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Abstract

OBJECTIVE

To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS).

ANIMALS

14 client-owned cats.

PROCEDURES

Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time.

RESULTS

Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status.

CLINICAL RELEVANCE

The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the effects of morphine on histamine release from 2 canine mast cell tumor (MCT) cell lines and on plasma histamine concentrations in dogs with cutaneous MCTs.

ANIMALS

10 dogs with cutaneous MCT and 10 dogs with soft tissue sarcoma (STS).

PROCEDURES

The study consisted of 2 phases. First, 2 canine MCT cell lines were exposed to 3 pharmacologically relevant morphine concentrations, and histamine concentrations were determined by an ELISA. Second, dogs with MCT or STS received 0.5 mg of morphine/kg, IM, before surgery for tumor excision. Clinical signs, respiratory rate, heart rate, arterial blood pressure, rectal temperature, and plasma histamine concentrations were recorded before and 5, 15, 30, and 60 minutes after morphine administration but prior to surgery. Data were compared by use of a 2-way ANOVA with the Sidak multiple comparisons test.

RESULTS

In the first phase, canine MCT cell lines did not release histamine when exposed to pharmacologically relevant morphine concentrations. In the second phase, no differences were noted for heart rate, arterial blood pressure, and rectal temperature between MCT and STS groups. Plasma histamine concentrations did not significantly differ over time within groups and between groups.

CONCLUSIONS AND CLINICAL RELEVANCE

No significant changes in histamine concentrations were noted for both in vitro and in vivo study phases, and no hemodynamic changes were noted for the in vivo study phase. These preliminary results suggested that morphine may be used safely in some dogs with MCT.

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To identify differential microRNA (miRNA) expression in dogs with splenic hemangiosarcoma, splenic hematoma, and histologically normal spleens.

ANIMALS

Dogs with splenic hemangiosarcoma (n = 10), splenic hematoma (n = 5), and histologically normal spleens (n = 5).

PROCEDURES

Splenic tissue and serum samples were collected from dogs with splenic masses (ie, hemangiosarcoma or hematoma samples) and healthy control dogs (ie, control samples), and total RNA was extracted. Reverse transcription quantitative real-time PCR was performed with 28 miRNAs associated with hemangiosarcoma, angiosarcoma, or associated genes. Differential expression analysis was performed.

RESULTS

Control tissue and serum samples had similar miRNA expression patterns, and hemangiosarcoma tissue and serum samples did not. Hemangiosarcoma serum samples had higher expression than hemangiosarcoma tissue for 13 miRNAs and lower expression for 1 miRNA. Control tissue and hemangiosarcoma tissue had varying expressions for 12 miRNAs, with 10 more highly expressed in control samples and 2 more highly expressed in hemangiosarcoma samples. Five miRNAs (miR-214-3p, miR-452, miR-494-3p, miR-497-5p, miR-543) had significantly different expression in serum between dogs with splenic masses (ie, hemangiosarcoma or hematoma) and serum of dogs with histologically normal spleens, with higher expression in the serum of dogs with splenic masses for all 5 miRNAs.

CONCLUSIONS AND CLINICAL RELEVANCE

5 circulating miRNAs were identified that distinguished dogs with splenic hemangiosarcoma or hematoma from those with histologically normal spleens. These 5 miRNAs had higher expression in dogs with splenic masses, indicating upregulation of these circulating miRNAs occurs in these splenic disease states. These miRNAs may be useful as a noninvasive screening tool that uses serum to identify dogs with splenic masses.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate the safety of oral administration of a d-ribose-l-cysteine (RibCys) supplement to dogs and the effect of this supplementation on erythrocyte glutathione (GSH) concentration.

ANIMALS

24 healthy adult dogs.

PROCEDURES

In a randomized, double-blinded, controlled trial, dogs received 500 mg of a RibCys supplement or placebo (n = 12/group), PO, every 12 hours for 4 weeks. Dogs were evaluated weekly by means of a physical examination, CBC, serum biochemical analysis, urinalysis, and owner-completed quality-of-life questionnaire. Erythrocyte GSH concentration was measured on day 0 (ie, the day before treatment began) and weekly during supplementation.

