Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

PURPOSE: Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. EXPERIMENTAL DESIGN: (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. RESULTS: (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. CONCLUSION: We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney.

BACKGROUND: A well-characterized dog model of the X-linked collagen disease Alport syndrome (XLAS) was used to study the effect of progressive glomerular disease on megalin-mediated endocytosis. In XLAS, altered structure and function of the glomerular basement membrane induces a progressive proteinuric nephropathy. METHODS: The investigation was performed in male XLAS dogs and age-matched normal male littermates. The urine profile and megalin-mediated endocytosis in the proximal tubule of six healthy and six XLAS dogs were examined at 2, 4, 6, 8 and 10 months of age using SDS-PAGE, immunoblotting and immunohistochemistry. RESULTS: Gradually increasing urinary excretion of proteins over time and a reduced content of the same proteins in proximal tubule cells were found. Besides the glomerular component of the proteinuria, a significant tubular component was seen, which is due to a progressive change in the uptake of low-molecular-weight (LMW) ligands by megalin. Furthermore, the protein overload present in the lumen of the proximal tubule exceeds the reabsorption capacity of megalin and the co-receptor cubilin and results in a combined low- and high-molecular-weight (HMW) proteinuria. Also, a shift in the distribution of lysosomes was seen in the XLAS dogs suggesting changes in the lysosomal degradation pattern in response to the altered endocytosis. CONCLUSIONS: The present study shows that the increased glomerular permeability and the subsequently altered megalin-mediated and megalin-dependent cubilin-mediated endocytosis lead to a partial LMW proteinuria and partial HMW proteinuria.

Cervical spinal locking plate in combination with cortical ring allograft for a one level fusion in dogs with cervical spondylotic myelopathy.

OBJECTIVE: To evaluate use of a surgical technique commonly used in humans for treatment of cervical spondylotic myelopathy (CSM) in dogs. DESIGN: Prospective case series. ANIMALS: Dogs with CSM (n=10). METHODS: Dogs weighing >30 kg that had CSM at 1 vertebral articulation were eligible for inclusion. Dogs had vertebral column distraction/fusion performed using a cortical ring allograft, cancellous autograft, and a spinal locking plate. Dogs were evaluated temporally by repeat neurological examinations and by client perception of postsurgical outcome, determined by telephone interview. RESULTS: Nine dogs survived the immediate postoperative period. Seven of 8 dogs had moderate to complete improvement without recurrence (mean follow-up, 2.48 years). The most common postsurgical complications were screw loosening (n=4) and plate shifting (2), neither of which required surgical revision. One dog had pseudoarthrosis that may have negatively impacted outcome. CONCLUSION: Treatment of single level CSM in dogs with ring allograft and a spinal locking plate system may lead to successful outcomes. The major problems encountered with included cost of the implants and adjusting the system designed for humans to fit the vertebral column of a dog. CLINICAL RELEVANCE: For dogs with CSM at a single level, the use of a spinal locking plate in combination with a cortical ring allograft can be an effective surgical treatment. Costs of the implants as well as anatomic differences in dogs make this type of surgery less appealing.

Echocardiographic and angiographic comparison of ductal dimensions in dogs with patent ductus arteriosus.

BACKGROUND: Transcatheter occlusion of patent ductus arteriosus (PDA) is a minimally invasive treatment option in dogs. Device selection based on appropriately acquired PDA dimensions and morphology can minimize procedural complications, including minimizing residual ductal flow and inappropriate embolization. HYPOTHESIS: Transesophageal echocardiographic (TEE) derived minimum ductal diameter measurements would most accurately reflect angiographic measurements. Color Doppler (CD) TEE and transthoracic echocardiographic (TTE) ductal measurements would overestimate two-dimensional (2D) measurements. ANIMALS: Fifteen client-owned dogs with PDA. METHODS: PDA dimensions obtained with angiography, 2D and CD TTE, 2D and CD TEE from the right and left views were prospectively evaluated. RESULTS: PDA dimensions were measured by using TEE most closely approximated angiographic measures. CD TTE and TEE frequently overestimated angiographic measures of minimum ductal diameter. TEE accurately identified a type III (tubular) PDA morphology in 1 dog. Fourteen of 15 dogs were determined to have hemodynamically significant reductions in left to right shunting documented by a first-pass nuclear angiocardiographic ratio of pulmonary to systemic blood flow < or = 1.2 and trivial (n = 3) to no (n = 11) CD TTE flow at approximately 1 month after PDA occlusion. CONCLUSIONS: TEE provided accurate anatomic information regarding PDA morphology and closely approximated angiographic ductal dimensions while aiding in both coil deployment and confirmation of intra-operative ductal closure.

