Determining success competencies.
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Education, Veterinary↗
Biomedical subjects
J S Klausner
Publications and source records attributed to J S Klausner.
Establishment of two vaccine-associated feline sarcoma cell lines and determination of in vitro chemosensitivity to doxorubicin and mitoxantrone.
OBJECTIVE: To establish 2 vaccine-associated feline sarcoma (VAFS) cell lines and to determine their in vitro sensitivity to the chemotherapeutic agents doxorubicin and mitoxantrone. SAMPLE POPULATION: Tumor specimens collected from 2 cats undergoing surgery for removal of vaccine-associated sarcomas. PROCEDURES: Tumor specimens were minced and treated with trypsin under aseptic conditions to obtain single-cell suspensions, which were then cultured in vitro in medium supplemented with 5% heat-inactivated fetal bovine serum. Growth rates and sensitivity after 24 hours of exposure to various concentrations (0.1 to 100 microg/ml) of doxorubicin and mitoxantrone were assessed for each cell line. Survival of cells was estimated 3 days after exposure to the 2 agents, and the concentration of each drug that resulted in a 50% reduction in the number of viable cells (IC50) was calculated. RESULTS: Two tumor-derived cell lines (FSA and FSB) were successfully established and determined to be sensitive to doxorubicin and mitoxantrone. Under the conditions tested, the IC50 of doxorubicin were 0.6 and 1.5 microg/ml for cell lines FSB and FSA, respectively. The IC50 of mitoxantrone was 0.4 microg/ml for both cell lines. CONCLUSIONS AND CLINICAL RELEVANCE: The establishment of VAFS cell lines provides a tool for the in vitro screening of antitumor drugs. Doxorubicin and mitoxantrone were effective in decreasing the number of viable cells in the 2 cell lines tested. Both of these anthracycline antibiotics have been used to treat various neoplasias in cats, and their efficacy for adjuvant treatment of vaccine-associated sarcomas should be further evaluated.
Animals↗
Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States.
OBJECTIVE: To determine age, breed, sex, body condition score, and diet of dogs and cats examined at private veterinary practices in the United States during 1995, and estimate prevalences of the most common disorders for these animals. DESIGN: Cross-sectional study. ANIMALS: 31,484 dogs and 15,226 cats examined by veterinary practitioners at 52 private veterinary practices. PROCEDURE: Information on age, breed, sex, body condition score, diet, and assigned diagnostic codes were collected electronically from participating practices and transferred to a relational database. Prevalence estimates and frequencies for population description were generated using statistical software. RESULTS: Dental calculus and gingivitis were the most commonly reported disorders. About 7% of dogs and 10% of cats examined by practitioners during the study were considered healthy. Many conditions were common to both species (e.g., flea infestation, conjunctivitis, diarrhea, vomiting). Dogs were likely to be examined because of lameness, disk disease, lipoma, and allergic dermatitis. Cats were likely to be examined because of renal disease, cystitis, feline urologic syndrome, and inappetence. CLINICAL IMPLICATIONS: Results can be used by veterinary practitioners to better understand and anticipate health problems of importance in cats and dogs they examine and to better communicate with clients regarding the most prevalent disorders in cats and dogs.
Age Distribution↗
Prostatic leiomyosarcoma in a dog.
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Animals↗
Randomized controlled trial of doxorubicin versus dactinomycin in a multiagent protocol for treatment of dogs with malignant lymphoma.
OBJECTIVE: To compare efficacy and toxicity of 2 multiagent chemotherapeutic protocols similar in all respects except that 1 incorporated dactinomycin and the other incorporated doxorubicin for treatment of dogs with malignant lymphoma. DESIGN: Randomized controlled trial. ANIMALS: 45 dogs with malignant lymphoma. PROCEDURE: Dogs were randomly assigned to a doxorubicin or dactinomycin treatment group. Time to first remission, duration of first remission, survival time, and prevalence of toxicoses, particularly number of episodes of dose-limiting neutropenia and gastrointestinal toxicoses, were compared between groups. RESULTS: 37 dogs received at least 1 dose of doxorubicin (21 dogs) or dactinomycin (16). Median time to first remission was not significantly different between groups, but median duration of first remission and median survival time were significantly longer for dogs in the doxorubicin treatment group than for dogs in the dactinomycin treatment group. Number of dogs that died, number of episodes of dose-limiting neutropenia, and number of episodes of gastrointestinal toxicoses were not significantly different between groups. CLINICAL IMPLICATIONS: A multiagent chemotherapeutic protocol incorporating doxorubicin was significantly more effective in dogs with malignant lymphoma than a similar protocol incorporating dactinomycin. Despite the lower cost and lack of cardiotoxicity, dactinomycin is not an equivalent substitute for doxorubicin in the initial treatment of dogs with malignant lymphoma.
Animals↗
Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases.
