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  • Author or Editor: Ilene D. Kurzman x
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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

Population characteristics, risk factors, and survival characteristics were evaluated in 74 cats with hypertrophic cardiomyopathy (hc) seen at North Carolina State University veterinary teaching hospital from 1985 to 1989, and compared with 82 clinically normal cats. The mean (± sd) age of cats with HC was 6.5 (4.0) years. Neutered males were at significantly greater risk (odds ratio 3.1) than neutered females. Breed, body weight, or coat color were not determined to be risk factors for hc. Tricolor cats were significantly underrepresented, probably reflecting the male predisposition for hc and not a true risk reduction associated with coat color. Forty-one cats were without clinical signs of heart disease (murmur and/or gallop sound only), 24 were in congestive heart failure, and 9 had systemic arterial embolism, 3 of which had concomitant congestive heart failure.

The median survival time for 61 cats with HC, for which survival information could be obtained and that were not euthanatized on day 1, was 732 days. Survival was not affected by age at diagnosis, breed, body weight, or sex. However, clinical signs were important in determining prognosis; cats with heart rates < 200 beats/min survived significantly longer (median survival > 1,830 days) than those with heart rates ≥ 200 beats/min (median survival = 152 days). Cats without clinical signs (median survival > 1,830 days) survived longer than those with clinical signs, and cats in heart failure survived a median of 92 days, compared with 61 days for those with systemic arterial embolism. Analysis of survival revealed no significant difference between the 2 groups of cats with clinical signs; however, all cats with embolism and only 60% of cats with heart failure were dead 6 months after diagnosis.

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

Comparisons of the MacKay-Marg and Tono-Pen applanation tonometers in open and closed in vitro systems were made for the eyes of cats. Both instruments significantly underestimated intraocular pressure (iop) vs direct manometry (P < 0.001), but in readily predictable manner, with high coefficients of determination (r 2 = 0.99). For tonometer 1 (MacKay-Marg), calculated actual iOP = 1.36 × (MacKay-Marg measurement) − 1.67 mm of Hg; and for tonometer 2 (Tono-Pen), calculated actual iop = 1.37 × (Tono-Pen measurement) + 0.8 mm of Hg, using measurements from 11 enucleated eyes. In vivo comparisons were initially made in 81 clinically normal eyes (n = 41 cats) by applying the Tono-Pen first followed by the MacKay-Marg. Compared with the MacKay-Marg, the Tono-Pen significantly (P < 0.001) underestimated iOP in these cats. When the order of tonometer applanation was subsequently reversed in 73 clinically normal eyes (n = 37 cats) the Tono-Pen again significantly (P < 0.001) underestimated iOP, compared with the MacKay-Marg. Alterations in tonometer order did not result in significant differences in measured iOP for the MacKay-Marg when compared with itself, but Tono-Pen measurements were significantly (P < 0.05) less when its use followed, rather than preceded, that of the MacKay-Marg. Mean (± sd) iop in clinically normal cats when each tonometer was used first was 22.6 ± 4.0 mm of Hg (range, 14 to 32 mm of Hg) for the MacKay-Marg and 19.7 ± 5.6 mm of Hg (9 to 31 mm of Hg) for the Tono-Pen. The mean (± sd) absolute value of the differences between MacKay-Marg measurements and those obtained by use of the Tono-Pen was 3.2 ± 3.1 (range, 0 to 13 mm of Hg difference).

Free access
in American Journal of Veterinary Research

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

Summary

Pretreatment characteristics of 138 dogs with malignant lymphoma were analyzed to determine prognostic factors associated with outcome (ie, complete response rate, time to relapse after complete response, survival time). Dogs were all treated for 10 weeks, using a standard induction chemotherapy protocol, and were then given asparaginase weekly. Once the disease became progressive, second-line chemotherapy was instituted.

Age, sex, weight, clinical stage, performance grade, immunophenotype, and malignancy grade assigned according to the National Cancer Institute's Working Formulation were not associated with complete response rate. However, malignancy grade assigned according to the Kiel classification was found to be associated with complete response rate; dogs with high-grade malignancies had a significantly higher complete response rate than did dogs with low-grade malignancies.

By means of multivariate analysis, clinical stage and immunophenotype were found to be prognostic factors for time to relapse (among dogs that had had a complete response) and survival time. In addition, malignancy grade assigned according to the Kiel classification was found to be a prognostic factor for time to relapse; whereas, malignancy grade assigned according to the Working Formulation was determined to be a prognostic factor for survival time.

Free access
in Journal of the American Veterinary Medical Association

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)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs.

Animals—111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved.

Procedures—58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death.

Results—Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because < 50% died of MM before the end of the observation period. No systemic reactions requiring veterinary intervention were associated with vaccination. Local reactions were primarily limited to acute wheal or hematoma formation, mild signs of pain at the injection site, and postvaccination bruising.

Conclusions and Clinical Relevance—Results support the safety and efficacy of the huTyr DNA vaccine in dogs as adjunctive treatment for oral MM.

Impact for Human Medicine—Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

Full access
in American Journal of Veterinary Research