Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs

OBJECTIVE: To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. ANIMALS: 8 client-owned dogs with clinical signs of osteoarthritis. PROCEDURES: Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. RESULTS: Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.     

Sensitivity and specificity of methods of assessing the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumors

OBJECTIVE: To determine sensitivity and specificity of physical examination, fine-needle aspiration, and needle core biopsy of the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumors. DESIGN: Case series. ANIMALS: 37 dogs and 7 cats. PROCEDURE: Regional lymph nodes were evaluated by means of physical examination (palpation), fine-needle aspiration, and needle core biopsy. Results were compared with results of histologic examination of the entire lymph node, the current standard. RESULTS: Tumors included 18 sarcomas, 16 carcinomas, 7 mast cell tumors, and 3 other tumors. Carcinomas were more likely to have metastasized to the regional lymph node (7/16 animals) than were sarcomas (2/18). Sensitivity and specificity of physical examination were 60 and 72%, respectively. Sensitivity and specificity of cytologic examination of fine-needle aspirates were 100 and 96%, respectively. Sensitivity and specificity of histologic examination of needle core biopsy specimens were 64 and 96%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that fine-needle aspiration may be a sensitive and specific method of evaluating the regional lymph nodes in dogs and cats with solid tumors, because results correlated well with results of histologic examination of the entire lymph node. Physical examination alone was not a reliable method and should not be used to decide whether to aspirate or biopsy the regional lymph nodes.     

Efficacy and toxicity of a dose-intensified doxorubicin protocol in canine hemangiosarcoma

The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-intensified doxorubicin protocol in canine hemangiosarcoma (HSA). Canine HSA is a highly malignant tumor, and most affected dogs die within 6 months of diagnosis. Doxorubicin is the most, and possibly the only, effective chemotherapeutic drug for this malignancy, but it provides only moderate improvement in survival. On the basis of previous studies reporting similar survival in dogs treated with doxorubicin as a single agent and doxorubicin-based combination chemotherapy and the concept of summation dose intensity, a dose-intensified single-agent doxorubicin protocol was initiated. Twenty dogs with HSA were recruited to participate in this study. Workup and staging were performed according to standard practice. Chemotherapy was initiated within 3 weeks of surgery. Doxorubicin was scheduled to be administered at 30 mg/m2 i.v. every 2 weeks for a total of 5 treatments. The dogs were monitored for toxicity and signs of recurrence during and at regular intervals after chemotherapy. The protocol was tolerated well. No dogs were hospitalized because of adverse effects or developed clinical signs consistent with doxorubicin-induced cardiomyopathy. There was a significant difference in survival in dogs with stage I and I1 HSA compared with dogs with stage III HSA. with median survival times of 257, 210, and 107 days, respectively. These results are slightly better than the historical control with respect to toxicity and efficacy but are not statistically different from what is achieved with standard treatments. There was no association between dose intensity and outcome.     

Evaluation of cyclooxygenase-1 and cyclooxygenase-2 expression and the effect of cyclooxygenase inhibitors in canine prostatic carcinoma

Prostatic carcinoma occurs primarily in older castrated male dogs and is typically a fatal disease (most dogs die within few months after the initial diagnosis). Surgery, i.e., total prostatectomy, or radiation therapy is often not pursued due to risks of complications and a high rate of distant metastasis. Cyclooxygenase‐2 (Cox‐2) expression has been documented in several malignancies, including canine prostatic carcinoma. Cox‐2 inhibition has been reported to have preventative effects on several human malignancies and has therapeutic effects on both laboratory and spontaneous tumour models. The purpose of this retrospective study was to evaluate Cox expression and the effects of Cox inhibitors on survival in dogs with prostatic carcinoma. 94.1 and 88.2% of the tumours expressed Cox‐1 and Cox‐2, respectively. Furthermore, dogs treated with Cox inhibitors (piroxicam or carprofen) lived significantly longer than untreated dogs, 6.9 versus 0.7 months (P < 0.0001), suggesting that Cox inhibitors may have an important role in canine prostate cancer therapy.     