Effect of computed tomography display window and image plane on diagnostic certainty for characteristics of dysplastic elbow joints in dogs.

OBJECTIVE: To test the effects of computed tomography (CT) image plane and window settings on diagnostic certainty for CT characteristics associated with dysplastic elbow joints (elbow joint dysplasia) in dogs and to provide optimal display guidelines for these CT characteristics. SAMPLE POPULATION: CT images of 50 dysplastic elbow joints from 49 lame dogs and 10 elbow joints from 5 sound dogs. PROCEDURES: CT image data were obtained in transverse, sagittal, and dorsal planes. Each plane was examined by use of 3 Hounsfield unit (HU) window settings. Two veterinary radiologists independently evaluated sets of CT images for evidence of 7 CT characteristics. Effect of elbow joint status, image plane, and window settings on diagnostic certainty for these CT characteristics was tested by use of a visual analogue scale. RESULTS: Diagnostic certainty for abnormalities of the medial coronoid process (MCP) and radial incisure was highest in the transverse plane, subchondral defects or sclerosis of the trochlea humeri was highest in the dorsal plane, and joint incongruity was highest in the sagittal plane. Certainty for hypoattenuating subchondral defects or fissures was highest at 2,500 or 3,500 HUs, whereas certainty for subchondral sclerosis was highest at 1,500 HUs and lowest at 3,500 HUs. CONCLUSIONS AND CLINICAL RELEVANCE: Diagnostic certainty for CT characteristics of elbow joint dysplasia in dogs was affected by image display variables. Diagnostic certainty for altered subchondral bone density was primarily influenced by window settings, whereas structural MCP abnormalities and joint incongruity were influenced most by image plane.

Effects of femur position on radiographic assessment of completeness of femoral head and neck excision in medium- to large-breed dogs.

OBJECTIVE: To determine the effect of femur positioning on radiographic assessment of completeness of excision after femoral head and neck excision (FHNE) in medium to large breed dogs. SAMPLE POPULATION: 10 femurs from canine cadavers (body weight > 20 kg). PROCEDURE: Complete FHNE was performed on 5 canine femurs. Excision consisting of inadequate removal of the medial distal aspect of the femoral neck was performed on the remaining 5 femurs. Each femur was positioned with predetermined amounts of internal and external rotation about the long axis and radiographed. Investigators evaluated a set of 8 radiographic views of each femur. Sensitivity (SE), specificity (SP), positive predictive value, negative predictive value, and completeness of excision assessment accuracy were estimated for each of the femur positions. RESULTS: Craniocaudal radiographic views of the femur positioned with external rotation of 15 degrees, 30 degrees, and 45 degrees as a group had the highest SE, SP, and completeness of excision assessment accuracy relative to other radiographic views. The SE, SP, and accuracy of assessment were higher when the degree of external rotation was increased from 15 degrees to 30 degrees or 45 degrees. CONCLUSIONS AND CLINICAL RELEVANCE: Craniocaudal radiographic views of the femur positioned in external rotation (15 degrees, 30 degrees, and 45 degrees) improved the ability to detect adequacy of excision relative to standard craniocaudal and lateromedial radiographic views. Evaluation of craniocaudal radiographic views of the femur positioned in external rotation may increase the ability to assess FHNE adequacy in medium- to large-breed dogs.

