Renal electrolyte and net acid excretion were characterized during generation and maintenance of hypochloremic metabolic alkalosis in a ruminant model. Two phases of renal response with regard to sodium and net acid excretion were documented. An initial decrease in net acid excretion was attributable to increase in bicarbonate excretion with associated increase in sodium excretion. As the metabolic disturbance became more advanced, a second phase of renal excretion was observed in which sodium and bicarbonate excretion were markedly decreased, leading to increase in net acid excretion and development of aciduria. Throughout the metabolic disturbance, chloride excretion was markedly decreased; potassium excretion also decreased. These changes were accompanied by increase in plasma renin and aldosterone concentrations. There was apparent failure to concentrate the urine optimally during the course of the metabolic disturbance, despite increasing plasma concentration of antidiuretic hormone.

Leukocytosis (34,600 WBC/microliter of blood) was detected in an apparently healthy 7-day-old Holstein heifer. Analysis of blood samples obtained over the next 41 days revealed chronic progressive neutrophilia, which peaked at greater than 85% neutrophils and exceeded 100,000 WBC/microliter. In vitro assessment of isolated blood neutrophils obtained from the heifer at 38 and 45 days of age revealed selected functional abnormalities. Endocytosis of immunoglobulin-opsonized Staphylococcus aureus and killing of this test organism by the calf's neutrophils were significantly diminished, as were phagocytosis-associated superoxide generation, chemiluminescence activity, and myeloperoxidase-catalyzed iodination. Diminished H2O2 elaboration by the calf's neutrophils was evident during ingestion of opsonized zymosan or on exposure to phorbol myristate acetate. Extracellular release (secretion) of elastase during ingestion of zymosan was also diminished, although total cell content of elastase was normal, compared with that of neutrophils from age-matched calves, and granular or other morphologic abnormalities of the calf's neutrophils were not evident by ultrastructural examination. Abnormalities of random migration were inconsistently detected, and normal or high degree of antibody-dependent cytotoxicity or natural killing by the calf's neutrophils was observed. Similar in vitro assessment of neutrophils obtained from the calf's dam revealed no functional abnormalities. The calf died at 48 days of age, with persistent fever and chronic diarrhea despite administration of antibiotics. Histologic examination at necropsy revealed large numbers of intravascular neutrophils in most tissues, including massive neutrophil sequestration in spleen. However, a striking lack of extravascular neutrophils was evident in inflamed submucosa mucosa adjacent to intestinal ulcers heavily contaminated with enteric microorganisms. Bone marrow examination revealed diffuse myeloid hyperplasia, but no other abnormalities. The clinical and pathologic features in this calf were similar to those in previously reported human patients or Irish Setters with genetic deficiency of the CD11/CD18 leukocyte glycoprotein complex, thus prompting further postmortem evaluations. Results of immunoblot analyses of the neutrophil lysates of the heifer calf (isolated and stored prior to death) documented severe deficiency of Mac-1 (CD11b/CD18). Results of immunofluorescent analyses indicated substantially diminished (intermediate) amounts of the Mac-1 beta subunit (CD18) on blood neutrophils of the calf's dam and sire and on neutrophils of 8 of 15 paternal half-siblings; findings were consistent with an autosomal recessive trait in the proband's kindred. Findings also indicate that genetic abnormalities of CD11/CD18 proteins may underlie the molecular pathogenesis of disease in this calf as well as other previously described examples of the granulocytopathy syndrome in Holstein cattle.

A technique for transvenous endomyocardial biopsy of the right ventricle was developed and evaluated for safety and efficacy in anesthetized healthy cats positioned in left lateral recumbency. At least 6 endomyocardial biopsy specimens were obtained from the right ventricle or interventricular septum of 11 cats. In 4 cats, the right jugular vein was torn during attempts to pass the introducing catheter into the right ventricle; however, in only 1 cat did this preclude catheter passage. This cat's heart was biopsied via the left jugular vein. Except for damage to the jugular vein, complications were infrequent, and the biopsy procedure was well tolerated by all cats.

Intranuclear inclusions indicative of adenovirus infection were detected microscopically in formalin-fixed intestinal tissues from preweanling Syrian hamsters. The amphophilic intranuclear inclusion bodies were observed in ileal enterocytes from 16-to 24-day-old hamsters. Electron microscopy revealed large numbers of 72 +/- 3-nm viral particles typical of adenoviridae in enterocytic nuclei. Serum antibodies reacted with mouse adenovirus strains K87 and, to a lesser extent, FL, by indirect fluorescent antibody testing. Clinical disease was not associated with the adenoviral infections. Hamsters from 10 production colonies, including all major commercial Syrian hamster suppliers in the United States, were surveyed and all had serologic or histopathologic evidence of adenovirus infection.

