Glenna E. Mauldin

Effects of dietary supplementation with fish oil on in vivo production of inflammatory mediators in clinically normal dogs

OBJECTIVE To evaluate the effect of diets enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on in vivo production of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha, prostaglandin E2 (PGE2), and platelet-activating factor (PAF) in dogs. ANIMALS 15 young healthy dogs. PROCEDURES Dogs were randomly allocated to receive an isocaloric ration supplemented with sunflower oil (n=5), fish oil (5), or fish oil plus vitamin E (5) for 12 weeks. At week 12, in vivo production of inflammatory mediators was evaluated in serum at multiple time points for 6 hours following stimulation with IV administration of lipopolysaccharide (LPS). RESULTS Serum activity or concentration (area under the curve) of IL-1, IL-6, and PGE2 significantly increased after LPS injection in all groups but to a lesser extent in dogs receiving the fish oil diet, compared with results for dogs receiving the sunflower oil diet. Serum activity of TNF-alpha and PAF concentration also increased significantly after LPS injection in all groups but did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE A fish oil-enriched diet consisting of 1.75 g of EPA/kg of diet and 2.2 g of DHA/kg of diet (dry-matter basis) with an n-6:n-3 fatty acid ratio of 3.4:1 was associated with significant reductions in serum PGE2 concentrations and IL-1 and IL-6 activities. Results supported the use of EPA- and DHA-enriched diets as part of antiinflammatory treatments for dogs with chronic inflammatory diseases. Additional studies in affected dogs are warranted to further evaluate beneficial anti-inflammatory effects of EPA- and DHA-enriched diets.

MOPP Chemotherapy for Treatment of Resistant Lymphoma in Dogs: A Retrospective Study of 117 Cases (1989–2000)

The purpose of this retrospective study was to evaluate the efficacy and toxicity of the MOPP chemotherapy protocol (mechlorethamine, vincristine, procarbazine, and prednisone) as a rescue regimen in dogs with lymphoma. One hundred seventeen dogs that had resistance to previously administered chemotherapy were evaluated. Before treatment with MOPP, all dogs received a median of 6 chemotherapy drugs for a median duration of 213 days. Thirty-one percent (36 of 117) had a complete response (CR) to MOPP for a median of 63 days, and 34% (40 of 117) had a partial response (PR) for a median of 47 days. Sixteen percent (19 of 117) had stable disease (SD) for a median of 33 days. Predictors for response to MOPP were not identified. Gastrointestinal (GI) toxicity occurred in 28% (33 of 117) of the dogs, and 13% (15 dogs) required hospitalization. Five dogs developed septicemia, and 2 died as a result. MOPP was an effective treatment for dogs with resistant lymphoma and was well tolerated by the majority of affected dogs.

Spinal tumors in 37 dogs: clinical outcome and long-term survival (1987-1994).

The current management of dogs with spinal canal neoplasia in a large veterinary institution was evaluated. Postoperative survival time and prognostic indicators for survival were examined. Spinal neoplasms in dogs and humans also were compared. Thirty-seven cases with histologically confirmed spinal tumors were included in the study. The cervical region was affected most commonly, and 23 (62%) of 37 cases had extradural tumors. A hemilaminectomy or a dorsal laminectomy was performed in each case; three cases received adjuvant treatment. Twelve (32%) cases were euthanized at the time of surgery, and two died immediately after surgery. One dog was euthanized 20 days after surgery because of persistent clinical signs. Twenty-two cases were followed postoperatively; nine different types of primary tumors were confirmed by histological examination of tissue specimens from these 22 cases, and three cases had metastatic lesions. The median survival time of these 22 cases was 240 days. Twelve (32%) of the 37 cases had nerve-sheath tumors; the median survival time for these 12 cases was 180 days. No prognostic indicators were identified. However, median survival times of cases with benign versus malignant tumor types were 1,410 days and 180 days, respectively (p of 0.07). Four cases each had a myxoma/myxosarcoma, a tumor previously unreported in the spinal canal in dogs.

Serum alpha 1-acid glycoprotein concentration in cats with lymphoma.

Serum alpha 1-acid glycoprotein (AGP) concentrations were evaluated in nine cats with lymphoma. Twenty-five healthy cats were used as controls. Blood samples were obtained from cats with lymphoma prior to induction chemotherapy, one week following induction, at complete response, and at monthly intervals. The median pretreatment AGP concentration for the nine cats with lymphoma was significantly higher than the median AGP concentration for the 25 control cats. Remission serum AGP concentration was not significantly different from the pretreatment AGP concentration in the cats with lymphoma. Serum AGP concentrations provided no useful information regarding response or survival in cats with lymphoma.

Efficacy and toxicity of BOPP and LOPP chemotherapy for the treatment of relapsed canine lymphoma.

