33 results on '"Mary Lynn Higginbotham"'
Search Results
2. Supplementary Figure 1 from Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Timothy M. Fan, Chand Khanna, Laura E. Selmic, Daniel L. Gustafson, Sara D. Allstadt, Janean L. Fidel, Michael O. Childress, Kristine Burgess, Antonella Borgatti, Olya Martin, Steven E. Suter, Angela L. McCleary-Wheeler, Cheryl E. Balkman, Lisa G. Barber, Cheryl A. London, Jennifer A. Mahoney, Erika Krick, Raelene M. Wouda, Mary Lynn Higginbotham, Shawna Klahn, Nikolaos Dervisis, Annette N. Smith, Stephanie Lindley, Brandan G. Wustefeld-Janssens, Heather Wilson-Robles, Haley Leeper, Kaitlin M. Curran, Corey Saba, Nicole C. Northrup, J. Paul Woods, Anthony J. Mutsaers, Jennifer L. Willcox, Jenna H. Burton, David M. Vail, Jeffrey N. Bryan, Brian K. Flesner, Kristen Weishaar, Susan E. Lana, Megan E. Brown, William C. Kisseberth, Erika P. Berger, Aswini Cherukuri, Christina N. Mazcko, and Amy K. LeBlanc
- Abstract
Supplementary Fig. 1 depicts the chronology of clinical trial visits and associated procedures for dogs enrolled in this clinical trial.
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- 2023
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3. Supplementary Table 2 from Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Timothy M. Fan, Chand Khanna, Laura E. Selmic, Daniel L. Gustafson, Sara D. Allstadt, Janean L. Fidel, Michael O. Childress, Kristine Burgess, Antonella Borgatti, Olya Martin, Steven E. Suter, Angela L. McCleary-Wheeler, Cheryl E. Balkman, Lisa G. Barber, Cheryl A. London, Jennifer A. Mahoney, Erika Krick, Raelene M. Wouda, Mary Lynn Higginbotham, Shawna Klahn, Nikolaos Dervisis, Annette N. Smith, Stephanie Lindley, Brandan G. Wustefeld-Janssens, Heather Wilson-Robles, Haley Leeper, Kaitlin M. Curran, Corey Saba, Nicole C. Northrup, J. Paul Woods, Anthony J. Mutsaers, Jennifer L. Willcox, Jenna H. Burton, David M. Vail, Jeffrey N. Bryan, Brian K. Flesner, Kristen Weishaar, Susan E. Lana, Megan E. Brown, William C. Kisseberth, Erika P. Berger, Aswini Cherukuri, Christina N. Mazcko, and Amy K. LeBlanc
- Abstract
Supplementary Table 2 contains the summary comparison of both the Intent-to-treat and Per-protocol analyses of clinical outcomes for dogs enrolled in Standard of Care (SOC) and Standard of Care + sirolimus
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- 2023
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4. Data from Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Timothy M. Fan, Chand Khanna, Laura E. Selmic, Daniel L. Gustafson, Sara D. Allstadt, Janean L. Fidel, Michael O. Childress, Kristine Burgess, Antonella Borgatti, Olya Martin, Steven E. Suter, Angela L. McCleary-Wheeler, Cheryl E. Balkman, Lisa G. Barber, Cheryl A. London, Jennifer A. Mahoney, Erika Krick, Raelene M. Wouda, Mary Lynn Higginbotham, Shawna Klahn, Nikolaos Dervisis, Annette N. Smith, Stephanie Lindley, Brandan G. Wustefeld-Janssens, Heather Wilson-Robles, Haley Leeper, Kaitlin M. Curran, Corey Saba, Nicole C. Northrup, J. Paul Woods, Anthony J. Mutsaers, Jennifer L. Willcox, Jenna H. Burton, David M. Vail, Jeffrey N. Bryan, Brian K. Flesner, Kristen Weishaar, Susan E. Lana, Megan E. Brown, William C. Kisseberth, Erika P. Berger, Aswini Cherukuri, Christina N. Mazcko, and Amy K. LeBlanc
- Abstract
Purpose:The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression.Patients and Methods:A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes.Results:There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively.Conclusions:In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.
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- 2023
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5. Supplementary Table 4 from Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Timothy M. Fan, Chand Khanna, Laura E. Selmic, Daniel L. Gustafson, Sara D. Allstadt, Janean L. Fidel, Michael O. Childress, Kristine Burgess, Antonella Borgatti, Olya Martin, Steven E. Suter, Angela L. McCleary-Wheeler, Cheryl E. Balkman, Lisa G. Barber, Cheryl A. London, Jennifer A. Mahoney, Erika Krick, Raelene M. Wouda, Mary Lynn Higginbotham, Shawna Klahn, Nikolaos Dervisis, Annette N. Smith, Stephanie Lindley, Brandan G. Wustefeld-Janssens, Heather Wilson-Robles, Haley Leeper, Kaitlin M. Curran, Corey Saba, Nicole C. Northrup, J. Paul Woods, Anthony J. Mutsaers, Jennifer L. Willcox, Jenna H. Burton, David M. Vail, Jeffrey N. Bryan, Brian K. Flesner, Kristen Weishaar, Susan E. Lana, Megan E. Brown, William C. Kisseberth, Erika P. Berger, Aswini Cherukuri, Christina N. Mazcko, and Amy K. LeBlanc
- Abstract
Supplementary Table 4 contains a summary of the outcomes, with statistical comparisons, of the dogs enrolled in the SOC + sirolimus clinical trial arm. This includes the DFI and outcomes of the groups of dogs stratified by tumor location and ALP status.
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- 2023
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6. Supplementary Table 1 from Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Timothy M. Fan, Chand Khanna, Laura E. Selmic, Daniel L. Gustafson, Sara D. Allstadt, Janean L. Fidel, Michael O. Childress, Kristine Burgess, Antonella Borgatti, Olya Martin, Steven E. Suter, Angela L. McCleary-Wheeler, Cheryl E. Balkman, Lisa G. Barber, Cheryl A. London, Jennifer A. Mahoney, Erika Krick, Raelene M. Wouda, Mary Lynn Higginbotham, Shawna Klahn, Nikolaos Dervisis, Annette N. Smith, Stephanie Lindley, Brandan G. Wustefeld-Janssens, Heather Wilson-Robles, Haley Leeper, Kaitlin M. Curran, Corey Saba, Nicole C. Northrup, J. Paul Woods, Anthony J. Mutsaers, Jennifer L. Willcox, Jenna H. Burton, David M. Vail, Jeffrey N. Bryan, Brian K. Flesner, Kristen Weishaar, Susan E. Lana, Megan E. Brown, William C. Kisseberth, Erika P. Berger, Aswini Cherukuri, Christina N. Mazcko, and Amy K. LeBlanc
- Abstract
Supplementary Table 1 contains the inclusion and exclusion criteria for pet dogs considered for enrollment into the SOC and SOC + S clinical trial arms.
