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Objectives: To evaluate the use of citrated recalcified (nonactivated) thromboelastography (TEG) in healthy horses and horses with colitis and suspected coagulopathies., Design: Prospective, observational study conducted between October 2007 and June 2009., Setting: Veterinary Teaching Hospital., Animals: Forty-five healthy adult horses and 12 sick adult horses with colitis and prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT)., Interventions: None., Measurements and Main Results: Whole blood was collected on admission. Coagulation profile (PT, aPTT, platelet count, and fibrinogen concentration) and citrated recalcified whole blood TEG analysis (R-time [R], K-time [K], angle [α], maximum amplitude [MA], G value [G], lysis at 60 min [LY60]) were evaluated. Mean values (SD) for TEG parameters in healthy horses were: R=10.4 (3.1) minutes; K=3.5 (1.2) minutes; α=46.3 (11.0)°; MA=55.6 (5.1) mm; G=6,429 (1,341) dyn/cm², and LY60=5.1 (2.4)%. Mean coefficients of variation for intra-assay/interindividual variability in healthy horses were: R=4.7%/30.7%, K=4.8%/35.3%, α=4.4%/23.8%, MA=1.4%/9.3%, G=3.4%/20.8%, and LY60=13.1%/47.7%, respectively. Horses with colitis and prolonged PT and/or aPTT had longer mean values for R (P<0.001) and K (P<0.001), narrower mean α (P<0.001), decreased mean MA (P=0.001), and smaller mean G (P=0.02); changes consistent with hypocoagulability., Conclusions: Citrated recalcified (nonactivated) TEG demonstrated changes consistent with hypocoagulability in horses with colitis that had preidentified coagulation abnormalities. This technique has high interindividual variability and low intra-assay variability. TEG may be useful for detecting hypocoagulable states in horses with colitis and suspected coagulopathies., (© Veterinary Emergency and Critical Care Society 2010.)

The purpose of this study was to evaluate prevalence of serum alanine transaminase (ALT) elevation in dogs receiving lomustine (CCNU) and to analyse the pattern of occurrence and potential risk factors. Serum ALT activity in 109 dogs during single-agent CCNU chemotherapy was retrospectively analysed. The median initial dose, dose-intensity and cumulative dose of CCNU were 64 mg m(-2), 21 mg m(-2) week(-1) and 171 mg m(-2), respectively. The overall prevalence of major ALT elevation [> 5-fold upper reference limit (URL)] was 29% (32/109) and developed most commonly after one to three doses of CCNU. These ALT elevations occurred without preceding mild ALT elevation in 53% (17/32) of the cases. Three dogs (2.8%) developed clinical hepatopathy. For severe ALT elevation (>10-fold URL), age < or =5-year-old was associated with higher risk. The findings of this study showed that elevation of ALT is common during CCNU chemotherapy in dogs and severe elevation can develop on a sudden onset.

Background: Retired racing Greyhounds are popular as pets. Greyhounds have several differences in physiological values compared with other breeds, including lower serum alpha- and beta-globulin concentrations. We hypothesized that lower acute phase protein (APP) concentrations could contribute to lower alpha- and beta-globulin concentrations in this breed., Objectives: The purpose of this study was to compare serum concentrations of several APPs in Greyhounds with those of other dog breeds., Methods: We measured the serum concentrations of C-reactive protein (CRP), haptoglobin (Hp), acid-soluble glycoprotein (ASG), ceruloplasmin (CP), and serum amyloid A (SAA) in 15 clinically healthy retired racing Greyhounds and 11 age- and gender-matched healthy nonGreyhound controls using previously validated methods. Results were compared by Student's t-tests., Results: The concentration of Hp by both colorimetric and immunoturbidimetric methods was significantly lower in Greyhounds than in nonGreyhound dogs (P=.0009 and .019, respectively). The concentration of ASG was also significantly (P=.007) lower in Greyhounds, but CRP and CP concentrations were not significantly different between groups. SAA concentration was below the detection limit of the method in all dogs., Conclusions: The low serum concentrations of Hp and ASG should be taken into consideration when interpreting APP results in Greyhounds. Because both Hp and some ASG migrate in the alpha-globulin fraction, these results may explain the low alpha-globulin concentrations in Greyhounds.

The aim of this study was to evaluate the effects of domperidone, a dopamine D2 receptor antagonist, in dogs naturally infected by Leishmania infantum. Ninety-eight dogs were treated with single-agent domperidone at 1mg/kg twice a day orally for 1 month. Clinical, serological, biochemical and immunological examinations were conducted for the following 12 months. Domperidone was effective in controlling and reducing clinical signs and antibody titre. Significant decreases in reciprocal serum antibodies were seen in 74.3% of the dogs with mild clinical signs and 40% of the dogs became seronegative. In dogs with several clinical signs and high antibody titres, clinical improvement occurred in 86% of animals and the reciprocal serum antibody titres decreased in 38% of these dogs. A significant increase was noted in the immune cellular status, as measured by the leishmanin skin test and a lymphocyte proliferation assay.

Background: Cardiac troponin I (cTnI) is a polypeptide found specifically in cardiac muscle tissue that has been used as a diagnostic and prognostic indicator of cardiomyopathy. Increases in cTnI are associated with myocardial pathologic processes. However, high serum cTnI concentrations have been observed in normal Greyhounds., Hypothesis: We hypothesized that Greyhounds have cTnI concentrations higher than non-Greyhound dogs, and that a separate reference range should be established for Greyhounds., Animals: Blood samples were collected from the jugular vein from a group of 20 healthy Greyhound blood donors., Methods: Analysis of serum cTnI was performed with an immunoassay system with a detection level of 0.01 ng/mL, as described previously. The Greyhound values were compared with 2 groups of Boxers with and without arrhythmogenic right ventricular cardiomyopathy (ARVC), and to a group of non-Boxer control dogs from a previous study., Results: The mean cTnI concentration in Greyhounds was significantly higher (P < .0001) than that in non-Greyhound control dogs, although not significantly different from normal Boxers (P= .50), or Boxers with ARVC (P= .58). Greyhound serum cTnI concentrations were in the range found in Boxers with ARVC. The proposed reference range for cTnI in Greyhounds is 0.05-0.16 ng/mL., Conclusions and Clinical Importance: Greyhounds have a reference range for serum cTnI concentrations that differs from that of other previously published reference ranges for dogs of other breeds. Until a broader database and more precise reference range can be established, caution should be exercised in interpreting serum cTnI concentrations in Greyhounds with suspected cardiac disease.

