Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin.

BACKGROUND: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. HYPOTHESIS/OBJECTIVES: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. ANIMALS: Fourteen client-owned dogs were prospectively enrolled. METHODS: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. RESULTS: A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.

A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats.

OBJECTIVE: Scottish fold cats, named for their unique ear shape, have a dominantly inherited osteochondrodysplasia involving malformation in the distal forelimbs, distal hindlimbs and tail, and progressive joint destruction. This study aimed to identify the gene and the underlying variant responsible for the osteochondrodysplasia. DESIGN: DNA samples from 44 Scottish fold and 54 control cats were genotyped using a feline DNA array and a case-control genome-wide association analysis conducted. The gene encoding a calcium permeable ion channel, transient receptor potential cation channel, subfamily V, member 4 (TRPV4) was identified as a candidate within the associated region and sequenced. Stably transfected HEK293 cells were used to compare wild-type and mutant TRPV4 expression, cell surface localisation and responses to activation with a synthetic agonist GSK1016709A, hypo-osmolarity, and protease-activated receptor 2 stimulation. RESULTS: The dominantly inherited folded ear and osteochondrodysplasia in Scottish fold cats is associated with a p.V342F substitution (c.1024G>T) in TRPV4. The change was not found in 648 unaffected cats. Functional analysis in HEK293 cells showed V342F mutant TRPV4 was poorly expressed at the cell surface compared to wild-type TRPV4 and as a consequence the maximum response to a synthetic agonist was reduced. Mutant TRPV4 channels had a higher basal activity and an increased response to hypotonic conditions. CONCLUSIONS: Access to a naturally-occurring TRPV4 mutation in the Scottish fold cat will allow further functional studies to identify how and why the mutations affect cartilage and bone development.

Prevalence of canine hip dysplasia in a veterinary teaching hospital population.

The purpose of this study was to determine the prevalence of canine HD in a population in which there was minimal or no prior screening of radiographs for the disorder. Patient information was obtained from the radiographic database at the University of Missouri-Columbia Veterinary Teaching Hospital during the five-year period of 1991-1995. The coxofemoral joints on ventrodorsal radiographs of the pelvis were independently evaluated by three veterinary radiologists. A consensus evaluation of normal, borderline, or dysplastic was compiled. There were 2885 dogs identified representing 116 breeds and the mixbreds. There were 2236 purebred dogs (1071 males and 1165 females) and the prevalence of HD was 19.7%. There were 649 mixbred dogs (340 males and 309 females) and the prevalence of HD was 17.7%. There was no significant difference in the prevalence of HD between sexes or between purebred and mixbred dogs (P = 0.16; P = 0.29). Degenerative joint disease (DJD) was the most common radiographic manifestation of HD and there appeared to be a threshold at 12 months of age after which the presence of DJD was the primary diagnostic criteria.

The use of a latissimus dorsi muscle flap for scapular reconstruction in a cat following fibrosarcoma excision.

A latissimus dorsi muscle flap was used to reconstruct a proximal scapular defect in a cat after excision of a fibrosarcoma that had recurred after eight surgeries, radiation therapy, and chemotherapy. To obtain appropriate surgical margins, infraspinatus and supraspinatus myectomy and scapular spinous ostectomy were performed. The latissimus dorsi muscle flap was rotated into the defect and anchored to four holes placed in the cranial border of the scapula. The cat showed no lameness at 6, 21, 42, and 147 days after surgery. The latissimus dorsi muscle flap was successful for proximal scapular reconstruction in this cat.

Comparison of abomasal emptying in neonatal calves with a nuclear scintigraphic procedure.