Vascular encephalopathy associated with bacterial endocarditis in four dogs.

Vascular encephalopathy is a commonly encountered clinical complication of infectious endocarditis in humans, but it has been infrequently reported in dogs. A series of four dogs with bacterial endocarditis that subsequently developed acute onset of neurological deficits is described. Clinical signs, diagnostic test results, and outcomes for each case are presented and compared with the human clinical syndrome.

Ectopic Intrathoracic Hepatic Tissue and Accessory Lung Lobe Aplasia in a Dog.

A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass.

First-pass nuclear angiocardiography in the evaluation of patent ductus arteriosus in dogs.

First-pass nuclear angiocardiography (FPNA) was performed in 5 normal dogs and in 19 dogs with left-to-right shunting patent ductus arteriosus (PDA). Affected dogs were evaluated before and after an occlusion procedure (surgical ligation or transarterial coil embolization). Two methods of analysis were used to evaluate the pulmonary time-activity curves and assess the magnitude of the shunt. One method involved the calculation of a simple count ratio (C2:C1). The other method used gamma variate modeling to estimate the ratio of pulmonary to systemic blood flow (QP:QS). Values for normal dogs (mean +/- SD) were C2:C1 = 0.39 +/- 0.11 and QP:QS = 1.10 +/- 0.03. Values for affected dogs were C2:C1 = 0.59 +/- 0.17, QP:QS = 2.01 +/- 0.46 before intervention and QP:QS = 1.21 +/- 0.17, C2:C1 = 0.42 +/- 0.12 after intervention. Both methods detected significant differences between normal and affected dogs (QP:QS, t-test, P < .001; C2:C1; t-test; P = .018) and between affected dogs pre- and postocclusion (QP:QS. paired t-test, P < .001; C2:C1, paired t-test, P = .002). However, QP:QS was a better separator of normal from affected animals. First-pass nuclear angiocardiography, by the gamma variate method, may be a useful, adjunct diagnostic test in evaluation of animals with left-to-fight shunting PDA, particularly in animals with residual shunting after an occlusion procedure.

Pulmonary embolization of vascular occlusion coils in dogs with patent ductus arteriosus.

Transcatheter coil embolization of patent ductus arteriosus (PDA) was performed in 206 dogs between 1994 and 2003 at Texas A&M University, of which 7 (3%) had embolization of coils to the pulmonary vasculature. Thoracic radiographs indicated that coils were located in the right pulmonary artery in 6 of the 7 dogs. Pulmonary perfusion scans were available for review in 5 dogs, and moderate perfusion defects were observed in the right caudal lung lobe in 4 dogs within 24 hours of embolization. Perfusion deficits observed initially in 2 of the dogs resolved on perfusion scans performed at 6 months and 3.1 years. One dog did not have evidence of focal perfusion defects on a perfusion scan performed 4.5 months after embolization. All pulmonary embolizations occurred during the procedure. Attempts at retrieval of coils were unsuccessful in the 2 dogs in which it was attempted. No short- or long-term clinical complications were observed in any of the dogs with pulmonary embolization. We conclude that pulmonary embolization of vascular occlusion coils is an uncommon event and is not typically associated with adverse clinical effects in dogs with PDA.

Thoracic duct ligation and pericardectomy for treatment of idiopathic chylothorax.

