Scholarly Works, Small Animal Clinical Sciences

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Transplacental transmission of a North American isolate of Leishmania infantum in an experimentally infected beagle
Rosypal, A. C.; Troy, Gregory C.; Zajac, Anne M.; Frank, G.; Lindsay, David S. (American Society of Parasitology, 2005-08)
Leishmania infantum, an etiologic agent of zoonotic visceral leishmaniasis, is widespread among foxhounds in the United States. Although sand flies are widely distributed throughout the United States, epidemiological data do not support a major role for sand flies in the transmission of L. infantum in foxhounds in this country. Congenital transmission of human visceral leishmaniasis is reported in humans and might also occur in dogs. We have previously isolated L. infantum from Virginia foxhounds and used this isolate (LIVT-1) to experimentally infect beagles. Four female beagles, chronically infected with LIVT-I, were bred to a male beagle chronically infected with L. infantum chagasi. One beagle was able to maintain her pregnancy, and 4 puppies were delivered by cesarean section. One puppy was malformed and autolytic at delivery, and tissues were not collected or analyzed. The remaining puppies were killed at the time of cesarean section, and selected tissues were collected for parasite culture and PCR. Promastigotes were not cultured from tissues in any of the puppies. Leishmania sp. DNA was detectable by PCR in liver, bone marrow, and heart from all 3 puppies and in the spleen, lymph node, kidney, and placenta in 2 puppies. Placental tissue from the dam was PCR negative. This is the first report of maternal transmission of a North American isolate of L. infantum from an experimentally infected dog.
Effects of descending positive end-expiratory pressure on lung mechanics and aeration in healthy anaesthetized piglets
Carvalho, A. R.; Jandre, F. C.; Pino, A. V.; Bozza, F. A.; Salluh, J. I.; Rodrigues, R.; Soares, J. H.; Giannella-Neto, A. (2006)
INTRODUCTION: Atelectasis and distal airway closure are common clinical entities of general anaesthesia. These two phenomena are expected to reduce the ventilation of dependent lung regions and represent major causes of arterial oxygenation impairment in anaesthetic conditions. In the present study, the behavior of the elastance of the respiratory system (Ers), as well as the lung aeration assessed by CT-scan, was evaluated during a descendent positive end-expiratory pressure (PEEP) titration. This work sought to evaluate the potential usefulness of the Ers monitoring to set the PEEP in order to prevent tidal recruitment and hyperinflation of healthy lungs under general anaesthesia. METHODS: PEEP titration (from 16 to 0 cmH2O, with a tidal volume of 8 ml/kg) was performed, and at each PEEP, helical CT-scans were obtained during end-expiratory and end-inspiratory pauses in six healthy, anaesthetized and paralyzed piglets. The distribution of lung compartments (hyperinflated (HA), normally- (NA), poorly- (PA), and non-aerated areas (N)) was determined and the tidal re-aeration was calculated as the difference between end-expiratory and end-inspiratory PA and NA areas. Similarly, the tidal hyperinflation was obtained as the difference between end-inspiratory and end-expiratory HA. The Ers was estimated on a breath-by-breath basis from the equation of motion of the respiratory system during all PEEP titration with the least squares method. RESULTS: HA decreased throughout PEEP descent from PEEP 16 cmH2O to ZEEP (ranges from 24-62% to 1-7% at end-expiratory and from 44-73% to 4-17% at end-inspiratory pauses) whereas NA areas increased (30-66% to 72-83% at end-expiratory and from 19-48% to 73-77% at end-inspiratory pauses). From 16 to 8 cmH2O, Ers decreased with a correspondent reduction in tidal hyperinflation. A flat minimum of Ers was observed from 8 to 4 cmH2O. For PEEP below 4 cmH2O, Ers increased associated with a rise in tidal re-aeration and a flat maximum of the NA areas. CONCLUSION: In healthy piglets under a descending PEEP protocol, the PEEP at minimum Ers presented a compromise between maximizing NA areas and minimizing tidal re-aeration and hyperinflation. High levels of PEEP, greater than 8 cmH2O, reduced tidal re-aeration but enlarged hyperinflation with a concomitant decrease in normally aerated areas.
Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphoma
Dervisis, Nikolaos G.; Dominguez, Pedro A.; Sarbu, Luminita; Newman, Rebecca G.; Cadile, Casey D.; Swanson, Christine N.; Kitchell, Barbara E. (American Veterinary Medical Association, 2007-08-15)
Objective: To compare results of treatment with temozolomide or dacarbazine, in combination with an anthracycline, in dogs with relapsed or refractory lymphoma. Design: Nonrandomized, controlled clinical trial. Animals: 63 dogs with relapsed or refractory lymphoma. Procedures: Chemotherapy was administered in 21-day cycles. A combination of temozolomide and an anthracycline (doxorubicin or dactinomycin) was administered to 21 dogs and a combination of dacarbazine and an anthracycline was administered to 42 dogs. Efficacy and toxicoses were assessed. Results: Thirteen of the 18 (72%) dogs treated with the temozolomide-anthracycline combination and 25 of the 35 (71%) dogs treated with the dacarbazine-anthracycline combination had a complete or partial response. Median duration of response to rescue chemotherapy was 40 days (range, 0 to 217 days) for dogs in the temozolomide group and 50 days (range, 0 to 587 days) for dogs in the dacarbazine group. The incidence of high-grade hematologic toxicoses was significantly higher among dogs in the dacarbazine group than among dogs in the temozolomide group, but the incidence of gastrointestinal tract toxicoses was not significantly different between groups. There were no significant differences between groups in regard to proportion of dogs with a complete or partial response, duration of response to rescue chemotherapy, survival time following rescue chemotherapy, or overall survival time. Conclusions and Clinical Relevance: Both combinations had promise in the treatment of dogs with relapsed or refractory lymphoma, although administration of temozolomide was more convenient than administration of dacarbazine and caused fewer hematologic toxicoses.
Measurement of serum carboxyterminal cross-linked telopeptide of type I collagen concentration in dogs with osteosarcoma
Hintermeister, John G.; Jones, Pamela D.; Hoffmann, Walter E.; Siegel, Arthur M.; Dervisis, Nikolaos G.; Kitchell, Barbara E. (American Veterinary Medical Association, 2008-11-01)
Objective—To evaluate the usefulness of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) concentrations for screening dogs for the presence of osteosarcoma. Sample Population—32 client-owned dogs with osteosarcoma (27 dogs with osteosarcoma of the appendicular skeleton and 5 dogs with osteosarcoma of the axial skeleton) and 44 non–tumor-bearing control dogs. Procedures—Serum was obtained from blood samples collected from dogs with osteosarcoma and from clinically normal dogs. The serum ICTP concentration was determined by use of a commercially available radioimmunoassay for ICTP. Results—Mean ± SD serum ICTP concentration in the tumor-bearing dogs was 7.32 ± 2.88 ng/mL, and in clinically normal dogs, it was 6.77 ± 2.31 ng/mL; values did not differ significantly. Mean serum ICTP concentration in dogs with appendicular osteosarcoma, compared with that of clinically normal dogs, was not significantly different. Mean serum ICTP concentration in dogs with axial skeletal tumor location was 10.82 ± 2.31 ng/mL, compared with a value of 6.73 ± 2.28 ng/mL in dogs with appendicular osteosarcoma. Conclusions and Clinical Relevance—On the basis of the results of this study, serum ICTP concentrations are not a clinically useful screening tool for the detection of appendicular osteosarcoma in dogs. Despite the observation that serum ICTP concentration was higher in dogs with axial osteosarcoma than in clinically normal dogs, serum ICTP concentration determination is not a suitable screening test for osteosarcoma.
Use of an axial pattern flap and nictitans to reconstruct medial eyelids and canthus in a dog
Jacobi, Susan; Stanley, Bryden J.; Petersen-Jones, Simon; Dervisis, Nikolaos G.; Dominguez, Pedro A. (Blackwell Publishing, 2008-11-01)
A 10-year-old male neutered Boxer presented with recurrence of a mast cell tumor at the right medial canthal area. Following excision including 2 cm margins, the medial one-half of the upper and lower eyelids and the medial canthus were reconstructed using an axial pattern flap based on the cutaneous branch of the superficial temporal artery. The bulbar conjunctiva of the nictitans was preserved and sutured to the medial flap edge, thus creating a conjunctival lining to the deep aspect of the flap, protecting corneal epithelium. This is a valuable surgical technique for closing a large skin defect and reconstructing the medial eyelids, thus preserving the globe.
