Solitary osseous plasmacytomas in dogs: 13 cases (2004-2019).

OBJECTIVES: To further characterise solitary osseous plasmacytoma in dogs, an extremely rare disease. To describe diagnosis, disease progression and treatment outcomes in dogs with solitary osseous plasmacytoma. MATERIALS AND METHODS: Retrospective review of dogs with solitary osseous plasmacytomas that were diagnosed and treated at a single institution from 2005 to 2019. Kaplan-Meier single group survival analysis was used to estimate median survival time and progression-free interval. RESULTS: Thirteen dogs met the inclusion criteria for the study, and of those, 11 were treated. The median age at diagnosis was 8 years (range 4 to 11). Most solitary osseous plasmacytomas occurred in the vertebrae (n=8). Other sites included the maxilla (n=2), the mandible (n=1), the tibia (n=1) and the carpus (n=1). The median survival time for all dogs with solitary osseous plasmacytoma was 912 days (range 5 to 2179), and the progression-free interval for treated dogs was 310 days (range 22 to 2179). Most dogs were treated with radiation therapy (n=10) with nine of 10 receiving a definitive, daily fractionated protocol and with five of ten having had neoadjuvant surgery. Seven dogs received chemotherapy, which was initiated after progressive disease in five dogs. The median survival time for dogs that completed radiation therapy (n=9) was 1166 days (range 545 to 2179). While five dogs developed lesions at other sites, no dogs progressed to multiple myeloma. CLINICAL SIGNIFICANCE: Canine solitary osseous plasmacytomas can be managed long term with appropriate local therapy. This observation reflects the biologic behaviour observed in humans.

Clinical and clinicopathological factors associated with survival in 44 horses with equine neorickettsiosis (Potomac horse Fever).

BACKGROUND: The epidemiology of equine neorickettsiosis (EN) has been extensively studied but limited clinical and clinicopathological data are available concerning naturally infected horses. HYPOTHESIS: Factors predictive of survival will be identified in horses diagnosed with EN. ANIMALS: Convenience sample of 44 horses with EN admitted to 2 referral institutions. METHODS: A retrospective study was performed. A diagnosis of EN was based on the presence of positive blood or fecal PCR. RESULTS: The most common clinical signs included diarrhea (66%), fever (50%), anorexia (45%), depression (39%), colic (39%), and lameness (18%). The median duration of hospitalization was 6 days and 73% of horses survived to discharge. Laminitis was present in 36% of horses, 88% of which were affected in all 4 feet. Serum creatinine and urea nitrogen concentrations, as well as RBC count, blood hemoglobin concentration, hematocrit, band neutrophils, serum AST activity, serum CK activity, and anion gap, were significantly (P < .05) higher in nonsurvivors. Serum chloride and sodium, concentrations as well as duration of hospitalization were significantly lower in nonsurvivors. The results of forward stepwise logistic regression indicated that blood hemoglobin concentration on admission and antimicrobial treatment with oxytetracycline were independent factors associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Severity of colitis as reflected by electrolyte loss, hemoconcentration, and prerenal azotemia were predictors of survival in horses diagnosed with EN. Treatment with oxytetracycline was associated with increased survival.

Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy.

Our purpose was to determine whether the administration of anti-oxidant vitamins could reduce dose-limiting toxicity from radio-immunotherapy (RAIT) and thereby allow higher escalation of RAIT doses. Lipophilic vitamins A and E were administered i.p. and hydrophilic vitamin C was administered i.m. for 14 days (3 days pre-RAIT through 11 days post-RAIT) alone or with bone marrow transplantation (BMT) to either BALB/c mice for toxicity studies or to nude mice bearing s.c. GW-39 human colonic cancer xenografts for therapy studies. The maximal tolerated dose (MTD) of RAIT ((131)I-MN14 anti-CEA IgG) that results in no lethality was determined for mice that did not receive vitamins or BMT and those that did receive one or both interventions. Body weight, peripheral white blood cell (pWBC) and platelet (PLT) counts and tumor growth were also measured. Administration of vitamins (equivalent of 3.5 IU/day vitamin A, 0.107 IU/day vitamin E and 4.0 mg/day ascorbic acid) to mice along with BMT increased the MTD by 42% and reduced body weight loss associated with RAIT. Vitamins also reduced the magnitude of RAIT-induced myelosuppression. As early as day 7 after RAIT, vitamins increased WBC counts following both a 400 microCi and a 500 microCi dose. On day 14 after the 400 microCi dose of RAIT (day 7 post-BMT), the additive effect of BMT and vitamin could be detected. Tumor growth was not adversely affected by vitamin administration.