RESULTS

No dose-limiting adverse effects were noted in any dog. Two dogs in each group had mild, self-limiting diarrhea and anemia. No significant increase in erythrocyte GSH concentration was noted in either group at any time point. Two dogs in the RibCys group had improved skin and coat health and improved clinical signs of osteoarthritis. No clinical or owner-perceived improvements were noted in the placebo group.

CONCLUSIONS AND CLINICAL RELEVANCE

The RibCys supplement was safe and well tolerated in all dogs. Owners reported improvements in dermatologic and orthopedic conditions in some dogs in the RibCys group. No significant differences were observed in erythrocyte GSH concentration before or after RibCys treatment. This lack of significant differences may have been attributable to the use of healthy dogs, which would not be expected to have depleted GSH concentrations. Given the observed safety profile of RibCys, additional research is warranted to explore the potential usefulness of RibCys supplementation in dogs with cancer and those undergoing treatment for cancer.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To investigate the use of microwave ablation (MWA) with cooling urethral perfusion and with no perfusion (MWA-UP and MWA-NP, respectively) for prostate gland ablation in canine cadavers.

ANIMALS

Cadavers of 18 sexually intact male dogs.

PROCEDURES

After technique refinement in 2 cadavers, laparotomy with ultrasound-guided MWA-UP (n = 8) or MWA-NP (8) of the prostate gland was performed in 16 cadavers. Normograde cystourethroscopy was performed before and after treatment; recorded images were reviewed in a blinded manner for scoring of urethral mucosal discoloration and loss of integrity. Difficulty with cystoscope insertion was recorded if present. Excised prostate glands were fixed for serial sectioning, gross measurements, and calculation of percentage ablation. Percentages of prostate tissue necrosis from MWA, denuded urethral mucosa, and depth of epithelial surface loss in an adjacent section of the colon were estimated histologically. Variables of interest were statistically analyzed.

RESULTS

Difficulty with cystoscope insertion after treatment was significantly more common and scores for urethral mucosal discoloration and loss of integrity were significantly higher (indicating more severe lesions) for the MWA-NP group than for the MWA-UP group. The histologically assessed percentage of denuded urethral mucosa was also greater for the MWA-NP group. Overall median percentage prostate gland ablation was 73%; this result was not associated with prostate gland volume or chronological order of treatment.

CONCLUSIONS AND CLINICAL RELEVANCE

MWA-UP induced subtotal thermal necrosis of prostate glands in canine cadavers while limiting urethral mucosal injury. Further study is required to optimize the technique and evaluate its safety and efficacy in vivo as a future curative-intent treatment for prostatic tumors in dogs.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs.

ANIMALS

I0 healthy purpose-bred sexually intact female hounds.

PROCEDURES

Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone.

RESULTS

7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score.

CONCLUSIONS AND CLINICAL RELEVANCE

In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To examine effects of a common mutation (2-base insertion in exon 5) of the TP53 gene on biological function of p53 protein in canine histiocytic sarcoma cells.

SAMPLE

Canine histiocytic tumor cell lines DH82 with deletion of TP53 and CHS-3 with the wild-type TP53 and canine wild-type and mutant TP53 fragments.

PROCEDURES

Wild-type or mutant TP53 with a polyprotein peptide tag at the N-terminus was transduced into DH82 and CHS-3 cells. Expression of p53 protein, changes in function as a transcription factor, and susceptibility to doxorubicin and nimustine were compared.

RESULTS

Transduced p53 protein was detected in wild-type TP53–transduced DH82 and CHS-3 cells, whereas expression was not detected in mutant TP53–transduced cells. There were significant increases in expression of target genes of p53 protein, including p21 and MDM2, in wild-type TP53–transduced cells, compared with results for native and mock-transfected cells, but not in mutant TP53–transduced cells. There was no significant difference in drug susceptibilities among native and derivative cells of CHS-3. However, cell viabilities of wild-type TP53–transduced DH82 cells incubated with doxorubicin were significantly lower than viabilities of native, mock-transfected, and AT insertion mutation–TP53–transduced DH82 cells; susceptibility to nimustine did not differ significantly among cells.

