Disposition kinetic variables of HI-6, a bispyridinium oxime, have been determined in mice, rats, rabbits, Rhesus monkeys, Beagles, sheep, and human beings. The drug has a short half-life, small apparent volume of distribution and high body clearance in these species, and is eliminated mainly by renal excretion. Using regression analysis and double logarithmic plots of the pharmacokinetic variables vs body weight of the various species, it was observed that body (systemic) clearance is the pharmacokinetic variable to use for interspecies comparison of elimination of the drug. The allometric exponent denoting the proportionality of body clearance of HI-6 to body weight of the 7 species studied was 0.76, which may be related to the renal excretion process for the drug. The apparent volume of distribution was similar (260 to 304 ml/kg of body weight) in the various species. The results indicate that volume of distribution, body clearance, and with less confidence, half-life might be used for interspecies scaling and for predicting these variables in other mammalian species. On the basis of the pharmacokinetic variables in selected species (rats and mice excluded), IV administration of III-6 at a dosing rate of 20 to 25 mg/kg at 4-hour intervals should provide an average steady-state plasma concentration of 16 to 20 micrograms/ml in domestic animals. The short half-life of III-6 precludes increasing the dosage interval.

The role of platelet-activating factor (PAF) in mediating the colonic damage that develops after large-colon torsion was studied in 14 ponies. Morphologic changes in areas of the ascending colon and selected abdominal and thoracic viscera after 1 hour of large-colon torsion and 3 to 5 hours of reperfusion were determined, as well as the protective effects of systemic administration of a specific PAF antagonist (WEB 2086). Ponies were selected then allocated at random and in equal numbers to 2 groups that received 1 of 2 treatments prior to induction of large-colon torsion: group 1 - control (saline solution), and group 2 WEB 2086 (3 mg/kg of body weight loading dose and 3 mg/kg/h for the remainder of the study). In each pony, full-thickness tissue specimens from the gastrointestinal tract-cecum, pelvic flexure, left and right ventral colon, and right dorsal colon - heart, left lung, liver, left adrenal gland, spleen, and right kidney were collected and histologically evaluated. Edema, mucosal necrosis, and neutrophil infiltration in colonic sections were graded from 0 (normal) to 3 (most severe changes). Sections of liver and lung from 3 ponies in each group, and colon from 1 pony in each group, also were examined by transmission electron microscopy to determine the presence of ultrastructural alterations. Ischemia and reperfusion induced marked changes in all sections of colon in all ponies: moderate to severe submucosal edema, moderate necrosis of the superficial epithelium and lamina propria, and necrosis of the mucosal crypt epithelium. Extra- vascular neutrophil accumulation was evident in all sections of colon and cecum, but not in other tissues. Ultrastructural lesions were not present in hepato- cytes or pneumocytes, or in the endothelial cells of liver, lung, and colon. Bacteria were observed by electron microscopy in 5% of hepatic sinusoids. Administration of a specific PAF antagonist, WEB 2086, failed to reduce severity of the observed lesions, indicating that it was not cytoprotective at the dosage used in this model of ischemia-reperfusion injury.

Breaking strength (torque at failure) of equine third metacarpal bones, with transfixation pins placed parallel in the frontal plane and 30 degrees divergent from the frontal plane, was determined in vitro. Two transfixation pins were placed through the distal metaphysis, using a jig designed to drill the holes in the assigned configuration. Paired metacarpal bones II through IV from 12 horses were tested in torsion. The torsional moment of the force applied through the transfixation pins at failure was compared for each limb. Metacarpal bones with divergent pins were significantly (P = 0.030) stronger, compared with those with parallel pins. Metacarpal bones with parallel pins failed with longitudinal oblique fractures through a proxidmal bone-pin interface, whereas those with divergent pins failed with more comminuted fractures through multiple bone-pin interfaces.

