Successful balloon angioplasty of pulmonary artery stenosis in two cats and associated complications

Two cats (2.5 months and 8 months old) were each evaluated due to a loud systolic murmur, and each was diagnosed with severe pulmonary artery stenosis at the bifurcation of the main pulmonary artery. Echocardiograms confirmed significant right atrial dilation and right ventricular dilation and/or hypertrophy that was progressive in one cat. Atenolol was initiated and the cats were referred for interventional therapy. Balloon angioplasty was performed via the jugular vein. In case 1, the pressure gradient across the stenosis was reduced from 169.7 mmHg to 23.6 mmHg and 52.4 mmHg across the left and right branch pulmonary arteries, respectively. In case 2, the stenotic echocardiographic gradient was reduced from 64 mmHg to 38.0 mmHg and 35.3 mmHg across the left branch and right-branched pulmonary arteries respectively. Both patients developed moderate to severe dynamic right ventricular outflow tract obstruction post angioplasty. Case 2 developed hypotension, desaturation, and ventricular arrhythmias intra-operatively. Case 1 was discharged but appeared to develop acute lung perfusion injury approximately 36 h after procedure that was manifested by radiographic pulmonary congestion and pulmonary infiltrate of the left lung fields. The congestion was successfully managed medically. Serial echocardiograms over the following 4 years in case 1 showed near complete resolution of the stenosis and associated right heart enlargement.     

Persistent polyuria in two dogs following adrenocorticolysis for pituitary‐dependent hyperadrenocorticism

Summary

In two dogs with pituitary‐dependent hyperadrenocorticism, adrenocorticolysis with o,p'‐DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water‐deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.     

Transvenous correction of patent ductus arteriosus in two toy-breed dogs with the Amplatzer™ Vascular Plug 4

Two Pomeranian dogs referred for interventional correction of a left-to-right shunting patent ductus arteriosus (PDA) had inadequate femoral arterial access for any occlusion device other than micro coils. The decision was made to attempt correction of the PDA using the Amplatzer™ Vascular Plug 4 (AVP4) from a femoral venous approach. An AVP4 was successfully deployed in each dog with complete occlusion noted within 5 min. Complete occlusion was persistent at 24 h after the procedure, while both dogs were subclinical, had no residual ductal flow, and complete or near complete reverse cardiac remodeling at subsequent visits. This report demonstrates the feasibility of PDA occlusion with the AVP4 from the femoral venous approach in small dogs where femoral arterial access is inadequate for other occlusion devices.     

Delayed embolization of an Amplatz® canine duct occluder in a dog

A 5-year old, 5.8 kg, castrated male Pomeranian was diagnosed with a type IIa patent ductus arteriosus (PDA) with a minimal ductal diameter of 3.5 mm and ampulla width of 7.1 mm based on angiographic assessment. A 6 mm Amplatz^® Canine Duct Occluder (ACDO) was deployed within the PDA. Once deployed, the device assumed it's native shape and back-and-forth maneuvering was performed with the delivery cable to assess device stability. Device position and complete occlusion were confirmed with both angiography and transesophageal echocardiography prior to and after release of the device. The device location was confirmed within the ductus arteriosus by echocardiography prior to discharge. The dog was discharged with instructions for strict activity restriction. Two days after discharge, the dog was left unsupervised in the backyard and shortly afterwards was found coughing with severe respiratory distress. The dog was evaluated at an emergency hospital and thoracic radiographs documented embolization of the ACDO to the main pulmonary artery along with a severe alveolar pattern throughout the right lung fields. Shortly after obtaining thoracic radiographs, the dog experienced cardiopulmonary arrest with unsuccessful resuscitation. This case describes a possible complication of transcatheter PDA occlusion with an ACDO, which has not been previously reported. An incident report, or catalog of adverse events with these devices, may prove useful in identifying additional fatal complications that others may have encountered, but are not reported in the literature. The report of this complication emphasizes the importance of strict activity restriction after device placement in dogs.     

