The efficacy of 4-methylpyrazole (4-MP) and ethanol as treatment for ethylene glycol (EG) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4-MP; those of another experimental group were given only EG. Cats of 3 experimental groups were intoxicated with EG and given 4-MP at 0 hour or 2 or 3 hours after EG ingestion, and those of 1 experimental group were given EG and treated with ethanol 3 hours after EG ingestion. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after EG ingestion, or 4-MP treatment in cats of the 4-MP only group. The half-life of EG and percentage of ingested EG excreted unchanged were determined for each group. 4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of EG. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after EG ingestion. Ethanol given 3 hours after EG ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after EG ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized. 4-Methylpyrazol given 2 or 3 hours after EG ingestion was less effective in preventing EG metabolism than was ethanol given 3 hours after EG ingestion. Therefore 4-MP, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of EG intoxication in cats.

Tidal breathing flow-volume (TBFV) loops were determined in a group of control horses and in horses affected with recurrent airway obstruction (heaves). The latter group was studied when the condition was in remission and under increasing amounts of airway obstruction as reflected by measurements of change in pleural pressure, pulmonary resistance, and dynamic compliance. The TBFV loops of control horses had biphasic inspiratory and expiratory patterns; peak inspiratory and peak expiratory flows were detected early in inspiration and expiration, respectively. Tidal volume was unaffected by heaves, but at all stages of heaves, respiratory frequency was increased principally because of shorter inspiratory time, and therefore, inspiratory flow rate was increased. In horses with heaves, TBFV loops did not have a biphasic pattern; peak inspiratory flow was observed late in inspiration, and peak expiratory flow was observed early in expiration. As airway obstruction became more severe, peak expiratory flow increased as pulmonary resistance increased so that, during severe airway obstruction, TBFV loops had a characteristic appearance with high peak expiratory flow early in expiration followed by low flow rate.

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m(2) of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was most strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.

The effect of right paralumbar fossa exploratory celiotomy and omentopexy on peritoneal fluid constituents was studied in 22 adult dairy cows. Six cows were eliminated on the basis of physical examination findings (n = 2), surgical findings (n = 2), or inability to obtain a sufficient volume of peritoneal fluid (n = 2). Sixteen cattle had normal results of Csc and serum biochemical analysis, and a minimum of 1 ml of peritoneal fluid was obtained by abdominocentesis. Abdominocentesis was repeated on days 1, 2, and 6 after surgery. Statistical analysis for repeated measures was performed, using a significance level of P < 0.05. Stage of gestation was evaluated for interaction with time. Mean total nucleated cell count was 3,200 cells/1 before surgery, was significantly increased 2 days after surgery (16,336 cells/microliter), and continued to increase through day 6 (20,542 cells/microliter). Mean polymorphonuclear cell count was 1,312 cells/microliter before surgery and was significantly higher at 2 (11,043 cells/microliter) and 6 (10,619 cells/microliter) days after surgery. Mean lymphocyte count was 254 cells/microliter before surgery and was significantly increased 2 days (1,911 cells/microliter) after surgery. By day 6, lymphocyte numbers were similar to preoperative values. Mean mononuclear cell count was 770 cells/microliter before surgery and was significantly increased on days 1 (3,084 cells/microliter), 2 (3,285 cells/microliter and 6 (2,349 cells/microliter) after surgery. Mean eosinophil numbers were 1,388 cells/microliter before surgery and were significantly increased on day 6 (6,347 cells/microliter) only. Interaction between time and stage of gestation was found only for specific gravity and total protein concentration. In general, specific gravity and total protein concentration increased after surgery (mean before surgery, 1.016 and 3.6 g/dl; mean after surgery, 1.021 and 5.6 g/dl).