Fiberoptic bronchoscopy was performed in pigs to assess bacterial contamination of bronchoalveolar lavage fluids (BALF) obtained by use of the method and to determine the aerobic bacterial species in bronchoalveolar airways of healthy pigs. Bacterial contamination of BALF caused by insertion of the bronchoscope was evaluated, using a chromogenic bacterial tracer strain, and was found to be 0.22% of total colony-forming units (CFU), with range between 0 and 1.6%. A total of 164 pulmonary-healthy pigs from 6 closed herds were selected. The BALF obtained from these pigs were examined bacteriologically. Bacteria could not be isolated from 10.4% of all BALF; 5.5% of the BALF samples yielded pure cultures; and 84.1% yielded mixed aerobic bacterial growth. In BALF from 29.2% of the pigs, less than or equal to 5 X 10(2) CFU of bacteria/ml were isolated. The total number of bacteria in BALF from 50% of the pigs varied between 5 X 10(2) and 10(3) CFU/ml; 10.4% of BALF samples contained between 10(3) CFU/ml and 5 X 103 CFU/ml. More than 1 bacterial species were isolated from a single lung lavage of 84.1% of the pigs. Up to 6 species were isolated from a single BALF sample. A total of 443 bacterial isolates were differentiated into 25 bacterial genera and species. Samples of BALF yielded staphylococci (67.6%: Staphylococcus hyicus from 13.4% of the samples and S aureus from 2.4%), alpha-hemolytic streptococci (49.4%), Escherichia coli (42.1%), non-hemolytic streptococci (26.2%), Klebsiella spp (18.3%), micrococci (12.8%), and Coryneformes (11.0%). Other bacterial species were found, but less frequently. In our study, BALF from all pigs yielded < 5 X 103 CFU/ ml. Thus, low numbers of bacteria known to be facultative pathogens were isolated from BALF without causing detectable pneumonia.

Axial stability of equine oblique proxidmal phalangeal osteotonies with application of the standard short limb cast or 1 of 3 configurations of transfixation casts was determined in vitro. Transfixation cast methods included use of parallel pins, divergent pins, or parallel pins incorporating a metal walking bar. Displacement at the osteotomy was recorded for each limb at 4,448 N. Standard short limb casts provided significantly (P = 0.0002) less axial stability than did any form of transfixation cast. Significant differences were not found between the 3 transfixation casts.

The position, dimensions, and structure of the thyroid gland, the portion of the esophagus in the neck the cervical lymph nodes, and the major blood vessels of the neck were determined via ultrasonography in cattle. The left and right ventral neck regions of 30 healthy Swiss Braunvieh cows were examined ultrasonographically, using 3.5- and 5.0-MHz linear transducers and a 3.5-MHz convex transducer. The external jugular vein was situated directly beneath the skin in the upper and middle parts of the neck and 2.7 to 6.6 cm from the body surface in the lower part of the neck. In contrast, the common carotid artery was located further from the body surface along the entire ventral neck region; depending on the measuring point, this distance varied from 2.6 to 10.9 cm. The external jugular vein narrowed from caudad to craniad. The diameter of the common carotid artery remained fairly constant along its course in the ventral part of the neck and varied from 0.9 to 1.4 cm. The thyroid gland was identified via ultrasonography caudodorsal to the larynx It appeared as an echogenic spindle-shaped structure with finely granular echogenic pattern. The esophagus appeared as a band-shaped structure in longitudinal section, and it could be followed to the thoracic inlet. Its width increased from craniad to caudad, and mean +/- SD diameter was 2.9 +/- 0.23 cm. The medulla, hilus, cortex, and capsule of the cervical lymph nodes could be clearly differentiated via ultrasonography. Mean length and width of the left cervical lymph node were 3.0 +/- 0.45 and 1.8 +/- 0.23 cm, respectively. To determine reproducibility and reliability of the results, 10 cows were examined by ultrasonography 10 times within 2 weeks. The interassay coefficients of variation determined from these examinations varied from 3.0 to 12.3%; most of the coefficients of variation ranged from 5 to 10%. The smallest coefficients of variation were determined for diameter of the common carotid artery, and the largest were for diameter of the external jugular vein. Description of the ultrasonographic appearance of the structures of the ventral neck region in healthy cattle represents the basis for use of diagnostic ultrasonography in cattle with suspected diseases involving this area. The technique is noninvasive and can be performed on cattle in standing position.

Thirty-two mixed-breed male and female cats were blocked by sex, arranged by body weight from greatest to least, and allocated to 4 groups of 8 (4 male, 4 female) cats, using random numbers. Cats in each of 3 groups were treated orally with a 7% suspension formulation of lufenuron at dosage of 15, 30, or 45 mg/kg of body weight. Cats in the fourth group were treated orally with an excipient suspension without lufenuron. Cats were infested with newly emerged, unfed cat fleas (Ctenocephalides felis felis) on days -7 and -3 before treatment and at approximately weekly intervals after treatment. Flea eggs were collected from beneath each cat on selected days before and after treatment and placed in an artificial rearing medium. Flea eggs and medium were kept for 35 days in an insectary to determine effects of lufenuron or excipient suspension on emergence of adults of the F1 generation. Lufenuron was 100% effective in inhibiting development of C felis at all dosages for 11 days after treatment. Thereafter, efficacy exceeded 92% in all dosages groups, On day 32, when the study was terminated, efficacy for each of the dosage groups was: 15 mg/kg, 95.2%; 30 mg/kg, 98.2%; and 45 mg/kg, 99.6%. Adverse reactions or side effects were not observed in cats, regardless of treatment dosage.