The use of adjuvant 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; lomustine) to treat incompletely excised canine mast cell tumors (MCTs) has not been evaluated. Medical records of 12 dogs with grade 2 MCT treated with incomplete surgical excision and adjuvant CCNU and prednisone chemotherapy were reviewed. Local recurrence rate, metastasis rate, and survival time were evaluated. None of the dogs developed local recurrence or regional/ distant metastases. Two dogs developed fatal liver failure. The 1- and 2-year progression-free rates of surviving dogs were 100% and 77%, respectively. Postoperative adjuvant CCNU appears to be a useful alternative to radiation therapy for incompletely excised canine cutaneous MCTs.

An 11-year-old female spayed domestic shorthair cat was referred to The Ohio State University Veterinary Teaching Hospital (OSU-VTH) for evaluation of a 6 x 4 x 3.5 cm mass in the left midcervical region causing increased respiratory sounds and lateral deviation of the trachea. A fine needle aspirate of the mass was obtained before referral and the cytology results were compatible with a reactive lymph node. Immunocytochemistry showed increased numbers of CD3+ T lymphocytes and small numbers of CD20+ and CD79a+ medium to large lymphocytes. Differential diagnoses from the referral pathologist were T-cell-rich B-cell lymphoma and feline Hodgkin's-like lymphoma. A subsequent fine needle aspirate performed at the OSU-VTH showed similar results. On flow cytometry the majority of cells were CD3+ T lymphocytes that were double positive for CD4 and CD8 (73%), compatible with either a double-positive (CD4+CD8+) T-cell lymphoma or lymphocytes from ectopic thymic tissue. The mass was surgically removed. Histopathology and immunohistochemistry of the mass revealed a predominant population of CD3+ small lymphocytes and small numbers of medium to large lymphocytes with moderate anisocytosis and anysokaryosis. A population of cytokeratin-positive epithelial cells surrounded small microcystic structures filled with eosinophilic material and structures interpreted as Hassall's corpuscles. These findings were consistent with thymic tissue and a diagnosis of ectopic thymoma was made. PCR results for lymphocyte antigen receptor rearrangement (PARR) were negative. The cat had no evidence of disease 16 months after removal of the mass. To our knowledge this is the first report of an ectopic cervical thymoma in a cat. The clinical and diagnostic features of this unusual case will be useful in helping veterinarians and pathologists obtain a presurgical diagnosis and establish a prognosis for similar lesions.

Background: Concentrations of von Willebrand factor (vWF) are less than 30% in approximately 10% of Greyhounds., Hypothesis: That sample collection, processing, and storage can affect the concentration of vWF in plasma of Greyhounds., Animals: Nineteen healthy former racing Greyhounds., Methods: Prospective study: Blood samples were obtained from the jugular vein of dogs at 4 times during the day. Samples were divided and processed in each of 3 ways. The 1st tube was centrifuged immediately, the 2nd tube was kept in a household refrigerator, and the 3rd tube was kept at room temperature for 3 hours before centrifugation and processing., Results: There were no significant differences in the vWF concentration between different sample storage and processing (P = 5.31). There was no statistically significant diurnal variation in vWF concentration in the samples evaluated (P = .37)., Conclusions and Clinical Importance: Time of sample collection and short-term storage temperature do not influence the vWF concentration in retired racing Greyhounds.

A 15-year-old female ground cuscus (Phalanger gymnotis) was presented with an isolated ulcerated, nonhealing lesion on the lateral thorax. Histopathology and immunohistochemistry were diagnostic for cutaneous T-cell lymphoma with incomplete excision. Oral chemotherapy with CCNU (lomustine) resulted in clinical remission that lasted 255 days, with no appreciable toxicity. Tumor recurrence was treated with radiation therapy, which resulted in 120 additional days of clinical remission. Subsequently, the tumor developed at a distant site and the cuscus was humanely euthanized. A slight decrease in appetite early in disease progression was the only adverse effect noted throughout the treatment period. Oral, minimally invasive chemotherapy, and adjunct radiation therapy were viable treatment options for this ground cuscus and should be considered for treatment of neoplasia in other nontraditional species.

Background: Some retired racing Greyhounds (RRG) that undergo surgery bleed excessively., Hypothesis: Greyhounds that bleed excessively will have one or more preoperative hemostatic abnormalities that can be used to predict the risk and severity of postoperative bleeding., Animals: Eighty-eight RRG undergoing ovariohysterectomy or castration., Methods: All dogs were evaluated preoperatively with a physical exam, CBC, platelet count, OSPT, APTT, platelet function with PFA-100(a); fibrinogen, d-dimer, plasminogen (Plmg), antiplasmin (AP), antithrombin (AT), and vWF concentration (vWF:Ag); vWF collagen binding assay (vWF:CBA), and Factor XIII assay. Assays were repeated in the dogs that bled, and in an age- and sex-matched control group of RRG., Results: Twenty-six percent of the dogs had bleeding 36-48 hours after surgery. AP (P <.0001) and AT concentration (P= .007) were significantly lower, and vWF:CBA (P= .0284) was higher preoperatively in the dogs with excessive hemorrhage. A lower platelet count (P= .001) and hematocrit (P= .002), shorter OSPT (P= .0002) and higher plasma fibrinogen (P <.0001), and AP (P= .001) concentration were detected at the time of bleeding compared with preoperative values in the dogs that bleed excessively. The same findings were observed postoperatively for the control group, except for the decrease in hematocrit., Conclusions and Clinical Importance: The results indicate that this excessive postoperative bleeding is not attributable to a primary or secondary hemostatic defect, but could result from altered fibrinolysis.

Objective: To evaluate the biological activity of dihydroartemisinin on canine osteosarcoma cell lines in vitro., Sample Population: 4 canine osteosarcoma cell lines., Procedures: Cell viability assays were performed on canine osteosarcoma cell lines OSCA2, OSCA16, OSCA50, and D17 after 24, 48, and 72 hours of treatment with dihydroartemisinin at concentrations of 0.1 to 100 microM. Apoptosis was assessed by use of an ELISA for free nuclosomal DNA fragmentation and by western blot analysis for cleavage of caspase 3. Cell cycle analysis was performed by use of staining with propidium iodide and flow cytometry. Detection of reactive oxygen species (ROS) was conducted in the D17 cell line by use of 6-carboxy-2',7'-dihydrofluorescein diacetate and flow cytometry., Results: The concentration of dihydroartemisinin required for 50% inhibition of cell viability (IC50) was achieved in all 4 canine osteosarcoma cell lines and ranged from 8.7 to 43.6 microM. Induction of apoptosis was evident as an increase in nucleosomal DNA fragmentation, cleavage of caspase 3, and an increase in the population in the sub G0/G1 phase of the cell cycle detected by flow cytometry. Exposure to dihydroartemisinin also resulted in a decrease in the G0/G1 population. Iron-dependent generation of ROS was detected in dihydroartemisinin-treated D17 cells; ROS generation increased in a dose-dependent manner., Conclusions and Clinical Relevance: Incubation with dihydroartemisinin resulted in biological activity against canine osteosarcoma cell lines, which included induction of apoptosis and arrest of the cell cycle. Clinical trials of dihydroartemisinin in dogs with osteosarcoma should be conducted.