Chylothorax is a devastating disease, and the success rates from either medical or surgical management are less than satisfactory. In some animals with chylothorax, a thickening of the pericardium occurs that is associated with chronic irritation induced by chyle. We hypothesized that pericardial thickening would lead to increased right-sided venous pressures and that abnormal venous pressures would act to impede the drainage of chyle via lymphaticovenous communications after thoracic duct (TD) ligation. We also hypothesized that serosanguineous effusions that occurred after TD ligation could effectively be treated or prevented by pericardectomy in affected animals. TD ligation plus pericardectomy was performed in 17 animals, and pericardectomy alone was performed in an additional 3 animals that presented during a 5.5-year period to the Texas A&M University (College Station, TX). Nineteen animals presented for an evaluation of idiopathic chylothorax (9 dogs and 10 cats), and 1 dog presented for serosanguineous pleural fluid after TD ligation that had been performed elsewhere. Echocardiography was normal in all animals, except for a subjectively thickened pericardium in 7 cats and 6 dogs. Clinical signs of pleural fluid accumulation resolved in 10 of 10 dogs and in 8 of 10 cats after surgery. The overall success rate for the surgical treatment of chylothorax (ie, the resolution of pleural fluid accumulation) in this study was 90% (100% in dogs and 80% in cats). These data suggest that TD ligation in conjunction with pericardectomy has a favorable outcome in animals with idiopathic chylothorax.

Evaluation of acetaminophen absorption in horses with experimentally induced delayed gastric emptying.

OBJECTIVE: To evaluate the correlation between the half-time of liquid-phase gastric emptying (T50) determined by use of nuclear scintigraphy, using technetiumTc 99m pentetate, and absorption variables of orally administered acetaminophen in horses with experimentally delayed gastric emptying. ANIMALS: 6 mature horses. PROCEDURE: Delayed gastric emptying was induced by IV injection of atropine sulfate. Twenty minutes later, acetaminophen and technetium Tc 99m pentetate were administered simultaneously via nasogastric tube. Serial lateral images of the stomach region were obtained, using a gamma camera. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness-of-fit of the data. Serial serum samples were obtained, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 480 minutes, and the appearance rate constant were determined, using a parameter estimation program. Correlations were calculated, using a Spearman rank correlation coefficient. RESULTS: A significant correlation was detected between T50 determined by use of scintigraphy and Tmax determined by use of acetaminophen absorption. Correlation between T50 and other absorption variables of acetaminophen was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: The acetaminophen absorption method was a valid technique in this model of delayed gastric emptying in horses. The method may be a valuable tool for use in research as well as in clinical evaluation of gastric emptying in horses.

Evaluation of gradual occlusion of the caudal vena cava in clinically normal dogs.

OBJECTIVES: To devise a technique for gradual occlusion of the caudal vena cava in dogs and determine effects of complete occlusion of the caudal vena cava. ANIMALS: 8 mixed-breed hounds that weighed between 25 and 30 kg. PROCEDURE: Baseline evaluation of dogs included serum biochemical analyses and determination of glomerular filtration rate (GFR) with dynamic renal scintigraphy and plasma clearance analysis. An occluder was placed around the vena cava in the region cranial to the renal veins. The occluder was attached to a vascular access port. The vena cava was gradually occluded over 2 weeks. The GFR was measured every 2 weeks after surgery, and venograms were performed every 3 weeks after surgery. Blood samples were collected every 48 hours for the first week and then weekly thereafter to measure BUN and creatinine concentrations and activities of alanine transaminase, alkaline phosphatase, and creatinine kinase. Dogs were euthanatized 6 weeks after surgery, and tissues were submitted for histologic examination. The GFR and biochemical data were compared with baseline values. RESULTS: Gradual occlusion of the caudal vena cava was easily and consistently performed with this method, and adverse clinical signs were not detected. Formation of collateral vessels allowed overall GFR to remain constant despite a decrease in function of the left kidney. Measured biochemical values did not deviate from reference ranges. CONCLUSIONS AND CLINICAL RELEVANCE: Gradual occlusion of the caudal vena cava may allow removal of adrenal gland tumors with vascular invasion that would otherwise be difficult or impossible to resect.

Transvenous retrograde portography for identification and characterization of portosystemic shunts in dogs.