Leukocyte adhesion deficiency was diagnosed in 4 Holstein calves from 1 to 4 months old. Calves had severe ulcers on oral mucous membranes, gingivitis, severe periodontitis, chronic pneumonia, and stunted growth associated with severe neutrophilia. Neutrophils from affected calves had function defect, characterized by severely decreased adherence, chemotactic movements, phagocytosis, luminol-dependent chemiluminescent response, and O2(-1)-producing activities. Deficient CD18 expression (0.1 to 1.7%) on neutrophils was clearly detected by use of flow cytometric analysis. These affected calves were linked to a common ancestral sire that has been documented to be a carrier. Clinical features, leukocyte functional abnormalities, deficient expression of CD18, and mode of inheritance indicated that affected calves had leukocyte adhesion deficiency. In vitro leukocyte functional abnormalities were associated with deficiency in the expression of CD11/CD18. Pathologic findings indicated possible increased susceptibility to infection associated with this disease.

Biplanar radiography was used to study normal growth of the left and right radius in 5 Beagles and growth of the left radius alone in 15 additional Beagles. We explored the applicability of this radiographic method in veterinary medicine by measuring the contribution to total radius length from each growth plate. Spherical tantalum markers (0.5 mm) were embedded in the proximal epiphysis, diaphysis, and distal epiphysis of each dog's radius at 10 weeks of age. Simultaneous biplanar radiographic views were obtained every 4 weeks until skeletal maturity was documented. A three-dimensional coordinate system was constructed allowing for measurement of growth (in millimeters). Resolution of the measuring system was 0.074 mm. Mean +/- SEM length of the skeletally mature Beagle's radius, as measured from proximal epiphyseal bead to distal epiphyseal bead, was 95.33 +/- 1.07 mm. The percentage of contribution to the total radius length from the proximal and distal growth plates was 36.76 and 64.73%, respectively, with 95% confidence interval of 2.29%. The percentage of contribution to radius length from the distal radial growth plate increased for each consecutive time segment, with the distal radial physis contributing 61.75% from 10 to 14 weeks of age and increasing to 70.22% from 22 to 26 weeks of age. Significant growth was not observed after 26 weeks of age. The period of most rapid growth was between 10 and 14 weeks of age. Biplanar radiography was accurate and precise in quantifying the relative contribution of the proximal and distal growth plate to radius length in Beagles. The method is applicable in veterinary research or clinical medicine for monitoring of axial and angular growth: physiologic, iatrogenic, or pathologic.

The effect of interleukin 1 (IL-1) on equine articular cartilage was investigated, using a cartilage explant culture system. Measurement of [35S]O4 incorporation revealed synthesis of matrix proteoglycan by cartilage to be decreased 45, 59.7, and 37.5% after 1, 3, and 5 days, respectively, in culture in the presence of 5 U of IL-1/ml. There was no change in proteoglycan degradation as determined by measurement of [35S]O4 release into the culture medium. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cartilage-conditioned medium indicated that exposure of cartilage to IL-1 caused a decrease in total protein synthesis by 45, 68, and 87% after 1, 3, and 5 days, respectively, in culture while selectively inducing synthesis of the 57-kd neutral metalloproteinase stromelysin (matrix metalloproteinase-3) in young and adult horses. Identification of stromelysin was confirmed by functional characterization and immunoprecipitation. Baseline total protein synthesis, as well as specific synthesis of stromelysin in cartilage from adult and aged horses, was markedly less than that of young horses. The IL-1-induced induced reduction in total protein synthesis may not be a characteristic of equine articular cartilage from affected joints of horses with naturally acquired osteoarthritis as indicated by an overall increase in protein synthesis by osteoarthritic explants. Introduction of IL-1 into an equine articular cartilage explant culture system resulted in decrease of matrix component synthesis and increase in specific degradative enzyme synthesis and activity. Articular cartilage from aged horses had markedly less overall metabolic activity, compared with cartilage from young horses. Articular cartilage from affected joints of horses with naturally acquired osteoarthritis did not have metabolic alterations identical to those of IL-1-stimulated normal articular cartilage from the same individual, necessitating reevaluation of the validity of the IL-1-induced model of osteoarthritis. Osteoarthritis is a common, naturally acquired disease of horses, and tissue from animals of all ages and stages of osteoarthritis is available. The equine model of osteoarthritis may afford an important means of studying the alterations in articular cartilage metabolism as a function of age and disease severity.