Renal clearance procedures were performed on adult mixed-breed dogs with a wide range of renal function. Endogenous creatinine clearance was computed after analyzing plasma and urine for creatinine by use of 2 methods, PAP and kinetic Jaffe. For 20-minute clearance procedures, [14C]inulin clearance was measured simultaneously with endogenous creatinine clearance. For 111 twenty-minute clearance procedures performed on 24 dogs, [14C]inulin clearance was highly correlated with creatinine clearance for both methods of creatinine analysis (R2 = 0.979 for [14C]inulin-PAP; R2 = 0.943 for [14C]inulin-Jaffe). The absolute values for PAP and [14C]inulin clearance were nearly the same (PAP-to-[14C]inulin clearance ratio = 1.03 +/- 0.08), but those for Jaffe clearance were substantially less than those for [14C] inulin clearance Jaffe-to-[14C]inulin clearance ratio = 0.88 +/- 0.10). The Jaffe-to-[14C] inulin clearance ratio was inversely correlated with degree of renal function (R2 = 0.464), whereas the PAP-to-[14C]inulin clearance ratio was not correlated with degree of renal function (R2 = 0.060). Thus, Jaffe-determined creatinine clearance varied, in relation to [14C] inulin clearance, depending on degree of renal function. In 4 clinically normal dogs, 20-minute and 24-hour sample collections analyzed by use of the PAP method gave clearance values significantly greater, for both periods, than did Jaffe analyses. The PAP-determined creatinine clearance values were less than, but not significantly different from 20-minute exogenous creatinine clearance values determined 10 days after 24-hour collections. For 20-minute and 24-hour collections, the difference in clearance values between the PAP and Jaffe methods was attributable mostly to lower plasma creatinine values for the PAP method (mean +/- SEM, plasma PAP-to-Jaffe ratio = 0.798 +/- 0.053). However, urine creatinine values also were less by use of the PAP method (urine PAP-to-Jaffe ratio = 0.943 +/- 0.103). We conclude that PAP-determined creatinine clearance reliably measured glomerular filtration rate during 20-minute collections, and probably during 24-hour collections as well. By contrast, Jaffe-determined creatinine clearance underestimated glomerular filtration rate by a variable amount.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.

Accumulation of D-xylose by jejunal mucosa from healthy horses and rabbits was studied in Vitro. When tissue sheets were incubated with 1 mM D-xylose for 60 minutes, mucosa from horses and rabbits accumulated D-xylose against a concentration gradient. There was no accumulation when equine specimens were incubated with 5 mM D-xylose. By comparison, equine jejunum accumulated D-glucose against a concentration gradient when incubated in 5 mM D-xylose glucose. In equine and rabbit jejunum, 13.3 +/- 7.0% and 36 +/- 11.0%, respectively, of accumulated D-xylose was phosphorylated when sheets were incubated in 1 mM D-xylose. Short-circuit current and potential difference were lower in equine jejunum than in rabbit jejunum, possibly because of differences in tissue thickness. None of the transmucosal electrical measurements increased after addition of D-xylose (1 mM and 5 mM) or D-glucose (5 mM). The active transport system for D-xylose has a low affinity for this sugar and becomes saturated at low intraluminal concentrations. Therefore, abnormal D-xylose absorption test results in horses are more likely caused by abnormalities in mucosal surface area and mucosal permeability than by abnormalities of nutrient carbohydrate absorption.

The severity of pulmonary thromboembolism and pulmonary hypertension induced by heartworms dying after administration of 2 adulticides was evaluated. Because melarsomine dihydrochloride (RM340) has been shown to be more effective in killing Dirofilaria immitis (heartworms) than the traditional approved adulticide, thiacetarsamide, an attempt was made to determine whether this new adulticide induced more severe lung disease. Before adulticide treatment, 32 dogs with naturally acquired heartworm infections received physical examinations, semiquantitative antigen concentration tests, CBC, platelet counts, serum biochemistry analyses, arterial blood gas determinations, thoracic radiography, pulmonary arteriography, and pulmonary hemodynamic tests. Eight dogs with a low burden and 9 dogs with a high burden of heartworms were treated with thiacetarsamide, and 7 dogs with a low burden and 8 dogs with a high burden were treated with RM340. Except for the heartworm-burden test, tests were repeated at regular intervals during the first 7 weeks after treatment. None of the dogs coughed or had dyspnea after treatment. Six of 9 dogs with high worm burdens and 4 of 8 dogs with low worm burdens had surviving heartworms after thiacetarsamide treatment, in contrast to only 3 of 15 RM340-treated dogs. Differences between the 2 adulticide treatments were minimal as determined by thoracic radiography, pulmonary hemodynamic tests, clinical laboratory analyses, pulmonary arteriography, or necropsy. The RM340 treatment was a more effective adulticide, but it did not increase the severity of hypertension and thromboembolism.

