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Abstract

Objective

To evaluate the effects of administration of a sterically stabilized liposome-encapsulated cisplatin (SSL-CDDP) to cats.

Animals

4 clinically normal cats.

Procedure

2 of the cats were given multiple IV injections of SSL-CDDP at a dosage of 70 mg of free CDDP equivalent/m2 of body surface area at 3-week intervals. The other 2 cats received single IV injections of identical liposome preparations not containing CDDP. Vital signs; appetite; attitude; hematologic, serum biochemical, and urinalysis findings; and thoracic radiographic views were evaluated at predetermined intervals.

Results

Sterically stabilized liposome-encapsulated cisplatin was well tolerated by all cats. The only significant alterations in measured variables were an increase in serum cholesterol concentration 2 days after injection, and repeatable pyrexia in the cats receiving SSL-CDDP that began 10 to 12 hours after injection and continued for 18 hours, peaking at 40.5 to 41 C. Alterations in rectal temperature were not significant in cats receiving empty liposome vehicle.

Conclusions

SSL-CDDP appears to be safe to administer to cats at a dosage of 70 mg of free CDDP equivalent/m2, a CDDP dose known to be therapeutic in dogs. Pyrexia, although marked, appears to be a short-term and well tolerated side effect.

Clinical Relevance

SSL-CDDP appears to abrogate the uniformly fatal side effects associated with administration of tumoricidal quantities of free CDDP to cats. This new formulation should allow investigation of the antitumor properties of CDDP against spontaneously arising neoplasms in cats. (Am J Vet Res 1998;59:286–289)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the acute and short-term adverse effects of a liposome-encapsulated form of cisplatin at increasing dosages of up to twice the known maximally tolerated dose (MTD) of unencapsulated cisplatin in clinically normal dogs.

Animals—4 healthy 2.5-year-old sexually intact female hound-type dogs.

Procedure—4 dosages (70, 100, 125, and 150 mg/m2) were evaluated, and the 4 dogs received a total of 9 infusions (1 to 3 infusions/dog). Dogs were monitored to detect changes in clinical and clinicopathologic status. Evaluations consisting of a physical examination, CBC, serum biochemical analysis, and urinalysis were performed before and 7 and 21 days after each infusion.

Results—Acute anaphylactic-like reactions to liposome- encapsulated cisplatin were common but clinically manageable. Nephrotoxicosis and substantial myelosuppression, toxic effects commonly associated with unencapsulated cisplatin, were not observed in dogs treated with liposome-encapsulated cisplatin at dosages equivalent to twice the known MTD of unencapsulated cisplatin.

Conclusions and Clinical Relevance—Liposome-encapsulated cisplatin can be safely administered to clinically normal dogs at dosages of up to 150 mg/m2 without the need for concurrent hydration protocols. This was a necessary prerequisite to enable phase I clinical trials in dogs with naturally developing cancers that could theoretically benefit from escalation in the dosage of cisplatin. Determination of an MTD, cumulative and long-term toxic effects, and efficacy can now be conducted in the context of phase I trials in tumorbearing dogs. (Am J Vet Res 2004;65:1474–1478)

Full access
in American Journal of Veterinary Research

SUMMARY

In 33 healthy dogs, 66 bronchoalveolar lavage samples from the right and left caudal lung lobes were analyzed for volume of return, cellularity, differential cellularity, and immunophenotypic lymphocyte subpopulations. Lavage return was 64.8% (mean) following 3 sequential 25-ml lavages, for a total lavage volume of 75 ml. With this technique, 21.1 × 106 cells/sample (mean) were obtained. The cellular components of bronchoalveolar lavage samples, in decreasing order of frequency, were alveolar macrophages (79.4%), lymphocytes (13.5%), eosinophils (3.6%), mast cells (2.1%), epithelial cells (0.8%), and neutrophils (0.6%). Mean alveolar lymphocyte subpopulation frequencies, determined in 18 samples, for pan T, CD4, and CD8 cells were 52, 21.9, and 17.8%, respectively, with a CD4/CD8 ratio of 1.3. Variables analyzed did not vary between right and left caudal lung lobes, nor were they affected by body weight.

