A radioimmunoassay test for tetracyclines (Charm II) was compared with high-pressure liquid chromatography (HPLC) for detection of oxytetracycline (OTC) residues in milk samples from individual lactating cows. Oxytetracycline was administered by 1 of 3 routes (IV, IM, or intrauterine) to 21 lactating dairy cows. A total of 292 duplicate milk samples were collected from milkings before and through 156 hours after OTC administration. Concentration of OTC in these samples was determined by use of the Charm II test and an HPLC method with a lower limit of quantitation, approximately 2 ng of OTC/ml. Samples were also classified with respect to presence of OTC residues relative to the FDA safe concentration (less than or equal to 30 ng/ml), using the Charm II (by control point determination) and HPLC methods. There was a significant (P less than or equal to 0.05) difference between test methods in classification of milk samples with respect to presence or absence of OTC at the FDA safe concentration. A total of 48 of the 292 test results (16.4%) did not agree. Using the HPLC test results as the standard with which Charm II test results were compared, 47 false presumptive-violative test results and 1 false presumptive-nonviolative Charm II test result (a sample containing 31 ng of OTC/ml, as evaluated by HPLC) were obtained. The samples with false presumptive-violative Charm II results contained (less than or equal to 30 ng of OTC/ml, as evaluated by HPLC. In some respects, the Charm II test performed appropriately as a screening test to detect OTC residues in milk samples from individual cows. However, the tendency for the test to yield presumptive-violative test results at OTC concentrations lower than the FDA safe concentration (as evaluated by HPLC), suggests that caution should be exercised in using the test as the sole basis on which a decision is made to reject milk. As indicated by the manufacturer, presumptive-violative Charm II test results should be confirmed by additional testing Although not specifically evaluated, the tendency for misclassification of milk samples as presumptive-violative by the Charm II test may or may not occur in commingled milk, compared with milk samples from individual cows.

Pharmacokinetic and pharmacodynamic variables of flunixin were studied in calves after IV administration of the drug at a dose rate of 2.2 mg/kg of body weight. The anti-inflammatory properties of flunixin were investigated, using a model of acute inflammation; this involved surgically implanting tissue cages at subcutaneous sites and stimulating the tissue cage granulation tissue by intracavitary injection of carrageenan. The actions of flunixin on exudate concentrations of several substances related to the inflammatory process, including proteases (metalloprotease [active and total] and cysteine and serine proteases), enzymes (lactate dehydrogenase, acid phosphatase, and beta-glucuronidase [beta-glu]), eicosanoid (prostaglandin E2 [PGE2], leukotriene B4, and serum thromboxane B2 [TXB2]) concentrations, and bradykinin (BK)-induced edema, were investigated. Flunixin had a long elimination half-life--6.87 +/- 0.49 hours--and volume of distribution was 2.11 +/- 0.37 L/kg, indicating extensive distribution of the drug in the body. Body clearance was 0.20 +/- 0.03 L/kg/h. Flunixin exerted inhibitory effects on serum TXB2 and exudate PGE2 concentrations, B-glu activity, and BK-induced swelling. Other enzymes and inflammatory mediators were not significantly affected. Pharmacokinetic/pharmacodynamic modeling of the data revealed similar mean concentration producing 50% of the maximal effect values for inhibition of exudate PGE2 and beta-glu and of BK-induced swelling (0.070 +/- 0.006, 0.064 +/- 0.040, and 0.061 +/- 0.030 microgram/ml), respectively). A lower concentration producing 50% of the maximal effect value was obtained for inhibition of serum TXB2 concentration (0.023 +/- 0.004 microgram/ml). Differences also were observed in equilibration half-life for these actions, suggesting the existence of 3 distribution compartments correlating with 3 sites of action--a central compartment and shallow and deep peripheral compartments. Pharmacokinetic/pharmacodynamic modeling proved to be a useful analytical method, providing a quantitative description of in vivo drug pharmacodynamics and indicating possible mechanisms of action.