Chronotolerance of experimental radioimmunotherapy: clearance, toxicity, and maximal tolerated dose of 131I-anti-carcinoembryonic antigen (CEA) IgG as a function of time of day of dosing in a murine model.

The temporal variation in bone marrow proliferation has been used to help define the optimal time of day to dose with approximately 30 chemotherapeutic agents, so that treatment efficacy is maximised and toxicity is minimised. Since myelosuppression is also the dose-limiting toxicity for most forms of radioimmunotherapy, we hypothesised that time of day of administration might also influence tolerance for radioantibody therapy. Bone marrow proliferative activity in BALB/c mice was determined using cell cycle analysis of propidium iodide-stained bone marrow samples collected at 3 h intervals. Myelosuppression was determined at weekly intervals after a therapeutic dose of 131I-NP-4 anti-CEA (carcinoembryonic antigen) intact IgG at either 0900 h (2 h after light onset [HALO]), 1300 h (6 HALO) or 1600 h (9 HALO). The highest bone marrow proliferative activity was noted between 20 HALO (0300 h) and 4 HALO (1100 h), and the lowest activity could be measured at 10-13 HALO (1700-2000 h). Seven days after a maximal tolerated dose (MTD) of radioantibody, granulocyte reduction was 50% at both 2 and 6 HALO and only 32% at 9 HALO (P < 0.003). Fourteen days after radioantibody therapy, an 87% granulocyte suppression was observed in mice treated at 2 HALO and only a 64% granulocyte loss was noted in the 9 HALO treated group (P < 0.001). The 2 HALO group recovered earlier than the 9 HALO group (P < 0.013; 22% loss from the 2 HALO dose and 40% loss from the 9 HALO dose) on day 28 post-radioimmunotherapy. The difference in magnitude of neutropenia, rather than duration, was critical for establishing the MTD. A 30% increase in the MTD was possible if mice were dosed at 9 HALO (320 microCi) versus 2 HALO (240 microCi). These studies suggest that principles of chronobiology may govern the magnitude of toxicity and the highest dose tolerated in radioantibody therapy in the same way that it does for cytotoxic drug therapy.

Coordinate regulation of NAD(P)H:quinone oxidoreductase and glutathione-S-transferases in primary cultures of rat neurons and glia: role of the antioxidant/electrophile responsive element.

NAD(P)H:quinone oxidoreductase (QR) and glutathione-S-transferases (GSTs) are among the enzymes believed to protect an organism against oxidative stress. To test if redox-cycling compounds regulate the expression of these enzymes in cells of neural origin, primary cultures of rat cerebellar neurons and glia were treated with tert-butylhydroquinone (tBHQ) and hydroquinone (HQ). Basal levels of endogenous QR and GST activity were significantly greater in glia than neurons; and QR, GSTP1, and A3 were increased in glial but not neuronal cultures by treatment with tBHQ and HQ. A possible role for protein kinase C (PKC) in the tBHQ-mediated increase in QR and GST was evaluated by activating PKC with phorbol 12-myristate 13-acetate or inhibiting PKC with bisindolylmaleimide I. PKC was not involved in maintaining basal expression or mediating the increased expression of GST or QR by tBHQ. Transcriptional activation of QR and rGSTP1 by tBHQ could be mediated through a common responsive element present in the 5'-flanking region of both genes, the antioxidant/electrophile responsive element (ARE/EpRE). Transient transfection of the glial cultures with rGSTP1- or rQR1-ARE/EpRE-luciferase reporter constructs demonstrated that tBHQ transcriptionally activates the ARE/EpRE. Thus, the increased expression of genes regulated by the ARE/EpRE in cells of the central nervous system may provide protection against oxidative stress.