Efficacy and Toxicity of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin (DOXIL) in Dogs with Hemangiosarcoma

Introduction:  Canine hemangiosarcoma (HSA) is a fatal malignancy and most dogs die within 6–8 months of diagnosis. The spleen is a common primary site, representing 50% of all cases. These dogs typically present with clinical signs due to tumor rupture and intra‐abdominal dissemination; the abdomen is also the main site of disease progression when these patients fail. Direct delivery of chemotherapy into the abdominal cavity may therefore be a rational approach in this malignancy.
Methods:  14 dogs with stage 2 or 3 splenic HSA were recruited. Doxil at a dose of 1 mg/kg was diluted in saline and administered via ultrasound‐guidance into the abdominal cavity. The dogs were scheduled to receive 4 treatments every 3 weeks. Samples of plasma and abdominal fluid were collected for pharmacokinetic analysis. All dogs were monitored for recurrence and complete necropsies were requested at death.
Results:  8 dogs with stage 3 and 6 dogs with stage 2 HSA were enrolled. All 14 dogs have died, 12/14 due to tumor and 2 from other causes. There was no difference in median survival days between stages (stage 2: 244, stage 3: 125, p = .22). All 12 dogs that died due to tumor‐related causes failed with intra‐abdominal recurrence. Necropsies showed that the dogs in this study had relatively fewer extra‐abdominal metastasis compared to dogs treated with systemic chemotherapy. Pk analysis showed detectable plasma doxorubicin 1 and 2 weeks after treatment.
Conclusion:  Direct abdominal administration of Doxil did not prevent intra‐abdominal recurrence; however, it appeared to provide effective systemic coverage.     

Characterization of the Biological Behavior of Appendicular Osteosarcoma in Rottweilers with a Comparison to Other Breeds

Introduction:  The clinical impression of many oncologists is that Rottweilers with appendicular osteosarcoma (OSA) have an unfavorable prognosis despite standard therapy (amputation and chemotherapy). The purpose of this study was to compare clinical characteristics, biological behavior and outcome of OSA in Rottweilers to that of other breeds.
Methods:  107 OSA cases were studied: 56 clinical cases (17 Rottweilers) and 54 necropsy submissions (13 Rottweilers) of OSA (3 cases overlapping). Information regarding signalment, prognostic factors, treatment and outcome was obtained from medical records and follow‐up with owners. Data were analyzed by chi‐square test, t‐test, and log rank test.
Preliminary Results:  Compared to other breeds Rottweilers were more likely to have femur (23% vs. 16%) and ulna (15% vs. 3%) and less likely to have tibia (8% vs. 27%) as their primary tumor location (p = 0.04). In the necropsy group, Rottweilers had a younger age at death (6.4 vs. 10 years, p = 0.0002) and a greater body weight at diagnosis (49 vs. 37 kg, p = 0.002). No statistical differences in the age at diagnosis or survival time were noted in Rottweilers vs. other breeds. Metastasis to lymph nodes (31% vs. 10%, p = 0.08) and lungs (64% vs. 49%, p = 0.24) was more frequent in Rottweilers. There was no difference in chemotherapy drugs given; however, Rottweilers were 20 times more likely to receive NSAIDs (p = 0.0004).
Conclusion:  Greater body weight with a predilection for certain tumor locations may contribute to OSA development in Rottweilers. A younger age at death may suggest a more aggressive phenotype.     

A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients

The objectives of this study were to prospectively identify and characterize weight loss and changes in body condition in feline cancer patients and to investigate the prognostic significance of these findings. Fifty-seven cats with neoplasia were evaluated. Body condition was assessed with a nine-point scoring system (BCS) and multiple sites were assessed for muscle and fat mass using four-point scoring systems. Feline cancer patients had a mean BCS of 4.4+/-2.1 kg (1=cachectic, 5=optimal, 9=obese). Fat mass was reduced in both sites assessed in 60% of the patients. Muscle mass was reduced at all three sites assessed in 91% of the patients. Feline cancer patients having a BCS <5 had a median survival time (MST) of 3.3 months compared to that of 16.7 months for cats with a BCS of > or = 5 (P=0.008).     

Psittacine plasma concentrations of elements: daily fluctuations and clinical implications.