Combined Gemcitabine and Carboplatin Therapy for Carcinomas in Dogs
Dominguez, Pedro A.; Dervisis, Nikolaos G.; Cadile, Casey D.; Sarbu, L.; Kitchell, B. E. (Wiley-Blackwell, 2009-01-01)
Background: Response and adverse reactions to combined gemcitabine (GEM) and carboplatin (CARBO) therapy in dogs with carcinomas are not documented. Hypothesis: GEM and CARBO are safe for the treatment of dogs with carcinomas. Animals: Thirty-seven dogs with histologically or cytologically confirmed carcinomas. Methods: Prospective clinical trial. Dogs were treated with GEM (2 mg/kg, 20–30-minute infusion IV) on Days 1 and 8 and 4 hours later, CARBO (10 mg/kg IV) on Day 1. The cycle was repeated on Day 22. Results: Thirty-seven dogs (29 with measurable tumor) received a median of 2 cycles (range 0.5–6) for a total of 101 cycles administered. Twelve dogs (32%) developed neutropenia (3 Grade 3, and 5 Grade 4) and 9 (24%) thrombocytopenia (2 Grade 3, and 1 Grade 4). Dogs 420 kg were twice as likely to develop thrombocytopenia (P 5 .023). Twenty-seven dogs (73%) had evidence of gastrointestinal (GI) toxicosis, but most signs were of mild to moderate severity and self-limiting. One dog died of treatment-related complications. Overall tumor response rate was 13%. One dog with metastatic prostatic carcinoma achieved a complete remission and 1 dog with intestinal adenocarcinoma and 1 with tonsillar squamous cell carcinoma achieved partial remission. Twelve dogs achieved stable disease for a median of 72 days. Conclusion and Clinical Importance: GEM and CARBO combination causes mild to moderate hematologic and GI toxicosis in dogs with carcinoma. Response rate in this study was modest, and optimization of dosing of this combination is required.
Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with Carcinomas
Martinez-Ruzafa, I.; Dominguez, Pedro A.; Dervisis, Nikolaos G.; Sarbu, L.; Newman, R. G.; Cadile, Casey D.; Kitchell, Barbara E. (Wiley-Blackwell, 2009-05-01)
Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas. Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats. Animals: Twenty cats with spontaneously occurring carcinomas. Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days. Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1–6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5–10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs). Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored.
Prevalence of Antibodies to Sarcocystis neurona in Cats From Virginia and Pennsylvania
Hsu, V.; Grant, David C.; Dubey, Jitender P.; Zajac, Anne M.; Lindsay, David S. (American Society of Parasitology, 2010-08)
Sarcocystis neurone, is best known as the causative agent of equine protozoal myeloencephalitis of horses in the Americas. Domestic cats (Felis domesticus) were the first animals described as an intermediate host for S. neurone,. However, S. neurona-associated encephalitis has also been reported in naturally infected cats in the United States. Thus, cats can be implicated in the life cycle of S. neurona as natural intermediate hosts. The present study examined the seroprevalence of IgG antibodies to merozoites of S. neurona in populations of domestic cats from Virginia and Pennsylvania. Overall, sera or plasma from 441 cats (Virginia = 232, Pennsylvania = 209) were tested by an indirect immunofluorescent assay at a 1:50 dilution. Antibodies to S. neurona were found in 32 (7%) of 441 cats. Of these, 22 (9%) of the 232 cats from Virginia and 10 (5%) of the 209 cats from Pennsylvania were seropositive for S. neurona.
Safety of concurrent administration of dexrazoxane and doxorubicin in the canine cancer patient
FitzPatrick, W. M.; Dervisis, Nikolaos G.; Kitchell, B. E. (Wiley-Blackwell, 2010-12-01)
Doxorubicinmay cause a rare but serious cardiotoxicity. Dexrazoxane is a cardioprotectant drug used to reduce the risk of cardiotoxicity in human patients. In this study, 25 tumour-bearing dogs were treated with concurrent doxorubicin and dexrazoxane. The total number of doses of dexrazoxane given was 54 (range 1–5 doses per dog, median 2 doses). Five dogs receivedmore than 165 mg m² cumulative doxorubicin dose before starting dexrazoxane. Haematologic, gastrointestinal and cardiovascular toxicities were considered tolerable. The combination of doxorubicin with dexrazoxane was well tolerated with minimal side-effects in this patient cohort. Future studies are required to evaluate potential cardioprotective effects of dexrazoxane given concurrently with doxorubicin.
Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology
Webster, J. D.; Dennis, M. M.; Dervisis, Nikolaos G.; Heller, J.; Bacon, N. J.; Bergman, P. J.; Bienzle, D.; Cassali, G.; Castagnaro, M.; Cullen, J.; Esplin, D. G.; Pena, L.; Goldschmidt, M. H.; Hahn, K. A.; Henry, C. J.; Hellmen, E.; Kamstock, D.; Kirpensteijn, J.; Kitchell, B. E.; Amorim, R. L.; Lenz, S. D.; Lipscomb, T. P.; McEntee, M.; McGill, L. D.; McKnight, C. A.; McManus, P. M.; Moore, A. S.; Moore, P. F.; Moroff, S. D.; Nakayama, H.; Northrup, N. C.; Sarli, G.; Scase, T.; Sorenmo, K.; Schulman, F. Y.; Shoieb, A. M.; Smedley, R. C.; Spangler, W. L.; Teske, E.; Thamm, D. H.; Valli, V. E.; Vernau, W.; von Euler, H.; Withrow, S. J.; Weisbrode, S. E.; Yager, J.; Kiupel, M. (SAGE, 2011-01-01)
There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists’ Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists’ Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.
Serological response of cats to experimental besnoitia darlingi and besnoitia neotomofelis infections and prevalence of antibodies to these parasites in cats from Virginia and Pennsylvania
Houk, Alice E.; Rosypal, A. C.; Grant, David C.; Dubey, Jitender P.; Zajac, Anne M.; Yabsley, Michael J.; Lindsay, David S. (American Society of Parasitology, 2011-04)
Besnoitia darlingi and Besnoitia neotomofelis are cyst-forming tissue apicomplexan parasites that use domestic cats (Felis domesticus) as definitive hosts and opossums (Didelphis virginiana) and Southern Plains woodrats (Neotoma micropus) as intermediate hosts, respectively. Nothing is known about the prevalence of B. darlingi or B. neotomofelis in cats from the United States. Besnoitia darlingi infections have been reported in naturally infected opossums from many states in the United States, and B. neotomofelis infections have been reported from Southern Plains woodrats from Texas, but naturally infected cats have not been identified. The present study examined the IgG antibody response of cats to experimental infection (B. darlingi n = 1 cat; B. neotomofelis n = 3 cats). Samples from these cats were used to develop an indirect immunofluorescent antibody test (IFAT), which was then used to examine seroprevalence of IgG antibodies to tachyzoites of B. darlingi and B. neotomofelis in a population of domestic cats from Virginia (N = 232 cats) and Pennsylvania (N = 209). The serum from cats inoculated with B. darlingi or B. neotomofelis cross-reacted with each other's tachyzoites. The titers to heterologous tachyzoites were 1 to 3 dilutions lower than to homologous tachyzoites. Sera from B. darlingi- or B. neotomofelis-infected cats did not react with tachyzoites of Toxoplasma gondii or Neospora caninum or merozoites of Sarcocystis neurona using the IFAT. Antibodies to B. darlingi were found in 14% and 2% of cats from Virginia and Pennsylvania, respectively. Antibodies to B. neotomofelis were found in 5% and 4% of cats from Virginia and Pennsylvania, respectively. Nine cats from Virginia and 1 cat from Pennsylvania were positive for both.
Treatment with DAV for Advanced-Stage Hemangiosarcoma in Dogs
Dervisis, Nikolaos G.; Dominguez, Pedro A.; Newman, R. G.; Cadile, Casey D.; Kitchell, B. E. (American Animal Hospital Association, 2011-05-01)
Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P¼0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P¼0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P¼0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.
Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcoma
Klahn, Shawna L.; Kitchell, Barbara E.; Dervisis, Nikolaos G. (American Veterinary Medical Association, 2011-07-01)
Objective—To evaluate and compare the outcomes of dogs with periarticular histiocytic sarcoma (PAHS) and histiocytic sarcoma of other anatomic locations (non-PAHS) and identify factors associated with outcome for dogs with PAHS. Design—Retrospective cohort study. Animals—19 dogs with PAHS and 31 dogs with non-PAHS. Procedures—Medical records of dogs with histiocytic sarcoma that underwent definitive local treatment (surgery or radiation), chemotherapy, or a combination of these were reviewed. Patient signalment, clinical signs, staging test results, clinicopathologic data, type of treatment, response, and outcome were collected, and potential risk factors in dogs with PAHS were identified and analyzed for an association with outcome. Results—Dogs with PAHS lived significantly longer than did dogs with non-PAHS, with an overall median survival times of 391 (range, 48 to 980) and 128 (range, 14 to 918) days, respectively, despite the presence of suspected metastasis at diagnosis in 13 of 19 dogs with PAHS. Dogs with PAHS without evidence of metastasis at diagnosis lived significantly longer than did dogs with PAHS with evidence of metastasis, with median survival times of 980 (range, 83 to 980) and 253 (range, 48 to 441) days, respectively. Administration of prednisone in dogs with PAHS was associated with a significantly shorter time to tumor progression (TTP) and increased risk of tumor progression and death. Conclusions and Clinical Relevance—Results indicated that dogs with PAHS may have a favorable outcome independent of metastatic status when treated with chemotherapy or aggressive multimodal treatment. The concurrent administration of prednisone may be a negative predictive factor for survival time and TTP in dogs with PAHS.
Canine tonsillar squamous cell carcinoma - a multi-centre retrospective review of 44 clinical cases
Mas, A.; Blackwood, L.; Cripps, P.; Murphy, S.; de Vos, J.; Dervisis, Nikolaos G.; Martano, M.; Polton, G. A. (Wiley-Blackwell, 2011-07-01)
OBJECTIVES: To review the presenting clinical signs, treatment and survival of dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful prognostic indicators. METHODS: Medical records of 44 dogs were reviewed retrospectively. Clinical signs, clinical stage, time of diagnosis, treatment and outcome were recorded. Data were analysed using the Kaplan-Meier, logrank, Student’s t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as appropriate. RESULTS: The most frequent clinical signs were cough (12 dogs, 27%), enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and lethargy were less common but were significantly associated with a poor outcome. No matter what treatment modalities were used, survival times were short and median survival time for all the dogs in the study was 179 days. However, there were a small number of long-term survivors. CLINICAL SIGNIFICANCE: Dogs with tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter survival times than patients without these clinical signs. Although surgery, chemotherapy and radiotherapy seem to increase the median survival time of dogs diagnosed with tonsillar squamous cell carcinoma, there is no highly effective treatment for canine tonsillar squamous cell carcinoma.
Determination of Testicular Blood Flow in Camelids Using Vascular Casting and Color Pulsed-Wave Doppler Ultrasonography
Kutzler, Michelle; Tyson, Reid; Grimes, Monica; Timm, Karen (Hindawi, 2011-09-19)
We describe the vasculature of the camelid testis using plastic casting. We also use color pulsed-wave Doppler ultrasonography to measure testicular blood flow and compare the differences between testicular blood flow in fertile and infertile camelids. The testicular artery originates from the ventral surface of the aorta, gives rise to an epididymal branch, and becomes very tortuous as it approaches the testis. Within the supratesticular arteries, peak systolic velocity (PSV) was higher in fertile males compared to infertile males (P=0.0004). In addition, end diastolic velocity (EDV) within the supratesticular arteries was higher for fertile males when compared to infertile males (P=0.0325). Within the marginal arteries, PSV was also higher in fertile males compared to infertile males (P=0.0104). However, EDV within the marginal arteries was not significantly different between fertile and infertile males (P=0.121). In addition, the resistance index was not significantly different between fertile and infertile males within the supratesticular (P=0.486) and marginal arteries (P=0.144). The significance of this research is that in addition to information obtained from a complete reproductive evaluation, a male camelid's fertility can be determined using testicular blood flow measured by Doppler ultrasonography.