Thirty young ponies were examined endoscopically for evidence of gastric ulceration. Seven ponies had noninduced gastric ulcers present at the initial examination and were eliminated from the study. In an attempt to induce gastric ulcers experimentally, flunixin meglumine (1.1 mg/kg of body weight, IM, q 8 h) was administered for 7 days to the 23 ponies with endoscopically normal gastric mucosa. During the 7 days of flunixin administration, 11 ponies developed gastric ulcers that were appropriate for study. The 11 ponies were randomly allotted to 2 groups. Group-A (n = 5) and group-B (n = 6) ponies received ranitidine (4.4 mg/kg, PO, q 8 h) and corn syrup, respectively, until ulcers healed or for a maximum of 40 days. General anesthesia was induced every 3 to 5 days for visual evaluation of ulcer healing by use of a video endoscope. The earliest complete healing of gastric lesions observed in a corn syrup-treated pony was at 17 days. At 40 days, 3 of 5 and 3 of 6 ponies of the ranitidine and corn syrup-treated groups, respectively, had healed ulcers. Results of this study indicate that: noninduced gastric ulcers may be common in young ponies, flunixin meglumine may be effective in inducing gastric ulcers for gastric healing studies in young ponies, and ranitidine (4.4 mg/kg, q 8 h) is not significantly effective in accelerating healing of experimentally induced gastric ulcers in ponies under conditions of this study.

Stimulatory effects of 6 zymosan preparations on luminol-dependent chemiluminescence (CL) responses of isolated bovine neutrophils were compared. Unopsonized zymosan particles and zymosan particles opsonized with bovine IgG1, IgG2, fresh serum, or serum from which zymosan-specific antibodies, but not complement, had been removed (C3- serum) induced strong CL responses, with nearly equal maximal peaks in the presence of extracellular Ca2+ and Mg2+, whereas the response to fetal bovine serumopsonized zymosan particles was markedly low. Removal of extracellular divalent cations almost completely blocked the CL reaction triggered by unopsonized, IgG1-opsonized, C3-opsonized, and fetal bovine serum-opsonized zymosan particles. By contrast, no change in the respiratory burst activity induced by serum-opsonized zymosan and only partial reduction in the response to IgG2-opsonized zymosan were seen under these conditions. Further experiments were performed with 4 zymosan preparations on neutrophils isolated from 2 calves with a genetic deficiency of CD11/CD18 membrane antigens. The unopsonized zymosan-induced CL reaction was absent in these cells. A reduced, but clear, response was observed with C3-opsonized zymosan. Unexpectedly, in the absence of extracellular Ca2+ and Mg2+ , serum-opsonized zymosan failed to generate the respiratory burst, whereas response to IgG2-opsonized zymosan was normal in the CDll/CD18-deficient neutrophils. These findings indicate that unopsonized zymosan may act in a divalent cation-dependent manner at the receptor for C3bi in bovine neutrophils, as it has been shown to do in the human system. In addition, it seems that IgG2-Fc receptors capable of signaling the respiratory burst in the absence of extracellular Ca2+ and Mg2+ exist on bovine neutrophils.

The effects of preanesthetic medication on ease of duodenal endoscopic intubation in dogs was evaluated. One of 12 combinations of preanesthetic medications (using atropine, glycopyrrolate, morphine, meperidine, acepromazine, and 0.9% NaCl solution) was administered IM to each of 12 dogs in a trial. Twelve endoscopic trials were performed so that each dog received each treatment combination once. Anesthesia was induced with thiamylal administered IV and maintained with halothane vaporized in oxygen. Electrocardiographic recordings, indirect blood pressure measurements, end-tidal carbon dioxide partial pressures, and halothane concentrations were monitored during the anesthetic period. The ease with which the fiberoptic endoscope was passed into the proximal portion of the duodenum was qualitatively scored on the basis of time and maneuvering effort. None of the preanesthetic combinations made intubation of the duodenum significantly easier than that with 0.9% Nacl solution (control). Only the combination of morphine and atropine induced gastropyloric conditions that resulted in significantly higher (more difficult) endoscopic scores than those after preanesthetic medication with 0.9% NaCl solution.