Serial sections of bone and soft tissue from the metacarpophalangeal joints of 2 mature and 2 immature horses were evaluated for substance P immunoreactive sensory nerve fibers. Formalin-fixed specimens were sectioned, either nondemineralized or demineralized with formic acid or EDTA. Rabbit antiserum to substance P (SP) was used in the strep. tavidin-biotin-peraxidase complex method for immunolocalization of SP antigen, and staining with 3,3'- diaminobenzidine was used for permanent identification of SP fibers. Abundant sensory nerve fibers were identified in the joint capsule, synovial membrane subintimal layers, collateral ligaments, suspensory ligament and distal sesamoidean ligament attachments to the sesamoid bones, and the periarticular periosteal layers. Sparse SP-immunoreactive nerve fibers were found in subchondral bone plates of the metacarpus, proximal first phalanx, and dorsal articular surface of the sesamoid bones. Most SP fibers were associated with blood vessels in the small cancellous spaces and haversian canals of the subchondral bone. The deeper marrow spaces contained increased numbers of SP sensory fibers; a few appeared in small groups and as several SP-immunoreactive fibers in a larger nerve. Cortical bone contained only a few SP fibers in the haversian canals. Substance P fibers were not identified in the osteocytic lacunae, canaliculi, or the bony lamellae of the haversian systems of the subchondral bone plate, and its extension to the metaphyseal and diaphyseal cortical bone. Equine metacarpophalangeal joint soft tissues have an abundant sensory nerve supply, similar to that of other species. However, the subchondral bone plate also has sparse sensory nerve fibers, which is a unique finding, and may help explain signs of bone pain associated with disease states of the fetlock.

The size and shape of the foramen magnum were studied in skulls from 75 adult and 5 juvenile Pekingese dogs. After maceration of the skulls, the height, width, and area of each foramen magnum were measured, and various skull indices were determined. The shape of the foramen varied from ovoid to rectangular and had a dorsal notch in aU but 2 skulls. Prolapse of cerebellum or brain stem through the enlarged opening was prevented by a fibrous membrane covering he dorsal notch. Mean +/- SD area of the foramen was 138.1 +/- 26.1 mm(2); its mean total height was 15.0 +/- 2.9 mm, and its mean maximal width was 13.3 +/- 1.1 mm. Statistically, variability in the area of the foramen was mainly correlated with total height of the foramen, including the dorsal notch. Total height of the foramen was not correlated with age or gender. The degree of dysplasia, notch index, and occipital index of each foramen magnum were determined. To allow a more accurate evaluation of the morphology of the foramen, the foramen magnum index, defined as the ratio between the maximal width and the total height of the foramen, was also computed. Mean +/- SD foramen magnum index was 91.8 +/- 17.1 in the adult Pekingese dogs. Foramen magnum index was not significantly correlated with age, but was significantly larger in male than in female dogs. The large variability in the shape and size of the foramen magnum and the absence of any neurologic problems in dogs of this study indicate that the dorsal notch of the foramen magnum in brachycephalic dogs is a normal morphologic variation, rather than a pathologic condition.

Polymorphonuclear neutrophils (PMN) from 4 cows were preincubated (30 minutes, 37 C) in either actinomycin D (100 micrograms/ml) or puromycin (10 micrograms/ml), inhibitors of mRNA transcription and protein translation, or in medium 199. The PMN were incubated for a further 4.5 hours in medium containing 100 U of recombinant bovine interferon-gamma (rboIfn-gamma). The PMN were then incubated with bovine IgG1, IgG2, IgM, or aggregated IgG (aIgG; 4 C, 12 hours) for flow cytometric analysis, using fluoresceinated isotype-specific antibody. The percentage of PMN binding the ligand and the logarithmic mean fluorescent channel (LMFC), an indicator of the amount of receptor (R) expression, were recorded. Competitive inhibition of ligand binding was measured by incubating PMN with fluoresceinated IgG2 in the presence or absence of 100-fold excess of IgG1, IgG2, and aIgG. Activation with rboIfn-gamma induced a 4.5-fold increase in binding of IgG1 and a fivefold increase in LMFC for IgG2. These increases were inhibited by actinomycin D and puromycin. Percentage of PMN binding aIgG decreased after activation by rboIfn-gamma. Interferon-gamma treatment did not affect binding or LMFC of IgM. However, binding of IgM was reduced by treatment with actinomycin D. Binding of fluoresceinated IgG2 was inhibited by unlabeled IgG1, IgG2, and aIgG. Results indicate that bovine PMN Fc receptors (FcR) for IgG1 and IgG2 were rboIfn-gamma inducible, that induction required de novo transcription and translation, that a heterogeneous population of FcR exist on bovine PMN, and that IgG1 and IgG2 share a common FcR. Further, bovine PMN are capable of gene activation and are responsive to changes in their environment, thus being amenable to modulation for effective pathogen destruction.