Background: Bleeding disorders in patients with normal coagulation test results are frequently reported in Greyhounds. The purpose of this study was to compare Greyhounds to non-Greyhounds by thromboelastography (TEG)., Hypothesis: TEG parameters in Greyhounds are different from those in non-Greyhounds., Animals: Forty-three healthy dogs (28 Greyhounds and 15 non-Greyhounds) based on the results of physical examination, CBC, activated partial thromboplastin time, prothrombin time, fibrinogen, and platelet count., Materials and Methods: Recalcified citrated native TEGs were performed in both groups; data were compared using Student's, Mann-Whitney, and Pearson's statistical tests., Results: In Greyhounds, mean +/- SD were as follows: R-time 4.3 +/- 1.7 minutes, K-time 3.8 +/- 1.4 minutes, angle (alpha) 50.0 +/- 8.0 degrees , maximum amplitude (MA) 47.6 +/- 5.6 mm, clot strength (G) 4,647 +/- 1,097 dyn/cm2, and percent lysis at 60 minutes (LY60) 2.8 +/- 5.0%. In the non-Greyhounds they were R-time 3.7 +/- 1.6 minutes, K-time 2.5 +/- 0.9 minutes, angle 59.8 +/- 7.0 degrees , MA 53.1 +/- 5.6 mm, G 5,811 +/- 1,256 dyn/cm2, and LY60 3.1 +/- 2.5%. All parameters were significantly different between the groups, except for R-time and LY60., Conclusion: In Greyhounds, clotting kinetics are slower and clot strength are weaker than in non-Greyhounds, supporting the increased tendency to bleed observed after minor trauma or surgical procedures in the breed. The findings may also be attributed to blood viscosity or to the concentration of citrate in the sample (ie, Greyhounds have higher hematocrit and less plasma per unit volume).

Background: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial., Purpose: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. CATS: Fifty-nine cats with measurable solid tumors., Methods: The starting dose of carboplatin was 160 mg/m(2) of body surface area IV. Doses were increased by 20 mg/m(2) in cohorts of 3-14 cats until the MTD was reached., Results: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m(2) and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6-22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7-168 days)., Conclusions and Clinical Importance: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m(2) IV every 3-4 weeks.

Background: Collection of 50 mL of blood (standard unit) in cats is a common procedure. There are several studies on the health status of donors, but to our knowledge there are no reports on the effects of blood collection on the feline donor., Hypothesis: Collection of a standard unit of blood from cats does not significantly change arterial blood pressure (BP), mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), PCV, and heart rate (HR) in healthy blood donor cats., Animals: Twenty-six healthy blood donor cats (6 spayed females and 20 castrated males)., Methods: An oscillometric method was used to measure MAP, SAP, DAP, and to quantify HR before and after blood collection; PCV was obtained before and immediately after blood collection., Results: Despite a significant decrease (P < .05) in all variables (ie, BP, PCV, HR) after blood collection, no adverse events were observed., Conclusions and Clinical Importance: The collection of a unit of blood for transfusion from healthy donor cats weighing more than 5 kg appears to be safe, but this procedure leads to a decrease in arterial BP, PCV, and HR.

Background: Various chemotherapy protocols for treating lymphoma in dogs have been published; however, comparison of protocols from different studies is difficult, especially when evaluating survival time and toxicoses., Hypothesis: The choice of COAP (C, cyclophosphamide; O, vincristine; A, cytosine arabinoside; P, prednisone) and a modified University of Wisconsin 19-week (UW-19) induction protocol has no influence on overall survival times in dogs with lymphoma., Animals: One hundred and one dogs with multicentric lymphoma., Methods: Retrospective study (2001-2006). Dogs induced with either an 8-week COP-based protocol (C, cyclophosphamide; O, vincristine; and P, prednisone) with maintenance therapy (COAP group) or a 19-week CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisone) based protocol (UW-19 group) were compared in terms of the duration of first remission, survival time, toxicoses, and cost., Results: There were 71 dogs in the COAP group and 30 dogs in the UW-19 group. Various protocols were used after the first relapse. The median duration of the first remission for the COAP and UW-19 groups were 94 days (range, 6-356 days) and 174 days (28-438 days), respectively (P < .01). The median survival times for dogs in the COAP and UW-19 groups were 309 days (6-620 days) and 275 days (70-1102+ days), respectively (P = .09). Dogs in the COAP group had a hazard ratio of 1.9 (95% CI 1.1-3.4) for death relative to the UW-19 group (P = .03), after controlling for the confounders (World Health Organization clinical stage, age, sex, use of doxorubicin during reinduction). The severity of neutropenia and gastrointestinal toxicoses were significantly higher in the UW-19 group than in the COAP group (P = .01 and P < .01, respectively)., Conclusion and Clinical Importance: Use of a long-term doxorubicin-containing sequential combination chemotherapy protocol is associated with a decreased risk of relapse and death relative to a non-doxorubicin-containing protocol.

Background: Adoption of retired racing Greyhounds has become increasingly popular during the past decade. To date, research has focused on the physiologic and clinicopathologic peculiarities of Greyhounds but there is little published information on disease prevalence in the breed., Objective: The objective of this study is to determine the prevalence of disease in retired racing Greyhounds., Animals: In this study, 747 Greyhounds were used., Methods: A standardized survey method was used, and survey responses were collected by an Internet survey. Owners could answer a survey for every Greyhound that they had owned since January 1, 2005., Results: Of the 692 eligible participants, 441 (63.7% response rate) completed surveys for 747 Greyhounds. The mortality rate for Greyhounds within the 2-year period was 15% (113 of 747 died). The most common cause of death reported was cancer (66 dogs, 58%), and the most common type of cancer listed as the cause of death was osteosarcoma (28 dogs, 25%). The most commonly reported groups of diseases or disorders were skeletal (232 dogs, 33%), skin (197 dogs, 28%), digestive (132 dogs, 18%), cancer (94 dogs, 13%), and endocrine (85 dogs, 11.9%). Forty-five percent of Greyhounds diagnosed with cancer and 6% of the overall population had osteosarcoma., Conclusions and Clinical Importance: The results of this study can be used by veterinary researchers to continue to investigate the most common diseases in this population. As more retired racing Greyhounds enter the pet population, the results of this study will help educate veterinarians and owners about the most prevalent diseases in the breed.

