39,711 +/- 24,488 leukocytes/mL. Higher pre-apheresis white blood cell (WBC) counts correlated with higher apheresis WBC yields (R=0.50, P<.0001). The correlations of collection time, inlet volume, and collection flow rate on WBC yields were statistically significant but only weak to moderate in magnitude (R=0.34, P=.0001; R=0.38, P=.0006; R=0.26, P=.002, respectively) as were the correlations of collection time and inlet volume on collection volumes (R=0.30, P=.002; R=0.42, P<.0001, respectively). All dogs recovered promptly after PBMC aphereses and catheter removal, without complications. CONCLUSIONS AND CLINICAL IMPORTANCE: These data may be useful for translating PBMC apheresis technology to the field of veterinary oncology for the treatment of dogs with hematologic malignancies.     

COMPARISON BETWEEN COMPUTED TOMOGRAPHY,FLUOROSCOPY, AND ULTRASONOGRAPHY FOR GUIDING PERCUTANEOUS INJECTION OF THE CANINE INTERVERTEBRAL DISC

A minimally invasive method for delivering injectable therapeutic agents would be desirable for the treatment of intervertebral disc disease in dogs. The purpose of this study was to compare computed tomography (CT), ultrasonography (US), and fluoroscopy modalities for guiding percutaneous injection into canine intervertebral discs. Intervertebral discs of 14 dog cadavers were injected with a gelified ethanol therapeutic agent. Successful injectate placement and injectate leakage were determined based on necropsy inspection of discs. Injection into the nucleus pulposus was successful in 55 of 78 (71%) of all injected discs. Injections guided using CT and fluoroscopy were significantly more successful than US‐guided injections. Odds of successful injection without leakage were greater for CT vs. US (P = 0.0026) but there was no significant difference between CT and fluoroscopy (P = 0.0620). Injection success rates did not differ among vertebral sites or dog cadavers of varying weights. Forty‐nine (63%) of injection sites had injectate leakage outside the disc and 10 of these involved structures within the vertebral canal. The highest rate of injection success with the least amount of leakage was achieved with CT guidance. Findings indicated that CT, fluoroscopy, and US are feasible modalities for guiding percutaneous injection of a gelified ethanol therapeutic agent into the canine intervertebral disc, with moderate to high success rates for different regions of the spine. However, a moderately high rate of injectate leakage occurred outside of the disc and this should be taken into consideration for future safety and efficacy studies.     

Noninvasive estimation of cardiac systolic function using continuous-wave Doppler echocardiography in dogs with experimental mitral regurgitation

OBJECTIVE: To evaluate the feasibility of noninvasive estimation of cardiac systolic function using transthoracic continuous-wave Doppler echocardiography in dogs with mitral regurgitation. PROCEDURE: Seven mongrel dogs with experimental mitral regurgitation were used. Left ventriculography and measurement of pulmonary capillary wedge pressure were performed under inhalational anaesthesia. A micromanometer-tipped catheter was placed into the left ventricle and transthoracic echocardiography was carried out. The peak rate of left ventricular pressure rise (peak dP/dt) was derived simultaneously by continuous-wave Doppler and manometer measurements. The Doppler-derived dP/dt was compared with the catheter-measured peak dP/dt in the dogs. RESULTS: Classification of the severity of mitral regurgitation in the dogs was as follows: 1+, 2 dogs; 2+, 1 dog; 3+, 2 dogs; 4+, 1 dog; and not examined, 1 dog. We were able to derive dP/dt from the transthoracic continuous-wave Doppler echocardiography in all dogs. Doppler-derived dP/dt had a significant correlation with the catheter-measured peak dP/dt (r = 0.90, P < 0.0001). CONCLUSION: It was demonstrated that transthoracic continuous-wave Doppler echocardiography is a feasible method of noninvasive estimation of cardiac systolic function in dogs with experimental mitral regurgitation and may have clinical usefulness in canine patients with spontaneous mitral regurgitation.     

Ultrasonographic findings in a cow with ascites due to thrombosis of the caudal vena cava.

This case report describes a three-year-old Swiss Braunvieh cow with ascites due to thrombosis of the caudal vena cava. Ultrasonography verified the ascites and revealed dilatation of the abdominal portion of the caudal vena cava (4.8 cm). It was presumed that the caudal vena cava was occluded by a thrombus or by perivenous compression cranial to the dilatation. Post mortem findings included: a massive accumulation of fluid in the abdominal cavity; a 15 cm long thrombus in the subphrenic region of the caudal vena cava; multiple pulmonary abscesses; severe thrombosis of the pulmonary vasculature; hepatic congestion; oedematous abomasal folds; and severe thrombophlebitis of the left jugular vein and both udder veins, due to poor intravenous injection technique. Ascites caused by thrombosis of the caudal vena cava is rare because collateral routes of venous return, including the udder veins, are usually established. It was therefore concluded that the ascites was attributable to bilateral thrombosis of the udder veins.     