Treatment-related toxicities in tumor-bearing cats treated with temozolomide alone or in combination with doxorubicin: a pilot assessment
Gagnon, Jerome; Dervisis, Nikolaos G.; Kitchell, Barbara E. (SAGE, 2012-08-01)
A retrospective study assessing treatment-related toxicities in tumor-bearing cats treated with temozolomide (TMZ) alone or in combination with doxorubicin was conducted. TMZ was administered orally once a day for 5 days every 3 weeks at a dose of 20 mg/cat. Tumor response was evaluated with standard World Health Organization criteria and toxicity was monitored using veterinary co-operative oncology group–common terminology criteria for adverse events (VCOG—CTCAE) criteria. Ten tumor-bearing cats with various types of malignancies were treated with TMZbased chemotherapy. Eight cats were evaluable for response. Two cats achieved a complete response, one achieved stable disease and five achieved a partial response. Four grade III and one grade IV hematological toxicities, and one grade IV gastrointestinal toxicity were observed. Four cats were euthanased as a result of apparent toxicity. One cat was euthanased as a result of severe and prolonged myelosuppression with fever. Three were euthanased for grade III pleural and pericardial effusions. Effusion was seen in cats treated with higher cumulative dose of TMZ (P = 0.0046). Planned additional case accrual was discontinued because of unacceptable levels of toxicity despite evidence of efficacy in some of the cats. Additional investigation is needed to elucidate this unexpected apparent cumulative toxicity.
Clinicopathologic Significance of Histologic Grade, Pgp, and P53 Expression in Canine Lymphoma
Dhaliwal, Ravinder S.; Kitchell, Barbara E.; Ehrhart, E. J.; Valli, Victor E.; Dervisis, Nikolaos G. (American Animal Hospital Association, 2013-05-01)
To characterize the expression of P-glycoprotein (Pgp) and p53 in different histologic grades of canine multicentric lymphosarcoma (LSA), 31 cases of LSA without prior treatment were studied. The expression levels of the Pgp and p53 proteins were evaluated for their clinicopathologic significance among standard histologic evaluation. Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded archival samples of 31 previously untreated LSA cases to detect the expression of Pgp and p53. All dogs were subsequently treated with a combination chemotherapy protocol. Remission and survival durations were evaluated for correlation with histologic grade and presence of drug resistance markers. Of the 31 cases, 24 (80%) and 7 (22%) were positive for Pgp and p53, respectively. Overall, the median survival and duration of remission in the study was 246 days and 137 days, respectively. The National Cancer Institute working formulation histologic grade was not associated with either survival or duration of first remission (DOR). The Pgp protein expression and DOR and survival was not statistically significant. Expression of p53 was statistically correlated with survival.
Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome
Sacornrattana, O.; Dervisis, Nikolaos G.; McNiel, E. A. (Wiley-Blackwell, 2013-09-01)
The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty-seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival.
New Agents for Targeting of IL-13RA2 Expressed in Primary Human and Canine Brain Tumors
Debinski, Waldemar; Dickinson, Peter J.; Rossmeisl, John H. Jr.; Robertson, John L.; Gibo, Denise M. (PLOS, 2013-10-16)
Interleukin 13 receptor alpha 2 (IL-13RA2) is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K) and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels and thus may be appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts.
Detection of Salmonella spp. Using a Generic and Differential FRET-PCR
Zhang, Jilei; Wei, Lanjing; Kelly, Patrick; Freeman, Mark; Jaegerson, Kirsten; Gong, Jiansen; Xu, Bu; Pan, Zhiming; Xu, Chuanling; Wang, Chengming (PLOS, 2013-10-16)
To facilitate the detection of Salmonella and to be able to rapidly and conveniently determine the species/subspecies present, we developed and tested a generic and differential FRET-PCR targeting their tetrathionate reductase response regulator gene. The differential pan-Salmonella FRET-PCR we developed successfully detected seven plasmids that contained partial sequences of S. bongori and the six S. enterica subspecies. The detection limit varied from ∼5 copies of target gene/per PCR reaction for S. enterica enterica to ∼200 for S. bongori. Melting curve analysis demonstrated a Tm of ∼68°C for S. enterica enterica, ∼62.5°C for S. enterica houtenae and S. enterica diarizonae, ∼57°C for S. enterica indica, and ∼54°C for S. bongori, S. enterica salamae and S. enterica arizonae. The differential pan-Salmonella FRET-PCR also detected and determined the subspecies of 4 reference strains and 47 Salmonella isolated from clinically ill birds or pigs. Finally, we found it could directly detect and differentiate Salmonella in feline (5/50 positive; 10%; one S. enterica salamae and 4 S. enterica enterica) and canine feces (15/114 positive; 13.2%; all S. enterica enterica). The differential pan-Salmonella FRET-PCR failed to react with 96 non-Salmonella bacterial strains. Our experiments show the differential pan-Salmonella FRET-PCR we developed is a rapid, sensitive and specific method to detect and differentiate Salmonella.

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