Free access
in American Journal of Veterinary Research

Summary

A bolus dose of methimazole (mmi) was administered iv over 1 minute to 5 healthy adult dogs at a dosage (40 mg/kg of body weight) known to impart protection against cisplatin-induced renal disease. Blood and urine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, CBC, determination of serum thyroid hormone concentrations, and serum biochemistry analysis were performed over a 10-day period to evaluate short-term toxicoses. At this dosage, mmi appears to be safe and well tolerated in dogs; only 1 of the 5 dogs had mild and transient increases in serum activity of hepatic enzymes. In addition, mmi did not alter serum thyroid hormone concentrations. Half-life of 8.82 hours and mean residence time of 12.18 hours were determined for mmi. Renal clearance of native mmi, along with sulfate and glucuronide conjugates, represented only 20 % of total systemic clearance. Results of this study provide further information concerning clinical use of mmi in dogs and may contribute to better understanding of the mechanism of mmi protection against chemically induced nephrotoxicosis.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To compare long-term results of radiotherapy alone versus radiotherapy followed by exenteration of the nasal cavity in dogs with malignant intranasal neoplasia.

Design—Retrospective study.

Animals—53 dogs with malignant intranasal neoplasia.

Procedure—All dogs underwent radiotherapy consisting of administration of 10 fractions of 4.2 Gy each on consecutive weekdays. For dogs in the surgery group (n = 13), follow-up computed tomography was performed, and dogs were scheduled for surgery if persistent or recurrent tumor was seen.

Results—Perioperative complications for dogs that underwent surgery included hemorrhage requiring transfusion (2 dogs) and subcutaneous emphysema (8). Rhinitis and osteomyelitis-osteonecrosis occurred significantly more frequently in dogs in the radiotherapy and surgery group (9 and 4 dogs, respectively) than in dogs in the radiotherapy-only group (4 and 3 dogs, respectively). Two- and 3-year survival rates were 44% and 24%, respectively, for dogs in the radiotherapy group and 69% and 58%, respectively, for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (47.7 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months).

Conclusions and Clinical Relevance—Results suggest that exenteration of the nasal cavity significantly prolongs survival time in dogs with intranasal neoplasia that have undergone radiotherapy. Exenteration after radiotherapy may increase the risk of chronic complications. (J Am Vet Med Assoc 2005;227:936–941)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare results of computed tomography (CT) and radiography with histopathologic findings in tracheobronchial lymph nodes (TBLNs) in dogs with primary lung tumors.

Design—Retrospective case series.

Animals—14 client-owned dogs.

Procedures—Criteria for inclusion were diagnosis of primary lung tumor, use of thoracic radiography and CT, and histologic confirmation of TBLN status. Medical records were reviewed for signalment; history; and physical examination, clinicopathologic, radiographic, CT, surgical, and histopathologic findings.

Results—Tracheobronchial lymphadenopathy was not identified via radiography in any dogs. Tracheobronchial lymphadenopathy was diagnosed in 5 dogs via CT. Six dogs had histologic confirmation of metastasis to TBLNs. Radiographic diagnosis yielded 6 false-negative and no false-positive results for tracheobronchial lymphadenopathy. Computed tomography yielded 1 falsenegative and no false-positive results. Sensitivity of CT for correctly assessing TBLN status was 83%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 89%. Dogs with lymphadenopathy via CT, histologic confirmation of TBLN metastasis, or primary tumors with a histologic grade > 1 had significantly shorter survival times than their counterparts.

Conclusions and Clinical Relevance—Results of CT evaluation of TBLN status were in agreement with histopathologic findings and more accurate than use of thoracic radiography for evaluating TBLNs in dogs with primary lung tumors. Computed tomography imaging should be considered as part of the staging process to more accurately assess the TBLNs in dogs with primary lung tumors.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To characterize demographics and clinical signs and evaluate outcomes of treatments in cats with transitional cell carcinoma (TCC) of the urinary bladder.

Design—Retrospective case series.

Animals—20 cats with TCC.

Procedures—Medical records of 20 cats with a bladder mass identified as a TCC that were examined at 2 veterinary institutions between 1990 and 2004 were evaluated. Signalment, treatments, and outcome were assessed.