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- 2023
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- View/download PDF
7. Supplementary Figure 2 from Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Timothy M. Fan, Chand Khanna, Laura E. Selmic, Daniel L. Gustafson, Sara D. Allstadt, Janean L. Fidel, Michael O. Childress, Kristine Burgess, Antonella Borgatti, Olya Martin, Steven E. Suter, Angela L. McCleary-Wheeler, Cheryl E. Balkman, Lisa G. Barber, Cheryl A. London, Jennifer A. Mahoney, Erika Krick, Raelene M. Wouda, Mary Lynn Higginbotham, Shawna Klahn, Nikolaos Dervisis, Annette N. Smith, Stephanie Lindley, Brandan G. Wustefeld-Janssens, Heather Wilson-Robles, Haley Leeper, Kaitlin M. Curran, Corey Saba, Nicole C. Northrup, J. Paul Woods, Anthony J. Mutsaers, Jennifer L. Willcox, Jenna H. Burton, David M. Vail, Jeffrey N. Bryan, Brian K. Flesner, Kristen Weishaar, Susan E. Lana, Megan E. Brown, William C. Kisseberth, Erika P. Berger, Aswini Cherukuri, Christina N. Mazcko, and Amy K. LeBlanc
- Abstract
Supplementary Fig. 2 shows the walk-in pharmacokinetics, both measured results and simulated values, for dogs treated with oral sirolimus in preparation for the definitive adjuvant trial.
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- 2023
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8. Zn-based physiometacomposite nanoparticles: distribution, tolerance, imaging, and antiviral and anticancer activity
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Sarah Young, Sagar Rayamajhi, Rowena A. Woode, Santosh Aryal, Sarah Schneider, Garry Glaspell, Steve Ensley, Tracy Miesner, Kartik Ghosh, Robert K. Delong, Pratiksha Khanal, Heman Shakeri, Zhoumeng Lin, Megan C. Niederwerder, Lane L. Clarke, Mary Lynn Higginbotham, Majid Jaberi-Douraki, Tej B. Shrestha, Elza Neelima Mathew, Ryan Swanson, Reza Mazloom, and Ramesh Marasini
- Subjects
Luminescence ,Cell Survival ,Swine ,Cell ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Spleen ,02 engineering and technology ,Development ,Antiviral Agents ,law.invention ,Flow cytometry ,Mice ,03 medical and health sciences ,Confocal microscopy ,law ,Cell Line, Tumor ,medicine ,Organoid ,Animals ,Distribution (pharmacology) ,General Materials Science ,Viability assay ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,Chemistry ,021001 nanoscience & nanotechnology ,Molecular biology ,Zinc ,medicine.anatomical_structure ,Nanoparticles ,0210 nano-technology ,Ex vivo - Abstract
The aim of this study was to investigate the distribution, tolerance, and anticancer and antiviral activity of Zn-based physiometacomposites (PMCs). Manganese, iron, nickel and cobalt-doped ZnO, ZnS or ZnSe were synthesized. Cell uptake, distribution into 3D culture and mice, and biochemical and chemotherapeutic activity were studied by fluorescence/bioluminescence, confocal microscopy, flow cytometry, viability, antitumor and virus titer assays. Luminescence and inductively coupled plasma mass spectrometry analysis showed that nanoparticle distribution was liver >spleen >kidney >lung >brain, without tissue or blood pathology. Photophysical characterization as ex vivo tissue probes and LL37 peptide, antisense oligomer or aptamer delivery targeting RAS/Ras binding domain (RBD) was investigated. Treatment at 25 μg/ml for 48 h showed ≥98–99% cell viability, 3D organoid uptake, 3-log inhibition of β-Galactosidase and porcine reproductive respiratory virus infection. Data support the preclinical development of PMCs for imaging and delivery targeting cancer and infectious disease.
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- 2021
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9. CD4 and CD8 double-negative immunophenotype of thymoma-associated lymphocytes in a dog
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David S. Biller, Nora L. Springer, William Vernau, Yvonne M Wikander, Mary Lynn Higginbotham, Kaori Knights, and Calli Coffee
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Male ,dogs ,Pathology ,medicine.medical_specialty ,Thymoma ,Lymphoma ,Lymphocytosis ,040301 veterinary sciences ,T-Lymphocytes ,Lymphocyte ,Immunophenotyping ,Flow cytometry ,0403 veterinary science ,03 medical and health sciences ,Dogs ,Rare Diseases ,hemic and lymphatic diseases ,medicine ,Animals ,Dog Diseases ,Veterinary Sciences ,Cancer ,030304 developmental biology ,Thymic Lymphoma ,0303 health sciences ,PCR for antigen receptor gene rearrangement ,General Veterinary ,medicine.diagnostic_test ,business.industry ,flow cytometry ,Thymus Neoplasms ,Hematology ,04 agricultural and veterinary sciences ,Flow Cytometry ,medicine.disease ,immunophenotype ,medicine.anatomical_structure ,HIV/AIDS ,Female ,medicine.symptom ,Brief Communications ,business ,Zoology ,CD8 - Abstract
Persistent small-cell lymphocytosis in dogs with a concurrent mediastinal mass has been associated with both thymoma and small-cell lymphoma. In thymomas, neoplastic thymic epithelial cells induce overproduction and release of polyclonal lymphocytes, whereas thymic lymphoma results in thymic effacement by a clonal expansion of neoplastic lymphocytes and subsequent leukemic phase of lymphoma. Flow cytometry has been used to differentiate these 2 entities by immunophenotyping mediastinal mass aspirates. It has been reported that cases with mediastinal masses in which ≥ 10% of the associated small-cell lymphocytes were double positive for CD4 and CD8 were thymomas, whereas masses associated with < 10% were suggestive of lymphoma. We report a unique case of thymoma-associated lymphocytosis lacking the classic CD4+CD8+ immunophenotype. Our findings suggest that there may be more diversity in the thymoma-associated lymphocyte immunophenotype than has been identified previously; immunophenotyping alone might not be sufficient to differentiate thymic small-cell lymphoma from thymoma-associated lymphocytosis. In dogs with mediastinal masses and peripheral lymphocytosis, employing a variety of testing modalities to avoid misdiagnosis is prudent. These modalities include cytologic and/or histologic evaluation, immunophenotyping, and clonality assessment.
