Kimberly A. Agnello

Intrathecal resiniferatoxin in a dog model: efficacy in bone cancer pain.

Abstract Resiniferatoxin (RTX) is the most potent among all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium-permeable nonselective cation channel, expressed on the peripheral and central terminals of small-diameter sensory neurons. Prolonged calcium influx induced by RTX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1-expressing C-fiber neuronal cell bodies in the dorsal root ganglia. The goal of this project was to provide preclinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single-blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n = 36) or 1.2 &mgr;g/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n = 36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; P < 0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (P < 0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies.

Intrathecal substance-p saporin in the dog: Efficacy in bone cancer pain

Background: Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor–bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. Methods: In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n = 35) or intrathecal SP-SAP (20–60 µg) in addition to standard-of-care analgesic therapy (n = 35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death. Results: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P < 0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P < 0.01). Conclusion: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.

Treatment of aldosterone-secreting adrenocortical tumors in cats by unilateral adrenalectomy: 10 cases (2002-2012).

Background Primary hyperaldosteronism (PHA) in cats occurs as a consequence of excessive hormone production by an adrenocortical tumor. Median survival time, association between tumor type and prognosis, and the likelihood that cats require continued medical therapy after surgery have not been systematically evaluated. Objectives To determine the median survival time of cats with PHA treated by unilateral adrenalectomy. To examine if tumor type, anesthesia time, or tumor location (left or right side) affect survival and if affected cats require continued postoperative treatment for persistent hypertension or hypokalemia. Animals Ten client‐owned cats. Methods Retrospective study. Cats were diagnosed with PHA based on clinical signs, increased plasma aldosterone concentration, and advanced imaging. Cats underwent unilateral adrenalectomy. Survival time (days alive after surgery) was determined for each cat. Factors affecting median survival time were investigated, including histopathology, anesthesia time, and location (side) of the tumor. Results Eight of 10 cats survived to discharge from the hospital post adrenalectomy. Overall median survival was 1,297 days (range 2–1,582 days). The only significant factor affecting median survival time was anesthesia time >4 hours. Tumor type and location (side) did not significantly affect median survival time. No cats required continued medical treatment for PHA. Conclusions and Clinical Importance Although PHA in cats is still considered an uncommon condition, it should be considered in middle to older aged cats with hypokalemic polymyopathy and systemic hypertension. Surgical correction by unilateral adrenalectomy is a viable approach to definitive treatment of PHA with no need for continued medical management.

Preoperative thoracic radiographic findings in dogs presenting for gastric dilatation-volvulus (2000-2010): 101 cases.

OBJECTIVE To identify the incidence of clinically significant findings on preoperative thoracic radiographs in dogs with gastric dilatation-volvulus (GDV) and to determine if those findings are associated with survival. DESIGN Retrospective study from 2000 to 2010. SETTING Urban university small animal teaching hospital. ANIMALS One hundred and one dogs diagnosed with GDV that had thoracic radiographs obtained preoperatively, and medical records available with the following information available: signalment, time of presentation, respiratory status, plasma lactate, presence of cardiac arrhythmias, reason for thoracic radiographs, radiographic findings, and outcome. INTERVENTIONS None. RESULTS Findings on preoperative thoracic radiographs included small vena cava (40%), esophageal dilation (39%), microcardia (34%), aspiration pneumonia (14%), cardiomegaly (5%), pulmonary nodule (4%), pulmonary edema (2%), sternal lymphadenopathy (1%), and pulmonary bullae (1%). Eighty-four percent of dogs (85 out of 101) survived to discharge. Dogs without cardiomegaly on presenting thoracic radiographs had a 10.2 greater odds of surviving to discharge. CONCLUSIONS The most common findings on preoperative thoracic radiographs include esophageal dilation, microcardia, and a small vena cava while the incidence of pulmonary nodules was low. A negative association between survival and presence of cardiomegaly on preoperative thoracic radiographs in dogs with GDV supports the need to obtain these images for prognostic information in spite of the emergency surgical nature of the GDV. The main limitations of this study include the possibilities of type I and type II errors, the retrospective nature of the study, and the lack of well-defined criteria for obtaining thoracic radiographs.Objective To identify the incidence of clinically significant findings on preoperative thoracic radiographs in dogs with gastric dilatation-volvulus (GDV) and to determine if those findings are associated with survival. Design Retrospective study from 2000 to 2010. Setting Urban university small animal teaching hospital. Animals One hundred and one dogs diagnosed with GDV that had thoracic radiographs obtained preoperatively, and medical records available with the following information available: signalment, time of presentation, respiratory status, plasma lactate, presence of cardiac arrhythmias, reason for thoracic radiographs, radiographic findings, and outcome. Interventions None. Results Findings on preoperative thoracic radiographs included small vena cava (40%), esophageal dilation (39%), microcardia (34%), aspiration pneumonia (14%), cardiomegaly (5%), pulmonary nodule (4%), pulmonary edema (2%), sternal lymphadenopathy (1%), and pulmonary bullae (1%). Eighty-four percent of dogs (85 out of 101) survived to discharge. Dogs without cardiomegaly on presenting thoracic radiographs had a 10.2 greater odds of surviving to discharge. Conclusions The most common findings on preoperative thoracic radiographs include esophageal dilation, microcardia, and a small vena cava while the incidence of pulmonary nodules was low. A negative association between survival and presence of cardiomegaly on preoperative thoracic radiographs in dogs with GDV supports the need to obtain these images for prognostic information in spite of the emergency surgical nature of the GDV. The main limitations of this study include the possibilities of type I and type II errors, the retrospective nature of the study, and the lack of well-defined criteria for obtaining thoracic radiographs.