Results—Breeds included domestic short hair (n = 14), long hair (2), and medium hair (2) cats, Siamese (1), and Abyssinian (1). All cats had been neutered at an early age (< 1 year old; 13 neutered males and 7 spayed females). The median age at diagnosis of TCC was 15.2 years. The trigone region was affected in 9 cats. Treatments included piroxicam administration, chemotherapy, or surgery as single interventions or in combination; 6 cats were not treated. At the time of diagnosis, 3 cats had pulmonary metastasis and 1 cat had metastasis to local lymph nodes. Median survival time for all 20 cats was 261 days. Nearly all deaths were attributable to progressive disease in the urinary tract. Five cats were lost to follow-up.

Conclusions and Clinical Relevance—In cats, TCC of the urinary bladder appears to be a rare and aggressive disease that is more prevalent in male cats and frequently develops at sites distant from the trigone (unlike TCC in dogs). Nevertheless, initial clinical signs of TCC in cats in this study were similar to those reported for affected dogs.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate time to first recurrence (TFR) and overall survival in cats with presumed vaccine-associated sarcomas (VAS) treated with excision.

Design—Retrospective study.

Animals—61 cats with presumed VAS.

Procedure—Medical records of cats that received excision as the only initial treatment for presumed VAS were reviewed to evaluate prognosis. Overall survival curves and TFR were determined.

Results—Median TFR was 94 days. Median TFR for tumors treated with excision performed at a referral institution (274 days) was significantly longer than that for tumors excised by a referring veterinarian (66 days). Radical first excision yielded significantly longer median TFR (325 days) than did marginal first excision (79 days). Cats with tumors located on the limbs had longer median TFR (325 days) than cats with tumors located in other sites (66 days). Median overall survival time was 576 days. Significant differences in survival times between groups were not detected. Few cats (13.8%) receiving only surgical treatment had longterm (> 2 years) survival.

Conclusions and Clinical Relevance—Radical first excision of presumed VAS is essential for extended TFR. Current recommendations for vaccination of the distal portions of the extremities are appropriate, because this practice permits radical excision of tumors (amputation) that develop at vaccination sites; however, surgery alone is seldom curative. ( J Am Vet Med Assoc 2000;216:58–61)

Full access
in Journal of the American Veterinary Medical Association

Objective

To determine for mast cell tumors in dogs whether frequency of argyrophilic nucleolar organizer regions (AgNOR) determined by examining fine-needle aspirates (FNA) correlated with frequencies determined by examining biopsy specimens or with histologic grade.

Design

Case series.

Animals

25 dogs with 32 histologically confirmed tumors.

Procedure

Biopsy specimens and FNA were collected from each tumor. Histologic grade and AgNOR frequency were determined.

Results

Frequency of AgNOR in FNA was significantly correlated with frequency in biopsy specimens and was significantly associated with histologic grade of the tumor.

Clinical Implications

Determining AgNOR frequency in FNA of mast cell tumors in dogs is a rapid, minimally invasive means of obtaining information that potentially could be used to help predict biological behavior of the tumor and to guide clinicians and owners in making decisions about further diagnostic tests and treatment. (J Am Vet Med Assoc 1996;209:1418–1420)

Free access
in Journal of the American Veterinary Medical Association

Summary

Nine dogs with intermediate- or high-grade lymphoma were prospectively entered into a protocol to be given a total of 15 weekly doses of doxorubicin (10 mg/m2 of body surface, iv) in an attempt to eliminate all clinical evidence of neoplasia, with minimal risk of drug toxicity. Eight of these dogs did not complete the protocol because of progression of the disease. The median number of doses administered to dogs that developed progressive disease before the regimen was completed was 5 (range, 2 to 9). Seven dogs achieved partial (n = 5) or complete (n = 2) remission, with median duration of 14 days (range, 7 to 231 days). The dog that was given all 15 weekly treatments remained in complete remission for 231 days. Complete remission that lasted for 14 days was observed in another dog. Toxicosis developed in 3 dogs; signs of toxicosis were generally mild and included colitis (n = 1), vomiting (n = 1), neutropenia (n = 1), and lethargy (n = 1). The lowest neutrophil count (1,876 cells/μl) was seen in one dog after 7 doses of doxorubicin were given. Doxorubicin at dosage of 10 mg/m2/wk appears to be safe, but is generally ineffective for treatment of lymphoma.

Free access
in Journal of the American Veterinary Medical Association