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- 2020
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10. Pathology in Practice
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Sabina P. Sheppard-Olivares, Ada Giselle Cino-Ozuna, Nora L. Springer, Vinay Shivanna, and Mary Lynn Higginbotham
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General Veterinary ,Animals - Published
- 2020
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11. Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
- Author
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Amy K. LeBlanc, Timothy M. Fan, Heather Wilson-Robles, Corey F. Saba, Janean Fidel, Nicole C. Northrup, Annette N. Smith, Michael O. Childress, Shawna Klahn, Jennifer L. Willcox, David M. Vail, William C. Kisseberth, Megan E. Brown, Lisa G. Barber, Erika L. Krick, Haley Leeper, Kristine Burgess, Chand Khanna, Raelene M. Wouda, Susan E. Lana, Nikolaos Dervisis, Olya Martin, Angela L McCleary-Wheeler, Mary Lynn Higginbotham, J. Paul Woods, Jeffrey N. Bryan, Aswini Cherukuri, Steven E. Suter, Stephanie S Lindley, Daniel L. Gustafson, Brandan G Wustefeld-Janssens, Laura E. Selmic, Kristen M. Weishaar, Brian K. Flesner, Christina Mazcko, Jenna H Burton, Erika P. Berger, Sara D. Allstadt, Antonella Borgatti, Jennifer A. Mahoney, Cheryl E. Balkman, Kaitlin M. Curran, Anthony J. Mutsaers, and Cheryl A. London
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Oncology ,Cancer Research ,medicine.medical_treatment ,law.invention ,Carboplatin ,0403 veterinary science ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Surgical ,Dog Diseases ,Prospective Studies ,Amputation ,Adjuvant ,Cancer ,Pediatric ,education.field_of_study ,Osteosarcoma ,TOR Serine-Threonine Kinases ,04 agricultural and veterinary sciences ,Pets ,Combined Modality Therapy ,Survival Rate ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,6.1 Pharmaceuticals ,medicine.drug ,Signal Transduction ,medicine.medical_specialty ,040301 veterinary sciences ,Population ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,Bone Neoplasms ,Amputation, Surgical ,Article ,03 medical and health sciences ,Dogs ,Rare Diseases ,Clinical Research ,Internal medicine ,medicine ,Animals ,Chemotherapy ,Oncology & Carcinogenesis ,Adverse effect ,education ,Sirolimus ,business.industry ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,Orphan Drug ,chemistry ,business - Abstract
Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. Patients and Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively. Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.
- Published
- 2021
12. Carboplatin-induced myelosuppression as related to body weight in dogs
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James K. Roush, Mary Lynn Higginbotham, and Calli Coffee
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Melphalan ,Male ,medicine.medical_specialty ,Neutropenia ,040301 veterinary sciences ,medicine.medical_treatment ,Antineoplastic Agents ,Veterinary oncology ,Body weight ,Gastroenterology ,Carboplatin ,0403 veterinary science ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dogs ,Risk Factors ,Internal medicine ,Neoplasms ,medicine ,Animals ,Dog Diseases ,Retrospective Studies ,Mitoxantrone ,Chemotherapy ,General Veterinary ,business.industry ,Body Weight ,Retrospective cohort study ,04 agricultural and veterinary sciences ,Kansas ,medicine.disease ,Thrombocytopenia ,chemistry ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Smaller dogs are known to have an increased risk of chemotherapy-induced myelosuppression for doxorubicin, mitoxantrone and melphalan. This retrospective study aimed to determine if dogs
- Published
- 2020
13. Metastatic intraocular hemangiopericytoma in a dog
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Mary Lynn Higginbotham, Rachel A. Allbaugh, Amy J. Rankin, Jonathan D. Pucket, and Leandro B. C. Teixeira
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medicine.medical_specialty ,genetic structures ,040301 veterinary sciences ,Enucleation ,Glaucoma ,Case Report ,Metastasis ,0403 veterinary science ,03 medical and health sciences ,0302 clinical medicine ,Ophthalmology ,medicine ,Hemangiopericytoma ,General Veterinary ,business.industry ,Secondary glaucoma ,04 agricultural and veterinary sciences ,Glaucoma, Hemangiopericytoma, Metastasis ,medicine.disease ,eye diseases ,QL1-991 ,030221 ophthalmology & optometry ,Immunohistochemistry ,Labrador Retriever ,Spindle cell sarcoma ,sense organs ,business ,Zoology - Abstract
A 10-year-old Labrador Retriever who had been undergoing therapy for a recurrent hemangiopericytoma of the right flank presented to the Kansas State University Ophthalmology service for evaluation of a painful left eye. Examination revealed secondary glaucoma and irreversible blindness of the affected eye and multifocal chorioretinal lesions in the fellow eye. Therapeutic and diagnostic enucleation of the left eye was performed and histopathologic examination demonstrated the presence of a presumed metastatic spindle cell sarcoma. Further immunohistochemical staining confirmed the intraocular neoplasia to be metastatic spread from the previously removed flank mass. Rapid progression in size and number of chorioretinal lesions in the right eye was noted in the post-operative period until the patient was euthanized one month after surgery. This case report is the first to document intraocular metastasis of hemangiopericytoma in a veterinary patient.Keywords: Glaucoma, Hemangiopericytoma, Metastasis
- Published
- 2017
14. Translating Nanomedicine to Comparative Oncology—the Case for Combining Zinc Oxide Nanomaterials with Nucleic Acid Therapeutic and Protein Delivery for Treating Metastatic Cancer
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Paige Pearson, Yi-Hsien Cheng, Raelene M. Wouda, Mary Lynn Higginbotham, Calli Coffee, Zhoumeng Lin, Robert K. Delong, Elza Neelima Mathew, and Amanda Hoffman
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Medical Oncology ,03 medical and health sciences ,0302 clinical medicine ,Drug Delivery Systems ,Lipid oxidation ,Internal medicine ,Neoplasms ,Nucleic Acids ,medicine ,Special Issue on Drug Delivery Technologies ,Animals ,Humans ,Neoplasm Metastasis ,Protein kinase B ,Pharmacology ,Tumor microenvironment ,Chemistry ,Kinase ,Melanoma ,Cancer ,Proteins ,medicine.disease ,Nanostructures ,030104 developmental biology ,Nanomedicine ,Cancer cell ,Molecular Medicine ,Zinc Oxide ,030217 neurology & neurosurgery - Abstract
The unique anticancer, biochemical, and immunologic properties of nanomaterials are becoming a new tool in biomedical research. Their translation into the clinic promises a new wave of targeted therapies. One nanomaterial of particular interest are zinc oxide (ZnO) nanoparticles (NPs), which has distinct mechanisms of anticancer activity including unique surface, induction of reactive oxygen species, lipid oxidation, pH, and also ionic gradients within cancer cells and the tumor microenvironment. It is recognized that ZnO NPs can serve as a direct enzyme inhibitor. Significantly, ZnO NPs inhibit extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis. Indeed, direct intratumoral injection of ZnO NPs or a complex of ZnO with RNA significantly suppresses ERK and AKT phosphorylation. These data suggest ZnO NPs and their complexes or conjugates with nucleic acid therapeutic or anticancer protein may represent a potential new strategy for the treatment of metastatic melanoma, and potentially other cancers. This review focuses on the anticancer mechanisms of ZnO NPs and what is currently known about its biochemical effects on melanoma, biologic activity, and pharmacokinetics in rodents and its potential for translation into large animal, spontaneously developing models of melanoma and other cancers, which represent models of comparative oncology.