Purpose: To assess the influence of the light-curing unit type and whether or not it was worth using surface sealant protection on resin composite restorative materials stained by coffee. Another objective was to propose the monitoring of coffee staining by FT-Raman spectroscopy using carbon-hydrogen (C-H) bonds as reference to the composite matrix degradation., Methods: Sixty cylindrical specimens of resin composite were prepared and divided into six groups: HC (control)--cured with a halogen light; LC (control) cured with a LED; HF--cured with a halogen light + Fortify Plus; LF--cured with a LED + Fortify Plus; HP--cured with a halogen light + PermaSeal; LP--cured with a LED + PermaSeal. After storage for 24 hours at 37% and 100% of relative humidity, the top surface was protected, and the other surfaces isolated. Polishing with paper discs was performed after 24 hours of curing and prior to FT-Raman spectroscopy and reflectance measurements. All specimens were submitted to coffee staining for 14 days and evaluated by both systems. Results were statistically analyzed by ANOVA and Tukey tests., Results: FT-Raman spectrum only showed significant changes in groups LC and LP (P< 0.05). Reflectance demonstrated that staining was present in all specimens protected by sealants. Sealant staining was larger in the HF (P < 0.001) group.

The vertebral heart size (VHS) is used to objectively assess cardiac dimensions on thoracic radiographs. A high VHS suggest the presence of cardiac pathology, such as dilated cardiomyopathy, degenerative atrioventricular valvular disease, pericardial effusion, pericardioperitoneal diaphragmatic hernia, tricuspid dysplasia, ventricular septal defect, or patent ductus arteriosus, among others. However, breed or body conformation can influence the VHS. Because Greyhounds have a high prevalence of physiologic systolic murmurs associated with high aortic velocity, and large cardiac dimensions when compared with dogs of similar size, they are frequently suspected of having heart disease. The purpose of this study was to compare the VHS in normal Greyhounds with those in Rottweilers, and a group of dogs from various other breeds using both analog and digital radiology. The VHS was significantly higher in Greyhounds (P< 0.0001), when compared with Rottweilers and to other dog breeds. The mean VHS on lateral radiographs for Greyhounds was 10.5 +/- 0.1, for Rottweilers it was 9.8 +/- 0.1, and for mixed breed dogs it was 10.1 +/- 0.2. This study confirms that the relative cardiomegaly reported in necropsy and echocardiographic studies in Greyhounds is easily detected using plain radiography and the VHS.

Background: Blood collection tubes containing 3.2% (0.109 M) sodium citrate, instead of 3.8% (0.129 M) sodium citrate, have recently become available in the United States. These tubes are visually indistinguishable from the traditional 3.8% sodium citrate tubes, except for wording on the label. Consequently, samples for hemostatic evaluation are frequently collected in tubes containing the lower concentration of sodium citrate., Hypothesis: Results of hemostasis assays are different in samples collected in 3.2% versus 3.8% sodium citrate., Animals: Twenty healthy dogs., Methods: This study aimed at determining whether results of standard coagulation tests, von Willebrand factor concentration (vWF:Ag), and platelet function with the platelet function analyzer PFA-100a were affected by the different concentrations of sodium citrate. Blood samples were collected in tubes containing either 3.2% or 3.8% sodium citrate concentrations and processed routinely for coagulation assays (one-stage prothrombin time [OSPT], activated partial thromboplastin time [aPTT], fibrinogen concentration, and platelet count), vWF:Ag, and platelet function assays with a PFA-100., Results: There was no significant difference between samples collected in 3.2% versus those collected in 3.8% sodium citrate for OSPT, aPTT, fibrinogen concentration, platelet count, or vWF:Ag. The closure times with collagen/adenosine diphosphate were significantly shorter (66 +/- 8.1 versus 74.8 +/- 9.7 seconds; P < .0001) with the 3.2% than with 3.8% sodium citrate concentration, and the hematocrit was significantly higher (47.9 +/- 5.6 versus 46.0 +/- 4.7 seconds; P = .03) in samples collected in 3.2% than in those collected in 3.8% sodium citrate., Conclusions and Clinical Importance: There is no clinically relevant effect of collection of blood into 3.2% or 3.8% sodium citrate.

Deregulation of the 3-phosphoinositide-dependent protein kinase-1 (PDK-1)/Akt signalling pathway is associated with prostate cancer development and progression. Inhibition of PDK-1/Akt signalling can be achieved using structurally optimized celecoxib derivatives such as OSU-03012. In this study, we treated the novel canine prostate cancer cell line, Ace-1, with OSU-03012 or dimethyl sulphoxide in vitro. We found that Akt was constitutively phosphorylated in the canine prostate cancer cell line Ace-1 and that there was a dose-dependent decrease in cell viability, and Akt and glycogen synthase kinase-3beta phosphorylation, in response to OSU-03012 treatment. This was accompanied by a dose-dependent increase in apoptosis. These data suggest that Akt signalling pathway inhibition is a potential strategy for the treatment of dogs with prostate cancer and that canine prostate cancer is a relevant large animal model for evaluating Akt pathway inhibitors such as OSU-03012 for use in people.

Background: Histiocytic sarcoma is an aggressive neoplasm of dendritic cells that carries a grave prognosis. The efficacy of chemotherapy against this disease is unknown. The purpose of this study was to determine the efficacy of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in dogs with incompletely resected or metastatic histiocytic sarcoma, to describe the clinical characteristics of these dogs, and to identify factors affecting prognosis., Hypothesis: Our hypothesis is that CCNU has activity against canine histiocytic sarcoma and can improve survival in dogs with advanced disease., Animals: Included in analysis are dogs diagnosed with histiocytic sarcoma who had gross measurable or residual microscopic disease and who received CCNU., Methods: A multi-institutional, retrospective, single-arm cohort study was conducted. Available biopsy samples were tested with an antibody against CD18 when possible to confirm the diagnosis of histiocytic sarcoma., Results: Fifty-nine dogs were treated at 8 institutions. Twenty-three tumor specimens were confirmed to be CD18 positive. Treatment with CCNU at 60 to 90 mg/m2 resulted in an overall response rate of 46% in the 56 dogs with gross measurable disease. All 3 dogs with minimal residual disease experienced tumor relapse but lived 433 days or more after starting CCNU. The median survival of all 59 dogs was 106 days. Thrombocytopenia (< 100,000 platelets/microL) and hypoalbuminemia were found to be negatively associated with prognosis and were predictive of < 1 month survival., Conclusions and Clinical Importance: Results suggest that CCNU is active against canine histiocytic sarcoma and may be useful in the treatment of dogs without negative prognostic factors.

Background: In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma., Hypothesis: That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma., Animals: Fifty-four dogs., Results: Seventy-two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2-467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog)., Conclusions and Clinical Importance: The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated.

