A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment, The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P < 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P < 0.05) with percentage of necrosis,.

In these studies, the effects of recombinant human interleukin 2 (rHuIL-2) were examined on in vitro tumor cytotoxicity by canine blood lymphocytes obtained from peripheral vessels through use of a chromium release microcytotoxicity assay. Cytotoxic activity by lymphokine-activated killer cells was significantly increased, compared with that by untreated lymphocytes in a dose-dependent manner. The maximal effect was attained with 300,000 IU of rHuIL-2/ml. Lymphokine-activated killing also was dependent on the duration of incubation with rHuIL-2. After 1 day of rHuIL-2 incubation, cytotoxicity was significantly increased, compared with that of untreated lymphocytes. Of the 3 times examined, cytotoxicity peaked after 3 days of rHuIL-2 incubation. High levels of cytotoxic activity were still present at 7 days of incubation. Numbers of granular lymphocytes increased over the times examined. These results demonstrate functional and morphologic changes in canine peripheral blood lymphocytes obtained from peripheral vessels after incubation with rHuIL-2 in a dose- and time-dependent manner.

Hydrated sodium calcium aluminosilicate (HSCAS), an anticaking agent for mixed feed, was added to the diets of growing wethers (mean body weight, 34.0 kg) and was evaluated for its ability to diminish the clinical signs of aflatoxicosis. The experimental design consisted of 4 treatment groups of 5 wethers each, consuming concentrations of 0 g of HSCAS and 0 g of aflatoxin (AF)/kg of feed (control; group 1); 20 g of HSCAS/kg (2.0%; group 2), 2.6 mg of AF/kg (group 3); or 20 g of HSCAS (2.0%) plus 2.6 mg of AF/kg (group 4). Wethers were maintained in indoor pens, with feed and water available ad libitum for 42 days. Lambs were observed twice daily and weighed weekly, and blood samples were obtained every 2 weeks for hematologic and serum biochemical analyses and for measurement of mitogen-induced lymphocyte-stimulation index. At the termination of the study, wethers were euthanatized and necropsied. Body weight gain was diminished significantly (P less than 0.05) by consumption of 2.6 mg of AF/kg of feed, whereas body weight of lambs consuming HSCAS plus AF did not differ from that of control wethers. The AF-alone treatment increased serum aspartate transaminase and gamma-glutamyltransferase activities, prothrombin time, and cholesterol, uric acid, and triglyceride values and decreased albumin, glucose, and urea nitrogen values, and urea-to-creatine ratio. A 27% decrease in lymphocyte stimulation index, increased spleen weight (as a percentage of body weight), and decreased liver weight were induced by AF-alone treatment. Results indicate that HSCAS may be a high-affinity sorbent for AF, that 2.6 mg of AF/kg of feed induces signs of aflatoxicosis in growing wethers, that lambs may not be as resistant to the effects of AF as previously thought, that 2.0% HSCAS can substantially reduce the toxic effects of 2.6 mg of AF/kg, and that sorbent compounds may offer a novel approach to the preventive management of aflatoxicosis in livestock.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

Previous studies of the amino acid analogue, alpha-ketoisocaproate (KIC), indicate that it can stimulate lymphocyte blastogenesis and antibody responses of sheep. To determine whether KIC could overcome the effects of adreno-corticotropic hormone (ACTH)-induced lymphocyte suppression, 24 lambs were fed a control diet, a diet supplemented with 0.05% KIC, or a diet supplemented with 0.05% of the parent amino acid leucine. Immune status was monitored by determining lymphocyte blastogenic responsiveness to phytohemagglutinin-P (PHA), concanavalin A (conA), and pokeweed mitogen (PWM) and percentages of T-cell subsets in the blood, using monoclonal antibodies and a flow cytometer. Serum cortisol, insulin, and glucagon concentrations also were determined. After 60 days of consuming the respective diet, lambs were administered either saline solution or ACTH (100 IU) twice daily for 3 consecutive days. Administration of ACTH increased serum cortisol and insulin concentrations; however, no effects were seen for serum glucagon concentration. Compared with saline administration, ACTH administration significantly (P < 0.05) suppressed mitogen-stimulated lymphocyte blastogenesis by approximately 50%, regardless of the mitogen used, and significantly (P < 0.01) decreased the percentage of circulating T lymphocytes and decreased (P < 0.01) the ratio of T4 to T8 cells. Lambs fed KIC had greater PHA- and conA-stimulated blastogenic responses and significantly (P < 0.05) increased ratio of T4 to T8 cells in the blood, compared with lambs fed the leucine-supplemented diet or the control diet and given corresponding injections. These data indicate that ACTH decreased in vitro lymphocyte blastogenesis and altered the subset ratios of blood lymphocytes in sheep. These changes were partially prevented by feeding KIC.