- Published
- 2019
15. Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study
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Raelene M. Wouda, Samuel E. Hocker, and Mary Lynn Higginbotham
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Male ,medicine.medical_specialty ,Indoles ,Toceranib ,040301 veterinary sciences ,medicine.medical_treatment ,Context (language use) ,Pharmacology ,Neutropenia ,Carboplatin ,0403 veterinary science ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dogs ,Neoplasms ,medicine ,Animals ,Doxorubicin ,Pyrroles ,Dog Diseases ,Chemotherapy ,General Veterinary ,business.industry ,Combination chemotherapy ,04 agricultural and veterinary sciences ,medicine.disease ,Surgery ,chemistry ,030220 oncology & carcinogenesis ,Toxicity ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Combination chemotherapy holds promise for improving outcomes in malignancy when compared with single-agent approaches. Care must be taken to avoid overlapping toxicity and to utilize agents with differing mechanisms of action. A phase I dose-finding trial was performed to determine the maximally tolerated dose (MTD) of a concurrent toceranib and doxorubicin (DOX) combination protocol where toceranib dose was maintained at or near 2.75 mg kg-1 by mouth every other day (PO EOD) while escalating DOX dosage. The dose-limiting toxicity was found to be neutropenia and the MTD of the combination was determined to be 25 mg m-2 of DOX q 21 days given concurrently with toceranib 2.75 mg kg-1 PO EOD. This combination was well tolerated with no excessive gastrointestinal toxicity nor novel adverse events (AEs) noted. Anti-tumour activity was observed in the majority of cases. This combination warrants further investigation in the context of phase II/III clinical trials to characterize efficacy and long-term AE profiles.
- Published
- 2017
16. Development and validation of a hemangiosarcoma likelihood prediction model in dogs presenting with spontaneous hemoabdomen: The HeLP score
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Ashley R. Schick, Kyle G. Mathews, Mary Lynn Higginbotham, Ameet Singh, J. Matthew Sherwood, and Galina M. Hayes
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Male ,medicine.medical_specialty ,040301 veterinary sciences ,Hemoabdomen ,Population ,Hemangiosarcoma ,Lower risk ,Severity of Illness Index ,0403 veterinary science ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Dogs ,Risk Factors ,Internal medicine ,medicine ,Animals ,Hemoperitoneum ,Dog Diseases ,education ,Retrospective Studies ,Ontario ,education.field_of_study ,Framingham Risk Score ,General Veterinary ,business.industry ,External validation ,Reproducibility of Results ,030208 emergency & critical care medicine ,04 agricultural and veterinary sciences ,medicine.disease ,United States ,Abdominal Neoplasms ,Female ,medicine.symptom ,business ,Cohort study - Abstract
To calculate a risk prediction model for hemangiosarcoma (HSA) diagnosis in dogs presenting with nontraumatic hemoabdomen.Retrospective multicenter observational cohort study enrolling dogs presented 2003-2016.Five academic veterinary medical centers.A total of 406 dogs with nontraumatic hemoabdomen as the presenting complaint that underwent surgical exploration or necropsy and received a histological diagnosis. Overall, 219 dogs from 3 centers provided the data for model construction, and 187 dogs from 2 centers provided the population for external validation.None.The risk score was modeled on 4 predictors: bodyweight (P = 0.01), total plasma protein (P0.01), platelet count (P0.01), and thoracic radiograph findings (P = 0.02). The incidence of HSA diagnosis was 36%, 76%, and 96% in the low risk (≤40), medium risk (41-55), and high risk (55) score groups, respectively. The risk score AUROC was 0.85 (95% CI 0.79-0.90) on the construction population, and 0.77 (95% CI 0.70-0.84) on the validation population.The risk of HSA diagnosis in dogs presenting with nontraumatic hemoabdomen could be predicted using a simple risk score, which could aid in identification and treatment of dogs at lower risk for this diagnosis.
- Published
- 2017
17. Intermittent Single-Agent Doxorubicin for the Treatment of Canine B-Cell Lymphoma
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Jerome C. Nietfeld, Mary Lynn Higginbotham, Diana Burr, James K. Roush, Kimberly B.Reeds, Melinda J. Wilkerson, and Dudley L. McCaw
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Oncology ,medicine.medical_specialty ,Lymphoma, B-Cell ,Disease ,Drug Administration Schedule ,Dogs ,Internal medicine ,medicine ,Animals ,Doxorubicin ,Dog Diseases ,Stage (cooking) ,Small Animals ,B-cell lymphoma ,Survival analysis ,Neoplasm Staging ,Canine Lymphoma ,Antibiotics, Antineoplastic ,business.industry ,Remission Induction ,medicine.disease ,Survival Analysis ,Lymphoma ,Surgery ,Clinical trial ,Treatment Outcome ,business ,medicine.drug - Abstract
Canine B-cell lymphoma is a highly treatable disease, but cost and logistical factors may hamper an owner’s ability to pursue treatment of their pet with this disease. The authors evaluated the use of single-agent doxorubicin in an intermittent fashion for efficacy in the treatment of this disease. Morphologic and clinical data were analyzed for prognostic significance. Eighteen dogs with B-cell lymphoma, all with multicentric disease, were enrolled. The overall complete response (CR) rate was 78%, median total doxorubicin remission time (TDR) was 80.5 days, and median overall survival (OS) was 169.5 days. The median number of doxorubicin doses administered was 4.5. First remission times were significantly affected by clinical stage and substage of disease. Outcome for the dogs in this study were similar to those previously reported for single-agent doxorubicin treatment. Additionally, the intermittent nature of the treatments made the described protocol more feasible for the owners who enrolled their pets in this study. Intermittent single-agent doxorubicin is not a substitute for multiagent chemotherapy protocols in the treatment of canine lymphoma; however, it is a reasonable alternative if the cost and time commitments are limiting factors for an owner.
