A challenge-exposure model was developed for dose-dependent induction of subclinical (moderate) atrophic rhinitis (AR) in conventionally raised Dutch Landrace and Large White pigs, about 4 weeks old. Under favorable climatic and housing conditions, pigs were intranasally challenge-exposed with Pasteurella multocida-derived toxin (Pm-T) 3 days after pretreatment by inoculation with 1% acetic acid. Pigs were challenge-exposed with 1 of the following Pm-T doses: 0 (control), 5, 13, 20, or 40 microgram of Pm-T/ml of phosphate-buffered saline solution (PBSS), 0.5 ml/ nostril/d on 3 consecutive days. Five weeks after challenge exposure, subclinical moderate) AR status was defined as intermediate conchal atrophy (grade 2 for ventral conchae on a 0 to 4 scale and grade 1 or 2 for dorsal conchae on a 0 to 3 scale, respectively) and perceptible difference in change in brachygnathia superior (CBS) between control and challenge-exposed pigs between the beginning and end of the study. All Pm-T-exposed pigs had nasal damage that was dose-dependent. The higher Pm-T doses resulted in higher ventral conchae atrophy and dorsal conchae atrophy scores. The CBS increased with applied Pm-T dose, resulting in significant (P < 0.05) differences between controls (3.88 mm) and the 13-, 20-, and 40-microgram Pm-T-treated groups (7.77, 6.58, and 7.98 mm, respectively). In response to the applied dose, weight gain per week for Pm-T-exposed pigs was lower than that of controls after week 3 (P < 0.01). Difference from controls was 32, 54, 52, and 96 g/d/pig for 5-, 13-, 20-, and 40-microgram Pm-T-treated groups respectively, in the last 2 weeks. For Dutch Landrace and Large White pigs, intranasally administered Pm-T mimicked the pathogenic effect of in vivo infection with toxigenic Pm strains. The optimal model to induce subclinical AR appeared to be 13 microgram of Pm-T/ml (0.5 ml/nostril/d) on 3 consecutive days.

We characterized the clinicopathologic manifestations of experimentally induced endotoxin-induced mastitis. Responses to hypertonic fluid therapy also were assessed. Eight cows received 1 mg of endotoxin by in infusion in the left forequarter. Four hours after endotoxin administration, cows received 0.9% NaCl, 5 ml/kg of body weight (n = 4) or 7.5% NaCl, 5 ml/kg (n = 4) IV. Endotoxin-infused cows had expanded plasma volume, hyponatremia, transient hyperchloremia and hypophosphatemia, increased serum glucose concentration, and decreased serum activities of liver- and muscle-specific enzymes. Calculated plasma volume increased at 6 hours in cows receiving hypertonic NaCl, and at 12, 24, and 48 hours after endotoxin infusion in both groups. Concurrent observations of decreased serum protein concentration, erythrocyte count, and hematocrit supported observations of increased plasma volume. Relative plasma volume was greater in cows receiving hypertonic NaCl (124.3%) than in cows receiving isotonic NaCl (106.6%) at 6 hours after endotoxin infusion. Cattle receiving hypertonic NaCl had increased voluntary water intake after IV fluid administration. Increased water consumption was not accompanied by increased body weight, indicating probable occurrence of offsetting body water loss. Serum sodium concentration in cows receiving hypertonic NaCl was increased 2 hours after fluid administration, but the magnitude of the change was minimal (< 4 mmol/L) and transient, indicating rapid equilibration with either interstitial or intracellular spaces. Serum sodium concentration was decreased in cows receiving isotonic NaCl at 12, 24, and 48 hours after endotoxin administration, compared with concentration prior to endotoxin administration, indicating selective loss of sodium.

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.

