A RETROSPECTIVE ANALYSIS OF 140 DOGS WITH ORAL MELANOMA TREATED WITH EXTERNAL BEAM RADIATION

Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long-term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy x 4 fractions; 30 Gy, 10 Gy x 3 fractions; or >45 Gy, 2-4 Gy x 12-19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4-6 months) and the median survival was 7.0 months (95% C.I., 6-9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p < .001, p < .001, and p = .04, respectively) and survival (p < .001, p < .001, and p = .05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.     

Evaluation of age of dam effects on maternal performance of multilactation daughters from high- and low-milk EPD sires at three locations in the southern United States

Angus bulls (n = 16) selected for either high- or low-milk EPD but similar growth EPD were mated within location at random to Angus cows. Daughters were bred to calve at 2 yr of age and annually until 6 yr of age. Milk yield was measured four times during lactation with a portable milking machine to estimate 12-h milk yield. Milk was collected for analysis of the percentage of fat and protein. A mixed model procedure was used to analyze the weaning weight, milk yield, and milk component data. The model for weaning weight included location, genetic line of sire, gender of calf, and age of dam. Calf age at weaning was used as a covariate. The model for the milk yield and components included location, genetic line of sire, gender of calf, period, and age of dam. Random effects for all models included sire of dam nested within line, sire of calf, and year. Genetic line was a significant source of variation for milk yield (P < 0.01) and weaning weight (P < 0.01) but not for percentage of fat or protein. Location was significant for milk yield (P < 0.01), fat (P < 0.01), protein (P < 0.01), and weaning weight (P < 0.01). The interaction of line with location was not significant except for percentage of protein (P < 0.01). Age of dam was significant for milk yield (P < 0.01), weaning weight (P < 0.01), and percentage of protein (P < 0.01), but not for percentage of fat (P = 0.29). Line difference for mean weaning weight was 18.1 kg, which is similar to the difference between lines for milk EPD (19 kg). Weaning weights from high-milk EPD line daughters were heavier (P < 0.01) than low-milk EPD line daughters at each age of dam evaluated. Cows nursed by males had higher milk yields (4.33 kg/12 h) than cows nursed by heifers (4.0 kg/12 h). The difference in yields for gender was significant for 2-, 3-, and 5-yr-old cows, but not for 4- (P < 0.052) and 6-yr old (P < 0.15) cows. Correlation coefficients between weaning weight and weaning EPD, milk EPD, and total maternal EPD were greater than zero (P < 0.01) (0.76, 0.65, and 0.89, respectively). Daughters of sires with high-milk EPD produced more milk at each age and weaned heavier calves than daughters of sires with low-milk EPD. These results confirm the value of milk EPD for improvement of weaning weights in beef cattle and also validate age of dam effects on milk yield and the associated effects on weaning weights.     

Osteomyelitis secondary to trauma involving the proximal end of the radius in horses: five cases (1987-2001)

OBJECTIVE: To determine clinical, radiographic, and scintigraphic abnormalities in and treatment and outcome of horses with trauma-induced osteomyelitis of the proximal aspect of the radius. DESIGN: Retrospective study. ANIMALS: 5 horses. PROCEDURE: Data collected from the medical records included signalment; history; horse use; degree of lameness; radiographic, ultrasonographic, and scintigraphic findings; treatment; and outcome. RESULTS: Duration of lameness prior to referral ranged from 14 to 60 days. Mean severity of lameness was grade 3 of 5, and all horses had a single limb affected. All horses had signs of pain during elbow joint manipulation and digital palpation over the lateral aspect of the proximal end of the radius. Radiographic lesions consisted of periosteal proliferation, osteolysis, and subchondral bone lysis. Scintigraphy in 3 horses revealed intense pharmaceutical uptake diffusely involving the proximal end of the radius. Two horses had sepsis of the elbow joint. All horses were treated with antimicrobials long-term; 1 horse was also treated by local perfusion of the radial medullary cavity through an indwelling cannulated screw. At follow-up, all horses had returned to their previous function. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that osteomyelitis of the proximal end of the radius can result from a traumatic injury to the antebrachium. Because lesions may be an extension of septic arthritis, a thorough examination of the wound area and elbow joint is recommended. Prolonged systemic antimicrobial treatment can result in a successful outcome.     