The purpose of the present study was to demonstrate that nuclear medicine technology allows observation of the effect that milk clotting has on abomasal emptying in the living neonatal calf. Scintigraphic evaluation of abomasal emptying was carried out in 6 healthy male Holstein calves. The calves were fed 10% of their body weight daily as whole cow's milk that was divided equally and consumed as 2 feedings via a nipple bottle. One day before the nuclear scintigraphic procedure, the calves were randomly fed whole cow's milk, or an oral rehydration solution (ORS) containing bicarbonate and high levels of soluble fibre was fed for 3 consecutive feedings an hour before the portion of milk. For each calf, both feeding programs were repeated twice at a one-week interval. Immediately following administration of the 99mTC-sulfur-colloid-containing milk, the calves were imaged with the gamma camera positioned lateral and ventral to the abomasum. Additional right lateral and ventral views of the abomasum were collected at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min after administration of the radionuclide. Blood glucose determination were performed at one-hour intervals for 7 h after feeding milk to evaluate milk digestibility in both feeding programs. No significant differences in the results of the glucose absorption test or in the radionuclide counts of the abomasum were found between both feeding programs. Scintigraphic evaluation of abomasal emptying was found to be a useful technique for visualization of milk clotting and to test the effect of an ORS on milk digestibility.

Hip dysplasia: a feline population study.

The study population consisted of cats presented to the University of Missouri-Columbia Veterinary Medical Teaching Hospital from January 1, 1991 through December 31, 1995. Ventrodorsal radiographs including the pelvic region were evaluated for radiographic evidence of hip dysplasia. Each radiograph was evaluated independently by three board-certified veterinary radiologists and a consensus normal of dysplastic evaluation was determined. There were 684 cats from 12 breeds. The data derived from this study indicate the frequency of feline hip dysplasia in this population to be about 6.6% (45/684) and that the incidence appears to be breed dependent. Also, the radiographic appearance of hip dysplasia in cats is different than in dogs. A shallow acetabulum with remodeling and proliferation involving the cranio-dorsal acetabular margin were the most common radiographic signs. Minimal remodeling of the femoral neck was seen.

Reliability of early radiographic evaluations for canine hip dysplasia obtained from the standard ventrodorsal radiographic projection.

OBJECTIVE: To determine reliability of preliminary evaluations for canine hip dysplasia (CHD) performed by the Orthopedic Foundation for Animals on dogs between 3 and 18 months of age. DESIGN: Retrospective analysis of data from the Orthopedic Foundation for Animals database. ANIMALS: 2,332 Golden Retrievers, Labrador Retrievers, German Shepherd Dogs, and Rottweilers for which preliminary evaluation had been performed between 3 and 18 months of age and for which results of a definitive evaluation performed after 24 months of age were available. PROCEDURE: Each radiograph was evaluated, and hip joint status was graded as excellent, good, fair, or borderline phenotype or mild, moderate, or severe dysplasia. Preliminary evaluations were performed by 1 radiologist; definitive evaluations were the consensus of 3 radiologists. Reliability of preliminary evaluations was calculated as the percentage of definitive evaluations (normal vs dysplastic) that were unchanged from preliminary evaluations. RESULTS: Reliability of a preliminary evaluation of normal hip joint phenotype decreased significantly as the preliminary evaluation changed from excellent (100%) to good (97.9%) to fair (76.9%) phenotype. Reliability of a preliminary evaluation of CHD increased significantly as the preliminary evaluation changed from mild (84.4%) to moderate (97.4%) CHD. Reliability of preliminary evaluations increased significantly as age at the time of preliminary evaluation increased, regardless of whether dogs received a preliminary evaluation of normal phenotype or CHD. CLINICAL IMPLICATIONS: Results suggest that preliminary evaluations of hip joint status in dogs are generally reliable. However, dogs that receive a preliminary evaluation of fair phenotype of mild CHD should be reevaluated after 24 months of age.

Evaluation of hyperplastic goiter in a colony of Syrian hamsters (Mesocricetus auratus).