Background: Low and nontoxic concentrations (10-50 microM) of suramin, which is a nonspecific inhibitor of multiple growth factors, including fibroblast growth factors, enhances the activities of cytotoxic chemotherapeutic agents, such as doxorubicin and paclitaxel, both in vitro and in vivo. Suramin has not been evaluated as a chemosensitizing agent in dogs with cancer., Hypothesis: Nontoxic suramin can be used safely as a chemosensitizer in dogs., Animals: Sixteen dogs of various breeds with measurable tumors were treated; 1 dog that had undergone amputation for osteosarcoma received adjuvant therapy., Methods: The dogs received 53 courses of treatment with suramin in combination with doxorubicin. The suramin dosage was 6.75 mg/kg IV 3 h before standard doxorubicin administration every 2 weeks. The pharmacokinetics and clinical efficacy were determined., Results: The pharmacokinetics of low-dose suramin followed a 2-compartment model with half-lives of 2 h and 6 days. The distribution volume was a 0.34 +/- 0.12 L/kg, and clearance was 1.86 +/- 0.76 mL/kg/h. During the time interval that doxorubicin was present at therapeutically active concentrations (ie, from the start of infusion to 24 hours), the plasma concentrations were maintained within 20% of the target range (8-60 microM) in 72% of the treatments. The toxicity of the suramin/doxorubicin combination was mild and comparable to the toxicity expected for doxorubicin monotherapy. Objective partial responses were observed in 2 out of 16 evaluable dogs (13%). All 5 dogs that previously received doxorubicin showed improved responses to the suramin/doxorubicin combination., Conclusions and Clinical Importance: A fixed, low-dose suramin regimen yields the desired target plasma concentrations in most dogs, and appears to enhance the activity of doxorubicin without enhancing toxicity.

Greyhounds have significantly higher serum creatinine (SCr) concentration than do non-Greyhound dogs that may be attributable to differences in glomerular filtration rate (GFR). By means of plasma clearance of technetium Tc 99m diethylenetriaminepentaacetic acid, GFR was measured in 10 Greyhounds and 10 non-Greyhound dogs with normal findings of physical examination, CBC, serum biochemical analysis, and urinalysis. Dogs were fed the same diet for a minimum of 6 weeks before GFR data collection. Greyhounds had significantly higher mean +/- SD GFR (3.0 +/- 0.1 vs 2.5 +/- 0.2 ml/min/ kg; P = .01) and SCr concentration (1.8 +/- 0.1 vs 1.5 +/- 0.1 mg/dL; P = .03) than did non-Greyhound dogs, but the serum urea nitrogen (SUN) concentration was not significantly different (18 +/- 1 vs 18 +/- 2 mg/dL; P = .8). Therefore, the higher SCr concentration in Greyhounds is not attributable to decreased GFR, and may be associated with the high muscle mass in the breed. Healthy Greyhounds have higher GFR than do non-Greyhound dogs.

Veterinarians involved in Greyhound rescue have anecdotally observed that 10-15% of Greyhounds bleed profusely after simple surgical procedures. In most patients, platelet counts and hemostasis profiles are normal; therefore, it is possible that these dogs have platelet dysfunction. The PFA-100 is a novel point-of-care platelet function analyzer that has recently been evaluated as a rapid method to assess platelet function in dogs. The objectives of this study were to characterize platelet function in a group of healthy Greyhounds by means of the PFA-100. Blood samples were collected from the jugular vein from 30 healthy Greyhounds. CBC, biochemical profile, PFA-100 assay with collagen/epinephrine (COL-EPI) and collagen/ adenosindiphosphate (COL-ADP), plasma von Willebrand factor antigen concentration (vWF:Ag), and vWF collagen-binding assay (vWF:CBA) were performed. PFA-100 closure times (CTs) with COL/ADP ranged from 63 to 92 seconds (mean +/- SD, 74.7 +/- 7.9 seconds) and with COL/EPI from 87 to 238 seconds (138 +/- 41 seconds); vWF: Ag ranged from 22 to 120% (87.52 +/- 25.5%) and vWF: CBA ranged from 36 to 102% (77.4 +/- 17.3%); and platelet counts ranged from 147 to 265 x 10(9)/L (194.6 +/- 31.64 x 10(9)/L). Greyhound CTs were significantly shorter than CTs in a mixed population of 50 healthy non-Greyhound dogs, in which the COL/ADP CTs ranged from 61 to 172 seconds (mean +/- SD, 87 +/- 21.6 seconds), and the COL/ EPI CTs ranged from 81 to 300 seconds (mean +/- SD, 183 +/- 67.6 seconds; P = 0.005 for COL/ADP CT; P = 0.001 for COL/ EPI CT). Also, platelet counts were significantly lower (P = 0.001) and packed cell volume was significantly higher (P = 0.001) in the Greyhound than in the non-Greyhound group. The PFA-100 is a reproducible method that can be used in the clinical setting to assess platelet function in Greyhounds; however, normal CTs in healthy Greyhounds are shorter than in other breeds. The results obtained in this study will be used to screen for abnormal platelet function in Greyhounds with postoperative bleeding.

Nineteen of 28 (67%) Greyhounds enrolled in the Blood Donor Program at The Veterinary Teaching Hospital, The Ohio State University (Columbus, OH), had a left basilar systolic murmur. Ten Greyhounds with murmurs and 9 without murmurs were evaluated to gain knowledge about the pathogenesis of this murmur. Echocardiograms were performed without sedation by means of a GE Vivid 7 Echocardiographic System with a continuous ECG; systolic arterial blood pressure (SABP) was measured with an Ultrasonic Doppler Flow detector model 811-B. The mean peak aortic velocity in the Greyhounds with murmurs (2.15 m/s; range, 1.8-2.2 m/s) was significantly higher than in the Greyhounds without murmurs (1.89 m/s; range, 1.6-2.0 m/s) (P < .001); there were no significant differences between groups for aortic valve or annulus diameter, fractional shortening, pulmonic velocity, SABP, hematocrit, serum protein concentration, or red blood cell counts. In this study, Greyhounds with soft, left basilar systolic murmurs had mildly (but significantly) higher mean peak aortic velocities than similar dogs without murmurs. In the dogs with murmurs (and higher velocities), we could not identify structural abnormalities, such as valvular lesions or other congenital defects. There was no inverse correlation between the systolic murmur and the higher hematocrit and red blood cell counts observed in this breed. This 1-2/6 basilar systolic murmur is common in Greyhounds, and it does not appear to be of any clinical consequence.

Background: Retired racing Greyhounds are becoming common as pets. Because of their unique physiology, results of routine laboratory tests are frequently outside the reference interval for dogs. Compared with other breeds, Greyhounds have low serum protein concentrations, but the concentrations of different serum protein fractions have not been reported., Objectives: Our objectives were to evaluate the results of serum protein electrophoresis (SPE) in healthy, retired racing Greyhounds and compare them with a control group of age- and gender-matched non-Greyhound dogs., Methods: Agarose gel electrophoresis was done using a standard method; the gels were stained with amido black and scanned with a Cliniscan 2 densitometer (Helena Laboratories, Beaumont, TX, USA). Protein fractions were identified by visual inspection of the electrophoretogram. A Student's t-test assuming equal variances was used to compare the concentration of the different fractions between groups., Results: The concentrations of total protein, total globulins, and alpha-1-, alpha-2-, beta-1-, and beta-2-globulins were significantly lower and the albumin to globulin (A:G) ratio was significantly higher in Greyhounds than in non-Greyhound dogs (P < .05). There was no significant difference in albumin or gamma-globulin concentrations., Conclusions: Low serum protein concentrations in Greyhounds are the result of low concentrations of a- and b-globulins. These results should be kept in mind when evaluating both healthy and sick Greyhounds. Additional studies are needed to identify the individual proteins associated with low alpha- and beta-globulin concentrations in Greyhounds.