Masitinib mesylate for metastatic and non‐resectable canine cutaneous mast cell tumours

Masitinib mesylate is a tyrosine kinase inhibitor approved for the treatment of gross, non‐metastatic grade II and III canine mast cell tumours (MCTs). This study evaluated the use of masitinib as a frontline and rescue agent for metastatic and non‐metastatic canine MCTs. Identification of toxicities and prognostic factors in these dogs was of secondary interest. Twenty‐six dogs were included in this study. The overall response rate to masitinib was 50%. The median survival time for dogs that responded to masitinib was 630 days versus 137 days for dogs that did not respond (P = 0.0033). Toxicity was recorded in 61.5% of treated dogs, but the majority of adverse events were mild and self‐limiting. Response to masitinib, not tumour grade, stage or location, was the most significant prognostic factor for survival in dogs with MCTs.     

Evaluation of urinary and serum level of chemokine (C‐C motif) ligand 2 as a potential biomarker in canine urothelial tumours

Chemokine (C‐C motif) ligand 2 (CCL2) is a chemotactic cytokine recruiting monocytes, releasing growth factors and promoting adhesion in vascular endothelium. Elevated serum and urinary CCL2 levels and expression of its receptor (CCR2) have been associated with tumorigenesis in human urinary malignancies. CCL2 implication has not been investigated in canine urothelial carcinoma. The aim of this study was to evaluate CCL2 serum and urine levels (measured by ELISA) in dogs with urothelial carcinoma or non‐neoplastic urinary tract disease. CCL2 serum and urine levels were significantly higher in diseased dogs compared with healthy dogs (P < 0.001). Dogs with carcinoma had significantly higher serum and urine CCL2 levels (P = 0.001) than healthy dogs. Dogs with metastases showed significantly lower serum and urine CCL2 levels compared with the non‐metastasised tumour group (P = 0.007). CCL2 as a diagnostic marker for urothelial carcinoma held a sensitivity of 95.2% and a specificity of 38.2% in the urine. As a staging marker, sensitivity was 85.7% and specificity was 57.1% with a positive predictive value of 75.7% and a negative predictive value of 71.9%. Further investigation is needed to define the role of CCL2 as a prognostic marker in canine urothelial carcinoma.     

B-MODE AND DOPPLER ULTRASOUND IMAGING OF THE SPLEEN WITH CANINE SPLENIC TORSION: A RETROSPECTIVE EVALUATION

The ultrasonographic appearance of splenic torsion has been described; the splenic parenchyma can be normal, hypoechoic or anechoic with interspersed linear echoes (coarse/"lacy" appearance). The ultrasonographic parenchymal appearance of 15 dogs in this report with splenic torsion varied: mottled hypoechoic regions (n=2), diffusely hypoechoic (n=11) and normal (n=2). Because splenic torsion causes vascular congestion due to splenic vein compression and eventual thrombosis, visible splenic vein intraluminal echogenicities compatible with thrombi were seen in 13 dogs using B-mode. Using spectral Doppler and color Doppler imaging of the splenic veins, no measurable flow velocities were detected in any of the 15 dogs. The varied B-mode ultrasonographic appearance of the splenic veins for intraluminal echoes and spectral or color Doppler evaluation for absent velocity flow.     

T2‐WEIGHTED MAGNETIC RESONANCE IMAGING MEASUREMENTS OF OPTIC NERVE SHEATH DIAMETER IN DOGS WITH AND WITHOUT PRESUMED INTRACRANIAL HYPERTENSION

Intracranial hypertension is a cause of cerebral ischemia and neurologic deficits in dogs. Goals of this retrospective study were to test interobserver agreement for MRI measurements of optic nerve sheath diameter and associations between optic nerve sheath diameter, signalment data, and presumed intracranial hypertension status in a cohort of dogs. A veterinary radiologist interpreted scans of 100 dogs and dogs were assigned to groups based on presence or absence of at least two MRI characteristics of presumed intracranial hypertension. Two observers who were unaware of group status independently measured optic nerve diameter from transverse T2‐weighted sequences. Mean optic nerve sheath diameter for all dogs was 3 mm (1–4 mm). The mean difference between observers was 0.3 mm (limits of agreement, ?0.4 and 1.0 mm). There was no correlation between optic nerve sheath diameter and age for either observer (r = ?0.06 to 0.00) but a moderate positive correlation was observed between optic nerve sheath diameter and body weight for both observers (r = 0.70–0.76). The 22 dogs with presumed intracranial hypertension weighed less than the 78 dogs without (P = 0.02) and were more often female (P = 0.04). Dogs with presumed intracranial hypertension had a larger ratio of optic nerve sheath diameter to body weight for each observer‐side pair (P = 0.01–0.04) than dogs without. Findings indicated that the ratio of MRI optic nerve sheath diameter relative to body weight may be a repeatable predictor of intracranial hypertension in dogs.     