Hyperplastic goiter was diagnosed during routine health monitoring of a closed Syrian hamster colony (SG). Adult and juvenile hamsters were affected at a prevalence of 45%. Histologic examination of the enlarged thyroid gland revealed marked follicular cell hyperplasia. Because prevalence of thyroid hyperplasia in this colony exceeded the 6 to 7% prevalence expected in aged hamsters, additional studies were performed to investigate the pathogenesis of this condition. Juvenile male SG hamsters and age- and sex-matched Syrian hamsters that did not have increased prevalence of goiter were obtained from an unrelated source (Fredrick Cancer Research and Development Center [FCRDC]). The thyroid glands of hamsters were evaluated by 123I radionuclide imaging. Eight of 18 SG hamsters and none of the FCRDC hamsters had a diagnosis of enlarged thyroid gland. Serum baseline and post-thyrotropin thyroxine concentrations in SG hamsters were not statistically different from those in FCRDC hamsters. To investigate whether diet played a role in development of hyperplastic goiter, for 6 months 15 FCRDC hamsters were fed the diet that had been fed to SG hamsters (mouse breeder diet), and five were fed a control diet. To determine whether dietary change would result in resolution of goiter, affected SG hamsters were fed a control diet for 3 months. At the end of each feeding trial, thyroid gland uptake of 123I was reevaluated. The amount of 123I taken up by the thyroid glands of FCRDC hamsters fed the mouse breeder diet was not significantly different from that of controls. In contrast, thyroid gland uptake of 123I remained high for all affected SG hamsters fed the control diet. On the basis of results of these investigations, diet was ruled out as the cause of goiter. Also, a diagnosis of euthyroid hyperplastic goiter was made for the SG hamsters. A genetic cause is suspected to play a role in the increased prevalence of goiter in SG hamsters.

Correlation of radiographic, necropsy and histologic findings in 8 dogs with elbow dysplasia.

Elbow dysplasia is osteoarthrosis/degenerative joint disease due to abnormal development of the elbow joint. The abnormal development is the result of specific inherited etiologies alone or in combination. This paper attempts to clarify the diagnosis of elbow dysplasia based on the presence of degenerative joint disease by correlating radiographic, necropsy, and histopathologic results using elbows from 8 German Shepherd dogs. All elbows had radiographic changes consistent with osteoarthrosis/degenerative joint disease which were identified best on the flexed medial-lateral projection. Radiographically, a specific diagnosis was made in seven elbows; ununited anconeal process (6) and osteochondrosis (1). At necropsy these lesions were confirmed plus 14 elbows were identified that had fragmented medial coronoid process (6), abnormally shaped medial coronoid processes or fissures in the articular cartilage of the medial coronoid process (8). Additionally, histopathologically there was proliferative synovitis at the radial notch of the ulna and degenerative changes on the proximal, nonarticular surface of the anconeal process at the site of insertion of the olecranon ligament and joint capsule. Therefore, for screening the elbow joint to identify elbow dysplasia, the recognition of osteoarthrosis/degenerative joint disease on an extreme flexed mediolateral radiograph appears to be sufficient.

Scintigraphic evaluation of 99mTc-methylene diphosphonate uptake in the navicular area of horses with lameness isolated to the foot by anesthesia of the palmar digital nerves.

OBJECTIVE: To evaluate distribution and intensity of 99mTc-methylene diphosphonate (99mTc-MDP) uptake in the navicular area in horses with forelimb lameness isolated to the palmar aspect of the foot. DESIGN: Prospective, case-controlled study. ANIMALS: 7 horses with clinical signs of navicular syndrome and 7 control horses. PROCEDURE: Palmar view, soft tissue-phase scintigraphic images of the foot were obtained between 7 and 12 minutes after injection of 120 to 170 mCi of 99mTc-MDP. Lateral and palmar view, bone-phase images were obtained at 30 minutes and 1, 2, and 4 hours after injection. Palmar views were evaluated by determining the ratio of image density in the navicular area to mean image density in the distal phalangeal area. Palmar and lateral view, bone-phase images were also scored on the basis of navicular area intensity (intense = 3, moderate = 2, mild = 1, and no uptake = 0). Density ratios and mean scores were evaluated as a three-way ANOVA. RESULTS: Mean navicular-to-distal phalangeal density ratio for affected horses (1.77) was significantly (P = 0.003) greater than that for control horses (0.97). The mean subjective score for affected horses when evaluating palmar views only (1.85) and when evaluating palmar and lateral view pairs together (1.99) was significantly (P < 0.01) higher than scores for control horses (0.51, 0.62). Images obtained 1 hour after injection were as good at differentiating affected from control horses as images obtained between 2 to 4 hours after injection. CONCLUSION: A substantial number of horses with palmar foot pain have increased scintigraphic uptake within the navicular bone 1 to 4 hours after injection of 99mTc-MDP. Lateral view, bone-phase images are less sensitive than palmar view, bone-phase images in revealing navicular area uptake. CLINICAL RELEVANCE: A combination of lateral and palmar view scintigraphic images obtained between 1 and 4 hours after injection of 99mTc-MDP is a useful diagnostic aid in evaluating navicular bone involvement in horses with forelimb lameness isolated to the palmar aspect of the foot.