The effect of xylazine, cisapride, and naloxone on myoelectric activity of the ileum, cecum, and proximal loop of the ascending colon (PLAC) was determined in 4 healthy Jersey cows implanted with 8 pairs of bipolar electrodes. A 4 X 4 Latin square design was used. The treatments included xylazine (0.04 mg/kg of body weight), cisapride (0.08 mg/kg), naloxone (0.05 mg/kg), and 0.9% sodium chloride solution (20 ml). All treatments were administered IV during early phase I of the migrating myoelectric complex in the ileum. Myoelectric activity was recorded for 4 hours after treatment, and data were analyzed for each hour separately. Xylazine significantly (P < 0.05) increased the duration of phase I of the first migrating myoelectric complex in the ileum to 220.72 +/- 26.89 minutes, compared with 30.91 +/- 10.11 minutes after administration of 0.9% sodium chloride solution. The number of cecocolic spikes per minute per electrode and the duration of cecocolic spike activity (percentage of recording time) were significantly (P < 0.05) decreased for the first 3 hours, and the number of propagated spike sequences in the cecum and PLAC was significantly (P < 0.05) decreased for the first 2 hours after administration of xylazine. Significant difference was not found between control and either,cisapride or naloxone treatment of healthy cows. However, during hour 1 after treatment with cisapride, number of spikes per minute, duration of spike activity, and number of propagated spike sequences were highest, compared with the other treatments. It was concluded that naloxone at the dosage used in this study was not suitable for medical treatment of cecal dilatation in cattle, when hypomotility of the cecum and PLAC must be reversed. Xylazine should not be used for relief of signs of pain in cases of cecal dilatation, because it significantly reduced myoelectric activity of the cecum and PLAC for at least 2 hours after treatment. Furthermore, results of this study indicated a trend (P > 0.05) toward increase of cecocolic myoelectric activity after administration of cisapride. It is the authors' opinion that the potential benefit of cisapride for medical treatment of cecal dilatation in cattle needs further evaluation.

The main objective of the study reported here was to determine whether signs typical of exocrine pancreatic insufficiency (EPI) are alleviated when affected dogs are fed a diet with low fat content, compared with feeding ordinary commercial dog food or food prepared by the owner. The most cost-effective amount of enzyme supplement also was estimated. The study consisted of 6 test periods. Duration of the first and third periods was 4 weeks, and that of the others was 2 weeks. During the first 2 periods, the dogs were fed their original diet. The amount of enzyme supplement was reduced by half between the first and the second period. During the last 4 periods, the dogs were fed only the low-fat diet, and amount of the enzyme supplement was reduced stepwise. During the entire study, owners were asked to assess daily the severity of 9 signs typical of EPI. A new index was established by adding the daily scores of each individual EPI sign. This index was designated the EPI index and was used as a measure of the general well-being of the dog. When the mean EPI indexes of the original diet periods were compared with those of the corresponding low-fat diet periods, there were no statistically significant differences by use of Turkeys test or the paired t-test. There was considerable variability between dogs, however. The fat content of the original diet did not correlate with the difference in EPI signs when the dogs were fed the low-fat diet. According to our study, feeding a low-fat diet to dogs with EPI did not significantly alleviate clinical signs of the disease. Decreasing the enzyme supplementation by 50% of the recommended of dose did not significantly increase severity of the cumulative EPI score. Decreasing the enzyme supplement by three-fourths of the recommended dose was excessive, and the severity of the clinical signs increased significantly (P < 0.05) The cost of the low-fat diet, compared with that of the original diet, was high.

Paired metacarpi obtained at necropsy from 100 horses ranging in age from term fetus to 35 years were examined to estimate the prevalence and sites of metacarpal fusion. Metacarpal fusion was seen in 192 of 200 metacarpi, and 78% of all horses 2 years or older had 2 or more fusions. Fusion of the second metacarpal bone to the third metacarpal bone was significantly (P < 0.001) more common than was fusion of the fourth to the third metacarpal bone. Fusions appeared for the most part in pairs and were bilaterally symmetric. Rooney-Prickett type-A carpometacarpal joint configurations (in which there is no measurable articulation between the third carpal and second metacarpal bones) were rare in this population, and Rooney-Prickett type-B configurations (in which there is a measurable articulation between the third carpal and second metacarpal bones) were observed in 98.5% of metacarpi. Medial metacarpal fusion was positively correlated with age, occupation, and proportion of the proximal projection of the carpometacarpal distal joint surface that was taken by the second metacarpal bone. Lateral metacarpal fusion was positively correlated with age and the proportion of the proximal projection of the carpometacarpal distal joint surface taken by the fourth metacarpal bone. Horses in performance careers (racing, race training, or show ring occupations) had an earlier development of the first 2 fusions than did horses in other or unknown occupations; development of the third and fourth fusions were not significantly different between occupation groups. The rate of metacarpal fusion per horse-year appeared to be at least 10 times higher than a clinically evident rate.