Risk factors for loosening of cementless threaded femoral implants in canine total hip arthroplasty

OBJECTIVE To determine the incidence and potential risk factors of femoral implant loosening in the canine Helica® total hip replacement (THR) system. METHOD Sixteen dogs with a Helica THR were included. Medical records were reviewed for signalment and size of implants. Stem angle, stem collar to lateral cortex distance, tip to cortex distance, stem collar to lateral cortex distance at a stem angle of 150°, lever arm distance, and the distance on the diaphysis measurements were calculated from the one year postoperative radiographs. Three ratios were determined from these measurements to take into account the size of the femur in relation to the size of the implant. Femoral implant loosening was identified by radiographic and clinical signs, and confirmed at the time of surgical explantation. Differences in the successful and femoral stem failure groups were compared using either a students t-test or a Mann Whitney test. Significance was set at p <0.003. RESULTS Six of the 16 dogs had loosening of the femoral prostheses within one year post-implantation. One dog had evidence of a septic cause for loosening. No significant risk factors could be identified in this group of dogs with Helica stem loosening. CLINICAL SIGNIFICANCE Helica femoral stem loosening was a common complication within one year post-implantation in this group of dogs. No risk factors were identified to potentially decrease the incidence of loosening. Therefore, due to this unacceptably high complication rate, the authors do not recommend this model of the Helica THR.

Factors associated with pathological fractures in dogs with appendicular primary bone neoplasia: 84 cases (2007–2013)

OBJECTIVE To determine the incidence of pathological fractures associated with appendicular primary bone tumors in dogs managed medically and to identify potential risk factors at the time of radiographic diagnosis that may be associated with eventual pathological fracture. DESIGN Retrospective case series. ANIMALS 84 dogs with primary long bone neoplasia treated medically. PROCEDURES Medical records for dogs with a diagnosis of primary long bone neoplasia based on results of radiography that was confirmed subsequently at necropsy were reviewed. Owners elected medical treatment at a pain clinic. Data regarding clinical signs, diagnostic testing, pathological findings, and outcome were evaluated. RESULTS 84 dogs met study inclusion criteria with 85 limbs affected. Osteosarcoma was the most common tumor and was identified in 78 of 85 (91.8%) limbs. The median time from diagnosis to euthanasia was 111 days (range, 28 to 447 days). Pathological fractures were identified in 33 of 85 limbs (38%), with the femur most commonly affected, (8/14 [57.1%]), followed by the tibia (9/17 [52.9%]), humerus (10/27 [37%]), radius (5/25 [20%]), and ulna (1/2 [50%]). Logistic regression analysis indicated that tumors arising from long bones other than the radius had odds of eventual fracture 5.05 as great as the odds for tumors of the radius, and lytic tumors had odds of eventual fracture 3.22 as great as the odds for tumors that appeared blastic or mixed lytic-blastic. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that radial primary bone tumors were less likely and lytic tumors were more likely to fracture. The overall incidence of pathological fractures secondary to appendicular primary bone neoplasia in this study with patients treated by means of intensive management for bone pain was higher than previously reported.