- Published
- 2013
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18. Evaluation of Environmental Cytotoxic Drug Contamination in a Clinical Setting
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Mary Lynn Higginbotham and Sara E. Fritz
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medicine.medical_specialty ,Cytotoxic drug ,040301 veterinary sciences ,Antineoplastic Agents ,Vial ,Teaching hospital ,0403 veterinary science ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Occupational Exposure ,medicine ,Animals ,Small Animals ,Intensive care medicine ,business.industry ,Treatment room ,Veterinary Drugs ,04 agricultural and veterinary sciences ,Contamination ,030210 environmental & occupational health ,Carboplatin ,Biological safety ,chemistry ,Equipment Contamination ,business ,Environmental Monitoring - Abstract
The use of cytotoxic drugs to treat neoplastic conditions is increasing in veterinary practices. Many agents have the potential to be genotoxic and evidence of exposure to cytotoxic drugs has been found in healthcare workers handling these pharmaceuticals. To date, limited contamination evaluations have been performed in veterinary practices. Evaluation for carboplatin contamination was performed at a veterinary teaching hospital involving twelve areas in the dispensary and treatment room. Detectable levels of platinum were found on the surface of the biological safety cabinet where drugs are transferred from vial to administration device. Results indicate contamination did occur and care must be taken during all phases of cytotoxic drug preparation and administration; precautionary procedures must be in place to limit the spread of surface contamination and personnel exposure.
- Published
- 2016
19. Evaluation of a novel immunomodulator composed of human chorionic gonadotropin and bacillus Calmette-Guerin for treatment of canine mast cell tumors in clinically affected dogs
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Sue Downing, Robert C. Rosenthal, Mary Lynn Higginbotham, John McMichael, Dudley L. McCaw, Mary K. Klein, Linda S. Fineman, J. Armando Villamil, Karri Meleo, and Carolyn J. Henry
- Subjects
Male ,medicine.medical_specialty ,Antineoplastic Agents ,Host factors ,Vinblastine ,Tumor response ,Chorionic Gonadotropin ,Gastroenterology ,Mast cell tumors ,Human chorionic gonadotropin ,Dogs ,Adjuvants, Immunologic ,Internal medicine ,medicine ,Animals ,Humans ,Dog Diseases ,Prospective Studies ,Adverse effect ,General Veterinary ,business.industry ,Clinical performance ,General Medicine ,Mastocytoma ,Endocrinology ,BCG Vaccine ,Female ,business ,medicine.drug - Abstract
Objective—To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine. Animals—95 dogs with measurable grade II or III mast cell tumors. Procedures—Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m2, IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed. Results—46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (≥50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group. Conclusions and Clinical Relevance—hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.
- Published
- 2007
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20. Regional Nodal Metastasis of Humeral Chondrosarcoma in a Dog
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Mary Lynn Higginbotham, Brad M. DeBey, Mandy Meindel, Lisa M. Pohlman, and Rachel Moon
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musculoskeletal diseases ,Male ,Axillary lymph nodes ,Elbow ,Chondrosarcoma ,Physical examination ,Bone Neoplasms ,Amputation, Surgical ,Metastasis ,Dogs ,Forelimb ,Medicine ,Animals ,Dog Diseases ,Small Animals ,Antibiotics, Antineoplastic ,medicine.diagnostic_test ,business.industry ,Anatomy ,medicine.disease ,medicine.anatomical_structure ,Lameness ,Doxorubicin ,Lymphatic Metastasis ,Lymph ,Lymph Nodes ,business - Abstract
A 6 yr old castrated male English springer spaniel was evaluated with a 1 mo history of progressive right forelimb lameness with recent swelling around the elbow joint. Physical examination findings included lameness of the right forelimb, muscle atrophy around the right shoulder, grade 2/6 heart murmur, and moderate dental disease. Results of a complete blood cell count and serum biochemical analysis were unremarkable with the exception of a mildly increased alkaline phosphatase (368 U/L; reference range, 128–328 U/L). Radiographs of the right elbow revealed a mixed lytic and proliferative osseous lesion most consistent with either neoplasia or infection. Thoracic radiographs and the echocardiogram were unremarkable. Fine-needle aspiration of the bone lesion was performed. The cytological diagnosis was chondrosarcoma. The right forelimb was amputated and the axillary lymph nodes were collected. Histopathological examination of the bone lesion and axillary lymph nodes revealed chondrosarcoma with metastasis to the lymph nodes. Lymph node metastasis of chondrosarcoma is rare and needs to be further evaluated as a prognostic indicator.
- Published
- 2015
21. Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours
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Linda Beaver, David M. Vail, Cheryl A. London, Tracy Ladue, Mary K. Klein, Pam Jones, Francisco J. Alvarez, C. J. McNeill, Siobhan Haney, Tamra Mathie, Erika L. Krick, Janet K. Carreras, Kate Vickery, Andrew Novasad, Betsey Hershey, Sarah Gillings, Mary Lynn Higginbotham, Jeffery Bryan, Lisa Fulton, Virginia L. Gill, Nicole Stingle, Carolyn J. Henry, Craig A. Clifford, Lorin Hillman, Brenda Phillips, Mike Kiselow, Susan Ettinger, Andrew Vaughan, Doug H. Thamm, and Meredith Gauthier
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Male ,medicine.medical_specialty ,Pathology ,Toceranib Phosphate ,Indoles ,Skin Neoplasms ,Toceranib ,Nose Neoplasms ,Antineoplastic Agents ,Bone Neoplasms ,Anal sac adenocarcinoma ,Adenocarcinoma ,Gastroenterology ,Article ,Thyroid carcinoma ,Dogs ,Internal medicine ,Neoplasms ,Carcinoma ,Medicine ,Animals ,Pyrroles ,Dog Diseases ,Thyroid Neoplasms ,Anal Sacs ,Prospective cohort study ,Osteosarcoma ,General Veterinary ,business.industry ,Apocrine ,Receptor Protein-Tyrosine Kinases ,medicine.disease ,Apocrine Glands ,Head and Neck Neoplasms ,Female ,Sarcoma ,business ,Anal Gland Neoplasms ,medicine.drug - Abstract
The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity.