CONCLUSIONS AND CLINICAL RELEVANCE

Expression of p53 protein and its function as a transcription factor were lost after addition of a 2-base insertion in the TP53 gene in canine histiocytic tumor cells. Additional studies are needed to investigate the clinical relevance of this mutation in histiocytic sarcomas of dogs.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate the efficacy of maropitant and loperamide for the prevention and reduction of adverse gastrointestinal effects associated with administration of paclitaxel to dogs with cancer.

ANIMALS

168 dogs with cancer.

PROCEDURES

The study comprised 2 phases. For phase 1, dogs in the intervention group were administered maropitant and loperamide followed by paclitaxel. Outcomes were compared with those for a control group that received only maropitant and paclitaxel. For phase 2, all dogs of phase 1 that did not receive maropitant and loperamide and that had adverse gastrointestinal effects were enrolled; they received maropitant and loperamide and another dose of paclitaxel.

RESULTS

In phase 1, significantly fewer dogs in the intervention group had adverse effects. For dogs that had adverse effects, the intervention group had a lower severity of lack of appetite and lethargy. Also, adverse effects for dogs in the intervention group were of significantly shorter duration than for the control group. In phase 2, significant reductions in adverse effects were observed after administration of maropitant and loperamide. In those dogs that still had adverse effects after administration of maropitant and loperamide, there was a significant reduction in severity of signs of nausea and lethargy.

CONCLUSIONS AND CLINICAL RELEVANCE

A combination of maropitant and loperamide was found to be safe for use and effective for reducing or preventing signs of paclitaxel-induced gastrointestinal effects in dogs.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma (BCL).

ANIMALS 45 dogs with multicentric BCL and 10 healthy control Beagles.

PROCEDURES The medical record database of a veterinary teaching hospital was searched to identify dogs with BCL that were treated between November 2005 and April 2015. Information regarding overall response to chemotherapy, progression-free survival (PFS) time, and overall survival time was extracted from each record. Archived lymph node aspirate specimens from dogs with BCL and lymph node aspirate specimens from the 10 control dogs underwent real-time PCR analysis to determine mRNA expression of CD44 variant isoforms of exons 3, 6, and 7 and the CD44 whole isoform. For each isoform, mRNA expression was compared between dogs with BCL and control dogs. The mean relative expression of each isoform was used to classify dogs with BCL into either a high- or low-expression group, and overall response rate, PFS time, and overall survival time (ie, indices of prognosis) were compared between the 2 groups.

RESULTS For all isoforms evaluated, mean relative mRNA expression for dogs with BCL was numerically lower than that for control dogs. Dogs with BCL and high CD44 isoform expression had a lower overall response rate, median PFS time, and median overall survival time, compared with dogs with BCL and low CD44 isoform expression.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for dogs with BCL, high expression of exons 3, 6, and 7 was associated with a poor prognosis.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate and compare surface and cross-sectional structure as well as localized electrochemical corrosion and ion release for cast stainless steel (SS) tibia plateau leveling osteotomy (TPLO) plates retrieved from dogs with and without osteosarcoma (OSA) and to compare these findings with similar variables for forged SS TPLO plates retrieved from dogs.

SAMPLE 47 TPLO plates explanted from 45 client-owned dogs (22 cast plates from dogs with OSA, 22 cast plates from dogs without OSA, and 3 forged plates from dogs without OSA).

PROCEDURES Histologic evaluations of tissue samples collected from implant sites at the time of plate retrieval were performed to confirm implant site tumor status of each dog. Surfaces and metallographic cross sections of retrieved plates were examined, and the microcell technique was used to obtain local electrochemical corrosion and ion release measurements.

RESULTS Findings indicated that all cast SS plates demonstrated high spatial variability of their electrochemical surface properties and inhomogeneous superficial and cross-sectional composition, compared with forged plates. Greater metal ion release was observed in cast plates than in forged plates and in cast plates from dogs with OSA than in cast or forged from dogs without OSA.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that accumulation of metal ions from implants could be a trigger for neoplastic transformation in neighboring cells. Metal ion release caused by corrosion of implants that do not comply with recommended standards of the American Society for Testing and Materials International or the International Organization for Standardization could potentially place patients at increased risk of tumor development.

Restricted access
in American Journal of Veterinary Research