BACKGROUND: Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Antineoplastic activity of IL-2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL-2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL-2 liposome therapy. METHODS: Dogs with pulmonary metastases (n = 7) and primary lung carcinoma (n = 2) were treated with aerosols of IL-2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoalveolar lavage (BAL) and from heparinized whole blood, were assessed for cell type, immunophenotype, and tumor cytolytic activity. Immunogenicity of human IL-2 and human serum albumin (HSA) in dogs was assessed by immunofluorescence assay. RESULTS: Two of four dogs with metastatic pulmonary osteosarcoma had complete regression of metastases; the regression remained stable for more than 12 and more than 20 months, respectively. One of two dogs with lung carcinoma had stabilization of disease for more than 8 months; the other had disease progression. Toxicity was minimal. BAL cell numbers increased more than fourfold (P = 0.01) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effector lytic activity was significantly greater after 15 days of IL-2 liposome inhalation compared with pretreatment activity (P = 0.01); however, mean BAL lytic activity decreased after 30 days and was no longer significantly greater than pretreatment BAL lytic activity. No allergic reactions were associated with inhaled IL-2 liposome therapy. Canine antibodies against human IL-2 and HSA were detected in all dogs. CONCLUSIONS: Pet dogs with naturally occurring pulmonary metastases and primary lung carcinomas accepted inhalation treatments easily. Nontoxic and effective treatment of pulmonary metastases of osteosarcoma is possible with nebulized IL-2 liposomes.
Aerosols↗
Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer.
Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin-fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta-E12), proliferative index (MIB-1), and microvessel density (Factor VIII-related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High-grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high-grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression.
Animals↗
Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution.
Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes. The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium (99mTc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1.98 microns and 2.02, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2: lipid:HSA) demonstrated a close correlation of size distributions (r = 0.9445; P < 0.001). The entrapment of interleukin 2 in liposomes was 93 +/- 4.3% before nebulization and 90 +/- 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean +/- s.d. central lung-to-peripheral lung deposition was 1.12 +/- 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen. The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers.
Aerosols↗
Evaluation of dogs and cats with tumors of the ear canal: 145 cases (1978-1992).
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.
Adenocarcinoma↗
Aerosol delivery of interleukin 2 liposomes is nontoxic and biologically effective: canine studies.
Administration of interleukin 2 (IL-2) has been associated with potent in vitro antitumor effects. However, systemic in vivo toxicity has been problematic. Because local delivery and liposomal formulations of IL-2 may improve the therapeutic index, we used dogs to evaluate and compare immunological activation of inhaled free IL-2 and IL-2 liposomes. Twelve normal dogs were treated with nebulized IL-2 formulations and controls for 2 to 7 weeks. Cellular immune activation of peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) effector leukocytes against tumor cell lines, changes in effector leukocyte populations, and toxicity were monitored. No toxicity was seen with either aerosolized free IL-2 or IL-2 liposomes. Free IL-2 given at 0.5 x 10(6) Biologic Response Modifier Program (BRMP) units twice daily to dogs resulted in increased peripheral blood mononuclear cell activation compared with saline control-treated dogs. IL-2 liposomes given at 0.5 x 10(6) BRMP units twice daily to dogs resulted in significantly increased BAL effector activation compared with IL-2 liposomes given at 1.0 x 10(6) BRMP units once daily (P = 0.018) and empty liposome controls (P = 0.016). The BAL leukocyte cell count was increased significantly after inhalation of IL-2 liposomes versus inhalation of free IL-2 (P = 0.011). BAL effector populations included a greater proportion and total number of lymphocytes and eosinophils after treatment with IL-2 liposomes. Nontoxic activation of pulmonary immune effectors for the treatment of cancer in the lung may be possible using nebulized IL-2 liposomes.
Aerosols↗
Calcium oxalate urolithiasis in a cat with a functional parathyroid adenocarcinoma.
A 9-year-old castrated male domestic shorthair cat with dysuria, anorexia, vomiting, and lethargy was admitted to the veterinary teaching hospital. A large, firm mass was palpable in the ventral cervical region. Hypercalcemia, azotemia, and nonregenerative anemia were evident on serum biochemical analysis and CBC, and multiple uroliths were detected by abdominal radiography. At necropsy, light microscopy of the ventral cervical mass revealed a parathyroid adenocarcinoma. Light microscopy of sections of the kidneys revealed multifocal, chronic, lymphocytic/plasmacytic, tubulointerstitial nephritis, as well as moderate multifocal acute tubular necrosis. On quantitative analysis, the uroliths were composed of calcium oxalate. Determination of serum calcium concentration is indicated in cats with calcium oxalate urolithiasis to aid in detection of primary hyperparathyroidism.
Adenocarcinoma↗
Comparison of microscopic and flow cytometric detection of platelet antibody in dogs suspected of having immune-mediated thrombocytopenia.