Characterization of CD34⁺ thymocytes in newborn dogs

Using two-color flow cytometry, we characterized CD34(+) cells in the newborn canine thymus. CD34(+) thymic cells comprised approximately 5% of cells recovered by thymus tissue teasing and both large and small thymocytes have been present in this population, the former being 7-12 times more frequent. All CD34(+) cells expressed the pan-leukocyte antigen CD45. The expression of CD44 profile on the large and small CD34(+) thymocytes differed: almost all large CD34(+) cells were CD44(+), while only 75% of small CD34(+) thymocytes co-expressed the CD44 antigen. We have previously described that CD172α is present on the surface of CD34(+) bone marrow cells in dogs. In the thymus, CD172α was expressed on 5-10% and less than 5% of large and small CD34(+) cells, respectively. Some CD34(+) thymocytes also co-expressed T-lineage-specific markers like CD3, CD4, CD8, TCR1 and TCR2. Their expression increased during the large-to-small thymocyte transition. Based on our findings we suggest that thymocyte progenitors enter their primary differentiation center as large CD34(+), CD44(+), CD45(+) and CD172α(+) cells. T-cell specific markers appear on their surface at early stages of differentiation. As the size of progenitors decreases with terminal primary differentiation, the CD34, CD44, and CD172α surface markers are down-regulated.     

Survey of bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Fortaleza, Ceará, Brazil

OBJECTIVE: The ocular microflora in dogs has not been established in north-east Brazil. Thus, the main aim of this research was to determine the bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Fortaleza, Ceará, Brazil. ANIMALS STUDIED: This study included 60 healthy dogs, 15 dogs with unilateral corneal ulcer, and three dogs with bilateral corneal ulcers. Procedure Samples were taken by a calibrated platinum loop (1 microL) placed directly onto the conjunctival sac and on sterile blood agar. The clinical specimens were incubated at 37 degrees C in an atmosphere of 5% CO2 for 48 h. RESULTS: Of the 120 samples from healthy dogs, only 47 (39%) had positive culture for bacteria, while all of the specimens from eyes with corneal ulcer were positive for bacterial growth. The group of dogs with corneal ulcer had a higher (P < 0.05) number of colony-forming units (CFU) per plate than the group of healthy animals. Of the 59 isolates from healthy eyes, only nine (15.3%) had more than 50 CFU per plate, while in the group of dogs with corneal ulcer, 23 (62.2%) of the 37 isolates presented more than 50 CFU per plate. In both groups Gram-positive bacteria (86.5%) predominated over Gram-negative (13.5%). Staphylococcus spp. was the most frequently isolated genus and S. intermedius predominated in both groups. CONCLUSION: The results of our study are directly applicable to initiate rational, preventive and therapeutic measures with greater accuracy in dogs with corneal ulcer.     

Intervertebral disc disease in dogs – Part 1: A new histological grading scheme for classification of intervertebral disc degeneration in dogs

Intervertebral disc (IVD) degeneration is common in dogs and can lead to serious disorders. Current treatments can relieve clinical signs of disease, but do not restore IVD function. The development of regenerative strategies for IVD dysfunction requires detailed knowledge of the pathogenesis of IVD degeneration and its underlying mechanisms. Histological examination of IVDs at different stages of degeneration might provide this knowledge, but as there is currently no histological grading scheme for canine IVD degeneration, the aim of this study, which is the first of a two-part series, was to design and validate an appropriate scheme.Three independent observers evaluated 35 IVDs at different stages of degeneration using the scheme. Glycosaminoglycan contents of the nucleus pulposus and macroscopic grading according to Thompson, which are considered ‘gold standards’ for IVD degeneration, were used to validate the scheme. Reproducibility was assessed by analysing the inter-observer reliability of all individual variables of the grading scheme, using a weighted κ analysis. Significant correlations were found between Thompson grading and total histological score (r = 0.94; P < 0.01) and between glycosaminoglycan content and total histological score (r = ?0.72; P < 0.01). Most individual histological variables showed ‘moderate’ to ‘almost perfect’ inter-observer reliability. The high correlation with the gold standards in combination with the high reproducibility indicates that the proposed histological grading scheme is reliable and objective for classification of IVD degeneration in both chondrodystrophic and non-chondrodystrophic dog breeds.     

