The disposition of doxycycline hyclate after IV administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (+/- SEM) total body clearance was 1.67 +/- 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 +/- 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 +/- 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.

The vascular permeability of the ocular fundus, alterations in the coagulation system, and plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in dogs following intradermal inoculation with 5 x 10(5) TCID50 of Rickettsia rickettsii. Twenty-four to 48 hours after the onset of fever and rickettsemia, multifocal areas of retinal vasculitis were evident, which corresponded to areas of altered vascular permeability demonstrated by fluorescein angiography. The number and intensity of retinal vessels with sodium fluorescein leakage peaked during the second week after inoculation, and retinal vascular permeability remained altered during the third week of infection, well past the phase of clinical and clinicopathologic recovery. Development of retinal vasculitic foci was associated with thrombocytopenia, increased concentrations of circulating fibrinogen, and slight prolongation of activated partial thromboplastin time. Increased concentrations of fibrin/fibrinogen degradation products were detected in 4 of 9 dogs. Despite the degree of vascular endothelial damage evident on fluorescein angiographic and histologic studies in these dogs, plasma TXB2 and 6-keto-PGF1 alpha concentrations were not increased.

The relative myocardial irritant properties of halothane, isoflurane, and pentobarbital were evaluated in chickens. Sixteen adult male broiler chickens were randomly assigned to 1 of 3 groups: group-1 chickens were anesthetized with pentobarbital (30 mg/kg, IV), group-2 chickens were anesthetized with halothane (end tidal halothane 1.2%), and group-3 chickens were anesthetized with isoflurane (end tidal isoflurane 2.1%). Birds in any 2 of the 3 treatment groups were tested on any 1 day. Local anesthesia was induced, and blood pressure, heart rate, ECG, and blood gas variables were measured before general anesthesia was induced. Positive-pressure ventilation with an inspired O2 fraction > 0.95 was adjusted to result in an end tidal CO2 concentration that reflected a PaCO2 similar to that obtained prior to anesthesia and ventilation. All measurements were repeated. The threshold for ventricular fibrillation in response to electrical stimulation of the heart was then determined for all birds. Effects of anesthesia on hemodynamic and blood gas variables were similar in all 3 groups. Compared with halothane or pentobarbital, isoflurane anesthesia resulted in a significantly (P < 0.05) lower threshold for electrical fibrillation of the heart.

The in vitro antimicrobial activities of aditoprim (AP), a new dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (MIC) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia. All B bronchiseptica strains were resistant to AP and TMP. The MIC50 values of AP and TMP for P multocida were 0.25 and 0.06 microgram/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 microgram/ml, respectively. The MIC50, values of SDM and SDM for B bronchiseptica were 4 and 1 microgram/ml, respectively; for P multocida, 16 and 8 microgram/ml, respectively; and for A pleuropneumoniae, 16 and 8 microgram/ml, respectively. The investigated combinations of the DHFR inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the MIC90 values of the combinations were less than or equal to 0.06 microgram/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The MIC of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the DHFR inhibitors in the combinations. For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type-9 strains to AP and TMP as well as to SDM and SMX (at least a fourfold difference in MIC between the 2 types of strains). The MIC of the combinations were similar for the 2 types of strains.

The pharmacokinetics of pipemidic acid after 2 single doses were studied in broiler chickens. Chickens were given single IV and oral doses of 10 and 30 mg of pipemidic acid/kg of body weight. Blood samples were collected over 8 hours after each dose administration. High-pressure liquid chromatography with UV detection was used to determine concentrations in plasma of pipemidic acid. The plasma concentration-time curves after IV administration followed 2-compartment characteristics, rapid initial distribution phase, and a terminal elimination phase. The pharmacokinetic variables differed significantly between single doses of 10 and 30 mg of pipemidic acid/kg. Mean disposition variables were a half-life at beta phase of 0.06 hours or 0.33 hours, a half-life at beta phase of 1.18 hours or 1.72 hours, a volume of distribution in the central compartment of 0.12 L/kg or 0.31 L/kg, a volume of distribution during the elimination beta phase of 1.64 L/kg or 1.05 L/kg, and a total plasma clearance of 0.97 L/h.kg or 0.41 L/h.kg, for the 10 or 30 mg/kg dose, respectively. After oral administration, the pipemidic acid plasma profile could be adequately described by a 1-compartment model. After the single oral doses of 10 and 30 mg of pipemidic acid/kg, pipemidic acid was absorbed rapidly (time to maximal concentration of 0.31 hours or 0.71 hours) and eliminated with a mean half-life of 0.86 hours or 0.61 hours, respectively. The bioavailability was 39% at 10 mg of pipemidic acid/kg and 61% at 30 mg of pipemidic acid/kg.

