Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study     

Chon E  McCartan L  Kubicek LN  Vail DM 《Veterinary and comparative oncology》2012,10(3):184-193

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.  相似文献   

Changes in Testicular Development, Ultrasonographic and Histological Appearance of the Testis in Buck Kids Immunized Against LHRH Using Recombinant LHRH Fusion Protein     

H Ülker  M Küçük  A Y&#;lmaz  M Yörük  L Arslan  DM deAvila  JJ Reeves 《Reproduction in domestic animals》2009,44(1):37-43

This study was designed to evaluate the effectiveness of recombinant Ovalbumin-LHRL (OL) immunization on changes in testicular size, histological appearance and testosterone production in buck kids. Thirty native buck kids at 18 weeks of age were divided into three groups, control (n = 10), immunization (n = 10) and castration (n = 10) groups. Immunized animals received OL protein generated by recombinant DNA technology. Ultrasonographic and histological examinations of the testes were performed. Animals were slaughtered at 44 weeks of age. Semen and epididymides were evaluated for the presence of sperm cells. Immunized animals generated anti-LHRH antibodies. Testosterone production, testicular and accessory glands development and sperm production were suppressed in the immunized animals (p < 0.01). Semineferous tubule diameters decreased (p < 0.01), basal membrane of the tubule was thickened and hyalinized in immunized kids. Immunization affected ultrasonographic appearance of the testes drastically. While testes of control animals gained their normal ultrasonographic appearance as the age increased, immunized animals had uniform hypoechogenic testicular structure as observed at 18 weeks of age until slaughter. Simultaneous histological and ultrasonographic evaluations indicated that the changes in testicular histology could partly be monitored via ultrasonographic imaging; nevertheless, it is difficult to claim that ultrasonographic image reflects the exact changes in such instances. In conclusion, these results indicate that recombinant OL fusion protein is effective in immunocastration in buck kids and has a potential to be used as an alternative to physical castration. Further researches should be conducted to help assessing reproductive status of testes from ultrasound images.  相似文献   

Third‐compartment cannulation in alpacas using a polyurethane gastrostomy tube     

GW Smith  MP Gerard  NB Campbell  DM Foster  SM Smith  JL Davis 《Australian veterinary journal》2009,87(12):487-491

Objective To develop a simple and effective surgical technique for third‐compartment cannulation in alpacas. Design Prospective study using six adult male alpacas. Methods General anaesthesia was induced and a polyurethane gastrostomy tube was surgically implanted into the distal portion of the third compartment. Results Three of the alpacas retained their cannulas for a 100‐day period; however, three cannulas were dislodged during the study. Two of the three dislodged cannulas were replaced during a second surgical procedure. Cannulas were well tolerated by the alpacas and all animals remained clinically healthy during the study period. Third compartment contents did not leak from the cannulation site. The tubes were manually removed following the completion of the study and the small defect in the body wall quickly healed over in all animals. Conclusion Surgical placement of polyurethane tubes designed for percutaneous endoscopic gastrostomy is a useful method of cannulating the third compartment in camelids. This technique can be used for experimental studies and possibly could be used for nutritional support and fluid therapy in sick camelids that might need long‐term care.  相似文献   

Medline acceptance and impact factor assignment     

Professor David J. Argyle  Professor David M. Vail 《Veterinary and comparative oncology》2009,7(3):151-152

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Congenital dyserythropoietic anaemia and dyskeratosis in Australian Poll Hereford calves     

AE Kessell  DM Hanshaw  JW Finnie  P Nosworthy 《Australian veterinary journal》2012,90(12):499-504

Congenital dyserythropoietic anaemia (CDA) is a heterogeneous group of rare genetic disorders that in humans is characterised by ineffective haematopoiesis with morphological abnormalities in erythroid precursor cells and secondary iron overload. In the 1990s, a syndrome of CDA with dyskeratosis and progressive alopecia was reported in Poll Hereford calves in Canada and the USA. We report the clinical and pathological findings in two Poll Hereford calves with this syndrome from separate properties in South Australia. The animals had a variably severe anaemia, associated with abnormal nucleated red blood cells in peripheral blood, and large numbers of rubricytes and metarubricytes with a characteristic nuclear ultrastructure in the bone marrow. Both calves were born with a wiry hair coat and a progressively ‘dirty‐faced’ appearance associated with hyperkeratosis and dyskeratosis (apoptosis).  相似文献   

An hGM‐CSF DNA‐Cationic Lipid Complexed Autologous Tumor Cell Vaccine did not Improve Remission Duration in Dogs with Lymphoma     

M. M. Turek  D. H. Thamm  A. M. Mitzey  I. D. Kurzman  M. K. Huelsmeyer  R. R. Dubielzig  D. M.  Vail 《Veterinary and comparative oncology》2005,3(1):59-59

Introduction:  Lymphoma is one of the most common cancers in dogs and while clinical remission can be induced using chemotherapy, very few dogs are cured. Since cytokine‐adjuvanted autologous whole‐tumor‐cell vaccines (ATCV) can induce potent antitumor immune responses against otherwise non‐immunogenic cancers we initiated a study of such an approach in dogs with lymphoma.
Methods:  Following achievement of a complete remission using a 19‐week CHOP‐based chemotherapy protocol, 51 dogs with B‐cell lymphoma were randomized to receive 8 treatments (4 weekly, then 4 additional at q2wk intervals) of vaccine or lipid‐equivalent placebo. Dogs were followed monthly for assessment of remission duration and survival. Surrogate indices of immune response (delayed‐type hypersensitivity, interferon‐γ quantitative RT‐PCR, lymphocyte proliferation, and flow cytometry for lymphoma‐specific antibodies) were also investigated before and after vaccination.
Results:  No significant difference in median remission duration was observed between dogs receiving vaccine (277 days) or placebo (258 days); the Kaplan‐Meier curves were virtually super‐imposable. No significant differences in surrogate indices of immune response were noted pre‐ and post‐vaccination.
Conclusions:  In this context, an hGM‐CSF DNA‐cationic lipid complexed ATCV vaccine did not enhance remission duration in dogs with lymphoma, likely due to lack of vaccine‐induced tumor‐specific immunity.  相似文献   