Mechlorethamine (Mustargen), Oncovin) (vincristine), procarbazine and prednisone (MOPP) chemotherapy is useful for relapsed canine lymphoma. This study evaluates the efficacy of MOPP after substitution of CCNU (lomustine, LOPP protocol) or BCNU (carmustine, BOPP protocol) for mechlorethamine in 60 dogs with relapsed lymphoma. Seven of 14 (50%) dogs treated with BOPP responded, for a median of 129.5 days for complete responders (range 9-354 days) and a median of 140 days for partial responders (range 4-276 days). Twenty-three of 44 (52%) dogs treated with LOPP responded for a median of 112 days for complete responders (range 48-250 days) and a median of 84.5 days for partial responders (range 69-290 days). Two dogs receiving a combination of LOPP and BOPP partially responded for 28 and 163 days, respectively. With BOPP chemotherapy, nine dogs (20.5%) and seven dogs (50%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seven dogs (50%) had one or more episodes of Grade II or higher gastrointestinal toxicity. While receiving LOPP chemotherapy, 28 dogs (63.6%) and 17 dogs (38.6%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seventeen dogs (38.6%) had one or more episodes of Grade II or higher gastrointestinal toxicity. Overall, there were 17 non-fatal treatment-related episodes of sepsis requiring hospitalization. Eight dogs (13%) died or were euthanized because of treatment-related sepsis and/or chemotherapy-related complications. Severe haematologic toxicity, coupled with the improved response duration observed in dogs receiving reduced doses during B/L-OPP rescue, underscores the need for protocol optimization.

Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP‐MA) for the treatment of canine lymphoma

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

Efficacy of Cobalt-60 Radiation Therapy for the Treatment of Nasal Cavity Nonkeratinizing Squamous Cell Carcinoma in the Dog

The purposes of this study were to evaluate the efficacy of cobalt-60 radiotherapy in the treatment of nonkeratinizing squamous cell carcinoma of the nasal cavity in dogs and to compare this treatment group to historical controls. Six dogs with histopathologically confirmed nasal cavity nonkeratinizing squamous cell carcinoma were treated with cobalt-60 radiotherapy to a total dose of either 63 Gy or 54 Gy. Overall survival times ranged from 30 days to 330 days, with a median survival time of 165 days. Nasal cavity nonkeratinizing squamous cell carcinoma in the dog is an aggressive tumor that responds poorly to radiotherapy.

Dietary-Related Skeletal Changes in a Shetland Sheepdog Puppy

A commercially available, renal failure diet was used to manage suspected renal failure in a 10-week-old Shetland sheepdog puppy. Rickets subsequently developed, possibly from low phosphorous intake and an increased calcium to phosphorus ratio. Decreased dietary calcium in addition to decreased phosphorus may have played a role in decreasing bone mineral density. Lethargy, decreased long bone growth, angular limb deformity, and osteopenia occurred, but these signs resolved within 3 months with nutritional management.

A comparison of toxicity of two dosing schemes for doxorubicin in the cat.

Doxorubicin is a commonly used and effective treatment for a variety of tumors in both people and cats. However, the use of this drug in cats has been associated with side effects such as renal injury, myelosuppression, anorexia, and weight loss. The goal of this study was to compare the toxicities associated with two dosing schemes for doxorubicin in tumor-bearing cats. Group A cats received 1 mg/kg of doxorubicin, while group B cats received 25 mg/m2 of doxorubicin plus 22 ml lactated Ringers solution per kilogram body weight subcutaneously. Toxicities were evaluated using laboratory data, physical examination, and history, and were graded using a standardized scale and compared between groups. Post-treatment neutrophil counts were significantly lower among cats in group B compared to cats in group A (P≤0.001), although complete blood counts were not evaluated at identical intervals in all cases. No other significant differences in the type, frequency or severity of clinical or laboratory toxicities were noted between groups, and no episodes of sepsis were recognized in either group. The results of this study suggest that higher doses of doxorubicin may not be associated with an increased risk of toxicity in the cat. Additional studies are still indicated to determine optimal dosing for doxorubicin in this species.

Radiosensitivity of canine osteosarcoma cells transfected with wild-type p53 in vitro*

The p53 gene is one of the important tumour suppressor genes that are involved with the cell survival signal pathway. One of the major functions of the p53 protein is to organize cell cycle regulation and induction of apoptosis for cellular genetic stability. It has been documented that more than 50% of all human cancers include a p53 mutation. We evaluated the difference in radiosensitivity between upregulating the expression of canine wild-type p53 (cp53) in cultured osteosarcoma (D17) cells and naive D17 cells in vitro. We found that upregulating transfected cp53 D17 cells increased their radiation sensitivity in vitro, and there was a significant decrease (P < 0.009) in survival between cp53-transfected D17 cells and naive D17 cells. In this experiment, a p53 enhancement ratio (p53ER) reached approximately 3.0 at high doses. The transfected cp53 D17 cells were significantly more radiosensitive at all doses evaluated than naive D17 cells, except at 1 Gy where too few data points were available. The p53ER increased rapidly at doses less than 4 Gy, achieving a maximum of about 3.0 for doses of 4 Gy and above. This study shows the enhanced radiosensitivity of the transfected p53 at clinically relevant doses.