During the past 2 decades, the potential for excessive exposure of pet birds to zinc has become a concern for many pet bird owners. Ideally, avian zinc toxicosis is diagnosed on the basis of history of exposure to zinc, radiographic evidence of ingested metal, occurrence of melena, detection of an elevated plasma zinc concentration, and response to treatment. However, most pet birds suspected of having zinc toxicosis present with vague signs and lack of radiographic evidence; therefore, the diagnosis relies on the presence of an elevated plasma zinc concentration. A question was, is there a significant diurnal variation in the zinc concentration in psittacine birds and could this be clinically relevant? Because studies in other species have shown that zinc is not the only element that shows a diurnal variation, the authors examined 13 other plasma elements including arsenic, cadmium, calcium, cobalt, copper, iodine, iron, magnesium, manganese, molybdenum, potassium, selenium, and total phosphorus. Fifteen adult psittacine birds housed in the same aviary were used in this study. Three blood samples, separated by 4 hours, were taken from the right jugular vein in each bird. All elements were measured in plasma. Zinc, copper, and molybdenum revealed diurnal fluctuations. The results of this study suggest that interpretation of clinical samples may be more complicated than previously believed. Furthermore, on the basis of the results of this study, it is possible that some avian reference ranges may need to be reexamined.     

Evaluation of a circumferential femoral head osteophyte as an early indicator of osteoarthritis characteristic of canine hip dysplasia in dogs

OBJECTIVE: To determine the relationship between a circumferential femoral head osteophyte (CFHO) and osteoarthritis characteristic of canine hip dysplasia, and to ascertain whether CFHO, like osteoarthritis, varies between diet-restricted and control-fed dogs. DESIGN: Longitudinal cohort study. ANIMALS: 48 Labrador Retrievers. PROCEDURES: Dogs were paired by size, sex, and litter and assigned to 1 of 2 equal groups at 2 months of age. The control-fed group was fed ad libitum, and the diet-restricted group was fed 25% less on a pairwise basis of the same diet for life. The dogs' hip joints were radiographed yearly for life. Each radiograph was evaluated for radiographic signs of osteoarthritis characteristic of hip dysplasia and for the presence and severity of a CFHO. RESULTS: 41 of the 48 (85.4%) dogs had a CFHO, which was detected at a median age of 5.4 years, and 33 of those 41 (80.5%) developed radiographic evidence of osteoarthritis. Nineteen (79.2%) dogs in the diet-restricted group and 22 (91.7%) in the control-fed group had a CFHO at a median age of 9 and 3 years, respectively. Of the dogs with a CFHO, 12 (63.2%) in the diet-restricted group and 20 (90.0%) in the control-fed group developed radiographic evidence of osteoarthritis characteristic of hip dysplasia at a median age of 11 and 6.5 years, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a relationship between the CFHO and subsequent development of radiographic signs of osteoarthritis. If a CFHO is present in Labrador Retrievers, it might be considered an early indicator of osteoarthritis.     

Comparison of dogs with septic peritonitis: 1988–1993 versus 1999–2003

Objective: To describe and compare the patient population, treatment, and outcome in dogs with septic peritonitis from 2 time periods at the same institution. Design: Retrospective study. Setting: The Matthew J. Ryan Veterinary Hospital at the University of Pennsylvania. Animals: Dogs treated surgically for septic peritonitis between 1988–1993 and 1999–2003. Interventions: None. Measurements: Preoperative physical and clinicopathologic data, surgical findings, anesthetic parameters, treatment, and outcome. Main results: No significant difference in survival among dogs treated surgically for septic peritonitis between 1988 and 1993 (21/33 [64%]) and 1999–2003 (29/51 [57%]) was detected. The patient populations of the two time periods were similar. Changes in treatment between the study periods reflected availability of new antibiotics and synthetic colloids, as well as greater attention to pain management and ulcer prevention. Duration of hospitalization was not significantly different between the two time periods, but the daily cost adjusted to 2005 dollars was higher in 1999–2003. Potential prognostic indicators were compared between survivors and non‐survivors after combining the data from both time periods, and although several parameters reached statistical significance, of greatest clinical significance were the higher blood pressure and preoperative serum albumin in survivors. Conclusions: Although new treatments were added to the supportive care of dogs with septic peritonitis, survival did not change sufficiently to detect a significant difference between the time periods evaluated. Identifying reliable prognostic indicators for septic peritonitis remains a challenge, but hypotension and decreased preoperative serum albumin were associated with non‐survival in this group of dogs.