Liposome-encapsulated doxorubicin (Doxil) and doxorubicin in the treatment of vaccine-associated sarcoma in cats     

Poirier VJ  Thamm DH  Kurzman ID  Jeglum KA  Chun R  Obradovich JE  O'Brien M  Fred RM  Phillips BS  Vail DM 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2002,16(6):726-731

The purpose of this randomized, multicenter study was to evaluate the toxicity and efficacy of liposome-encapsulated doxorubicin (LED) and doxorubicin (DOX) in the treatment of feline vaccine-associated sarcoma (VAS). Cats were divided according to their disease status into a microscopic arm (no evidence of gross disease) and a macroscopic arm (evidence of gross disease). Each arm was randomized to receive either LED (1-1.5 mg/kg i.v. q3 weeks) or DOX (1 mg/kg i.v. q3 weeks). Thirty-three cats were entered in the macroscopic arm of the study with an overall response rate of 39% (5 complete response and 8 partial response) and a median time to progression of 84 days. Response rates were not different between LED and DOX. Seventy-five cats were entered into the microscopic arm. When compared to a similar historical control population treated with surgery alone, the cats receiving chemotherapy had a prolonged median disease-free interval (388 days versus 93 days). No difference in efficacy was detected between LED and DOX. LED at 1.5 mg/kg induced delayed nephrotoxicosis in 23%, necessitating a decrease in the recommended dosage to 1 mg/kg, and cutaneous toxicosis in 21.7% of treated cats. This study showed that both DOX and LED are efficacious in the treatment of VAS and should be considered in the treatment of this tumor.  相似文献   

Feline Lymphoma (145 Cases): Proliferation Indices, Cluster of Differentiation 3 Immunoreactivity, and Their Association with Prognosis in 90 Cats   总被引：2，自引：0，他引：2  

David M. Vail  Antony S. Moore  Gregory K. Ogilvie  Lynn M. Volk 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1998,12(5):349-354

Paraffin-embedded, formalin-fixed tissue samples from 145 cats with lymphoma were analyzed for cluster of differentiation 3 (CD3, a surface antigen) immunoreactivity, argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). This information along with signalment, anatomic site, and feline leukemia virus (FeLV) antigen status was used to determine the potential of these indicators to predict response to therapy, remission, and survival times, and to characterize cats with lymphoma in the era of general availability of FeLV testing and vaccination. Alimentary lymphoma, primarily occurring in older, FeLV-negative cats, was the most common site of involvement. Although the majority of tumors from FeLV-positive cats were CD3-immunoreactive, only one half of CD3-immunoreactive tumors occurred in FeLV-positive cats. Median remission duration and survival times were 126 days and 143 days, respectively, for all cats. Measures of tumor cell proliferation (AgNOR frequency and PCNA-LI) and CD3-immunoreactivity were not predictive of outcome. When all prognostic factors were accounted for by multivariate analysis, response to therapy, FeLV status, and clinical substage were predictive of outcome. FeLV-negative cats that achieved a complete response following induction therapy were likely to have durable (ie, > 6-month) responses, particularly when doxorubicin was included in the chemotherapy protocol. However, FeLV-positive cats had significantly shorter remission and survival times with available chemotherapeutic protocols.  相似文献   

LABELING CHEMICAL SPECIMENS     

Vail CE 《Science (New York, N.Y.)》1915,42(1088):656-657

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Efficacy of injectable maropitant (Cerenia™) in a randomized clinical trial for prevention and treatment of cisplatin-induced emesis in dogs presented as veterinary patients     

D. M. Vail  H. S. Rodabaugh  G. A. Conder  J. F. Boucher  S. Mathur 《Veterinary and comparative oncology》2007,5(1):38-46

Chemotherapy‐induced nausea and vomiting (CINV) is a common side‐effect of cisplatin therapy. Maropitant (Cerenia?), a novel neurokinin‐1 receptor antagonist, was evaluated for prevention and treatment of cisplatin‐induced emesis in tumour‐bearing dogs. Dogs (n= 122) were randomly allocated to three treatment groups: T01, placebo before and after cisplatin; T02, placebo before and maropitant after cisplatin; or T03, maropitant before and placebo after cisplatin. Maropitant treatment (T02) following a cisplatin‐induced‐emetic event resulted in significantly fewer subsequent emetic events (P= 0.0005) than in placebo‐treated dogs (T01). In placebo‐treated (T01) dogs, 56.4% were withdrawn from the study because of treatment failure compared with 5.3% in group T02. When maropitant was administered prior to cisplatin treatment (T03) in a prevention regime, 94.9% did not vomit compared with only 4.9% of placebo‐treated dogs, and significantly fewer emetic events (P < 0.0001) were observed in those dogs that did vomit. In summary, maropitant was safe and highly effective in reducing or completely preventing cisplatin‐induced emesis.  相似文献