Tissue drug residue research often involves the killing of an animal every time tissue concentrations are determined. To decrease the number of animals required to perform tissue depletion studies and to circumvent the statistical problems associated with determining tissue depletion kinetic properties, using multiple animals, the renal depletion profile of gentamicin from individual sheep was studied, using a bilateral renal translocation technique. Seven ewes were surgically altered, allowed to stabilize, and then allocated into 2 groups; groups-1 sheep (n = 4) were given 3 mg of gentamicin/kg, IM, q 12 h for 10 days, and group-2 sheep (n = 3) were not given gentamicin. The kidneys from all ewes were biopsied 9 times over 74 days after the termination of gentamicin treatment. The renal concentrations of gentamicin were measured by use of a validated tissue digestion procedure coupled with a liquid-phase fluorescence polarization immunoassay. On days 75 and 77 after the end of gentamicin treatment, all ewes were euthanatized and necropsied. The concentrations of gentamicin in the biopsy specimens ranged from 71.9 to 183 microgram/g on days 1 and 2 after dosing, and decreased to concentrations ranging from 3.99 to 7.35 microgram/g on days 73 and 74 after the end of dosing. The decrease in renal gentamicin concentrations was best described by a biexponential equation, The early phase half-life was 2.8 days, whereas the terminal phase half-life was 59 days (harmonic means). There was no difference in the appearance or histologic features of the kidneys from groups 1 and 2. The only lesions noticed were linear fibroses that were attributed to the biopsy procedure.

A study was undertaken to determine the pressor and toxic effects of etoposide, an antineoplastic agent, when administered IV in 0.9% sodium chloride solution (0.4 mg of etoposide/ml) over a 30-minute period to dogs at a dosage of 40 mg/m2 of body surface. On day 1, 6 adult German Shorthaired Pointers were anesthetized with halothane, and blood pressures were measured via a femoral artery catheter before, during, and after the etoposide was administered. Systolic, diastolic, and mean blood pressures of each dog increased significantly (P less than 0.01) within 30 minutes after initiation of etoposide infusion. On day 3, when the dogs were not anesthetized, etoposide was again administered to each dog, using the same dosage. Each dog developed a moderate to severe cutaneous reaction characterized by moderate to severe pruritus, urticaria, and swelling of the head and extremities that began during the second infusion of etoposide. These same cutaneous reactions were seen on day 30, when etoposide was administered to 3 of the previously treated dogs and 2 previously untreated Beagles. We concluded that the administration of the commercial preparation of etoposide is likely to cause a significant reduction in blood pressure of anesthetized dogs, and that the drug is likely to induce a moderate to severe cutaneous reaction when administered to unanesthetized dogs.

A commerical radioimmunoassay kit designed for measuring gastrin in human serum was validated for use with equine serum. This nonextraction, double-antibody procedure uses an antiserum with broad specificity for molecular forms of gastrin. Synthetic human gastrin (G17-I) was added to pooled equine serum, and the observed assay values were compared with the mass added. Recovery was 99 to 115% in the gastrin concentration range of 40 to 640 pg/ml. Dilutions of postprandial serum with serum from fasted horses were assayed, and the inhibition curves were compared with those of the human gastrin kit standards, using a log-logit transformation. The slopes of the sample dilution plots were not significantly different from the slopes ofthe standard curves. Ethylenediamine tetraacetate and heparin adversely affected the assay, resulting in lower assayed gastrin concentration values. The intra-assay coefficient of variation (n = 10) was 3.8%, and the interassay coefficient of variation (n = 6) was 11.2%. The assay sensitivity, as reported by the manufacturer, is 8 pg/ml. Gastrin concentrations in serum from fasted horses ranged from undetectable values (less than 8 pg/ml) to 17.5 pg/ml, and peaked at a mean value (n = 6) of 70 pg/ml 3 hours after feeding. Serum cortisol values monitored during the postprandial blood collection period were in the normal range for horses.