Transvenous retrograde portography for identification and characterization of portosystemic shunts in dogs A method for transvenous retrograde portography (TRP) in dogs suspected to have a portosystemic shunt (PSS) and results in 20 dogs are described. For TRP, dogs were anesthetized and positioned in left lateral recumbency A dual-lumen balloon-tipped catheter was inserted into the right jugular vein and advanced into the azygos vein. The balloon was inflated to occlude the azygos vein, and contrast material was injected during fluoroscopic evaluation. The catheter was then positioned in the caudal vena cava just cranial to the diaphragm. The balloon was again inflated to occlude the vena cava, and contrast material was again injected. Once a shunt was identified, selective catheterization was attempted with a guide wire and angled catheter. A PSS was identified in 18 of the 20 dogs. In 10 of the 18, the shunt vessel could be selectively catheterized, allowing measurement of portal pressures while the shunt was occluded with the balloon. In 1 dog, results of TRP were normal, but subsequent exploratory celiotomy revealed a single extrahepatic PSS, which was surgically attenuated. The other dog in which results of TRP were normal did not have a macroscopic PSS. In dogs suspected to have a PSS, TRP may be a useful adjunctive diagnostic test that is less invasive than operative mesenteric vein portography and allows measurement of portal pressures before and after temporary shunt occlusion.

Neurologic complications after melarsomine dihydrochloride treatment for Dirofilaria immitis in three dogs.

Melarsomine dihydrochloride is highly effective against both sexes of adult and L5 Dirofilaria immitis. Common adverse reactions include injection site irritation and reluctance to move. Neurologic complications associated with i.m. injection of melarsomine dihydrochloride for treatment of heartworm disease in 3 dogs are described. Different degrees of neurologic complications have been identified; the pathophysiologic features are unknown. It is speculated that the compound migrates out of the injection site via fascial planes and causes an ascending inflammation along nerve roots. The resulting extradural cord compression secondary to extensive inflammation and necrosis of epidural fat could induce a variety of neurologic deficits. Alternatively, inappropriate injection technique may result in direct contact of melarsomine with neural tissue. A heightened awareness of proper injection technique might prevent the development of most neurologic complications.

Presumptive subdural empyema in a dog.

A 13 mo old mixed-breed dog was referred for acute lateralized forebrain signs. MRI of the brain demonstrated abnormalities consistent with severe meningitis and subdural empyema secondary to a retrobulbar abscess. The dog's clinical signs improved with antibiotic therapy, and repeat imaging showed resolution of subdural fluid accumulation presumed to be empyema with mild residual meningeal enhancement. Subdural empyema is an infrequent cause of encephalopathy in small animals and usually develops through direct extension of a pericranial infection. This report presents a case of presumptive subdural empyema in a dog that was successfully treated without surgical intervention. MRI is the preferred imaging modality for diagnosis of subdural empyema, and the characteristic imaging features are described.

Evaluation of 99MTC-diethylenetriaminepentaacetic acid renal scintigram curves in normal dogs after induction of diuresis.

The normal 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigram curve has 3 distinct phases; an arterial phase followed by progressive uptake and subsequent excretion from the kidney. In dogs with X-linked hereditary nephritis, a distinct flattening of the renal scintigram curve has been observed prior to any decline in glomerular filtration rate (GFR). The cause of this shape change is not known, however, it coincided with decreased urine-specific gravity and thus might be related to polyuria. To further evaluate this possibility, we assessed whether diuresis without concurrent renal disease could flatten the 99mTc-DTPA renal scintigram curve. GFR scintigraphy was performed in six healthy dogs once as a baseline, and again after induction of diuresis by each of four different methods. Scintigram curves were evaluated subjectively as well as quantitatively by calculation of GFR estimates, mean renal transit times, time to peak activity and half-time clearance. Complete flattening of the renal scintigram curve did not occur with diuresis alone, and therefore, flattening of the scintigram curve may serve as an early indicator of renal dysfunction. However, during diuresis after intravenous saline administration, alterations in time to peak activity and mean renal transit time may create inaccuracies in GFR estimates based on the conventional regression formula that cause a false lowering of the resultant global GFR value.