4-Methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (EG) intoxication. Eleven dogs were given 10.6 g of EG/kg of body weight; 5 dogs were treated with 4-MP 5 hours after EG ingestion and 6 dogs were treated with 4-MP 8 hours after EG ingestion. 4-Methylpyrazole was administered IV as a 50-mg/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/ kg; at 24 hours after initial dose, 10 mg/kg, and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after EG ingestion. Dogs of both groups developed clinicopathologic signs associated with EG intoxication, including CNS depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after EG ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after EG ingestion that developed acute renal failure. All dogs treated 5 hours after EG ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after EG ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after EG ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment. Of the dogs treated 8 hours after EG ingestion, 3 recovered without morphologic, biochemical, or clinical evidence of renal impairment. Serum half-life of EG was prolonged in the dogs treated 8 hours after EG ingestion. Percentage of EG excreted unchanged was 84 +/- 2% in the dogs treated 5 hours after EG ingestion, and was 40 +/- 10% in the dogs treated 8 hours after EG ingestion. 4-Methylpyrazole was effective in preventing renal failure in all dogs given 10.6 g of EG/kg when treatment was initiated by 5 hours after EG ingestion, and in 4 of 6 dogs when treatment was initiated by 8 hours after EG ingestion.

Hypothyroidism is a possible predisposing factor in a number of disorders of companion psittacine birds. We developed and validated a thyroid-stimulating hormone (TSH) response testing protocol for cockatiels (Nymphicus hollandicus), using 0.1 IU of TSH/bird given IM, with blood sample collection at 0 and 6 hours after TSH, and a commercial radioimmunoassay for thyroxine T4). This protocol was used to document a seasonal sex difference in stimulated T4 values-females responded with higher T4 values than those in males in summer- and a stress-induced depression of baseline T4 values was detected in a group of cockatiels with normal TSH response. An experimental model for mature-onset hypothyroidism in cockatiels was created by radiothyroidectomizing cockatiels with 3.7 MBq (100 microCi) of 131I/bird given IV. Induction of the hypothyroid state was confirmed by baseline T4 concentration, TSH response test results, thyroid pertechnetate scintigraphy, and gross and microscopic examinations. Classical signs of hypothyroidism (eg, hypercholesterolemia, obesity, poor feathering) were lacking or mild at 48 days after thyroid ablation.

A crude, whole-body extract of female or male heartworms was injected IV into 28 dogs with and 22 dogs without heartworm (HW) infection. The female HW extract caused shock in 22 of 24 dogs with and 12 of 20 dogs without HW infection. The male HW extract induced shock in 4 of 4 dogs with and 1 of 2 dogs without HW infection. Prevalence of shock caused by female HW extract was significantly (P < 0.05) higher in dogs with than without HW infection; shock developed 5 to 30 minutes after HW injection. These signs were observed: marked decrease in blood pressure; collapse (initial collapse); paleness of mucous membranes; weak heart sounds; dyspnea; skin coldness; intestinal hyperperistalsis, and defecation; increases in RBC count, serum total protein concentration, serum osmolality, serum Na and blood glucose concentrations; and decreases in neutrophil, eosinophil, and platelet counts. Alanine transaminase, alkaline phosphatase, and lactate dehydrogenase activities increased substantially from the time of initial collapse to 24 hours after HW injection. Of 39 dogs with shock, 29 recovered from initial collapse, but 5 of the 29 subsequently collapsed again (secondary collapse), with bloody diarrhea followed by death. Of these 39 dogs, 6 died during initial collapse without bloody diarrhea, and 4 were euthanatized during initial collapse. It was confirmed that HW extract had, in fact, induced shock. These clinical, hematologic, and biochemical findings were fundamentally similar to those associated with shock resulting from administration of drugs, such as diethylcarbamazine and milbemycin D, in microfilaremic dogs with HW infection.

Sheep given powdered Ferula communis variety brevifolia at dosage of 2.5 g/kg of body weight/d for 15 days developed classical clinical signs of intoxication: anorexia, somnolence, apparent weakness, and hemorrhage. Marked reduction of vitamin K-dependent coagulation factors and prolongation of prothrombin time and activated partial thromboplastin time were consistent with presence of ferulenol, a toxic coumarinic factor in the plant. Changes induced in the coagulation system developed by the second day of plant administration and were normal within 4 days after dosing was stopped. There was no evidence of primary liver damage or platelet malfunction. Of 6 intoxicated sheep, 2 died with only minimal evidence of hemorrhage.