Parasite-free, 4-month-old-calves were inoculated with Ostertagia ostertagi and/or Trichostrongylus axei, followed 6 weeks later by inoculation with increasing doses of O ostertagi for 8 weeks in the 2 groups (n = 9) of calves that had been given O ostertagi. Gastrin immunoreactivity concentration in serum was measured before and after infection and was correlated with changes in mucosal thickness. Gastrin immunoreactivity concentration in preinoculation control sera ranged from 95.2 to 287.1 pg/ml, and increased values were measured in all parasitized calves after 15 weeks. Significantly (P < 0.05) increased serum gastrin immunoreactivity concentration compared with the preinfection value, was found in calves infected with O ostertagi or T axei, and highly significant (P < 0.01) values were observed in calves infected with both parasites. Abomasal mucosal hyperplasia was observed in all parasitized calves; increased mucosal thickness and mucosal cross-sectional area were most prominent in calves infected with O ostertagi and T axei.

In the first of 2 separate trials, the efficacy of febantel, given at a dosage of 5 mg/kg of body weight, was assessed in calves with 60-day experimentally induced Bunostomum phlebotomum infection. Ten calves were given febantel paste, and 10 were given the vehicle only. All 20 calves were necropsied 7 days after cessation of treatment. Compared with untreated calves, febantel-treated calves harbored 99.4% fewer nematodes. In the second trial, the efficacy of ivermectin, given as a paste formulation at a dosage of 0.2 mg/kg, was assessed in calves with experimentally induced B phlebotomum infection. Ivermectin was given at 18 (n = 6) and 60 (n = 6) days after infection. At each treatment date, 3 additional calves were given vehicle only. At 67 days after infection, all calves were euthanatized. Efficacies of ivermectin against 18- and 60-day infections were 100 and 99.8%, respectively. Both anthelmintic preparations were easily administered, and adverse reactions were not observed.

Intramammary devices (IMD) were abraded with medium-grade emery cloth or were left smooth. One IMD of each type was inserted into a mammary quarter of each of 5 lactating cows. The remaining 2 quarters served as controls. Quarter foremilk, bucket milk, and stripping milk samples were collected for 3 consecutive days at 2 weeks after IMD insertion, and milk somatic cell counts (SCC) were determined. Milk samples also were collected immmediately after and 0.5, 1,2,4,6,8, and 11 hours after milking. All quarters were challenge exposed with 250 colony-forming units of Streptococcus uberis at 2 months after IMD insertion. Foremilk and stripping milk samples were collected for bacteriologic culture and SCC at the next 10 milkings. Mean foremilk, bucket milk, and stripping milk SCC (X 10(6) cells/ml) were 0.18, 0.07, and 0.91, respectively, for quarters with abraded IMD; 0.06, 0.05, and 0.43, respectively, for quarters with smooth IMD; and 0.03, 0.03, and 0.15, respectively, for control quarters. Mean SCC after milking (X 10(6) cells/ml) for the various intervals were 0.70, 1.29, 0.70, 0.97, 1.15, 1.17, 0.77, and 0.85 for quarters with abraded IMD; 0.43, 0.62, 0.61, 0.45, 0.64, 0.60, 0.31, and 0.26 for quarters with smooth IMD; and 0.15, 0.24, 0.15, 0.19, 0.15, 0.15, 0.14, and 0.06 for control quarters. After challenge exposure, 2 of 5 of the quarters with abraded IMD, 4 of 5 of the quarters with smooth IMD, and 8 of 9 of control quarters became infected. Results indicated that abraded IMD increased SCC in stripping milk to concentrations that provided 60% portection against challenge eexposure with S uberis.