A commercially available microbiological identification system and DNA:DNA hybridization were used to determine relationships between and within serovars 1-13 of Pasteurella haemolytica, and between P haemolytica and P multocida and 4 species of Actinobacillus. All serovars of P haemolytica that belonged to biovar A were related with mean DNA homology of 78%, whereas all serovars of P haemolytica that belonged to biovar T were related to each other with mean DNA homology of 90%. The DNA:DNA hybridization between strains of biovars A and T ranged from 3 to 13%, indicating little or no genetic relationship between the 2 biovars of P haemolytica. The DNA homology between all serovars of P haemolytica and other species of non-P haemolytica bacteria tested (P multocida and actinobacilli) was < 14%, suggestive of essentially no genetic relationship of P haemolytica with the ATCC reference strains of the genus Pasteurella or the genus Actinobacillus. Enzymatic differences were observed between P haemolytica and the other non-P haemolytica bacteria tested; however, the microbiological identification system that uses enzymatic reactions could not distinguish among biovars of P haemolytica. Results of this research support other data that suggest that biovars A and T of P haemolytica should be classified as separate species, but do not support the inclusion of either biovar A or T within the genus Actinobacillus.

Four virgin heifers were experimentally inoculated intravaginally with 7 X 10(6) Tritrichomonas foetus, and 2 heifers served as uninfected controls. The durations of infection were 13, 20, 21, and 28 weeks, respectively. An ELISA that used whole T foetus antigen was used to detect anti-T foetus immunoglobulins (IgA, IgG1, IgG2, and IgM) in vaginal, cervical, and uterine secretions, and sera during the course of infection. The vaginal and cervical antibody responses were characterized by significantly increased T foetus-specific IgA and IgG1 at 7 to 9 weeks of infection, whereas uterine IgA and IgG1 responses peaked at 10 to 12 weeks. The antibody response in serum was predominantly of the IgG1 and IgG2 subclasses. In all reproductive tract regions, IgA persisted at least until the time of T foetus clearance, and usually longer. The next most persistent isotype was IgG1, lasting longest in the vagina, then cervix, and for the shortest time in the uterus. In local secretions, IgG2 was seen only transiently, increasing at weeks 13 to 15 in the vagina, and at weeks 10 to 12 in the cervix. Little IgM, relative to that present before infection, was detected in any secretion or serum, although cervical secretions had the greatest amount. Eight to 12 weeks after clearance, the 4 experimental heifers were inoculated intravaginally with 1 x 10(5) T foetus, transient infections (2 to 3 weeks' duration) were established in only 2 of 4 heifers, as determined by culturing of reproductive tract secretions. The lag times of antibody responses during this reinfection were shorter than in the initial infection, and ELISA optical densities were at least as high as during the primary infection, suggesting an anamnestic response.

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.

Streptococcal species isolated from dairy cows with clinical mastitis were obtained from mastitis research workers in Florida, Louisiana, New York, Vermont, Washington, and West Virginia. Seventy-one streptococcal isolates were tested, including 39 strains of Streptococcus agalactiae, 21 strains of S dysgalactiae, and 11 strains of S uberis. The minimal inhibitory concentration of erythromycin, lincomycin, oxytetracycline, penicillin, spectinomycin, streptomycin, and tetracycline was determined for each isolate. Differences were not detected among strains with respect to geographic origin. None of the strains was resistant to penicillin. Lincomycin was the next most effective antimicrobial, with only 2 resistant strains of each streptococcal species. There were no differences among the streptococcal species with respect to resistance to either penicillin or lincomycin. Streptococcus uberis was more likely to be resistant to erythromycin than were S agalactiae and S dysgalactiae (P < 0.02). Streptococcus agalactiae and S uberis had similar distributions for resistance to oxytetracycline, tetracycline, spectinomycin, and streptomycin. Strains of S dysgalactiae were more likely to have intermediate resistance to oxytetracycline and streptomycin than were strains of S agalactiae and S uberis, which were highly resistant to oxytetracycline and streptomycin (P < 0.001). Differences were not detected among the streptococcal species with respect to resistance to spectinomycin. Resistance to multiple antimicrobials was observed in all streptococcal species tested. Although S dysgalactiae appeared to have a greater percentage of strains (73%) that were resistant to multiple antimicrobials than did S agalactiae (31%) or S uberis (45%), differences were not statistically significant.

Data at admission and at surgery were collected on 458 cows with right displacement of the abomasum or abomasal volvulus, to derive multiple logistic regression models for predicting postsurgical outcome (productive, salvaged, or terminal). The derived models contained few and easily obtained variables. The weight associated with each variable was determined objectively. Three admission variables (heart rate, base excess, and plasma chloride concentration), and 5 surgical variables (heart rate, base excess, diagnosis, method of decompression used, and appearance of abomasal serosa) were used in the final models. Predicted outcomes that used the admission and surgical models were closely related with actual outcomes. Total correct classification for satisfactory (productive) versus unsatisfactory outcome (salvaged and terminal) was 78.2% for the admission model and 82.7% for the surgical model. Combining data on cows with productive and salvaged outcomes as satisfactory outcome, and terminal as unsatisfactory outcome, total correct classification was 90.7% for the admission model and 93.2% for the surgical model. Using predicted probabilities, the market value of productive and salvaged cows, and the medical and surgical costs, one can calculate the expected economic value of each outcome. Treatment can be justified if the sum of the expected value of productive and salvaged outcome exceeds the sum of the medical and surgical costs and the expected salvaged value of the cow that was not treated surgically.