Wnt5a expression in canine osteosarcoma

Osteosarcoma is the most common primary malignancy of bone in dogs and is associated with poor long‐term outcomes due to its highly metastatic nature. A better understanding of the signalling pathways and proteins involved with osteosarcoma pathogenesis may aid in improved outcomes through the use of targeted therapies. The Wnt5a protein, a ligand for the non‐canonical Wnt signalling pathway, is implicated in mediating the aggressiveness of cancer cell lines, including those of human osteosarcoma origin. Given the close relationship between human and canine osteosarcoma, the primary goal of this study was to characterize Wnt5a expression in canine osteosarcoma. Second, if Wnt5a expression was present in canine osteosarcoma, the study aimed to determine any potential association with clinical outcome and clinical variables in similarly treated osteosarcoma‐bearing dogs. Wnt5a expression was present in 26 of the 48 (54%) cases of canine osteosarcoma. Wnt5a expression was not associated with progression‐free survival (P = 0.4) or overall survival (P = 0.1).     

NORMAL DUPLEX DOPPLER WAVEFORMS OF MAJOR ABDOMINAL BLOOD VESSELS IN DOGS: A REVIEW

The normal flow velocity profile and duplex Doppler waveform of the major abdominal blood vessels (aorta, caudal vena cava and the portal vein as well as their major branches) were examined by Doppler ultrasound. The flow velocity profile of an artery is largely determined by its diameter. The pulsatility of the waveform is related to the vascular impedance downstream to the point of measurement. Early systolic peak is present in the Doppler pattern of some vessels in some dogs. The waveform of the veins is mainly affected by the pressure conditions of the right atrium and the intrathoracic and intraabdominal pressure changes due to the respiration. Simultaneous electrocardiogram was used to reveal the effect of the heart beats on the Doppler patterns of the veins.     

Sequence and structural analysis of the presumed downstream promoter of the canine mdr1 gene

The product of the canine mdr1 gene, P‐glycoprotein (P‐gp), plays an important role in chemotherapeutic drug resistance of several canine tumours. Increased expression of P‐gp by tumour cells is associated with the multidrug‐resistant phenotype. Because of its importance in cancer chemotherapy, a great deal is known about the regulation of mdr1 gene expression in human cancer patients and rodent cancer models. In contrast, there is no information regarding the regulation of P‐gp expression in dogs. Initial information regarding the regulation of mdr1 gene expression can be gained by evaluating the mdr1 promoter. The downstream promoter of the canine mdr1 gene was sequenced. Several regulatory elements were identified, including an AP‐1 site, AP‐2 site and SP‐1 site. The presumed canine mdr1 promoter was similar to that of other species; however, low overall sequence homology may suggest that aspects of P‐gp regulation are distinctive in dogs.     

Estimation of left ventricular filling pressure by Doppler echocardiography in dogs with pacing-induced heart failure

BACKGROUND: Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. HYPOTHESIS: Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. ANIMALS: Five male hound dogs. METHODS: Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160-180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). RESULTS: Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R(2)= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. CONCLUSION AND CLINICAL IMPORTANCE: E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing.     

A study of experimental autoimmune encephalomyelitis in dogs as a disease model for canine necrotizing encephalitis

In the present study, the use of dogs with experimental autoimmune encephalomyelitis (EAE) as a disease model for necrotizing encephalitis (NE) was assessed. Twelve healthy dogs were included in this study. Canine forebrain tissues (8 g), including white and grey matter, were homogenized with 4 mL of phosphate-buffered saline for 5 min in an ice bath. The suspension was emulsified with the same volume of Freund''s complete adjuvant containing 1 mg/mL of killed Mycobacterium tuberculosis H37Ra. Under sedation, each dog was injected subcutaneously with canine brain homogenate at four sites: two in the inguinal and two in the axillary regions. A second injection (booster) was administered to all the dogs using the same procedure 7 days after the first injection. Clinical assessment, magnetic resonance imaging, cerebrospinal fluid analyses, necropsies, and histopathological and immunohistochemical examinations were performed for the dogs with EAE. Out of the 12 animals, seven (58%) developed clinically manifest EAE at various times after immunization. Characteristics of canine EAE models were very similar to canine NE, suggesting that canine EAE can be a disease model for NE in dogs.