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- Author or Editor: David M. Vail x
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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.
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.
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)
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)
Abstract
Objective—To determine clinical response and toxic effects of cis-bis-neodecanoato-trans-R,R-1,2- diaminocyclohexane platinum (II) (L-NDDP) administered IV at escalating doses to cats with oral squamous cell carcinoma (SCC).
Animals—18 cats with oral SCC.
Procedure—Cats that failed to respond to conventional treatment or had nonresectable tumors were included. Data included a CBC, serum biochemical analyses, urinalysis, cytologic examination of a fineneedle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered IV. At 21-day intervals, subsequent doses increased by the rate of 5 or 10 mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic radiography. Quality of life was assessed by owners, using a performance status questionnaire.
Results—On average, cats received 2 treatments. Toxicoses included an intermittent, acute anaphylactoid- parasympathomimetic reaction, lethargy or sedation (≤ 24 hours), inappetence or signs of depression (≤ 72 hours), mild to moderate increase in hepatic enzyme activity, and melena. Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance status surveys indicated normal behavior and grooming or decreased activity and self-care (19/20 assessments), ate well with or without assistance (15/20), and did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1 days).
Conclusions and Clinical Relevance—L-NDDP was ineffective for treatment of cats with oral SCC. None of the cats had a complete or partial remission. Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L-NDDP in cats, unless dosage, frequency, and administration procedures can be improved. (Am J Vet Res 2000;61: 791–795)
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.
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.
Summary
One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, iv) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian.
A partial or complete remission (>50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1).
Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.
Objective
To characterize the frequency, clinical signs, biologic behavior, and response to treatment of tumors of the ear canal in dogs and cats.
Design
Retrospective analysis of medical records.
Animals
Medical records of 81 dogs (48 malignant tumors, 33 benign tumors) and 64 cats (56 malignant tumors, 8 benign tumors).
Procedure
Data were analyzed for cats and dogs with malignant tumors, and risk factors were analyzed for their potential impact on survival time.
Results
Malignant tumor types most commonly reported included ceruminous gland adenocarcinoma, squamous cell carcinoma, and carcinoma of undetermined origin. Median survival time of dogs with malignant aural tumors was > 58 months, whereas that of cats was 11.7 months. A poor prognosis was indicated by extensive tumor involvement (dogs) and by neurologic signs at time of diagnosis, diagnosis of squamous cell carcinoma or carcinoma of undetermined origin, and invasion into lymphatics or blood vessels (cats).
Clinical Implications
Malignant tumors of the ear canal in dogs and cats have a propensity for local invasion, but tend not to metastasize. Squamous cell carcinoma and carcinoma of undetermined origin were the most locally aggressive tumors. Malignant tumors of the ear canal are best managed by aggressive surgical excision. Radiotherapy may be useful when tumors cannot be completely removed. (J Am Vet Med Assoc 1996;208:1413-1418)
Summary
Medical records of 36 dogs with synovial sarcoma confirmed by microscopic examination of h&e-stained sections of tissue were selected for retrospective analysis from dogs admitted between 1986 and 1991 to participating institutions of the Veterinary Cooperative Oncology Group. Metastasis was evident at the time of diagnosis in 8 (22%) dogs, and 15 (41%) dogs ultimately developed metastatic tumors. Median survival time for all dogs, as determined by lije-table analysis, was 17 months. For dogs that were subsequently treated and became tumor free, the median disease-free interval was 30 months. Nine dogs had previously had localized excision attempted, but all had recurrence of the tumor locally (median, 4.5 months). Of 29 dogs that underwent amputation, including the 9 with localized recurrence, 2 had tumor recurrence on the amputation stump. Most dogs had survival time and disease-free interval of > 36 months after amputation. Four dogs that had received chemotherapy for tumors of advanced clinical stages did not respond to treatment. One dog that had received locally applied radiotherapy after localized excision did not have evidence of tumor recurrence 2 years after radiotherapy. Clinical stage, histologic grade, and a positive result for tests that used cytokeratin immunohistochemical staining significantly (P < 0.05) influenced survival time and disease-free interval. Analysis of data for the study reported here suggested that histologic criteria can be an excellent predictor of dogs that are likely to have tumor recurrence after amputation and that would most likely benefit from aggressive treatment with adjuvants.