Hybridomas secreting monoclonal antibodies (MAB) to transmissible gastroenteritis virus (TGEV) were produced by fusion of SP2/0 myeloma cells and splenic lymphocytes of BALB/c mice immunized with the virulent cell-passaged Miller strain of TGEV. The MAB secreted by these hybridomas were partially characterized; 4 of them (MA4, MA5, MH11, MB2) had high-neutralization titer for TGEV. The remaining 7 (MC6, MD9, ME5, MG5, MF2, ME9, MG7) did not neutralize TGEV at 1:25 dilution. All 4 neutralizing and 2 of the nonneutralizing MAB reacted with the E2 protein of TGEV in a radioimmunoprecipitation assay. The remaining 5 MAB reacted with the E1 protein of TGEV. Reactivity of the MAB was tested in an indirect immunofluorescent assay with 3 cell culture-adapted strains of TGEV (Miller, Purdue, and Illinois) and 13 wild-type isolates of TGEV. Neutralizing MAB reacted with all 13 wild-type isolates and the 3 cell culture-adapted strains of TGEV. In contrast, nonneutralizing MAB that reacted with the Miller strain of TGEV varied in their reactivity with the wild-type TGEV isolates. Reactivity of neutralizing MAB was also tested, using plaque-reduction neutralization assays with Miller, Purdue, and Illinois strains and 5 wild-type isolates. All 4 neutralizing MAB neutralized the 8 virus isolates, but the neutralization titer was higher with the homologous virus than with the heterologous virus isolates. However, neutralization titers of the 4 neutralizing MAB were 4 to 16 times higher for the homologous Miller strain of TGEV than for the heterologous Illinois and Purdue strains, and were 4 to 1,000 times higher than for the wild-type isolates. Extensive antigenic heterogeneity was observed among TGEV isolates on epitopes recognized by the nonneutralizing MAB directed against either E1 or E2 protein.

In 6 female goats, the mean threshold for glucosuria was 159.5 +/- 4.3 mg/dl. During increasing filtered loads of glucose, renal reabsorption of glucose reached maximal capacity, which was not exceeded when plasma glucose concentration was increased further. Measured in 10 female goats, the transport maximum for glucose was 119.1 +/- 9.1 mg of glucose reabsorbed/min. During infusion of glucose, there was a significant (P < 0.05) time-dependent reduction in inulin clearance indicating that IV glucose administration may be inappropriate in goats with compromised renal function.

The reactivity of bovine lymphocytes to 4 species of Brucella was tested in thymidine-uptake assays, using long-term cultured lymphocytes and freshly obtained blood mononuclear cells. Lymphocytes were taken from cows that had been challenge exposed with a virulent strain of B abortus at midgestation. The cows were classified retrospectively as being naturally resistant or susceptible to brucellosis. Lymphocytes taken from these cows had 3 patterns of reactivity with species of Brucella: pattern 1 was defined by reactivity with 4 species (B abortus, B canis, B suis, and B melitensis); pattern 2 was defined by reactivity with all these species, except B melitensis; pattern 3 was defined by reactivity with B abortus and B canis, but not with B suis or B melitensis. There was a statistically significant correlation between susceptibility to brucellosis and expression of lymphocyte cross-reactivity with B suis (P < 0.01) and with B melitensis (P < 0.001).

A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP after treatment with thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that thelambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected.

Absorption rate and plasma and fat disposition oflindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 microgram/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 microgram/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 microgram/g (ie, lower than the generally accepted tolerance level of 2 microgram/g).

Eight adult female cattle (6 Holstein, 1 Jersey, 1 Brown Swiss) were used to determine the antagonistic effects of tolazoline, an alpha 2-adrenoceptor antagonist, on xylazine-induced (via caudal epidural administration) depression of CNS, respiratory, and cardiovascular activity and rumen motility. A 2% solution of xylazine HCl was injected into the epidural space at the first coccygeal interspace, using a dosage of 0.05 mg/kg of body weight, diluted to a 5-ml volume with sterile water, and administered at a rate of approximately 1 ml/30 s. Eight minutes after xylazine injection, either tolazoline (0.3 mg/kg) or saline solution (4 ml) was administered IV. All 8 cattle were treated, using both regimens in a random sequence; at least 1 week elapsed between treatments. Epidurally administered xylazine induced caudal analgesia (S3 to coccyx), as evaluated by no response to superficial and deep muscular pinprick, and induced sedation, cardiopulmonary depression, and inhibition of rumen motility, but all cattle remained standing. Tolazoline effectively reversed xylazine-induced rumen hypomotility, and partially antagonized xylazine-induced cardiopulmonary depression without affecting sedation and desirable local (S3 to coccyx) analgesic effects.