Multiple cardiac anomalies in a cat.

A 7-week-old domestic shorthair cat was examined because of congestive heart failure. Echocardiography and angiography were used to identify multiple cardiac anomalies. Because of the uncorrectable nature of the defects, the cat was euthanatized. Necropsy revealed persistent left vena cava, patent foramen ovale, and a right atrial/left ventricular canal. The right atrioventricular valve was replaced by a small ostium, and no chordae tendinae or papillary muscles were observed around the ostium. The pulmonary trunk originated from the right atrium. The right ventricular free wall was approximately 1 mm thick.

Clinical and clinicopathologic response of canine bone tumor patients to treatment with samarium-153-EDTMP.

Forty dogs with spontaneous skeletal neoplasia were treated with 153Sm-EDTMP (ethylenediaminetetramethylene phosphonic acid). Both primary and metastatic lesions were treated. Two treatment regimes, a single (37 MBq (1.0 mCi)/kg dose or two 37 MBq (1.0 mCi)/kg doses separated by 1 wk) were tested. Response to treatment was varied. Large lesions with minimal tumor bone formation responded poorly, while primary lesions with substantial ossification usually exhibited a transient response. Small lesions with minimal lysis, metastatic lesions, and axial skeleton lesions generally responded well. The major adverse side effects of treatment were platelet and white blood cell count depression below baseline values for up to 4 wk (p less than 0.05). Minor depression of packed cell volume and transient elevation of serum alkaline phosphatase were also noted (p less than 0.05). No significant differences (p greater than 0.05) between the two treatment groups, either in treatment effect or undesirable side effects, were detected.

Clinical and clinicopathologic effects of samarium-153-EDTMP administered intravenously to normal beagle dogs.

A study was undertaken to determine the degree of acute bone marrow and vital organs injury sustained when dogs were administered doses of 153Sm-EDTMP calculated to irradiate an acute bone lesion arising from cancer metastasis to a dose considered palliative or even therapeutic (20-160 Gy). The study revealed significant (p less than 0.05) temporary depression of the bone marrow in all doses in the therapeutic (greater than 40 Gy) range. Palliative (20 Gy) doses caused significant leukocyte depression but insignificant (p greater than 0.05) depression of platelet and packed cell volumes when compared to control animals. A mild transient rise in the levels of serum alkaline phosphatase occurred immediately following radioisotope administration. All hematologic parameters had returned to normal by six weeks after the last injection of radioisotope. The study indicates potential for this compound as a safe, therapeutic radiopharmaceutical for treatment of cancer bone metastasis.

Idiopathic hematuria of unilateral renal origin in a dog.

Idiopathic hematuria of unilateral renal origin was diagnosed in a 3-month-old male Weimaraner. The hematuria had been visible grossly for 6 weeks. Extensive clinicopathologic, radiographic, and histologic evaluations localized the source of the hematuria to the right kidney, but could not identify a cause. Nephrectomy of the right kidney resolved the problem. This case report supports a previous article comparing canine idiopathic hematuria of renal origin with benign essential hematuria of human beings.