Effects of growth hormone and feeding level on endocrine measurements,hormone receptors,muscle growth and performance of prepubertal heifers

Prepubertal Friesian heifer calves (n = 24, initial BW = 195 +/- 5 kg) were assigned to a 2 x 2 factorial block design and used to evaluate the effects of daily GH treatment (0 or 15 mg/d) at either a low or a high feeding level in a 5-wk treatment period on endocrine measurements, hormone receptors, muscle growth, and overall performance. In the pretreatment period, a low feeding level was employed for all calves. During the treatment period, animals at the low feeding level had free access to a roughage-based mixture, whereas animals at the high feeding level had free access to a concentrate mixture and were offered 2 kg/d of the roughage-based mixture. Blood samples were collected weekly starting 3 wk before treatment. Longissimus (LM) and supraspinatus (SS) muscles were obtained at slaughter. Metabolizable energy intake was 81% higher, digestible CP intake was 140% higher, and ADG was 115% higher (all P < 0.001) at the high vs. low feeding level. Feed (DMI, ME, and protein) intake was not affected by GH treatment, but ADG was 18% higher (P < 0.13) in GH-treated than in control heifers at both feeding levels. Although of different magnitudes, the muscle anabolic effects of GH treatment and high vs. low feeding level were additive, and both treatments increased carcass weights (P < 0.02 and P < 0.001, respectively), LM (P < 0.05 and P < 0.001), and SS (P < 0.06 and P < 0.003). The anabolic effect of GH treatment was similar in both muscles, whereas the effect of feeding level was most pronounced in LM. Overall, GH treatment increased plasma GH, IGF-I (both P < 0.001), and IGFBP-3 (P < 0.02); however, GH treatment increased total IGF-I, free IGF-I, and IGFBP-3, and decreased IGFBP-2 mainly at the high feeding level (GH x feeding level interaction; P < 0.02, 0.01, 0.03, and 0.10, respectively). The high feeding level increased insulin, free and total IGF-I, and IGFBP-3 (all P < 0.001), but decreased GH and IGFBP-2 (both P < 0.001). High feeding increased type-1 IGF receptor density (P < 0.02), mainly in LM, in accordance with the largest anabolic response in this muscle, whereas GH treatment had no effect on type-1 IGF receptors. The results suggest that in skeletal muscle, the anabolic effects of exogenous GH are related to endocrine changes in the GH-IGF axis, whereas the effects of feeding level also seem to rely on IGF receptor density in the muscles.     

Growth hormone modulates cholecalciferol metabolism with moderate effects on intestinal mineral absorption and specific effects on bone formation in growing dogs raised on balanced food

The aim of the study was to investigate the influence of growth hormone (GH) on Vitamin D3 metabolism and the subsequent effects on calcium (Ca) homeostasis and skeletal growth in growing dogs. A group of Miniature Poodles received supraphysiological doses of GH (GH group; n = 6; 0.5 IU GH per kg body per day) from 12 to 21 weeks of age and was compared with a control placebo-treated group (n = 8). Biologic activity of GH in the GH compared to the control group was indicated by (a) the 2.5- to 3.5-fold increase in the plasma concentrations of insulin-like growth factor I (IGF-I), (b) the increased production of 1,25-dihydroxycholecalciferol as indicated by the significantly increased plasma 1,25-dihydroxycholecalciferol concentrations and the 12.9-fold increase in renal 1alpha-hydroxylase gene expression, and (c) the inhibited production of 24,25-dihydroxycholecalciferol as indicated by the significantly lower plasma 24,25-dihydroxycholecalciferol concentrations and the similar levels of renal 24-hydroxylase gene expression. Despite the distinct effects on Vitamin D(3) metabolism in the GH group, there were only moderate effects on the intestine, i.e. at 20 weeks of age there was a significant increase of 14.4 and 5.6% in fractional absorption of Ca and phosphate (Pi), respectively, compared to the control group. GH administration resulted in significantly elevated glomerular filtration rate, with no differences in Pi urine excretion as a result of a concomitant increase in the tubular reabsorption of Pi. GH had only limited disturbing effects on endochondral ossification as indicated by the maintenance of the regularity of the growth plates. However, GH had specific anabolic effects on bone formation without concomitant effect on bone resorption that may result in disorders of skeletal remodeling and manifestation of enostosis.     

Leishmania donovani-derived lipophosphoglycan plus BCG induces a Th1 type immune response but does not protect Syrian golden hamsters (Mesocricetus auratus) and BALB/c mice against Leishmania donovani

The efficacy of Leishmania donovani-derived lipophosphoglycan (LPG) plus Mycobacterium bovis Bacille Calmette-Guerin (BCG) as a vaccine candidate against visceral leishmaniosis in susceptible BALB/c mouse and Syrian golden hamster (Mesocricetus auratus) models was investigated. Following a triple vaccination with a total dose of 150 microl BCG plus 60 microg or 30 microg of LPG for hamsters and BALB/c mice respectively, there were no noticeable side effects both locally and systemically; implying that the molecule was safe at this dosage level. Vaccinated animals demonstrated an activation of both the humoral as well as cell-mediated responses to LPG, which correlated with resistance against the disease. Protection by LPG plus BCG, was however, poor as the remaining immunized animals showed disease progression leading to severity of the disease as illustrated by emaciation, mass loss and heavy splenic parasitaemia in hamsters. These data nevertheless suggest that it may be rewarding to further evaluate the potential of LPG as a vaccine candidate in leishmaniosis using other adjuvants, which may enhance its immunogenicity.