- Published
- 2012
22. In vitro Effects of Canine Wharton’s Jelly Mesenchymal Stromal Cells and Micellar Nanoparticles on Canine Osteosarcoma D17 Cell Viability
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Gwi-Moon Seo, Dery, L.Troyer, Dudley L. McCaw, Marla Pyle, Mary Lynn Higginbotham, Kimberly B.Reeds, Raja Shekar Rachakatla, and Carla L.Goad
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Pathology ,medicine.medical_specialty ,Stromal cell ,General Veterinary ,Cell growth ,business.industry ,Mesenchymal stem cell ,technology, industry, and agriculture ,macromolecular substances ,Molecular biology ,Canine Osteosarcoma ,carbohydrates (lipids) ,In vivo ,polycyclic compounds ,medicine ,MTT assay ,Viability assay ,Cytotoxicity ,business - Abstract
Objectives: To isolate and maintain canine Wharton’s jelly mesenchymal stromal cells (WJMSC) in culture, determine the effects of micellar nanoparticles containing doxorubicin (DOX) on WJMSC and canine osteosarcoma (OSA) D17 cells, and determine the effects of WJMSC loaded with micellar nanoparticles containing DOX on OSA D17 cell viability. Procedures: Stromal cells were isolated from canine umbilical cords. Micellar nanoparticles containing DOX were prepared and added to individual culture plates containing canine WJMSC and OSA D17 cells to determine DOX in micelles (DOX-M) effects on cell growth and viability. Conditioned media (CM) from culture plates containing canine WJMSC incubated with various DOX-M concentrations was added to OSA D17 cells. An MTT assay was performed to assess osteosarcoma D17 cell viability. A trypan blue stain was utilized to perform cell counts to determine the effect of the DOX-M on WJMSC growth. Results: WJMSC were successfully isolated and maintained in culture. Micellar nanoparticles containing DOX decreased viability of OSA D17 cells. Osteosarcoma D17 cell viability decreased following incubation with CM obtained from WJMSC loaded with DOX-M. Significant decreases in OSA D17 cell viability were observed after incubation with the CM of canine WJMSC loaded with 10 μM DOX-M at 96 hours (p=0.0037). Significant decreases were also observed with the CM from WJMSC loaded with 1 μM DOX-M at 96 hours (p=0.0222). WJMSC numbers decreased in a dose dependent manner following incubation with DOX-M. The decrease in WJMSC number was not secondary to cytotoxicity as all variables produced similar percentages of dead WJMSC. Conclusions: Canine WJMSC can be isolated and maintained in culture. DOX-M produces OSA D17 cytotoxicity and slows proliferation of canine WJMSC. WJMSC containing DOX-M cause OSA D17 cell cytotoxicity. These data support in vivo experiments utilizing canine WJMSC and micellar nanoparticles.
- Published
- 2012
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23. Web-based documentation of clinical skills to assess the competency of veterinary students
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Mary Lynn Higginbotham, Bonnie R. Rush, Emily Klocke, David C. Rankin, Matt D. Miesner, David S. Biller, and Elizabeth G. Davis
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Program evaluation ,Veterinary medicine ,Medical education ,Class (computer programming) ,Internet ,Students, Medical ,General Veterinary ,business.industry ,MEDLINE ,General Medicine ,Documentation ,Kansas ,Education ,Formative assessment ,Medicine ,Web application ,Humans ,Clinical Competence ,Educational Measurement ,business ,Education, Veterinary ,Curriculum ,Graduation ,Program Evaluation - Abstract
Kansas State University implemented a Web-based program to assess students' competency to perform technical skills during clinical rotations throughout the fourth year of the veterinary curriculum. The classes of 2009 and 2010 recorded a minimum number of procedures (104 and 103, respectively) from a menu of more than 220 recommended procedures. Procedures were categorized by species (small animal, equine, food animal) and disciplines (imaging, anesthesia, diagnostic medicine/necropsy). Ophthalmology was added as a fourth discipline for the class of 2010. Students recorded procedures into the Web-based system, including information about the patient, procedure performed, supervisor, and a self-assessment of performance. Faculty, staff, and house officers evaluated the procedures electronically by confirming that they witnessed the procedure and providing qualitative and written feedback. The class of 2009 recorded 18,492 procedures (M=171/student) and the class of 2010 recorded 16,935 procedures (M=158/student). Two students from each class (2009 and 2010) did not complete the minimum required skills during clinical rotations and returned to perform procedures immediately before (n=3) or immediately after (n=1) graduation to receive their diploma. The Web-based system captured a large number of assessments of technical competency performed in the clinical setting. The system provided students with formative feedback throughout the clinical year, ensured equitable distribution of procedural opportunities across the student body, and required minimal additional resources.
- Published
- 2011
24. Supportive Care of the Cancer Patient
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Mary Lynn Higginbotham
- Subjects
medicine.medical_specialty ,business.industry ,medicine ,Cancer ,medicine.disease ,business ,Intensive care medicine - Published
- 2010
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25. Tumors of the Head and Neck
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Carolyn J. Henry and Mary Lynn Higginbotham
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business.industry ,Medicine ,Anatomy ,Head and neck ,business - Published
- 2010
- Full Text
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26. Cancer Management in Small Animal Practice - E-Book : Cancer Management in Small Animal Practice - E-Book
- Author
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Carolyn J. Henry, Mary Lynn Higginbotham, Carolyn J. Henry, and Mary Lynn Higginbotham
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- Veterinary oncology
- Abstract
Cancer Management in Small Animal Practice provides you with all the tools needed to diagnose, stage, and manage the many different disease entities known as'cancer.'This manual is designed to provide you with easy-to-access, clinically relevant details for complete care of the small animal cancer patient, while considering the needs, concerns, and capabilities of the client. It provides quick reference sections for information not included in current oncology texts, including drug interactions and resources for participation in clinical trials. All information is well referenced and the reference section on the accompanying website includes links to the original and related articles. - The latest information including diagnostic procedures, treatment modalities, and outcome predictions to help clients make the best decisions for their pets. - Expert contributors, renowned for clinical, as well as academic and research expertise, offer a wide breadth and depth of expertise. - Full-color format provides accurate visual depictions of specific diseases and procedures to enhance your diagnostic capabilities. - Key Points highlight critical information, enabling quick, easy access. - Systems approach to diagnosis and management offers logical, systematic, head-to-tail procedure for accurate diagnosis, treatment, and prognosis. - Extensive discussions of supportive care limit adverse events and increase patient survival and puts emergency information at the practitioner's fingertips. - Suggested readings highlight the latest information for further investigation and research. - Comprehensive drug safety guidelines thoroughly discuss all information required to safely handle and administer cancer drugs. - Helpful drug formularies offer available formulations, recommended dosages, toxicities, and relative costs. - Chapter on how to access clinical trials provides helpful information and hope for patients and their caregivers.