A study was undertaken to investigate the combined effects of fasting and different diets on interferon (IFN) production and virus replication measured in nasal secretions of calves inoculated with a vaccine strain of infectious bovine rhinotracheitis virus. Four groups of calves were inoculated intranasally with infectious bovine rhinotracheitis virus. Two groups were inoculated 24 hours after onset of a 3-day fast; upon refeeding, 1 group was fed a maintenance diet (M diet) of hay, and the other was fed a higher energy diet (HE diet) of hay and concentrate. Nonfasted control groups were fed the M diet or the HE diet. Overall IFN production was highest (P less than 0.01) in nonfasted calves fed the M diet throughtout the study and lowest in nonfasted calves fed the HE diet. Fasted calves refed the HE diet produced consistently and significantly more IFN than did nonfasted calves fed this diet. Fasted calves refed the M diet, however, produced significantly less IFN, compared with control calves fed the M diet throughout the study. Overall mean virus excretion was similar in all groups; therefore, the amount of virus replication per se did not account for the differences in IFN production, nor did greater IFN production result in less virus excretion. Serum cortisol concentrations and immune responses were not significantly affected by fasting or diet.

Amendments to the Animal Welfare Act (PL 99-198) require that an exercise program for dogs be established by the attending veterinarian. A 6-week study was conducted to determine the effects of a moderate exercise program in purpose-bred Beagles. Sixteen male Beagles (4/group) were maintained as follows: (1) standard cage without exercise; (2) standard cage with individual exercise periods (35 minutes, 3 times/week); (3) large cage without exercise; and (4) standard cage with group-release exercise periods. Blood samples were collected for CBC, serum biochemical analysis including determination of serum cortisol concentration, and immune function (lymphocyte transformation assay). Group-released dogs interacted with each other during most of the exercise time. Fighting in these dogs occurred only during the third week. Dogs had little inclination to exercise when released along into the exercise area. Regardless of the size of the cage, dogs did not exercise unless human beings were present in the room. There were no significant differences in laboratory findings among dogs in the 4 groups. This moderate exercise program had no demonstrable effects. Similarly, continuous cage housing, without a formal exercise program, could not be determined to be detrimental to the physiologic or health status of dogs.

The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 microgram of TMP/ml and 4.75 microgram of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination-30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, after inoculation with S aureus but before antimicrobial treatment, and after inoculation at various hourly intervals after oral administration of the TMP-SDZ combination. The TMP-SDZ combination was administered daily in the 2 dosages for 21 days. Samples were collected after day 3 of repetitive drug administration so that drug steady-state concentration would have been achieved. Serum and synovial fluid samples were analyzed for TMP and SDZ concentrations. Administration of the TMP-SDZ combination at a dosage of 30 mg/kg once daily was not effective in maintaining TMP or SDZ concentrations above the MIC of TMP-SDZ for the S aureus (0.25 and 4.75 microgram/ml for TMP and SDZ, respectively) in the infected synovial fluid or in maintaining adequate TMP concentration in the serum. The alternative use of the TMP-SDZ combination at a dosage of 60 mg/kg given as 30 mg/kg every 12 hours was effective in maintaining serum and synovial fluid concentrations of TMP and SDZ that were greater than the MIC for the infective organism. Sulfadiazine concentration was significantly (P less than or equal to 0.05) lower in the infected synovial fluid sample than that in the corresponding serum sample. We concluded that administration of 60 mg of TMP-SDZ/kg given as 30 mg/kg every 12 hours is more effective than 30 mg/kg given once daily for the treatment of equine infectious arthritis caused by organisms for which the MIC of TMP-SDZ is less than or equal to 0.25-4.75 microgram/ml.

Neutralizing and nonneutralizing antibodies to bovine viral diarrhae (BVD) virus were detected in 3 cows persistently infected with noncytopathic BVD virus after vaccination with modified-live cytopathic BVD virus. Neutralizing antibodies detected in serum samples from each persistently infected cow at 3 weeks after vaccination were highly specific for certain isolates of cytopathic BVD virus and reacted only with a viral protein with a molecular weight of 53,000. Neutralizing antibodies to 1 of 3 isolates of noncytopathic BVD virus were detected in a serum sample obtained at 12 weeks after vaccination from 1 of 3 persistently infected cows. Nonneutralizing antibodies were detected in all cows at 7 to 12 weeks after vaccination.The nonneutralizing antibodies were less specific for isolates of BVD virus and reacted with viral proteins with molecular weights of 115,000, 80,000, 53,000, and 47,000.