Clinical,echocardiographic and advanced imaging characteristics of 13 dogs with systemic-to-pulmonary arteriovenous fistulas

Objectives

The objective is to describe the clinical, radiographic, echocardiographic and angiographic findings in dogs with systemic-to-pulmonary arteriovenous fistula (SPAVF).

Pro‐tumorigenic Effects of Transforming Growth Factor Beta 1 in Canine Osteosarcoma

Background

Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities.

Hypothesis

Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro‐tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations.

Animals

Thirty‐three dogs with appendicular OS.

Methods

Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption.

Results

Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS‐bearing dogs, circulating TGFβ1 concentrations correlate with urine N‐telopeptide excretion.

Conclusions and Clinical Importance

Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro‐tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs.     

Phase II Evaluation of VDC‐1101 in Canine Cutaneous T‐Cell Lymphoma

Background

Canine cutaneous T‐cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC‐1101 (formerly known as GS‐9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC‐1101 to the skin.

Hypothesis/Objectives

The primary study objective was to identify the objective response rate (ORR) to VDC‐1101 in canine CTCL; secondary objectives included characterization of progression‐free survival (PFS) and adverse events (AEs).

Animals

Twelve dogs with chemotherapy‐naïve or relapsed, histologically and immunohistochemically confirmed CTCL.

Methods

Dogs received VDC‐1101 as a 30‐minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently.

Results

In 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE.

Conclusions and Clinical Importance

VDC‐1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis.     

Investigation of serum concentrations and immunohistochemical localization of α1-acid glycoprotein in tumor dogs

The purpose of this study was to measure the dynamics of serum α1-acid glycoprotein (AGP) concentration in dogs with various tumors, and to investigate the localization of AGP in some tissues using immunohistochemical staining. Sera were obtained from 171 dogs bearing tumors of various types. Serum AGP concentration was measured by single radial immunodiffusion. Tumors occurring in the liver and spleen were also investigated immunohistochemically using anti-canine AGP antibody. Mean serum AGP levels were 749 ± 602 mg/L in dogs with carcinoma (n = 39), 1,014 ± 971 mg/L with sarcoma (n = 18), and 887 ± 935 mg/L with round cell tumors (n = 46), all significantly higher than serum AGP level in healthy dogs (n = 137, 364 ± 106 mg/L). Mean serum AGP levels were significantly higher than in healthy dogs in complex mammary gland carcinoma (n = 5, 876 ± 721 mg/L), malignant melanoma (n = 7, 1,010 ± 821 mg/L), and hepatocellular carcinoma (n = 5, 936 ± 741 mg/L) among carcinomas, hemangiosarcoma (n = 5, 1,740 ± 1,323 mg/L) among sarcomas, and lymphoma (n = 19, 1,072 ± 965 mg/L) and histiocytic tumor (n = 6, 1,800 ± 1,387 mg/L) among round cell tumors. In an immunohistochemical investigation of AGP localization, both weak and strong staining for anti-AGP antibody were seen in hepatic tissue in dogs with primary non-tumorous lesions originating in the spleen (hematoma) and elevated serum AGP, but all tumor tissue in the spleen was negative. Among dogs with primary tumor lesions of the spleen (hemangiosarcoma) and elevated serum AGP levels, both weak, moderate and strong staining for anti-AGP antibody were seen in hepatic tissue, while strong positive staining was apparent in all tumorous tissue from the spleen. In primary tumor lesions in the liver (hepatocellular carcinoma), both moderate and strong staining for anti-AGP antibody were seen in normal hepatic tissue, and both weak, moderate and strong staining were seen in tumor tissues of the liver. AGP levels thus appear to be elevated in dogs with carcinomas, sarcomas, and round cell tumors. With some of these malignant tumors, localization of AGP in tumor tissue was seen.