- Published
- 2010
27. Evaluation of a bladder tumor antigen test as a screening test for transitional cell carcinoma of the lower urinary tract in dogs
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Tracy Stokol, Dudley L. McCaw, Karen A Flessland, Mary Lynn Higginbotham, Kenita S. Rogers, Laura D. Garrett, Pam Koffend Stokes, Jeff W. Tyler, Ruthanne Chun, Margaret C. McEntee, and Carolyn J. Henry
- Subjects
Male ,medicine.medical_specialty ,Urinary system ,Urology ,Urine ,urologic and male genital diseases ,Dogs ,Antigen ,Antigens, Neoplasm ,Carcinoma ,Medicine ,Animals ,Mass Screening ,Dog Diseases ,Carcinoma, Transitional Cell ,General Veterinary ,business.industry ,General Medicine ,medicine.disease ,Bladder tumor Antigen ,Latex fixation test ,Test (assessment) ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,Female ,business - Abstract
Objective—To evaluate the veterinary version of the bladder tumor antigen (V-BTA) test as a screening test for transitional cell carcinoma (TCC) of the lower urinary tract of dogs. Animals—229 client-owned dogs. Procedure—Urine samples from dogs were shipped overnight to a single laboratory to facilitate testing within 48 hours of collection by use of the V-BTA rapid latex agglutination urine dipstick test. Groups of dogs included the following: 1) dogs with TCC of the lower urinary tract, 2) healthy control dogs, 3) unhealthy control dogs with non-TCC urinary tract disease, and 4) unhealthy control dogs without urinary tract disease. Test sensitivity and specificity were calculated by use of standard methods. Logistic models were developed to assess the effect of disease status, test conditions, urine composition, and signalment on the performance of the V-BTA test. Results—A total of 229 urine samples were analyzed, including 48 from dogs with suspected (n = 3) or confirmed (45) TCC. Test sensitivities were 88, 87, and 85% for all dogs with (suspected and confirmed) TCC, dogs with confirmed TCC at any site, and dogs with confirmed TCC of the urinary bladder, respectively. Test specificities were 84, 41, and 86% for healthy control dogs, unhealthy control dogs with non-TCC urinary tract disease, and unhealthy control dogs without urinary tract disease, respectively. The test performed slightly better on centrifuged urine samples than on uncentrifuged urine samples. Conclusions and Clinical Relevance—Our results indicate that the V-BTA test is useful in screening for urinary tract TCC in dogs. (Am J Vet Res 2003;64:1017–1020)
- Published
- 2003
28. Preclinical tolerance and pharmacokinetic assessment of MU-Gold, a novel chemotherapeutic agent, in laboratory dogs
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Mary Lynn, Higginbotham, Carolyn J, Henry, Kattesh V, Katti, Stan W, Casteel, Patricia M, Dowling, and Nagavarakishore, Pillarsetty
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Male ,Dogs ,Molecular Structure ,Phosphines ,Injections, Intravenous ,Organometallic Compounds ,Animals ,Antineoplastic Agents ,Organogold Compounds ,Gold Compounds ,Half-Life - Abstract
MU-Gold, tetrakis (trishydroxymethyl) phosphine gold(I) chloride, a novel gold compound, has cytotoxic effects against human androgen-dependent and -independent prostatic, gastric, and colonic carcinoma in cell culture and against malignant lymphoma in rodent models. A pilot study was conducted to evaluate the tolerance and pharmacokinetic properties of MU-Gold in normal dogs in anticipation of clinical trials in cancer-bearing dogs. MU-Gold (10 mg/kg) was administered by i.v. injection to three purpose-bred dogs. Serum was collected from all dogs for measurement of gold levels via atomic absorption spectrometry. In addition, complete blood counts and biochemical profiles were monitored for Dogs 2 and 3 every 7 days for 30 days. A two-compartment i.v. bolus model with first-order kinetics, mean elimination half-life of approximately 40 hours, and mean volume of distribution of 0.6 L/kg was established. Serum gold concentrations ranging from 10 to 50 mcg/ml were sustained for 2 to 3 days with no clinically significant toxicities observed. Based on in vitro results in earlier studies and preliminary pharmacokinetic data collected in the present study, Phase I clinical trials should be conducted to define the optimal dosage, dose-limiting toxicities, and other characteristics of MU-Gold that will be used to design Phase II clinical trials.
- Published
- 2003
29. Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma
- Author
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Carolyn J, Henry, Dudley L, McCaw, Susan E, Turnquist, Jeff W, Tyler, Lina, Bravo, Sarah, Sheafor, Rodney C, Straw, William S, Dernell, Bruce R, Madewell, Linda, Jorgensen, Michael A, Scott, Mary Lynn, Higginbotham, and Ruthanne, Chun
- Subjects
Male ,Carcinoma, Transitional Cell ,Ovariectomy ,Antineoplastic Agents ,Survival Analysis ,Disease Models, Animal ,Piroxicam ,Dogs ,Urinary Bladder Neoplasms ,Animals ,Humans ,Female ,Neoplasm Invasiveness ,Mitoxantrone ,Orchiectomy - Abstract
Cyclooxygenase inhibitors show promise in chemoprevention and therapy of certain carcinomas, an effect that may be additive to that of standard chemotherapy. The purpose of this study was to evaluate the efficacy of combined therapy using the cyclooxygenase inhibitor, piroxicam, and mitoxantrone against a relevant canine model of human invasive bladder cancer.Fifty-five dogs with transitional cell carcinoma of the urinary bladder were enrolled in this nonrandomized one-armed prospective multi-institutional clinical trial. Mitoxantrone was administered i.v. (5 mg/m(2)) every 21 days for four treatments, and piroxicam was administered p.o. (0.3 mg/kg/day) for the study duration. Tumor staging was performed at baseline, day 42 and every 3 months after protocol completion. Endpoints included time-to-treatment failure and survival time (ST).Response data were available for 48 dogs and included one complete response, 16 partial responses, 22 with disease stabilization, and 9 with progressive disease for an overall 35.4% measurable response rate. Subjective improvement occurred in 75% of treated dogs. Median time-to-treatment failure and ST were 194 and 350 days, respectively. Using censoring and end point definitions similar to those of previous reports of dogs treated with piroxicam alone, the median ST in this study was 291 days, compared with 181 days with piroxicam alone. Diarrhea and azotemia were the most common treatment complications.Mitoxantrone/piroxicam induced remission more frequently than previously reported for either drug as a single agent in this canine model of invasive human transitional cell carcinoma. Additional evaluation of these drugs in combination protocols should be explored.