Intragastric pH monitoring was investigated in ponies. In cadaver stomachs, close contact with the mucosa led to high pH readings if nonweighted electrodes were used. However, pH recorded by weighted electrodes was markedly less affected by mucosal contact (P < 0.001). The latter were used for subsequent trials. In vivo, high correlations were found between pH recorded by weighted electrodes with or without a wire guard to prevent mucosal contact (correlation, r = 0.866; P < 0.001). Readings from each correlated well with those from simultaneous gastric aspirates (r = 0.774 and r = 0.807, respectively; P < 0.001 for both correlations). Plain electrodes recorded more highly variable (temporally heterogeneous) pH than did guarded electrodes. In vitro, trials using equine gastric fluid indicated that this resulted from greater responsiveness of the plain electrode. In vivo, episodes of nearly neutral pH were a common feature, and high pH correlated with intensely yellow-green, neutral fluid in the stomach (rank correlation, p = 0.626; P < 0.01). Concentration of bile acids did not correlate with pH or color score (p = -0.158 and p = 0.076, respectively). Causes of the episodes could include salivary influx, duodenogastric reflux, and variable gastric acid secretion. Pentagastrin infusion (0.6 micrograms/kg of body weight/ h) reduced intragastric pH (P = 0.018), but episodes of neutrality still occurred. Experiments in fed ponies indicated possible existence of a stable pH gradient, from neutral dorsally to heterogeneous and more acidic ventrally. Care was required in the rational choice of summary variables for expression of monitored pH data. Of the frequency distributions of 3 summary variables assessed in this study (mean, median, and percentage of data > pH 4), only that of the mean approached normality. Thus, use of the mean may allow analysis by parametric statistical methods. Intragastric pH monitoring was found to be a useful technique. Episodes of increased pH were often identified. These may represent episodic duodenogastric reflux.

Bordetella avium is an important respiratory tract pathogen of turkeys. In common with other pathogenic bordetellae, B avium manifests a tissue tropism for cilia of the respiratory tract epithelium. To determine the molecular characteristics of the host cell receptors for B avium, we used hemagglutination and in vivo adherence assays. Carbohydrates, mucus, sialic acid-specific lectin, and other glycoconjugates were evaluated for their ability to competitively inhibit binding of B avium to host cells. The gangliosides, GD(1a) and GT(1b), completely inhibited hemagglutination, whereas N-acetylneuraminic acid (sialic acid) partially inhibited hemagglutination. Adherence to turkey tracheal mucosa in vivo was significantly (P < 0.01) inhibited by GD(1a) and GT(1b) gangliosides, N-acetylneuraminic acid, bovine sub-maxillary mucin, and horseshoe crab (Limulus polyphemus) lectin. Treatment of the tracheal mucosa with neuraminidase also inhibited adherence of B avium. We conclude that N-acetylneuraminic acid and the gangliosides, GD(1a) and GT(1b) may be important components of the tracheal mucosa receptor for B avium in turkeys.

Procedures were developed to count neutrophils in milk using a flow cytometer. Milk samples from 2 experiments were counted: 1 with 4 noninfected cows and a second with 5 noninfected cows that were injected with endotoxin in 2 mammary quarters. Thus, the procedures were evaluated on normal milk and on that with high somatic cell count. Flow cytometric procedures involved fluorescence detection (from the dye carboxydimethylfluorescein diacetate) to distinguish intact and viable from fragmented cells, forward light scatter to detect cell size differences, and right-angle side scatter to detect cellular granularity. High fluorescence, large size, and high degree of granularity identified viable neutrophils. For all samples, neutrophils were also counted manually, using the cytologic centrifugation approach to create the slides; manual counts were used as the standard for comparison. In experiment 1 (normal milk), mean values for percentage of viable neutrophils estimated by manual and flow cytometry procedures agreed closely (26% vs 25.8% for foremilk and 28.8% vs 26.6% for bucket milk). Sources of variation in manual and flow cytometric estimates of percentage of neutrophils were examined. Cow variation was significant (P < 0.01) for manual and flow cytometric counts, but was larger for flow cytometric counts. Day-to-day variation in counts on milk from the same cow was negligible for manual counts, but was significant (P < 0.01) for flow cytometric counts. Coefficients of variation were considerably Larger for manual counts than for flow cytometry. In experiment 2 (milk with high cell count, foremilk), agreement between mean values obtained by flow cytometry and by manual counting was somewhat less. However, predicting manual percentage of neutrophils, using the flow cytometric estimate, had R2 of 0.77. Regression of the manual percentage of neutrophils value on the flow cytometric percentage of neutrophil value was close to 1.0, with only a small negative intercept. Some additional refinement of flow cytometric procedures may be required before flow cytometric estimates of percentage of neutrophils can be accepted without simultaneous validation by use of manual counting. In particular, causes of day-to-day variation in flow cytometric results should be identified and reduced.