Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997-2008).

OBJECTIVE: To evaluate clinical characteristics, outcome, and prognostic variables in a cohort of dogs surviving > 1 year after an initial diagnosis of osteosarcoma. DESIGN: Retrospective case series. ANIMALS: 90 client-owned dogs. PROCEDURES: Medical records for an 11-year period from 1997 through 2008 were reviewed, and patients with appendicular osteosarcoma that lived > 1 year after initial histopathologic diagnosis were studied. Variables including signalment, weight, serum alkaline phosphatase activity, tumor location, surgery, and adjuvant therapies were recorded. Median survival times were calculated by means of a Kaplan-Meier survival function. Univariate analysis was conducted to compare the survival function for categorical variables, and the Cox proportional hazard model was used to evaluate the likelihood of death > 1 year after diagnosis on the basis of the selected risk factors. RESULTS: 90 dogs met the inclusion criteria; clinical laboratory information was not available in all cases. Median age was 8.2 years (range, 2.7 to 13.3 years), and median weight was 38 kg (83.6 lb; range, 21 to 80 kg [46.2 to 176 lb]). Serum alkaline phosphatase activity was high in 29 of 60 (48%) dogs. The most common tumor location was the distal portion of the radius (54/90 [60%]). Eighty-nine of 90 (99%) dogs underwent surgery, and 78 (87%) received chemotherapy. Overall, 49 of 90 (54%) dogs developed metastatic disease. The median survival time beyond 1 year was 243 days (range, 1 to 1,899 days). Dogs that developed a surgical-site infection after limb-sparing surgery had a significantly improved prognosis > 1 year after osteosarcoma diagnosis, compared with dogs that did not develop infections. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study indicated that dogs with an initial diagnosis of osteosarcoma that lived > 1 year had a median survival time beyond the initial year of approximately 8 months. As reported previously, the development of a surgical-site infection in dogs undergoing a limb-sparing surgery significantly affected prognosis and warrants further study.

Serial temperature monitoring and comparison of rectal and muscle temperatures in immobilized free-ranging black rhinoceros (Diceros bicornis).

Control of body temperature is critical to a successful anesthetic outcome, particularly during field immobilization of wild animals. Hyperthermia associated with exertion can lead to serious and potentially life-threatening complications such as organ damage (including myopathy) and death. Methods for monitoring core body temperature must accurately reflect the physiologic status of the animal in order for interventions to be effective. The goal of this preliminary study was to compare serial rectal and muscle temperatures in field-immobilized black rhinoceros (Diceros bicornis) and evaluate a possible association. Twenty-four free-ranging black rhinoceros were immobilized between February and March of 2010 in Ethosha National Park, Namibia. Pairwise comparisons showed a correlation of 0.73 (95% CI; 0.70-0.75) between rectal and muscle temperature measurements. Results from a multivariable model indicate that muscle temperature readings were, on average, 0.46 degrees C (95% CI; 0.36-0.57 degrees C) higher than rectal temperatures while adjusting for repeated measurements on the same rhinoceros, effect of duration of immobilization, and effect of ambient temperature on rhinoceroses' temperature readings. As immobilization time increased, muscle and rectal temperature values within an individual rhinoceros tended to equilibrate. The overall temperatures decreased by an average of 0.00059 degrees C/min (95% CI; -0.0047 to -0.0035 degrees C/min; P = 0.779). As the ambient temperature at time of immobilization increased by 1 degree C, the average rhinoceros temperature increased by 0.09 degrees C (95% CI; 0.06-0.11 degrees C, P < 0.0001). Higher body temperature creates a potential for cellular damage leading to complications that include myopathy. Methods for monitoring rectal, muscle, and ambient temperatures should be incorporated into anesthetic monitoring protocols for large ungulates, particularly under field conditions.

UDP-galactose 4' epimerase (GALE) is essential for development of Drosophila melanogaster.

UDP-galactose 4' epimerase (GALE) catalyzes the interconversion of UDP-galactose and UDP-glucose in the final step of the Leloir pathway; human GALE (hGALE) also interconverts UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine. GALE therefore plays key roles in the metabolism of dietary galactose, in the production of endogenous galactose, and in maintaining the ratios of key substrates for glycoprotein and glycolipid biosynthesis. Partial impairment of hGALE results in the potentially lethal disorder epimerase-deficiency galactosemia. We report here the generation and initial characterization of a first whole-animal model of GALE deficiency using the fruit fly Drosophila melanogaster. Our results confirm that GALE function is essential in developing animals; Drosophila lacking GALE die as embryos but are rescued by the expression of a human GALE transgene. Larvae in which GALE has been conditionally knocked down die within days of GALE loss. Conditional knockdown and transgene expression studies further demonstrate that GALE expression in the gut primordium and Malpighian tubules is both necessary and sufficient for survival. Finally, like patients with generalized epimerase deficiency galactosemia, Drosophila with partial GALE loss survive in the absence of galactose but succumb in development if exposed to dietary galactose. These data establish the utility of the fly model of GALE deficiency and set the stage for future studies to define the mechanism(s) and modifiers of outcome in epimerase deficiency galactosemia.

A Drosophila melanogaster model of classic galactosemia.

Classic galactosemia is a potentially lethal disorder that results from profound impairment of galactose-1-phosphate uridylyltransferase (GALT). Despite decades of research, the underlying pathophysiology of classic galactosemia remains unclear, in part owing to the lack of an appropriate animal model. Here, we report the establishment of a Drosophila melanogaster model of classic galactosemia; this is the first whole-animal genetic model to mimic aspects of the patient phenotype. Analogous to humans, GALT-deficient D. melanogaster survive under conditions of galactose restriction, but accumulate elevated levels of galactose-1-phosphate and succumb during larval development following galactose exposure. As in patients, the potentially lethal damage is reversible if dietary galactose restriction is initiated early in life. GALT-deficient Drosophila also exhibit locomotor complications despite dietary galactose restriction, and both the acute and long-term complications can be rescued by transgenic expression of human GALT. Using this new Drosophila model, we have begun to dissect the timing, extent and mechanism(s) of galactose sensitivity in the absence of GALT activity.