The purpose of this study was to evaluate changes in systolic arterial blood pressure (SABP) immediately after collection of blood for transfusion in retired racing Greyhounds. We prospectively evaluated 19 blood donor Greyhounds before and after the collection of a unit (450 mL) of blood. The SABP was measured with Doppler in the right forearm after the dogs had been in the blood collection room for a few minutes (PRE-FLOOR) and again 5-10 minutes after the dogs were placed on the table where they would be bled (PRE-TABLE). A total of 3-5 minutes after completing the blood collection, the SABP was measured again while the dogs were still in lateral recumbency on the table (POST-TABLE) and once more 60-90 minutes later, when the dogs were on the floor after completing the donation (POST-FLOOR). All dogs were monitored for clinical signs of hypotension, including depression, weakness, collapse, and pallor, for a minimum of 2 hours after donation. There was a significant difference in SABP for the group between PRE-FLOOR and POST-TABLE (P = .02) and between PRE-TABLE and POST-TABLE determinations (P = .01). There were no significant differences for any of the other time points; there were no adverse events. Therefore, we conclude that the collection of 450 mL of blood from normal Greyhounds results in a short-lived yet significant decrease in SABP, but the likelihood of adverse events is negligible.

Background: "Vacuolated" eosinophils (ie, eosinophils with empty, nonstaining granules) have been described previously in normal Greyhounds. However, to our knowledge, detailed studies of granules in vacuolated and normal eosinophils in this breed have not been performed., Objective: The objective of this prospective study was to characterize some of the morphologic, ultrastructural, and cytochemical staining features of specific (primary) granules in both normal and vacuolated eosinophils in Greyhound blood., Methods: Morphologic features of eosinophils in Wright's- and Diff-Quik-stained peripheral blood smears from 49 Greyhounds were compared with 200 blood smears from non-Greyhound dogs. Transmission electron microscopy was done on blood from 3 Greyhounds with vacuolated eosinophils and 3 with normal eosinophil granules. Blood smears from 4 of these dogs also were stained cytochemically with alkaline phosphatase (AP), chloracetate esterase (CAE), and alpha naphthyl butyrate esterase (ANBE). The morphologic features and tinctorial properties of vacuolated and normal eosinophils were compared., Results: Twenty-six Greyhounds (53%) had vacuolated eosinophils and 23 (47%) had normal granulated eosinophils in smears stained with Wright's stain. Only 1% of eosinophils were vacuolated in non-Greyhound dogs. Twenty of the 23 (85%) Greyhounds with normal granulated eosinophils on Wright's-stained smears had vacuolated eosinophils in smears stained with Diff-Quik. Ultrastructurally, no morphologic differences were observed between granules of vacuolated and normal eosinophils. Both vacuolated and normal eosinophils in Greyhounds were positive for AP and negative for CAE and ANBE, as expected for normal dogs., Conclusion: Vacuolated eosinophils in Greyhounds likely reflect, at least in part, differential staining properties of the specific granules with different hematologic stains. Ultrastuctural and cytochemical features of eosinophil granules were similar in normal and vacuolated eosinophils from Greyhounds.

We conducted a clinical evaluation of gemcitabine in 19 dogs with spontaneously occurring malignancies. The principal objectives of this study were to characterize toxicity and seek preliminary evidence of antitumor activity of gemcitabine administered every 2 weeks (biweekly) as a 30-minute IV infusion. A total of 64 doses, ranging from 300 mg/m2 to 675 mg/m2, were administered during the initial 8-week evaluation period, and an additional 131 doses were administered during the extended evaluation period. The total cumulative dose for the 10 dogs receiving gemcitabine in the extended evaluation period ranged from 1,500 mg/m2 to 24,300 mg/m2. Clinical evidence of toxicity was minimal. Cumulative myelosuppression was not apparent. Unexplained retinal hemorrhages occurred in 1 dog. No complete or partial remissions were observed during the initial evaluation period; however, objective responses were observed in 2 dogs during the extended evaluation period. Gemcitabine is a promising new chemotherapeutic agent that can be used safely in dogs with cancer. Biweekly administration of doses of 675 mg/m2 IV results in minimal and acceptable toxicity.

The records of the Transfusion Medicine Service of the Veterinary Teaching Hospital at The Ohio State University were searched for client-owned cats that received whole blood (WB), packed red blood cells (PRBCs), or fresh frozen plasma (FFP) transfusions between December 1, 1997, and April 1, 2000. Eighty-one cats received 112 units of blood products, consisting of 49 units of WB (administered to 35 cats), 44 units of PRBCs (administered to 34 cats), and 19 units of FFP (administered to 13 cats); 10 cats received more than 1 product each. Anemia was the most common reason for transfusing RBC-containing blood products, requiring 33 units of WB (75%) and 39 units of PRBCs (80%). The 2 most common causes of anemia were blood loss (27%) and renal disease (20%). Hypoalbuminemia (n = 9) and coagulopathies (n = 6), primarily due to liver disease (n = 7), were the 2 most common reasons for cats to receive transfusions of FFP. There were no differences in increase in PCV after administration of either 1 unit of WB or 1 unit of PRBCs (P = .22). Transfusion reactions occurred in 3 cats; 2 reactions were mild febrile events, but a fatal reaction occurred when a type B cat inadvertently received type A blood.

Background: Greyhounds frequently have laboratory values that are outside reference intervals established for dogs. Our recognition of increased serum creatinine concentrations in several Greyhounds posed a problem when evaluating a Greyhound with suspected renal disease., Objective: The purpose of this study was to compare serum creatinine concentrations between Greyhound and non-Greyhound dogs., Methods: Thirty retired racing Greyhounds and 30 age- and gender-matched control non-Greyhound dogs were evaluated. Serum creatinine concentrations in both groups were measured using a standard biochemical method and compared statistically using a Kruskal-Wallis test., Results: Creatinine concentration was significantly higher in the Greyhounds (P <.01) than in the control group., Conclusion: Greyhounds have a higher serum creatinine concentration than do non-Greyhound dogs. This idiosyncrasy should be taken into account when evaluating healthy Greyhounds and those with suspected renal disease.

Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).