Piroxicam and other nonsteroidal anti-inflammatory drugs (NSAID) have antitumor activity against naturally acquired cancer in dogs and human beings, and against experimentally induced tumors in rodents. We are investigating potential mechanisms of NSAID anti-tumor activity. The direct cytotoxicity of piroxicam, indomethacin, and aspirin against 4, canine tumor cell lines (transitional cell carcinoma, squamous cell carcinoma, melanoma, and soft tissue sarcoma) was determined in short-term growth rate assays and in clonogenic assays. Piroxicam was evaluated alone and in combination with the lipoxygenase inhibitor zileuton, and in combination with the chemotherapeutic agents cisplatin and carboplatin. The 50% inhibitory concentrations (IC50) against melanoma cells in short-term growth rate assays were: 530 micromolar piroxicam, 180 micromolar indomethacin, and greater than 1 mM aspirin. These IC50 values were over 10 times greater than serum concentrations of these drugs that could safely be achieved in vivo. The IC50 of zileuton combined with piroxicam (280 micromolar) was not different from the IC50 of zileuton alone (230 micromolar; ANOVA P = 0.47) in melanoma cells. Similarly, addition of piroxicam did not alter the IC50 of either cisplatin (1.6 micromolar) or carboplatin (6.1 micromolar). These results suggest that NSAID, at serum concentrations achievable in vivo, do not have direct cytotoxicity against canine tumor cells tested. It is unlikely that the in vivo antitumor activity of NSAID is attributable to a direct cytotoxic effect.

A virologic survey was conducted on calves with diarrhea associated with bovine rotavirus (BRV) on a closed dairy farm. The BRV was detected from 32 of 219 (14.6%) fecal specimens repeatedly collected from 56 calves born during the years 1992-1993, regardless of whether they had diarrhea. Most of the 32 strains were isolated from fecal specimens obtained from 2-to 6-week-old calves. After electrophoresis of doublestranded viral RNA from the 32 strains, genomic RNA migration patterns were similar to those of the predominant BRV strains isolated at the same farm during the years 1990-1991. All representative strains were identified as G serotype 6 (G6) and P type 5 (P5) by results of the virus-neutralization test and polymerase chain reaction procedure. Thus, BRV had no change in genomic RNA electropherotypes and serologic antigenicities in a closed dairy herd over a period of several years.

Eleven pairs of canine metacarpal bones, 10 pairs of metatarsal bones, and 7 pairs of ribs were harvested cleanly and prepared for banking at -20 C for 1 year. One bone of each pair was randomly assigned to 1 type of storage: plastic pack vs immersion in a normal solution of sodium chloride. The contralateral bone was assigned to the opposite treatment. Six pairs of metacarpal bones and 5 pairs of metatarsal bones were tested in torsion to failure. No significant difference was found within pairs. All ribs, 5 pairs of metacarpal bones, and 5 pairs of metatarsal bones were loaded in 4-point bending to failure. The energy absorbed at failure and the ultimate displacement of ribs and metacarpal and metatarsal bones were increased by 25 to 30% and 18 to 24%, respectively, when the bones were frozen in isotonic saline solution. Corticocancellous grafts frozen in normal saline solution are biomechanically less fragile and brittle than grafts stored in plastic without saline solution.

Pharmacodynamic variables of enrofloxacin were investigated in a neutropenic mouse Escherichia coli and staphylococcal thigh infection model. Enrofloxacin pharmacokinetics in clinically normal mice and dogs were compared to confirm that doses evaluated in the mouse model would include enrofloxacin doses appropriate for use in dogs. Mice were made neutropenic by treatment with cyclophosphamide and injected in the thigh muscle with approximately 10(6) colony-forming units of E. coli (n = 2) or a staphylococcal (n = 2) clinical isolate. Enrofloxacin dosages tested ranged from 0.78 to 50 mg/kg of body weight and 6.25 to 200 mg/kg in the E. coli and staphylococcal infection trials, respectively. In each 24-hour dosage trial, enrofloxacin was administered SC as a single dose or in divided doses given every 3, 6, or 12 hours. Comparison of log(10) colony-forming units per thigh muscle in untreated control mice and mice treated with enrofloxacin was used as a measure of efficacy. Two-way ANOVA was used to determine that the enrofloxacin total dose, but not the dose frequency, was significant in determining drug efficacy. Pharmacokinetic values analyzed by use of multivariant stepwise linear regression analysis indicated that the area under the concentration-time curve, but not time above minimum inhibitory concentration, was significant in predicting efficacy of enrofloxacin treatment. We conclude that enrofloxacin killing of E. coli and staphylococci is concentration dependent and not time dependent.

The effects of short-term restraint stress, by means of snaring, on plasma concentrations of catecholamines, beta-endorphin, and cortisol were studied in 6 gilts. A catheter was inserted into the jugular vein, and 2 blood samples were collected before onset of stress. Thereafter, a hog snare was applied, and blood samples were collected at 0.5, 2, and 3.5 minutes after the start of snaring. Plasma epinephrine and norepinephrine concentrations increased (P < 0.001) within 0.5 minute after start of restraint and decreased thereafter. Plasma concentration of beta-endorphin increased (P < 0.05) within 2 minutes after start of restraint, whereas that of cortisol increased (P < 0.05) 3.5 minutes after start of restraint. Taken together, short-term stress, such as snaring, may increase the plasma concentration of catecholamines, beta-endorphin, and cortisol in pigs.