- Published
- 2003
30. Feline non-ocular melanoma: a retrospective study of 23 cases (1991-1999)
- Author
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J C Graham, Antony S. Moore, L D Luna, Carolyn J. Henry, Mary Lynn Higginbotham, and Susan E. Turnquist
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0301 basic medicine ,Male ,medicine.medical_specialty ,Pathology ,Skin Neoplasms ,040301 veterinary sciences ,Ocular Melanoma ,Nose ,Malignancy ,Cat Diseases ,0403 veterinary science ,Diagnosis, Differential ,03 medical and health sciences ,medicine ,Animals ,Small Animals ,Melanoma ,Retrospective Studies ,CATS ,business.industry ,Benignity ,Records ,Retrospective cohort study ,Ear ,04 agricultural and veterinary sciences ,Toes ,medicine.disease ,030104 developmental biology ,Cats ,Histopathology ,Female ,Differential diagnosis ,business - Abstract
Non-ocular melanoma is considered to be a rare neoplasm in cats; however, more than 150 cases have been reported in the literature since 1961. The objective of this study was to characterise this tumour better by evaluating case outcome and survival data for cats with melanoma and to compare clinical and histopathological findings with those of previous reports. Twenty-three feline non-ocular melanomas were identified, the most common locations being the nose, digit and pinna. Cats with digital melanomas had survival rates similar to their canine counterparts. Histological assignation of benignity, malignancy or junctional activity was not found to be an accurate predictor of clinical behaviour. Melanoma should be considered as a differential diagnosis for cats presenting with pigmented or non-pigmented masses and histopathology is essential for definitive diagnosis, as other tumours may clinically appear quite similar. Regular follow-up examinations are recommended indefinitely for benign or malignant feline melanomas.
- Published
- 2001
31. Association between cancer chemotherapy and canine distemper virus, canine parvovirus, and rabies virus antibody titers in tumor-bearing dogs
- Author
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Deborah J. Tate, Mary Lynn Higginbotham, Aaron M. Stoker, Jeff W. Tyler, Kenny V. Brock, Dudley L. McCaw, and Carolyn J. Henry
- Subjects
Lymphoma ,Parvovirus, Canine ,animal diseases ,viruses ,Fluorescent Antibody Technique ,Antineoplastic Agents ,Antibodies, Viral ,Virus ,Dogs ,Neutralization Tests ,Neoplasms ,medicine ,Immune Tolerance ,Animals ,Dog Diseases ,Prospective Studies ,Distemper Virus, Canine ,Hemagglutination assay ,General Veterinary ,biology ,Parvovirus ,business.industry ,Canine distemper ,Canine parvovirus ,Hemagglutination Inhibition Tests ,biology.organism_classification ,medicine.disease ,Virology ,Titer ,Rabies virus ,Immunoglobulin G ,Immunology ,biology.protein ,Rabies ,Disease Susceptibility ,Antibody ,business - Abstract
Objective—To determine the association between cancer chemotherapy and serum canine distemper virus (CDV), canine parvovirus (CPV), and rabies virus antibody titers in tumor-bearing dogs.Design—Prospective study.Animals—21 client-owned dogs with various malignancies and 16 client-owned dogs with lymphoma.Procedure—In study A, serum antibody titers were measured by use of hemagglutination inhibition (CPV titers) or serum neutralization (CDV titers) before and at least 1 month after initiation of chemotherapy. Baseline values were compared with values obtained from a control population of 122 healthy dogs seen for routine revaccination. Titers were considered protective at ≥ 1:96 for CDV and ≥ 1:80 for CPV.In study B, serum IgG titers were measured by use of immunofluorescent assay (CDV and CPV titers) and rapid fluorescent focus inhibition test (RFFIT, rabies titers) at baseline and again at weeks 5, 8, and 24 of a standard chemotherapy protocol for treatment of lymphoma. An IgG titer of ≥ 1:50 was considered protective for CPV and CDV. An RFFIT titer of ≥ 0.5 U/ml was considered protective for rabies virus.Results—Significant changes were not detected in CDV, CPV, and rabies virus titers following chemotherapy in tumor-bearing dogs.Conclusions and Clinical Relevance—Results suggest that established immunity to CDV, CPV, and rabies virus from previous vaccination is not significantly compromised by standard chemotherapy used to treat tumor-bearing dogs. (J Am Vet Med Assoc2001;219:1238–1241)
- Published
- 2001
32. SAFE HANDLING OF CYTOTOXIC AGENTS
- Author
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Mary Lynn Higginbotham
- Subjects
business.industry ,Medicine ,Safe handling ,business - Published
- 2001
- Full Text
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33. CONTRIBUTORS
- Author
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Laura J. Armbrust, Philip J. Bergman, David S. Biller, Ruthanne Chun, Steven I. Cooper, Rick L. Cowell, Steven E. Crow, Karen E. Dorsey, Linda S. Fineman, James A. Flanders, Kevin A. Hahn, Alan S. Hammer, Carolyn J. Henry, Mary Lynn Higginbotham, Dennis W. Macy, Glenna E. Mauldin, G. Neal Mauldin, Dudley McCaw, Karelle A. Meleo, Barbara Norton, Greg Ogilvie, Jeffrey C. Philibert, Robert C. Rosenthal, Peter H. Rowland, Stacy B. Smith, John Speciale, Kimberly M. Stanz, Steven J. Susaneck, Richard E. Weller, and John Paul Woods
- Published
- 2001
- Full Text
- View/download PDF
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