Case information and histologic slides for 688 admissions of feline tissues from 12 veterinary institutions were assembled and reviewed to determine tissues obtained by biopsy or necropsy, age and sex of cat, tumor topography, feline leukemia viral antigen status, histologic frequency of mitoses, diagnosis, presence of necrosis, and presence and degree of sclerosis. Histologic sections were examined to place the lesions in one of the diagnostic categories of the National Cancer Institute working formulation (NCI WF) for lymphomas or lymphoid leukemia. Correlations between the various factors determined were tested using contingency tables and chi-square analysis to provide a statistical comparison between the levels of observations determined by case examination with the numbers expected from chance alone. Significant correlations (P < or = 0.05) were found between diagnosis and tumor topography, the frequency of mitoses, necrosis, sclerosis, and age, between mitoses and necrosis, topography, age, and feline leukemia viral infection status, between topography and necrosis and age, and between leukemia viral status and age. Significant correlations between diagnosis and tumor topography included a greater than expected number of cases of acute and chronic lymphoid leukemia and multicentric distribution of tumor. Small cell lymphomas were more frequent than expected in enteric and cutaneous areas and less frequent than expected in mediastinal, renal, and multicentric areas. In contrast, the high-grade small noncleaved type of lymphomas was found significantly more frequently than expected in the mediastinum and less frequently than expected in enteric tissues. In comparing diagnosis and frequency of mitoses, the lymphomas classified as low grade by the NCI WF were significantly more frequent than expected in the lower categories (0-2/100x) of mitoses, and those classified as high-grade lymphomas were more frequent than expected in the higher categories (4-8/1OOx) of mitoses. In comparing diagnosis and sclerosis, diffuse sclerosis was more frequent than expected for the intermediate grade lymphomas of mixed cell type and for the high-grade lymphomas of the immunoblastic polymorphous type. In comparing diagnosis and locally extensive necrosis, this feature was more frequently observed than expected for cases of intermediate grade lymphoma of the small-cleaved cell category and for the high-grade lymphoma of the immunoblastic cell type. In comparing mitoses and necrosis, the lower grade lymphomas were, in general, characterized by a lower frequency of mitoses and a lower incidence of necrosis then would be expected from chance alone. In contrast, the higher grade lymphomas were characterized by more frequent mitoses and a higher incidence of necrosis. In tests comparing mitoses and tumor topography, lymphomas of the alimentary tract were more frequently observed than expected in the category with the lowest level of mitoses (0-1/100x), whereas lymphomas of the mediastinum and kidney were more frequently observed than expected in the categories with a higher level (4-20/ 100x) of mitoses.

A 21-mo-old female southern black rhinoceros (Diceros bicornis minor) developed acute upper respiratory dyspnea in association with lymphadenopathy and marked immature lymphocytosis. A diagnosis of acute lymphoblastic leukemia was reached on the basis of the morphologic and cytochemical characteristics of peripheral lymphoblasts. Antineoplastic chemotherapy included administration of cytarabine, cyclophosphamide, vincristine, and doxorubicin, with clinical remission achieved 19 days after initiation of treatment. The rhinoceros died, however, of congestive heart failure, presumably secondary to doxorubicin cardiotoxicity and a particular sensitivity of rhinoceros myocardial tissue to free hydroxyl radicals. The pharmacologic effects of any therapeutic agent need to be carefully considered before use in the black rhinoceros, especially within the context of the unique physiology of this species.

Platelet aggregation before and after administration of 0.5 mg/m2 of vincristine (VCR) was evaluated in 7 dogs with spontaneously occuring lymphoma. Aggregation on platelet-rich plasma separated from blood collected in 3.8% sodium citrate was performed using adenosine diphosphate (ADP), arachidonic acid (AA), and collagen (COL) as agonists. The slope for aggregation in response to ADP was significantly lower after administration of VCR (P = .032). Maximal aggregation after administration of VCR was significantly lower in response to ADP, COL, and AA (P = .03, P = .04, and P = .03, respectively).

We conducted a clinical evaluation of FCE 23762, a methoxymorpholino analog of doxorubicin, in 48 dogs with metastatic, nonresectable, or chemotherapy-resistant spontaneous malignancies at an initial dosage of 50-60 microg/kg IV every 3 weeks. Clinical evidence of toxicity was minimal; 6 dogs developed grades I, II, and III hematologic toxicities after the 1st treatment, and 1 dog developed grade II gastrointestinal toxicity. One dog became pancytopenic 4 months after discontinuation of FCE 23762. No other adverse effects were noted. Partial or complete remissions were observed in 32% of the dogs. Responses were observed both in previously untreated dogs and in those that had received prior chemotherapy, including doxorubicin. FCE 23762 is a promising new antineoplastic agent that can be used safely in dogs with cancer; doses higher than those used in this study may be used eventually in practice.

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.

Objective: To determine prevalence of p53 tumor suppressor protein overexpression in spontaneously arising tumors of dogs, using the CM-1 polyclonal antibody and immunohistochemical methods. DESIGN AND SAMPLE POPULATION: Retrospective analysis was performed on archived, paraffin-embedded tumor tissue from dogs. A total of 226 tumors were evaluated, including tumors of epithelial, mesenchymal, and round cell origins., Procedures: Overexpression of p53 was detected by indirect immunohistochemical methods, using the CM-1 rabbit anti-human p53 polyclonal primary antibody. Protein overexpression was determined by use of a grading system based on percentage of stained tumor nuclei., Results: Nuclear overexpression of p53 was detected in most squamous cell carcinomas, nasal adenocarcinomas, and perianal gland adenocarcinomas. Hemangiopericytomas, transitional cell carcinomas, mammary adenocarcinomas, apocrine gland adenocarcinomas, intestinal adenocarcinomas, mast cell tumors, and cutaneous histiocytomas had low numbers of nuclei overexpressing p53. Remaining tumor types had intermediate p53 nuclear overexpression. Cytoplasmic staining was observed in some carcinomas, particularly intestinal adenocarcinomas., Conclusions: Overexpression of p53 is common in spontaneously arising neoplasms of dogs., Clinical Relevance: Prospective determination of p53 status in some tumor types may be as clinically useful in determining prognosis and predicting survival times for dogs with cancer as it is for human beings with cancer.

The clinical presentation of a dog with acute lymphoblastic leukemia (ALL) which resembled lymphosarcoma (LSA) is described. The differences between acute leukemias and LSA are explained and the most common clinical features of ALL reported in the veterinary literature are listed.

Lymphangiosarcoma was diagnosed from biopsy material obtained from an 8-week-old puppy with a progressively enlarging subcutaneous inguinal swelling. Histologically, the tumor was composed of endothelial cells immediately adjacent to large collagen bundles. Tumor cells formed irregular vascular channels which extended along the connective tissue investments of small vessels and nerves of the subcutis and deep dermis. Similar neoplastic tissue extensively infiltrated an inguinal lymph node. Neoplastic cells were immunohistochemically stained for factor 8-related antigen and were weakly positive when compared with several hemangiomas and hemangiosarcomas. Transmission electron microscopy revealed numerous micropinocytotic vesicles and a continuous basal lamina. The puppy was euthanatized at 8 months of age due to severe septic polyarthritis. Lymphangiosarcoma was documented at the site of the original tumor as well as in the axillary lymph node at necropsy.