Articular Cartilage Lesions of the Patellofemoral Joint in Dogs With Naturally Occurring Cranial Cruciate Ligament Disease

OBJECTIVE To evaluate frequency, severity, and location of patellofemoral (PF) osteoarthritis (OA) in dogs with naturally occurring cranial cruciate ligament (CCL) disease. STUDY DESIGN Cross-sectional observational study. ANIMALS Dogs (n = 40; stifles, 44). METHODS Stifle arthroscopic video recordings and radiographs were performed. Cartilage pathology was scored at 3 locations (proximal, middle, distal) in the trochlear groove and patella. A radiographic osteoarthrosis and synovial pathology score were assigned. A Kruskal-Wallis test was used to determine if lesion severity varied by site, synovitis, and osteoarthrosis, and the Dunns test was used for pairwise comparisons. The variability of body weight was evaluated using 1 way ANOVA; P < .05 was considered significant. RESULTS Cartilage pathology and synovitis was identified in all PF joints. The proximal aspect of the trochlear groove had significantly higher cartilage scores than the middle and distal sites and the middle groove site was significantly higher than the distal site. The distal aspect of the patella had significantly greater scores than the middle and proximal patellar locations. Higher synovitis scores were associated with increased cartilage scores. Cartilage scores were significantly greater in stifles with higher radiographic osteophytosis, tibial sclerosis, and patellar enthesiophytosis scores. Higher body weights were significantly associated with greater synovial and radiographic scores. CONCLUSIONS Dogs with CCL disease have a high incidence of PF cartilage pathology and the severity of cartilage lesions varies depending on location within the joint.

Effects of transection of the cranial arm of the medial glenohumeral ligament on shoulder stability in adult Beagles

OBJECTIVE To assess the effects of arthroscopic transection of the cranial arm of the medial glenohumeral ligament on shoulder stability. ANIMALS Six adult Beagles. PROCEDURES After transection, the effects were compared with baseline values by orthopaedic and radiographic examinations, by synovial fluid analysis at two, four, and six weeks, and by arthroscopic evaluation at six weeks. The articular surfaces of the glenoid cavity and humeral head were evaluated radiographically and arthroscopically for evidence of arthritis, and five intra-articular regions were examined arthroscopically for villus reactions and vascularisation. RESULTS According to orthopaedic examinations (including measurement of the abduction angle), radiography, and synovial fluid analyses, there were no abnormal findings. Arthroscopically, the articular surfaces of the glenoid cavity and humeral head showed no signs of degeneration, but the craniomedial and caudal joint capsules had significant villus reactions and the subscapularis tendon and medial glenohumeral ligament had significant vascularisation. The biceps tendon was unchanged. CONCLUSIONS Transection of the cranial arm of the medial glenohumeral ligament in normal Beagles did not appear to affect shoulder stability. However, villus reactions and vascularisation in the medial compartment suggest that damage to the medial glenohumeral ligament may trigger a process in which inflammation can lead to enzymatic breakdown of cartilage. Exacerbated by weight bearing and repetitive motion, this may result in shoulder instability over time.

Proximal tibial metaphyseal fractures in immature dogs

OBJECTIVE To describe proximal tibial metaphyseal fractures in immature dogs. MATERIALS AND METHODS Medical records of immature dogs with metaphyseal fractures of the proximal tibia were reviewed and data were collected on signalment and history of trauma. Craniocaudal and mediolateral radiographs were evaluated for the determination of the bones fractured, location of the fracture within the bone, fracture configuration, and the presence of fracture segment displacement and angulation. RESULTS Eighteen dogs with 22 proximal tibial metaphyseal fractures fulfilled the inclusion criteria. All fractures had a curvilinear, complete fracture of the proximal tibial metaphysis. Displacement was identified in 16 fractures and angulation in 15 fractures. All affected breeds were terrier or small breed dogs less than six months of age. The majority of dogs weighed less than or equal to 5 kg at the time of injury. The most common type of trauma that occurred was a jump or fall from a short distance. CLINICAL SIGNIFICANCE Proximal tibial metaphyseal fractures are an uncommon injury that occur in skeletally immature dogs from minimal trauma. Proximal tibial metaphyseal fractures have a characteristic curvilinear fracture configuration that affects mainly small breed dogs with a predominance for terrier breeds.