Cortical bone screws were implanted into the proximal portion of the right and left radius and ulna of 6 newborn Quarter Horse foals as radiographic markers for measurement of growth. Distance between markers on a lateral radiographic view was measured. Radiographs were taken at 2-week intervals until the horses were 8 weeks old, at 4-week intervals until they were 48 weeks old, and at 12-week intervals until they were 72 weeks old. The proximal radius and ulna grew at similar rates during the 72-week period of evaluation, and growth continued throughout 72 weeks. The proximal radius grew 3.5 cm, and the ulna grew 3.4 cm. Although the rates of growth were similar, growth from the ulnar physis contributed only to the length of the olecranon; growth was not transmitted to the ulnar diaphysis distal to the cubital joint. The proximal radius slid distally in relation to the ulna as growth occurred at the proximal radial physis. These findings suggest that transfixing the ulna to the radius while growth is occurring at the proximal radial physis impedes the natural shifting process, and subluxation of the elbow can result. Severity of subluxation would be inversely related to the age of the horse at the time of transfixation.

Renal mass was surgically reduced in 78 dogs by uninephrectomy or by combined renal infarction and uninephrectomy. Renal clearance of inulin and renal clearance of exogenous creatinine were determined simultaneously, and the creatinine to inulin clearance (C/I) ratio was calculated. Clearance procedures were performed 2 to 3 months after reduction of renal mass, and were repeated at intervals thereafter. Overall, the C/I ratio was 1.008 +/- 0.007 for 192 determinations, with a highly significant correlation (R2 = 0.994, P < 0.0001) between creatinine clearance and inulin clearance. There was no significant effect of gender of dogs, time after partial renal ablation, or dietary protein intake on C/I ratios. Degree of renal ablation did not affect C/I ratios. The results indicated that exogenous creatinine clearance is a valid measure of glomerular filtration rate in both male and female dogs with reduced renal mass.

To compare the effects of milk stasis and milk flow on Brucella abortus infection of the mammary gland under the same systemic conditions, primiparous goats (n = 5) were inoculated IV with B abortus on the day of parturition, and suckling by their neonates was restricted to one mammary gland. Goats were euthanatized and necropsied at 3 weeks after inoculation, and milk, mammary glands, and supramammary lymph nodes were evaluated by bacteriologic, histologic, and immunoenzymatic staining techniques. Nonnursed mammary glands had high titers of brucellae in milk, moderate interstitial mastitis, and brucellar antigen in macrophages located primarily in alveolar and ductal lumina. Brucellae often filled the macrophage cytoplasm. In contrast, nursed mammary glands had fewer brucellae in milk, minimal inflammatory changes, and no detectable brucellar antigen in histologic sections. Hyperplastic changes were only seen in supramammary lymph nodes draining nonnursed mammary glands; these contained more brucellae than lymph nodes draining nursed mammary glands. These studies show that milk stasis may be the sole cause of increased susceptibility of nonnursed mammary glands to B abortus infection.

We compared the frequency and severity of osteochondrosis lesions in young Thoroughbred horses with cervical stenotic myelopathy (CSM) vs that in clinically normal Thoroughbreds of the same age. All lesions of the cervical vertebrae and appendicular skeleton were classified histologically as osteochondrosis or nonosteochondrosis and were measured for severity. Minimal sagittal diameter was significantly smaller in horses with CSM from C2 through C6; no difference was detected at C7. Severity of cervical vertebral osteochondrosis was greater in the horses with CSM, however frequency was not different. Frequency and severity of nonosteochondrosis lesions were not different in cervical vertebrae or appendicular skeleton. Frequency and severity of appendicular skeleton osteochondrosis lesions were both greater in horses with CSM. Osteochondrosis and nonosteochondrosis lesions were more severe on facets at sites of compression than on facets at noncompressed sites in horses with CSM. However, compression was also observed at sites with no articular facet lesions. The association of widespread osteochondrosis and spinal canal narrowing with CSM suggests CSM may represent a systemic failure in the development or maturation of cartilage and bone.

Larkspur poisoning is a major cause of acute death of cattle on mountain and high plains rangelands of western United States. A nonlethal method to quantify dose response in cattle is needed to better estimate the toxicity of larkspur plants and the response of cattle to larkspur poisoning and to provide a basis for reference during studies. A numerical system of rating the clinical signs of larkspur poisoning was developed and used to describe the response of 10 Hereford cows given a repeated single daily dose of larkspur (Delphinium occidentale X barbeyi) by gavage. Larkspur poisoning resulted from a short-term cumulative effect, and a statistically significant increase in score was essentially maximal by 4 days. At the dose given, this effect did not persist for more than 4 days after cessation of dosing. Poisoning was most severe between 5 and 9 hours after dosing. Early signs of poisoning can be subtle and sometimes brief. The effect of larkspur poisoning can be exacerbated temporarily by exertion. Therefore, cattle could probably repeatedly consume an otherwise toxic daily dose, without manifesting marked signs of poisoning, if consumption decreased to a sufficient degree intermittently at 2- to 4-day intervals.