A flow cytometric platelet immunofluorescence assay (FC-PIFA) was compared with a previously developed microscopic platelet immunofluorescence assay (MI-PIFA) for detection of circulating platelet antibody. Both assays were performed on serum from 10 healthy dogs with normal platelet count, and on serum from 27 thrombocytopenic dogs--18 had primary immune-mediated thrombocytopenia (IMT), and 9 had IMT in addition to other immune-mediated disease (secondary IMT). Both assays yielded negative results for all control dogs. The MI-PIFA and FC-PIFA results were in agreement in 23 dogs with IMT (14 positive and 9 negative). There was linear correlation between MI-PIFA scores and FC-PIFA results (r = 0.873). Positive results were obtained for 55.5% of the dogs with suspected IMT, using the MI-PIFA, compared with 67%, using the FC-PIFA; however, the difference was not statistically significant. Use of fresh or frozen fixed donor platelets as the antigen source yielded similar results in the FC-PIFA.
Animals↗
Prostatic hemangiosarcoma in a dog: clinical and pathologic findings.
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Animals↗
Clinical and pathologic features of prostatic adenocarcinoma in sexually intact and castrated dogs: 31 cases (1970-1987).
The medical records of 31 dogs diagnosed with prostatic carcinoma at the teaching hospital between January 1970 and October 1987 were reviewed to determine whether gender status had an effect on the clinical features or biologic behavior of the disease. The only significant difference between sexually intact and castrated dogs was increased prevalence of pulmonary metastasis in castrated dogs.
Adenocarcinoma↗
Clinical remission following plasmapheresis and corticosteroid treatment in a dog with acquired myasthenia gravis.
A 7-year-old sexually intact male Labrador Retriever with regurgitation and generalized muscular weakness resulting from acquired myasthenia gravis received 2 plasmapheresis treatments in combination with corticosteroid treatment. Plasmapheresis was performed in an attempt to rapidly lower serum acetylcholine receptor binding antibody (AChR Ab) concentration. Seven days after the second plasmapheresis treatment, the dog's muscular strength was normal, which coincided with a 70% decrease in serum AChR Ab concentration. Because the dog also received corticosteroids, it is impossible to determine how much of the clinical improvement resulted from plasmapheresis.
Animals↗
Drug-associated aplastic anemia in dogs: eight cases (1984-1988).
Records of 8 dogs with drug-associated aplastic anemia were reviewed. Drugs suspected as being causative included estradiol cyclopentylpropionate (3 dogs), phenylbutazone (2 dogs), meclofenamic acid (1 dog), trimethoprim-sulfadiazine and fenbendazole (1 dog), and quinidine (1 dog). Five of the dogs died or were euthanatized. One dog with estrogen-associated aplasia recovered after prolonged treatment. The dogs with trimethoprim-sulfadiazine and quinidine-associated marrow aplasia recovered promptly after treatment was discontinued.
Anemia, Aplastic↗
Hypercalcemia in two cats with squamous cell carcinomas.
Hypercalcemia was identified in 2 cats with squamous cell carcinomas. One cat was referred because of multiple cutaneous tumors; the second cat had metastatic disease from an oral squamous cell carcinoma. In both cats, serum immunoreactive midmolecule parathyroid hormone concentration was within the range determined for clinically normal cats. The high serum calcium concentration in these cats may have resulted from the neoplastic disease, as evidenced by the reduction in serum calcium concentration after decrease in tumor size in response to treatment, and by failure to identify other known causes of hypercalcemia.
Animals↗
Phase II evaluation of doxorubicin for treatment of various canine neoplasms.
One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a prospective study to determine the response to 2 doses of the anthracycline antitumor antibiotic, doxorubicin. Eighty-three dogs had been refractory to one or more previous treatment modalities (surgery, n = 54; chemotherapy, n = 22; radiation, n = 10; hyperthermia, n = 1; biological response modifier, n = 1). The extent of neoplastic disease was determined immediately prior to and 3 weeks after 2 doses of doxorubicin were administered (30 mg/m2 of body surface area, iv) 21 days apart. Eighty-four percent (n = 157) of the dogs received 2 doses of doxorubicin and were evaluated. Of the 28 dogs ruled ineligible, 4 had serious side effects to the first dose of doxorubicin, and 24 others acquired complications resulting from their malignant tumors. A partial or complete remission was obtained in 41% (64/157) of all evaluable dogs: 26% (11/43) of the dogs with carcinoma, 67% (42/63) of the dogs with lymphoma, and 22% (11/51) of the dogs with sarcoma. Tumors in which there was at least a 50% volume reduction (partial or complete remission) included malignant lymphoma (42/63), fibrosarcoma (1/14), solid follicular thyroid carcinoma (3/13), mammary adenocarcinoma (2/8), hemangiosarcoma (2/8), osteosarcoma (1/6), circumanal carcinoma (3/5), synovial cell sarcoma (2/3), undifferentiated sarcoma (2/3), nasal adenocarcinoma (1/2), liposarcoma (1/2), infiltrating lipoma (1/1), malignant melanoma (1/1), sclerosing mesothelioma (1/1), and neurofibrosarcoma (1/2).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