We evaluated the feasibility of using miniosmotic pumps as a way to continuously treat cattle with a singular ergot alkaloid (ergonovine) of known content, thus mimicking the natural fescue toxicosis disease state, but allowing study of specific alkaloid effects. Dosing animals with increasing amounts of ergonovine via miniosmotic pumps, followed by daily acquisition of plasma samples for high-performance liquid chromatographic determination of the alkaloid, resulted in stepwise increases in plasma ergonovine concentration. However, despite the detectable blood concentration of ergonovine, calves did not have typical clinical signs of ergot alkaloid toxicosis. Similarly, serum prolactin concentration was unaffected by ergonovine in these cattle, implicating some other alkaloid of endophyte-infested fescue as causative of the usual prolactin-suppressive response. The results confirm use of this animal dosing method to study biological effects of singular purified alkaloids of known amount, without bioavailability concerns. Thus, this dosing method will facilitate studies to determine the harmful effects of individual alkaloids found in toxic tall fescue, and ultimately, to alleviate their costly effects in cattle, horses, and other species.

A challenge-exposure model was developed for dose-dependent induction of subclinical (moderate) atrophic rhinitis (AR) in conventionally raised Dutch Landrace and Large White pigs, about 4 weeks old. Under favorable climatic and housing conditions, pigs were intranasally challenge-exposed with Pasteurella multocida-derived toxin (Pm-T) 3 days after pretreatment by inoculation with 1% acetic acid. Pigs were challenge-exposed with 1 of the following Pm-T doses: 0 (control), 5, 13, 20, or 40 microgram of Pm-T/ml of phosphate-buffered saline solution (PBSS), 0.5 ml/ nostril/d on 3 consecutive days. Five weeks after challenge exposure, subclinical moderate) AR status was defined as intermediate conchal atrophy (grade 2 for ventral conchae on a 0 to 4 scale and grade 1 or 2 for dorsal conchae on a 0 to 3 scale, respectively) and perceptible difference in change in brachygnathia superior (CBS) between control and challenge-exposed pigs between the beginning and end of the study. All Pm-T-exposed pigs had nasal damage that was dose-dependent. The higher Pm-T doses resulted in higher ventral conchae atrophy and dorsal conchae atrophy scores. The CBS increased with applied Pm-T dose, resulting in significant (P < 0.05) differences between controls (3.88 mm) and the 13-, 20-, and 40-microgram Pm-T-treated groups (7.77, 6.58, and 7.98 mm, respectively). In response to the applied dose, weight gain per week for Pm-T-exposed pigs was lower than that of controls after week 3 (P < 0.01). Difference from controls was 32, 54, 52, and 96 g/d/pig for 5-, 13-, 20-, and 40-microgram Pm-T-treated groups respectively, in the last 2 weeks. For Dutch Landrace and Large White pigs, intranasally administered Pm-T mimicked the pathogenic effect of in vivo infection with toxigenic Pm strains. The optimal model to induce subclinical AR appeared to be 13 microgram of Pm-T/ml (0.5 ml/nostril/d) on 3 consecutive days. Our model should enable studies of exogenous and endogenous factors involved in development of AR, independent of the colonizing ability of the Pm strain used.

Leukocyte adhesion deficiency was diagnosed in 4 Holstein calves from 1 to 4 months old. Calves had severe ulcers on oral mucous membranes, gingivitis, severe periodontitis, chronic pneumonia, and stunted growth associated with severe neutrophilia. Neutrophils from affected calves had function defect, characterized by severely decreased adherence, chemotactic movements, phagocytosis, luminol-dependent chemiluminescent response, and O2(-1)-producing activities. Deficient CD18 expression (0.1 to 1.7%) on neutrophils was clearly detected by use of flow cytometric analysis. These affected calves were linked to a common ancestral sire that has been documented to be a carrier. Clinical features, leukocyte functional abnormalities, deficient expression of CD18, and mode of inheritance indicated that affected calves had leukocyte adhesion deficiency. In vitro leukocyte functional abnormalities were associated with deficiency in the expression of CD11/CD18. Pathologic findings indicated possible increased susceptibility to infection associated with this disease.