A relation exists between colloid osmotic pressure and serum total protein concentration; equations describing this relation have been used to determine a calculated value for colloid osmotic pressure. However, the relation between total protein concentration and colloid osmotic pressure is altered by the method used to measure protein and by changes in the ratio of concentrations of albumin (A) to globulin (G). We developed nomograms for estimating colloid osmotic pressure from A and G concentrations, using samples obtained from clinically normal animals and compared the accuracy of these nomograms with that of previously described equations relating colloid osmotic pressure to total protein concentration. For comparison, serum samples from canine (n = 106), equine (n = 79), feline (n = 24), and bovine (n = 27) patients admitted to the University of Georgia Veterinary Medical Teaching Hospital were used. Results indicated that nomograms based on protein concentration estimated by a refractometer generally were the least reliable. Although predictive nomograms, using total protein concentration determined by the biuret method, provided better results for serum samples, there was considerable variation between measured and calculated values for colloid osmotic pressure in all species studied. Calculated values for colloid osmotic pressure derived from A and G concentrations were most closely related to measured values for colloid osmotic pressure in dogs, horses, and cats. However, calculated values for colloid osmotic pressure differed from measured values by as much as 5 mm of Hg for some samples by each of the methods of estimation. These results indicate that, although calculated values for colloid osmotic pressure may be most accurate when variations in the A-to-G ratio are accounted for in the nomogram, none of the calculation methods provided a consistently accurate estimate of colloid osmotic pressure.

Pharmacokinetic variables of skeletal muscle creatine kinase (CK) activity after IV administration of a muscle extract; CK bioavailability after IM administration of the muscle extract; and effect of IM administration of saline solution, to appreciate the possible release of CK consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived. Administration of saline solution IM had no effect on plasma CK activity (ANOVA, P > 0.05) in any of the cows. After IV administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of CK were 0.027 +/- 0.007 L/kg, 520 +/- 109 minutes, and 6.43 +/- 2.29 ml/kg/h, respectively. After IM administration (150 U/kg), mean bioavailability of CK was 51 +/- 17% and maximal plasma CK activity (500 +/- 97 U/L) was observed at 454 +/- 131 minutes. The rate of CK activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after IM administration, and the second appeared at 3.3 +/- 1.1 hours. Amplitudes were 6.31 +/- 4.45 and 6.57 +/- 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of CK liberated from control muscle was 0.69 +/- 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 +/- 1.0 mg of muscle/kg. From these results, the following equation can be proposed to determine the corresponding mean equivalent of destroyed muscle (Qmuscle, test article) after IM administration of a test article: Qmuscle, test article (g/kg) = 4.41 X 10(-6) AUC (U/h/L), with AUC being the CK plasma activity area under the curve.

During the hunting season of 1992, 322 black bears from Pennsylvania were examined for Toxoplasma gondii- and Trichinella spp-induced infections. Toxoplasma gondii antibodies were found in 79.8% of 322 bears--titer < 1:25 in 65 (20.2%), 1:25 in 18 (5.6%), 1:50 in 11 (34.5%) and 1:500 in 128 (38.7%) bears--by use of the modified agglutination test. Muscle tissues from 89 of these bears were bioassayed for T gondii parasites. Muscles from 64 bears, including heart from 1 bear, and heart alone from another bear, were digested in pepsin, and the digested samples were bioassayed in mice. Toxoplasma gondii was isolated from 5 bears; from the heart of 1, heart and skeletal muscles of 1, and skeletal muscles of 3. The T gondii antibody titers for the 5 bears with detectable T gondii were: greater than or equal to 1:25 in all 5 bears by use of the modified agglutination test; < 1:10 (3 bears, considered Toxoplasma-negative), 1:20 and 1:320 by use of the Sabin-Feldman dye test; < 1:64 (3 bears, considered Toxoplasma-negative), 1:128, 1:512 by use of the indirect hemagglutination test, and < 1:16 (2 bears, considered Toxoplasma-negative), 1:32, 1:64, and 1:512 by use of the latex agglutination test. Toxoplasma gondii was not isolated from feces of 5 cats fed muscles from the remaining 25 bears with T gondii antibody titer < 1:25. Tissue cysts of the 4 T gondii isolates from bears were rendered noninfective by freezing at -13 C. Antibodies against Trichinella spp were found in 6 (1.8%) of 319 bear sera; Trichinella spp larvae were detected in muscle digests of 2 of 63 bears, and in histologic sections of muscles from 3 of 162 bears. Genetic typing indicated that the 2 Trichinella isolates from bears were a sylvatic genotype and were not the species found in domestic pigs.