Alterations in the p53 tumor suppressor gene have been implicated in the genesis and/or progression of the majority of human cancers, including osteosarcoma. Stabilization of the protein by mutation or interaction with other proteins prolongs its half-life, rendering it detectable by immunohistochemistry. Osteosarcoma is the most common primary canine bone tumor and is characterized by frequent early metastases. Multilobular tumors of bone involve primarily flat bones of the head and are low-grade malignancies with lower metastatic potential. The objectives of this study were to determine the prevalence of p53 protein overexpression in 106 osteogenic tumors of dogs using an indirect immunohistochemical method and to compare p53 overexpression between tumors with different clinical behavior. A polyclonal p53 antibody (CM-1) served as the primary antibody. Tumors were scored based upon an estimate of the percentage of tumor cells stained. Significant differences in the prevalence of overexpression were observed between osteosarcomas (72%) and multilobular tumors of bone (20%, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p53 overexpression (84%) than did osteosarcomas of the axial skeleton (56%, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher prevalence of overexpression in osteosarcomas versus multilobular tumors of bone and in osteosarcomas of the appendicular skeleton versus those of the axial skeleton suggests that alterations in p53 expression correlate with highly aggressive tumor behavior.

A 55-kd protein with mRNA transport activity found in fetal rat liver cells and plasma from mice, rats, and human beings with malignant neoplasms has been designated oncofetal protein 55 (OFP55). Monoclonal antibody produced to rat OFP55 cross-reacts with human OFP55. Using this monoclonal antibody in a bioassay measuring mRNA transport stimulated by OFP55, we tested the plasma from 19 dogs with a variety of malignant neoplasms, including carcinomas, sarcomas, lymphomas, and melanomas, and compared the results with plasma from 20 clinically normal dogs without evidence of neoplasia. The mean mRNA transport activity from the group of dogs with malignant neoplasms was 0.43 +/- 0.28%/mg of protein. Mean transport activity from the group of control dogs was 0.04 +/- 0.02%/mg of protein. These means were significantly different (P < 0.0001). The degree of overlap between these 2 groups in their OFP55-related mRNA transport activity was minimal, and measurement of this protein appears to have potential for the early detection of malignant neoplasms in dogs.

Myeloid and megakaryocytic bone marrow hypoplasia in association with moderate to profound neutropenia was observed in 8 young Standardbred horses sired by the same stallion; 7 horses were intermittently thrombocytopenic. Evaluation of serial neutrophil counts in 2 horses suggested that a cyclic variation in neutrophil numbers was present, that lymphocyte numbers increased when neutrophil counts decreased, and that platelet counts decreased when neutrophil counts decreased. Preliminary bone marrow cultures indicated that myeloid progenitor cells were present and that these cells were able to respond to exogenous growth factors by differentiating. A bone marrow microenvironment or growth factor defect is suspected. Seven of 8 horses died or were euthanized. One horse with moderate neutropenia and a normal platelet count has been racing for 3 years. Necropsies in 4 horses did not reveal a cause for the myeloid hypoplasia. A familial basis for the disease is suspected.

Hemostasis profiles from 101 cats presented for medical or surgical evaluation to The Ohio State University Veterinary Teaching Hospital from 1986 through 1991 were reviewed retrospectively; 69% were abnormal. Commonly identified abnormalities included a mixed hemostatic defect compatible with disseminated intravascular coagulation, thrombocytopenia, isolated prolongation of the activated partial thromboplastin time (APTT), and prolongation of both the APTT and one-stage prothrombin time. The most common disorders associated with abnormal hemostasis profiles in this study were liver disease, neoplasia, and feline infectious peritonitis.

Twenty-four horses were randomly allocated to 3 groups. All horses underwent a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls, group-2 horses underwent 6 hours of colonic ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline blood samples were collected, then low-flow colonic ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. All horses were monitored for 6 hours. Citrated systemic venous (SV) blood samples were collected from the main pulmonary artery, and colonic venous (CV) samples were collected from the colonic vein draining the ventral colon. Samples were collected at 0, and 2, 3, 3.25, 4, and 6 hours for determination of one-stage prothrombin time, activated partial thromboplastin time, antithrombin III activity, and fibrinogen concentration. Data were analyzed statistically, using two-way ANOVA for repeated measures, and post-hoc comparisons were made by use of Student Newman Keul's test. Statistical significance was set at P < 0.05. There were significant decreases in all hemostatic variables by 2 hours in SV and CV samples from horses of all 3 groups, but there were no differences among the 3 groups for any of these variables. These hemostatic alterations could have been secondary to a hypercoagulable state or to fluid therapy-induced hemodilution. Colonic ischemia-reperfusion was not the cause of these alterations because these alterations also were observed in the sham-operated control horses. Significant temporal alterations existed even after accounting for the hemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)

A 3-year-old female Basset Hound was examined because of fever and lameness of 2 months' duration. Physical examination revealed a small cranial abdominal mass, which had an ultrasonographic appearance of a large abdominal lymph node. Cytologic examination of an ultrasound-guided fine-needle aspirate of the mass revealed a few macrophages that contained numerous linear unstained structures consistent with mycobacteria. Intracellular acid-fast bacilli were identified in an aspirate that was stained with modified Ziehl-Neelsen. Exploratory laparotomy revealed wide-spread abdominal lymphadenopathy. Histologic examination of hepatic and lymph node biopsy specimens revealed chronic granulomatous hepatitis and lymphadenitis. Acid-fast organisms isolated after bacteriologic culturing of a mesenteric lymph node specimen were identified as Mycobacterium smegmatis. Because the prognosis was poor, the dog was euthanatized.

Hemangiosarcomas confined to the skin and underlying muscle were surgically excised in 25 dogs. Tumors were staged based on their histological location (ie, dermal, hypodermal, and deep). Dermal (stage I) hemangiosarcomas were small, most commonly ventral-abdominal or prepucial in location, and were associated with prolonged survival times (median survival, 780 days). Tumors with hypodermal (stage II) and underlying muscular involvement (stage III) were grouped together because of their larger size, bruise-like appearance, lack of anatomic predilection, biological behavior, and shorter survival times (median survival of 172 and 307 days for dogs with stages II and III, respectively). We conclude that dermal hemangiosarcomas may be effectively treated with surgery alone, whereas hemangiosarcomas located within the hypodermal tissues bear a poor prognosis and warrant wide surgical excision with adjuvant chemotherapy.